Forschungstag 2008 Bereich operative Medizin Departement Anästhesie Universitätsspital Basel Mittwoch 10. September 2008 Der jetzige Forschungstag der Departemente Anästhesie und Chirurgie ist bereits die 12. Auflage dieser gemeinsamen Veranstaltung und wiederum findet dieser Forschungstag in Verbindung mit dem Tag der Ehemaligen des Departements Chirurgie statt, mit dem Ziel weiteren Interessierten einen Einblick in die vielfältigen Forschungstätigkeiten zu erlauben. Erneut steht der Informations- und Gedankenaustausch im Vordergrund. Insgesamt wurde die erfreuliche Anzahl von 112 Projekten eingereicht, die alle im vorliegenden Abstractband zusammengefasst sind. Eine leider beschränkte Anzahl der eingereichten Projekte werden im Verlaufe des heutigen Tages im Rahmen von Kurzvorträgen vorgestellt. Gerne freuen wir uns auf rege Diskussionen, die dem gegenseitigen fachübergreifenden Austausch förderlich sein werden. Wir hoffen diesen mit einem themenbezogenen Index im Abstractband zu weiter zu unterstützen. Erneut wurde für die Mittagspause ein Stehlunch organisiert mit dem Gedanken damit Gelegenheit für weitere informelle persönliche Begegnungen zu schaffen. Besten Dank an Frau Greub, Departement Chirurgie und Frau Schaller, UKBB für ihre organisatorischen Beiträge. Prof. D. Oertli Departement Chirurgie Prof. D. Scheidegger Departement Anästhesie 1 09:00 - 09:15 Begrüssung / Eröffnung: Prof. D. Scheidegger Sitzung 1 Moderation: Th. Wolff 09:15 – 09:30 N. Ebinger Mundorff Vergleich zwischen rechts- und linksseitiger retroperitoneoskopischer Lebendnierenspende nach 179 Operationen 09:30 – 09:45 F. Haecker Subureteral Endoscopic Injection Using Stabilized Non-Animal Hyaluronic Acid/ Dextranomer Gel (Deflux®) as First Line Treatment of Vesicoureteral Reflux (VUR) in Children 09:45 – 10:00 M. Zürcher Early intraosseous epinephrine increases coronary perfusion pressure comparable to late intravenous administration and improves 24h post-resuscitation neurological outcome in a swine model of prolonged ventricular fibrillation 10:00 – 10:15 D. Frey Vagal Block for Obesity Control (VBLOC™) – preliminary results of an ongoing, open-label, phase I clinical study from a single center 10:15 – 10:30 C. Burkhart Pathophysiology of Postoperative Delirium and Postoperative Cognitive Dysfunction - The Role of Inflammation and Cerebral Perfusion 10:30 – 11:00 Pause Sitzung 2 120 32 15 26 Moderation: C. Viehl 11:00 – 11:15 X. Huber IL-17 favours the expansion of IL-17-producing CD4+ T cells by amplifying LPStriggered cytokine-production by monocytes/macrophages. 11:15 – 11:30 A. Banfi Controlled angiogenesis by FACS-purified engineered myoblasts that homogeneously express specific levels of VEGF – Optimization of sorting parameters 11:30 – 11:45 M. Savic Effekt von Stammzellen bei chronischen Wunden am Modell des Dekubitalulkus. Eine Pilotstudie zur Machbarkeit, Verträglichkeit und möglichen Wirkung 11:45 – 12:00 A. Papadimitropoulos Towards an in-vitro 3D multi-cell co-culture model of bone tissue 12:00 – 12:15 J. Benthien Die autologe matrixinduzierte chondrogenese (AMIC®)- ein neues Verfahren zur Behandlung von Knorpeldefekten 12:15 – 13:30 Mittagspause / Stehlunch Das Abstractbuch kann auch aus dem Internet unter: www.anaesthesie.ch/FT08/ heruntergeladen werden. Anästhesie (SGAR): 5 creditpoints 2 134 Chirurgie (SGC): 6 creditpoints 101 99 131 110 51 Sitzung 3 Moderation: M. Siegemund 13:30 – 13:45 E. Taub Bipallidal Stimulation Improves Glottal Closure in the Dysphonia of Parkinson’s Disease: Case Report with Videographic Documentation 13:45 – 14:00 M. Hirschmann Bestimmung der anterioren Beckenebene mittels Freihand-3D-Ultraschall für die Pfannenorientierung in der navigierten Hüfttotalprothetik 14:00 – 14:15 A. Müller Capturing infant faces with cleft lip in the operation theatre using the T-Scan! 14:15 – 14:30 W. Ruppen Correlation of SPECT-CT scans findings and diagnostic-prognostic blockades of zygapophysial joint in patients with nonspecific low back pain 14:30 – 14:45 A. Leumann SPECT-CT: a new imaging diagnostic tool for osteochondral lesions (OCL) of the talus – comparison to MRI 14:45 – 15:15 Pause Sitzung 4 127 59 117 31 66 Moderation: W. Ruppen 15:15 – 15:30 T. Grussenmeyer Quantitative Proteomanalyse in einem Tiermodell der Hypertonie-induzierten Herzinsuffizienz 15:30 – 15:45 G. Lurati-Buse Postoperative troponin T release is associated with 12-month mortality after onpump cardiac surgery in adults 15:45 – 16:00 O. Bandschapp Effects of anesthetics on chloride channel related myotonia 16:00 – 16:15 J. Schulze Clinical results after Sauvé-Kapandji operation of the arthritic distal radioulnar joint 16:15 – 16:30 B. Göpfert Analysis of Muscular Coordination in Different Jumping Elements in Aerial Freestyle Skiiing 16:30 Ende Forschungstag 90 29 25 88 55 Das Abstractbuch kann auch aus dem Internet unter: www.anaesthesie.ch/FT08/ heruntergeladen werden. Anästhesie (SGAR): 5 creditpoints Chirurgie (SGC): 6 creditpoints 3 Inhaltsverzeichnis Allgemeinchirurgie Randomized clinical trial of Lichtensteins’s operation versus mesh plug repair for inguinal hernia repair – long term results s.15 Daniel M. Frey1,2, Edin Mujagic1,2, Markus Zuber3, Jürg Metzger4, Daniel Oertli1, Christian T. Hamel1 Vagal Block for Obesity Control (VBLOC™) – preliminary results of an ongoing, open-label, phase I clinical study from a single center s.16 Daniel M. Frey1, Carsten T. Viehl1, Rolf Stöckli2, Henrik Zulewski2, Mark Vollmer3, Richard R. Wilson3, Ulrich Keller2, Daniel Oertli1 Vergleich der intraoperativen Leberverformung mit der präoperativen durch 3D-Bildgebung unterstützten Operationsplanung: Prospektive Pilotstudie s.17 O. Heizmann1, Ch. Kettelhach1, H. Bourquain2, S. Pottast3, D. Oertli1. Th1- and Th2-type cytokines in plasma after Major Trauma s.18 Oleg Heizmann,MD , Manfred Koeller,PhD , Gert Muhr, MD , Daniel Oertli,MD, FACS , and Christian Schinkel,MD, FACS2 1 2 2 1 Surgical Glove Perforation and the Risk of Surgical Site Infection s.19 Heidi Misteli , Walter P. Weber , Stefan Reck , Rachel Rosenthal , Marcel Zwahlen , Philipp Fueglistaler , Martin K. Bolli1, Daniel Oertli1, Andreas F. Widmer2 and Walter R. Marti1 1 1 1 1 3 1 Early versus delayed cholecystectomy in patients with biliary acute pancreatitis s.20 Christian A. Nebiker, Christian T. Hamel, Daniel Oertli, Christoph Kettelhack, Daniel M. Frey Quality of surveillance after curative surgery for colon cancer s.21 A. Ochsner , U. von Holzen , C.T. Viehl , R. Cecini , U. Güller , I. Langer , U. Laffer , D. Oertli , M. Zuber ; 1 4 1 2 1 3 2 1 4 Monitoring of cellular immune responses in whole blood: a simple, sensitive and accurate PCR based method s.22 Elke Schultz-Thater1, Paul Zajac1, Daniela Margelli2, Giulio C. Spagnoli1, Daniel M. Frey1,3 Sentinel lymph node procedure in resectable colon cancer – Results from the prospective Swiss multicenter study s.23 Carsten T. Viehl1, Ulrich Guller1, Ramona Cecini2, Igor Langer1, Alex Ochsner1, Luigi Terracciano4, Hans-Martin Riehle5, Urban Laffer2, Daniel Oertli1, Markus Zuber3 Anästhesie Analgesic and antihyperalgesic properties of propofol and its solvent in a human pain model s.25 Bandschapp O , Filitz J , Urwyler A , Koppert W , Ruppen W 1 2 1 2 1 Effects of anesthetics on chloride channel related myotonia s.26 O. Bandschapp*, C. Soule°, A. Urwyler*, P. Iaizzo°, T. Girard* Pathophysiology of Postoperative Delirium and Postoperative Cognitive Dysfunction - The Role of Inflammation and Cerebral Perfusion s.27 Burkhart CS, Gamberini M, Möckli A, Monsch A, Strebel SP, Steiner LA Effect of intravenous lidocaine on laryngeal reflex responses in children anesthetized with sevoflurane T.O. Erb, B. von Ungern-Sternberg, K. Keller, F.J. Frei, 4 s.28 s.28 Elevated BNP values does not allow for diagnosing cardiac dysfunction in young subjects s.29 Kasper J., Bolliger D, Seeberger M, Filipovic M. Postoperative troponin T release is associated with 12-month mortality after on-pump cardiac surgery in adults s.30 G Lurati Buse1, C Brüni1, J Kasper1, M Grapow2, E Seeberger1, D Bolliger1, M Seeberger1, M Filipovic1 Paramedic based transmission of 12 lead-ECG in patients with an acute coronary syndrome reduces the “call-to-balloon-time” s.31 Marc Lüthya, Mathias Zürchera, Daniel Kellerb, Yves Meuryc, Wolfgang Ummenhofera, Stephan Marschd, Patrick Hunzikerd Correlation of SPECT-CT scans findings and diagnostic-prognostic blockades of zygapophysial joint in patients with nonspecific low back pain s.32 Wilhelm Ruppen1), Esther Wettig1), Martin Kretschmar2), Stefan Schären3), Deniz Bilecen2), Augustinus Ludwig Jacob2), Armin Aeschbach1),Brugger Stefan1), Helmut Rasch4), Albert Urwyler1) Early intraosseous epinephrine increases coronary perfusion pressure comparable to late intravenous administration and improves 24h post-resuscitation neurological outcome in a swine model of prolonged ventricular fibrillation s.33 Mathias Zuercher1,5 MD; Karl B. Kern1,2 MD; Michael Loedl4, BS; Ronald W. Hilwig1 DVM, PhD; Robert A. Berg1,3 MD; Wolfgang Ummenhofer5 MD; Gordon A. Ewy1,2 MD Resequencing Arrays for Pharmacogenetic Investigations in Anaesthesia s.34 Soledad Levano, Albert Urwyler, Thierry Girard Investigations for Malignant Hyperthermia Susceptibility: An Update s.35 M. Singer , J. Benthien , S. Levano , A. Matter , A. Urwyler , T. Girard 1 2 1 1 1 1 Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45 s.36 Osvaldo Delbono , Jinyu Xia†, Susan Treves†, Zhong-Min Wang , Ramon Jimenez-Moreno , Anthony M. Payne , Laura Messi*, Alexandre Briguet°, Florian Schaerer°, Myuki Nishi#, Hiroshi Takeshima#, Francesco Zorzato† * * * * Recessive ryanodine receptor 1 mutation in a CCD patient affects RyR/Cav1.1 functional coupling s.37 Mirko Vukcevic, Farshid Ghassemi, Le Xu, Haiyan Zhou, Gerhard Meissner, Francesco Muntoni, Heinz Jungbluth, Francesco Zorzato and 2Susan Treves 1 2 2 3 2 3 4 2,5 METAP – a guideline to facilitate ethically appropriate decision making s.38 Meyer-Zehnder B (1,2), Albisser Schleger H (1), Mertz M (1), Pargger H (2), Reiter-Theil S (1) Basel Starch Evaluation in Sepsis (BaSES) Trial s.39 Martin Siegemund, Hans Pargger, Luzius Steiner, Walter Weber, Christian Müller, Evelyne Häfliger, Evelyne Bucher, Patrick Hunziker, Stephan Marsch. Succinylcholin versus Rocuronium für notfallmässige Intubationen auf der Intensivstation s.40 Martin Siegemund, Hans Pargger, Stephan Marsch Ileal and renal microcirculation during supramesenteric aortic cross clamping and reperfusion s.41 Martin Siegemund*,†, Jasper van Bommel*,‡, Wolfgang Studer†, Mat van Iterson*, Sandra Annaheim†, Michiel E. Stegenga*, Hans Pargger†, Can Ince* 5 Orthopädie - BZB Interdisziplinäre und interprofessionelle Behandlung von geriatrischen Frakturpatienten im „Kompetenznetzwerk Altersfrakturen“ s.43 M. Pretto1, R.W. Kressig2, M. Frank3, D. Bareis4, R. Spirig1, M. Jakob, N. Suhm4 Morphology of 3D-printed porous HA scaffolds for bone augmentation s.44 Fabienne C. Fierz , Felix Beckmann , Marius Huser , Stephan H. Irsen , Barbara Leukers , Frank Witte , Özer Degistirici f, Adrian Andronache b, Michael Thie f, and Bert Müller a,b,g a,b c b d d e Nuclear magnetic resonance (NMR) spectroscopy: Implications in synovial fluid analysis s.45 Thomas Hügle , Till Kühn , Helena Kovaks , Victor Valderrabano 1 2 2 3 Frontal and lateral characteristics of the osseous configuration in chronic ankle instability s.46 Magerkurth O, Frigg A, Hintermann B, Dick W, Valderrabano V. Cartilage stiffness and histological analysis of the human ankle joint cartilage s.47 Olaf Buettner1, André Leumann1,2, Magdalena Müller-Gerbl2, Victor Valderrabano1 Added Value of SPECT-CT imaging in degenerative joint disease of the foot and ankle s.48 Geert Pagenstert , André Leumann , Helmut Rasch , Jan Müller-Brandt , Beat Hintermann , Victor Valderrabano 1 2 3 3 1 2 Range of Motion of Standard and High-Flexion Posterior Cruciate Retaining Total Knee Prosthesis. A matched controlled study s.49 Geert Pagenstert1, Andreas Elsner1, Martin Bachmann1, Susanna Häfliger1, Beat Hintermann1, Victor Valderrabano2 Sports and Recreation Activity of Ankle Osteoarthritis Patients Before and After Distal Tibia Osteotomy s.50 Pagenstert G , Leumann A , Hintermann B , Valderrabano V 1 2 1 2 DUAL-MODE DYNAMIC FUNCTIONAL STIFFNESS OF ARTICULAR CARTILAGE s.51 H. Ardura Garcia , B. Goepfert , A.U. Daniels , D. Wirz 1,2 1 1 1 Die autologe matrixinduzierte Chondrogenese (AMIC®)- ein neues Verfahren zur Behandlung von Knorpeldefekten s.52 J.P. Benthien, M . Jakob Effects of antimicrobial materials on microorganism growth kinetics can be determined by isothermal micro-nano calorimetry (IMNC) s.53 A.U. Daniels, D. Wirz, U. von Ah Muskelatrophie am Unterschenkel bei Arthrose des oberen Sprunggelenkes s.54 K. Dopke , T. Egelhof , T. Wischer , W. Dick , V .Valderrabano 1 2 3 4 4 Tantalum for Ankle- and Hindfoot-Reconstruction - Analysis with Micro-CT s.55 Frigg A , Dougall H , Boyd S , Nigg B , Russell I , Valderrabano V 1,2 1 3 3 1 2 Analysis of Muscular Coordination in Different Jumping Elements in Aerial Freestyle Skiing s.56 Beat Göpfert , Cora Huber ,Anton Lüthi , Dieter Wirz 1 1 2 1 Adult-onset Still’s disease (AOSD) - a rare osteoarthritis entity for the orthopedic surgeon s.57 Dorian Hauke ,Franziska Saxer ,Alexander Tzankov , Victor Valderrabano 1 1 2 1 Arthroscopic repair of massive rotator cuff tears: correlation of functional results with muscle atrophy, fatty infiltration and integrity of the cuff in a prospective, MRI controlled study s.58 Dorian Hauke 1, Sven Lichtenberg 2, Dennis Liem 3, Robert Varga 2, Petra Magosch 2 and Peter Habermeyer 2 6 Die Kraftmessung im Constant Murley Scores: Wie verlässlich und präzise messen wir überhaupt? s.59 Hirschmann MT , Wind B , Amsler F , Regazzoni P , Gross T 1 1 2 3 4 Bestimmung der anterioren Beckenebene mittels Freihand-3D-Ultraschall für die Pfannenorientierung in der navigierten Hüfttotalprothetik s.60 Hirschmann MT1, Helfrich C 1, Schäfer T 1, Schwägli T2, Overhoff HM3, Friederich NF1 Mediane 5-Jahres-Ergebnisse nach winkelstabiler Plattenosteosynthese proximaler Humerusfrakturen s.61 Hirschmann MT , Fallegger B , Amsler F , Regazzoni P , Gross T 1 1 2 3 4 Longterm Outcome of Isolated Subtalar Arthrodesis with Two Screws Fixation s.62 Monika Horisberger Andreas M. Müller, André Leumann, Arné Mehrkens, Olaf Buettner, Martin Wiewiorski, Victor Valderrabano , Spherical separation detects the effect of endurance and sprint training in the wavelet transformed EMG spectra s.63 Cora Huber1, Beat Göpfert1, Dieter Wirz1, Reinald Brunner2, Vinzenz von Tscharner3 Klinische, radiologische und biomechanische Analyse von Talonavicular-Arthrodesen s.64 Sandra Kölblin, André Leumann, Martin Wiewiorski, Thomas Egelhof, Victor Valderrabano Chronische Achillessehnenossifikation – Fallbericht und Diskussion therapeutischer Optionen s.65 André Leumann, Claudio Rosso, Victor Valderrabano Analysis of the subchondral bone plate density of the talus by means of CT-Osteoabsorptiometry (CTOAM) s.66 Leumann A1,2, Müller-Gerbl M2, Büttner O1, Dick W1, Valderrabano V1 SPECT-CT: a new imaging diagnostic tool for osteochondral lesions (OCL) of the talus – comparison to MRI s.67 Leumann André MD*, Pagenstert Geert I. MDç, Plaass Christian MD*, Rasch Helmut MD+, Egelhof Thomas MD°, Hintermann Beat MDç, Valderrabano Victor MD PhD* Mid- and Long-term Results of Medial Malleolar Osteotomy for Treatment of Medial Talus Osteochondral Lesions s.68 Antonios Konstantinidis, André Leumann, Olaf Buettner, Monika Horisberger, Kai-Uwe Steuber, Victor Valderrabano Prospektive klinische Evaluation einer Methode zur intraoperativen Messung der Knochenfestigkeit – erste Ergebnisse aus der Pilotstudie s.69 Andreas Marc Müller 1, Michael Hirschmann 2 , Norbert Suhm 1 Wavelet-EMG-analysis of the co-contraction of the leg muscles in fencing during a flèche attack s.70 Corina Nüesch , Beat Göpfert , Marcel Fischer , Julien Frere , Dieter Wirz , Niklaus Friederich 1,3 1 1,2 1,4 1,2 The Effect of Restricted Knee Extension on Gait in Healthy Subjects 2 s.71 Jacqueline Romkes, Christine Seppi, Reinald Brunner TIME-FREQUENCY ANALYSIS OF LEG MUSCLES DURING GAIT IN PATIENTS WITH DIPLEGIC CEREBRAL PALSY s.72 Jacqueline Romkes and Reinald Brunner Calf Muscle Atrophy after Achilles Tendon Rupture – A Clinical-Radiological-Biomechanical Multicenter Study s.73 Rosso Claudio1, Majewski Martin1, Heisterbach Patricia1, Egelhof Thomas2, Polzer Caroline1, Regazzoni Pietro1, Valderrabano Victor1 7 Preoperative Botulinum Toxin To Avoid Poor Surgical Results of Muscle Lengthening in Patients With Cerebral Palsy s.74 Rutz E. MD, Hofmann E. MS, Brunner R. MD Total hip arthroplasty after hip joint arthrodesis Erich Rutz, MD 1,2 s.75 , Dirk Schäfer, MD , Victor Valderrabano, MD, PhD + 2 Intertrochantere Korrekturosteotomien mit der LCP-Pädiatrie-Hüftplatte s.76 Erich Rutz, Reinald Brunner Suprakondyläre Femur- Korrekturosteotomien mit einer modifizierten LCP-Pädiatrie-Hüftplatte s.77 Erich Rutz, Reinald Brunner High tibial closing wedge osteotomy in middle-aged patients. A 10 year experience s.78 Kai Sprengel, Andreas Schmid°, Victor Valderrabano , Christian Flamme* # Position of the patella after high tibial closing wedge osteotomy s.79 Kai Sprengel, Andreas Schmid°, Victor Valderrabano , Christian Flamme* # Osteotomy of the fibula in high tibial closing wedge osteotomy s.80 Kai Sprengel, Andreas Schmid°, Victor Valderrabano , Christian Flamme* # CT-guided Robotically-assisted Retrograde Drilling of Osteochondral Lesions s.81 Victor Valderrabano , Martin Wiewiorski , André Leumann , Olaf Büttner , Martin Kretzschmar , Helmut Rasch , Tanja Markus4, Severine Dziergwa4, Deniz Bilecen4, Augustinus Ludwig Jacob4 1 1 1 1 2 3 Origin of Pain in Osteochondral Lesions s.82 Victor Valderrabano , Martin Wiewiorski , Monika Horisberger , Olaf Buettner , André Leumann , Martin Kretzschmar2, Helmut Rasch3, Deniz Bilecen4, Augustinus Ludwig Jacob4 1 1 1 1 1 Early results of a New Retrograde Lower Leg/Hindfoot Arthrodesis Nail – A prospective Study s.83 Victor Valderrabano , Monika Horisberger , Andreas M. Müller , Arne Mehrkens , André Leumann , Kai-Uwe Steuber1 1 1 1 1 1 Analysis of a New Hemostatic and Analgetic Bioresorbable Putty for Bone Surgery s.84 Victor Valderrabano , Andreas M. Müller , Lars Walz , Susanne Müller , Arne Mehrkens 1 1 2 2 1 Swiss Prospective Randomized Study on Use of Orthobiologics in a Subtalar Arthrodesis Model s.85 Victor Valderrrabano , Ernst-Wilhelm Radü , Andreas Müller , Arne Mehrkens , Marcel Jakob , Ivan Martin , Norman Espinosa 4 , Lars Walz5 , Christiane Pauli Magnus 5 1 2 1 1 1 99mTc-DPD-SPECT-CT for Localization of Symptomatic Osteoarthritic Joints 3 s.86 Martin Wiewiorski1, Martin Kretzschmar2, Helmut Rasch3, Deniz Bilecen4, Augustinus Ludwig Jacob4 , Victor Valderrabano1 90° Peel Off Test for Measuring Osteochondral Bonding in Tissue-engineered Constructs s.87 Wirz D , Buergin V , Francioli S , Barbero A , Martin I , Goepfert B , Daniels AU 1 1 2 2 2 1 1 Handchirurgie Clinical results after Sauvé-Kapandji Operation of the arthritic distal radioulnar joint Jens Schulze, Sabina Lang, Urs Genewein, Hans Troeger 8 s.89 Herzchirurgie Quantitative Proteomanalyse in einem Tiermodell der Hypertonie-induzierten Herzinsuffizienz s.91 Thomas Grussenmeyer1, Ivan Lefkovits1, Silvia Meili-Butz2, Thomas Dieterle2, Thierry Carrel1,3, Friedrich Eckstein1. Rapamycin impairs endothelial cell function in human arteries s.92 Martin T. R. Grapow, David C. Reineke, Moritz A. Konerding, Thomas Grussenmeyer, Peter Matt, Thierry P. Carrel, Else Mueller-Schweinitzer, Friedrich S. Eckstein TGF-beta Is A Promising Biomarker For Monitoring The Aortic Root Dilatation And Losartan Therapy In Marfan Syndrome s.93 Peter Matt12; Jennifer Habashi1; Tammy Holm1; Qin Fu1; Florian Schoenhoff1; Friedrich Eckstein2; David Huso3; Jennifer Van Eyk1; Harry Dietz1 A New Mouse Model of Acute Aortic Dissection Type A in Marfan Syndrome s.94 Peter Matt ; Jennifer Habashi ; James Black ; Friedrich Eckstein , Martin Grapow ; Florian Rueter ; David Huso ; Jennifer Van Eyk1; Harry Dietz1 12 1 1 2 2 2 1 Activated Rho/Rho kinase and modified calcium sensitivity in cryopreserved human saphenous veins s.95 Else Müller-Schweinitzer a,b*, David C. Reineke c, Erika Glusa d, Anthony B. Ebeigbe e,Martin T. R. Grapow a,b , Thierry P. Carrel a,b,c, Friedrich S. Ecksteina,b ICSF Dose-dependent angiogenic effects of VEGF164 and PDGF-BB co-delivery s.97 R. Gianni-Barrera, P. Fueglistaler, T. Wolff, H. Misteli, L. Gürke, M. Heberer and A. Banfi Recombinant vaccinia virus expressing CD40 ligand enhances the expansion of CD8+ T cells with a memory phenotype s.98 Chantal FEDER-MENGUS, Walter P. WEBER, Nermin RAAFAT, Elke SCHULTZ-THATER, Michel ADAMINA, Daniel OERTLI, Michael HEBERER, Giulio C. SPAGNOLI and Paul ZAJAC. Impaired responsiveness to homeostatic cytokines and CD8+ T cells exhaustion in prostatic diseases s.99 Chantal Feder-Mengus, Clémentine Le Magnen, Robin Ruszat, Alexander Bachmann, Michael Heberer, Giulio Spagnoli and Stephen Wyler. Controlled angiogenesis by FACS-purified engineered myoblasts that homogeneously express specific levels of VEGF – Optimization of sorting parameters s.100 P. Fueglistaler, T. Wolff, H. Misteli, R. Gianni-Barrera, L. Gürke, M. Heberer, A. Banfi Nutzenpotential workflowgestützter Kodierung am Beispiel der Handchirurgie s.101 Urs Genewein, MD, MME, IL-17 favours the expansion of IL-17-producing CD4+ T cells by amplifying LPS-triggered cytokine-production by monocytes/macrophages s.102 X.S. Huber, C. Feder-Mengus, D.M. Frey, R.A. Droeser, M. Heberer, G.C. Spagnoli, G. Iezzi Characterization of putative cancer stem cells in colorectal carcinoma cell lines s.103 M.G. Muraro, C. Giovenzana, X.S. Huber, R. Droeser, L. Tornillo, I. Zlobec, M. Heberer, D.M. Frey, G.C. Spagnoli, D. Oertli and G. Iezzi. Feasibility of cell-based therapeutic angiogenesis by FACS-purification of VEGF-expressing human myoblasts s.104 E. Mujagic, A. Patel, T. Wolff, R. Giannì-Barrera, L. Gürke, M. Heberer, A. Banfi 9 Modulation of immunogenicity of viral cancer vaccine s.105 Dr. Nermin RAAFAT, Prof. Giulio SPAGNOLI, Prof. Michael HEBERER and Dr. Paul ZAJAC. Adenoviral co-delivery of VEGF164 and PDGF-BB for therapeutic angiogenesis s.106 S. Reginato, R. Gianni-Barrera, T. Wolff, L. Gürke, M. Heberer and A. Banfi Safety and efficacy of controlled VEGF expression in chronic hind limb ischemia s.107 T. Wolff, E. Mujagic, P. Fueglistaler, R. Gianni-Barrera, L. Gürke, M. Heberer, A. Banfi ARE ANKLE CHONDROCYTES FROM DAMAGED FRAGMENTS A SUITABLE CELL SOURCE FOR TISSUE ENGINEERING-BASED CARTILAGE REPAIR? s.108 Candrian C.1;2*, Miot S.1, Wolf F1. Bonacina E.1, Valderrabano V.1 , Dickinson S.3, Wirz D. 4, Jakob M. 1, Daniels A.U. 4, Heberer M.1, Martin I.1, Barbero A.1 FGF-2 selects and maintains a population of in vitro self-renewing, highly potent, non-adherent mesenchymal progenitors s.109 Di Maggio N., Banfi A., Schaeren S., Heberer M., Martin I. Platelet lysate as a serum substitute for 2D-static and 3D-perfusion culture of human stromal-vascular fraction cells of adipose tissue s.110 Andreas Marc Müller 1, Michael Davenport 1, Sophie Verrier 2, Mauro Alini 2, Chiara Bocelli-Tyndall 1,3, Michael Heberer 1, Ivan Martin 1 and Arnaud Scherberich 1 Towards an in-vitro 3D multi-cell co-culture model of bone tissue s.111 Papadimitropoulos, A. Mehrkens, M. Heberer, A. Scherberich and I. Martin Bioreactor based engineering of large-scale engineered cartilage grafts for joint resurfacing s.112 Santoro, R; 2Brans, G; 3Olivares, D; 3Lacroix, D; 4 Wirz, D; 1Jakob, M; 1Martin, I; 1Wendt, D 1 ENGINEERING OSTECHONDRAL TISSUES WITH HUMAN ARTICULAR CHONDROCYTES AND CLINICALLY USED BIOMATERIALS s.113 Scotti C.1, Wolf F.1, Wirz D.2, Schaefer D.J.1,3, Candrian C.1,4, Valderrabano V. 5, Heberer M.1, Daniels A.U. 2, Martin I.1, Barbero A.1 From primary chondrocytes to engineered grafts: Streamlined bioreactor-based engineering of human cartilage tissue s.114 Tonnarelli, B; Jakob, M; Martin, I; and Wendt, D. Konzept zur Produktivitätsmessung von Krankenhäusern s.115 Arlett Prengel, Michael Heberer Kiefer- und Gesichtschirurgie Oculodynamic MRI- a helpful tool for maxillofacial surgeons? s.117 B.-I. Berg , C. Kunz , K. Schwenzer-Zimmerer , E.W. Radü , C. Kober , K. Scheffler , C. Buitrago-Téllez and A. Palmowski-Wolfe 1, 2 1, 2 1, 2 3 4 5 6 Capturing infant faces with cleft lip in the operation theatre using the T-Scan® s.118 B.-I. Berg , A.A. Müller , B. Williger , P. Jürgens , A. Ringenbach , E. Schkommodau , K. Schwenzer-Zimmerer 1,2 1,2 1,2 1,2 1,2 3 3 Neurobiologische Parameter bei Kindern vor und nach dem Lippen-Kiefer-Gaumenspaltverschluss – eine longitudinale Querschnittsstudie s.119 Andreas Müller1,2, Serge Brand3, Edith Holsboer-Trachsler3, Robert Sader2,4, Hans-Florian Zeilhofer1,2, Katja SchwenzerZimmerer1,2 10 Kinderchirurgie Subureteral Endoscopic Injection Using Stabilized Non-Animal Hyaluronic Acid/Dextranomer Gel (Deflux®) as First Line Treatment of Vesicoureteral Reflux (VUR) in Children s.121 Haecker FM1, Dörfler M1, von Rotz M1, Rudin C2, Mayr J1 Die Saugglocke nach E. Klobe zur konservativen Therapie der Trichterbrust: eine alternative Therapie? s.122 Frank-Martin Häcker, Jozef Bielek, Johannes Mayr FAST RECOVERY FOLLOWING ENDOSCOPIC STENTING FOR PANCREATIC DUCT INJURY s.123 M. Köhler1, D Siabalis1, FM Häcker1, L Degen2, J Mayr1. Neurochirurgie The influence of blood on energy metabolism, brain edema, histological damage and functional outcome after evacuation of acute subdural hematoma in rats s.125 H. Baechli1, M. Behzad2, A. Heimannr2, H.-G. Buchholz3, O. Kempski2, B. Alessandri2 Role of dopaminergic transmission in extinction of conditioned fear in the prefrontal cortex of mice s.126 H. Bächli , C.K. Thöringer , N. Edlbergmeier , C. Flachskamm , C.T. Wotjak 1 2 2 2 2 Neoadjuvant Targeting of Glioblastome Multiforme with Radiolabelled Substance P – Results from a Phase I Study s.127 D. Cordier1, S. Kneifel2, F. Forrer2, Martin Sailer1, J.C. Reubi 3, H. Mäcke2, J. Müller-Brand2, A. Merlo 1 Bipallidal Stimulation Improves Glottal Closure in the Dysphonia of Parkinson’s Disease: Case Report with Videographic Documentation s.128 Ethan Taub1, Adrian Merlo1, Peter Fuhr2 und Claudio Storck3 A New Assessment Tool for Evaluation of Normal Pressure Hydrocephalus (NPH): Quantitative Volumetric CSF Drainage s.129 Wasner M.G. Plastische, rekonstruktive und ästhetische Chirurgie Tissue Engineered Autologous 3D-Arthroplasty of the First Carpo-Metacarpal Joint in Thumb Basal Joint Osteoarthritis s.131 Marina Barandun a, Magdalena Müller-Gerbl b, Thomas Egelhof c, Victor Valderrabano d, Marcel Jakob d, Michael Heberer e, Ivan Martin e, Dirk J. Schaefer a Effekt von Stammzellen bei chronischen Wunden am Modell des Dekubitalulkus. Eine Pilotstudie zur Machbarkeit,Verträglichkeit und möglichen Wirkung s.132 Savic M1, Zweifel M1, Scheufler O1, Kalbermatten D1, Schmid D1, Gratwohl A2, Halter J2, Dirnhofer S3, Baumberger M4, Schaefer DJ1, Pierer G1 Vascularized tissue engineered bone flaps s.133 Dirk J Schaefer1, C. Jaquiéry2, R Verstappen1, D. Schmid1, A. Scherberich, M. 3 Heberer3, I Martin3 11 Urologie Vergleich zwischen rechts- und linksseitiger retroperitoneoskopoischer Lebendnierenspende nach 179 Operationen s.135 N. Ebinger Mundorff, S. Wyler, C. Abe, T. Gasser, A. Bachmann Greenlight Laser Vaporisation der Prostata – Erfahrungen und Langzeitergebnisse nach 500 Eingriffen M. Rieken, S. Wyler, C. Abe, G. Bonkat, T. Gasser, A. Bachmann 12 s.136 Allgemeinchirurgie 13 Randomized clinical trial of Lichtensteins’s operation versus mesh plug repair for inguinal hernia repair – long term results Daniel M. Frey1,2, Edin Mujagic1,2, Markus Zuber3, Jürg Metzger4, Daniel Oertli1, Christian T. Hamel1 Department of Surgery, University of Basel, 2Institute for Surgical Research and Hospital Management (ICFS), University of Basel, 3Department of Surgery, Kantonsspital Olten, 4Department of Surgery, Kantonsspital Lucerne 1 Background The technique of choice in open prosthetic tensionfree hernia repair remains a subject of ongoing debate. It has become clear that morbidity associated with this operation mainly consists of chronic groin pain. The objective of the present investigation was to compare the two most commonly used surgical procedures with respect to recurrence rate and associated morbidity. Long-term randomized studies with 5-year follow-up to investigate recurrence rate and chronic groin pain have not been published yet. Here we report the results at 6.5 years of followup. Methods The study was designed as a prospective, randomized multicentre trial, conducted at three teaching hospitals in Switzerland. Five hundred and ninety-five patients with 700 primary or recurrent inguinal hernias were randomized to undergo either Lichtenstein’s operation or mesh plug repair. Primary endpoint of the investigation was the longterm recurrence rate. Secondary endpoints were perioperative complications, reoperation rates and chronic groin pain. Results At the 6.5 years follow-up, 528 (75.5%) cases were clinically evaluated. The cumulative recurrence rate between the two groups was statistically not significant (p = 0.871). Twenty (7.8%) recurrences 14 occurred in the Lichtenstein group, and another 20 (7.4%) could be detected in patients after mesh plug repair. Likewise, there were no significant differences regarding perioperative complications and reoperation rates (p = 0.1435). Fifty-eight (22.5%) patients in the Lichtenstein group and sixty-two (22.9%) patients in the mesh plug group complaint of chronic pain (p = 1.00). Conclusions With an excellent rate of follow-up at 6.5 years (75.5%), the evaluation of the long-term outcomes provided no evidence that either technique is superior. The overall recurrence rate of 7.6 per cent was higher than expected, but presumably represent the real life outside specialized hernia centres. Chronic pain remains a problematic late complication in prosthetic tension-free hernia repair. We could not observe any statistically significant difference between the two subsets.The overall rate of chronic pain was 22.7 per cent, which is fairly comparable with other published long-term results. Our data suggest that the Lichtenstein’s operation and the mesh plug repair are absolutely comparable with respect to recurrence rate and late complications. In general, recurrence rates may be underestimated as recurrences continue to develop for up to 6.5 years after surgery. Vagal Block for Obesity Control (VBLOC™) – preliminary results of an ongoing, open-label, phase I clinical study from a single center Daniel M. Frey1, Carsten T. Viehl1, Rolf Stöckli2, Henrik Zulewski2, Mark Vollmer3, Richard R. Wilson3, Ulrich Keller2, Daniel Oertli1 Department of General Surgery, University Hospital of Basel, 2Division of Endocrinology, Diabetes & Clinical Nutrition, University Hospital of Basel, Switzerland, 3EnteroMedics Inc., St. Paul, MN, USA 1 Background Obesity is a global medical problem with increasing prevalence, associated with a high morbidity and mortality. The currently available treatment options do not meet the needs of all obese patients. Activation and up-regulation of the efferent and afferent fibers of the intra-abdominal vagal nerve trunks is a pivotal physiological mechanism for food ingestion, mechanical processing, enzymatic digestion and calorie absorption. A novel medical device (Maestro™ System) has been designed to take therapeutic benefit from these physiological principles by reversibly and controllably downregulating/blocking both the anterior and posterior intra-abdominal vagal trunk in order to: (1) reduce food intake by reducing gastric volume; (2) initiate early and prolonged satiation by delaying gastric emptying; and (3) decrease calorie absorption by down-regulating pancreatic exocrine secretion and nutrient assimilation. The objective of the present investigation is to evaluate the safety, efficacy and treatment algorithms of the Maestro™ system causing weight loss in obese subjects. Methods The study was designed as an open-label, multicenter, prospective clinical trial with four participating University Hospitals in Mexico City, Adelaide, Trondheim and Basel. The vagal blocking system (Maestro™, EnteroMedics Inc., St. Paul, MN, USA) was laparoscopically implanted after patient’s informed consent was obtained. Two weeks later, vagal blocking was initiated using optimized therapy algorithms based on data from an earlier feasibility trial. Subjects have been followed to 6 and 12 months respectively for excess weight loss (EWL) and for adverse events with physical and lab exams. Results Nine subjects (median BMI: 37.5 kg/m2) were implanted at the University Hospital of Basel. The mean excess weight loss 6 and 12 months after implant was 18% (10.4 kg) and 15% (9.2 kg).Appetite (as measured by a visual analogue scale, 1 -100 mm) was reduced from 69 to 41 mm.Waist circumference was reduced by 11 cm (range 0 -18 cm).There were no serious adverse events associated with the device, although one subject was hospitalized for two days because of peripheral lung embolism. One subject left the study after 6 months because of weight loss she considered insufficient and unsatisfactory suppression of appetite. The remaining subjects demonstrated ongoing weight loss up to the last follow-up. Conclusions Based on the preliminary results, we suggest that intermittent, intra-abdominal vagal blocking using a novel, programmable medical device is associated with both significant excess weight loss and a desirable safety profile. Patients will continue in a long-term follow-up protocol. 15 Vergleich der intraoperativen Leberverformung mit der präoperativen durch 3D-Bildgebung unterstützten Operationsplanung: Prospektive Pilotstudie O. Heizmann1, Ch. Kettelhach1, H. Bourquain2, S. Pottast3, D. Oertli1. Klinik für Viszeral- und Gefässchirurgie, Universitätsspital Basel MEVIS-Research Institut, Universität Bremen 3 Institut für Radiologie, Universitätsspital Basel 1 2 Einführung Navigationssysteme und 3-D-Planung werden in vielen chirurgischen Disziplinen mit grossem Erfolg eingesetzt. Das Etablieren solcher Systeme, vor allem in der Leberchirurgie, ist vom besonderen Wert und Gegenstand der intensiven Forschung. Der Einsatz solcher Systeme wird aber aktuell von den klinischen Anwendern auf Grund hohen technischen Aufwand im Transfer der Anwendungen von starren anatomischen Strukturen auf atembewegliche und verformbare Organe kontrovers diskutiert. Mit den Segmentierungssystemen kann die Darstellung der Lebersegmente, der Tumorlage bezüglich der Gefäßsysteme, wie auch Volumenbestimmung des Restvolumens berechnet und dargestellt werden. Basis der Datenakquisition ist die Computertomographie(CT). Das Ziel der Studie war es zu untersuchen, ob die präoperative Operationsplanung mittels 3D-Visualisierung, • für die routinemässige klinische Anwendung in der Leber- bzw. Viszeralchirurgie geeignet ist, indem die prä- als auch intraoperative Bildgebung gegen einander verglichen werden. • Grundlage eines späteren Navigationsprotokolls für parechymsparende Leberresektionen und exaktere Durchführung von Radio-FrequenzAblation (RFA). Sowie zu untersuchen, ob die Unterschiede zwischen prä- und intraoperativer Bildgebung, wenn diese vorhanden, einer Gesetztmässigkeit unterliegen. Patienten und Methoden 10 konsekutive Patienten der Viszeralchirurgie, die einen resektionsbedürftigen Lebertumor haben. Die Leberresektion wird nach präoperativer Planung mit Hilfe der 3D-Bildgebung (HepaVision2, MeVis Bremen) im Multifunktionsraum für Bildgebung und Interventionen (MBI) durchgeführt. Nach 16 Mobilisation der Leber, der Darstellung und Sicherung der zu- und abführenden Lebergefäße wird unter Wahrung strenger chirurgischer Sterilität eine intraoperative CT durchgeführt. Die Dauer der Untersuchung beträgt ca. 30min. Anschließend wird die Leberresektion in üblicher Weiser vollendet. Die Überwachung aller Vitalparameter ist ununterbrochen gewährleistet. Resultate Die Durchführung der Leberresektion im MBI mit intraoperativer CT ist möglich. Die operationsbedingte Organverformung und ihr Ausmass wurden erstmalig mittels intraoperativer CT dokumentiert. Bei fehlender Gesetzmässigkeit dieser Verformung bezüglich der Referenzpunkte (Gefässverzweigungen 1. und 2. Ordnung) ist die Berechnung der Vektoren mit Hilfe einer Software nicht möglich. Signifikanz Diese Pilotstudie zeigte, dass die präoperative Operationsplanung mit Hilfe der 3D-Visualisierung auch für die Leberchirurgie bzw. für die Chirurgie parenchymatöser Organe gut geeignet ist. Allerdings kann die präoperative 3D-Segmentierung auf Grund der hier gezeigten operationsbedingten Organverformung mit fehlender Gesetzmässigkeit nicht als Grundlage eines Navigationsprotokolls angesehen werden. Weiterhin kann der CTgesteuerten Navigation in der Leberchirurgie durch enormen technischen und personellen Aufwand keine grössere Zukunft beigemessen werden. Anhand der publizierten Daten und unseren bisherigen Erfahrungen wird die Navigation in der Leberchirurgie auf Ultraschallbasis basieren. Th1- and Th2-type cytokines in plasma after Major Trauma Oleg Heizmann,MD1, Manfred Koeller,PhD2, Gert Muhr, MD2, Daniel Oertli,MD, FACS1, and Christian Schinkel,MD, FACS2 Allgemeinchirurgische Klinik, Department of Surgery, University Hospital Basel, Switzerland BG Kliniken Bergmannsheil, Department of Surgery, Ruhr University Bochum, Germany 1 2 BACKGROUND Major trauma induces a dysregulation of immune response supported in parts by lymphocyte dysfunction. Controversial data about a shift within the T-helper cell subsets Th1/Th2 are reported. METHODS To prove whether Th1/Th2-type cytokine plasma levels reflect the postulated Th2 shift after trauma, we investigated in a retrospective study 195 severely injured patients (47 female, 148 male; mean age 39.7 p 15.8 yrs.; ISS 32.0 p 11.3 pts.; overall 1887 samples) during their ICU stay post trauma. Mortality rate was 19 %. Th1-type cytokines IL-2, IFN-G, IL-12 (p70), IL-18 and Th2-type cytokines IL-4, IL-10, and IL-11 were determined using the ELISA technique in patients and in healthy controls. RESULTS IL-2 and IFN-G were seldom detectable. All other mediators were significantly increased matched to controls (p<0.05). All cytokines were elevated most prominent during week 1 and 2 post trauma and declined thereafter. A trend towards lower levels in non-survivors was seen for both groups of cytokines. However significant differences were only seen for ISS, age, WBC and CRP. All mediators correlated positively with each other (p<0.01), a Th2-type shift was not observed. Two groups of patients were identified: one group with generally high plasma levels of all cytokines investigated and a second group of non-responders that presented with low or diminished plasma levels in which most non-survivors were found. CONCLUSION We conclude that in plasma no Th1/Th2-shift can be observed after major trauma. 17 Surgical Glove Perforation and the Risk of Surgical Site Infection Heidi Misteli1, Walter P. Weber1, Stefan Reck1, Rachel Rosenthal1, Marcel Zwahlen3, Philipp Fueglistaler1, Martin K. Bolli1, Daniel Oertli1, Andreas F. Widmer2 and Walter R. Marti1 Department of Surgery1, Hospital Hygiene2 University Hospital of Basel, ISPM University Bern3 Background While surgical glove leakage is a known risk factor in the transfer of pathogens during surgery, the implications of such a breach in asepsis for the development of surgical site infections (SSI) has not been thoroughly investigated. The present study was conducted to test the hypothesis that clinically visible surgical glove perforation is associated with an increased SSI incidence. Methods The data for this prospective observational cohort study of 4147 surgical procedures were collected between January 1, 2000 and December 31, 2001 at Basel University Hospital. All procedures performed in the Vascular, Visceral and Traumatology Divisions were consecutively enrolled. Patients received prophylactic antibiotics if they underwent surgery classified as wound class 2-3, eventually in wound class 1.Wound class 4 was excluded because of periand postoperative antibiotic therapy and the disease inherent preexisting high bacterial contamination. Outcome of interest was the incidence of SSI which was assessed pursuant to Centers for Disease Control and Prevention standards. Eighty two variables were recorded for each surgical procedure. The main predictor variable was compromised asepsis due to visible glove perforation. The use of single gloves was standard practice. 18 Results Of a total of 6540 procedures, 6283 were monitored. After excluding wound class 4 and cases with missing information, 4147 procedures were further analyzed. The overall SSI rate was 4.5% (188/4147). From 677 interventions with compromised asepsis, 7.5% (51) SSI were recorded, compared to 4.0% (137) from 3470 procedures where asepsis was not breached. Crude analysis showed a higher likelihood of SSI in which gloves were perforated than in interventions, where asepsis was maintained (odds ratio 1.98; 95% confidence interval, 1.4 to 2.8; p < 0.001). Most importantly crude and multivariate logistic regression analyses showed that the increase of SSI risk with perforation of gloves was predominantly based upon the criteria of antimicrobial prophylaxis (test for effect modification: p=0.005): In the absence of surgical antimicrobial prophylaxis, glove perforation entailed significantly higher odds of SSI than in the reference group (i.e., with no breach of asepsis) (odds ratio 4.24; 95% confidence interval, 1.7 to 10.8; p = 0.003), whereas when surgical antimicrobial prophylaxis was applied, the likelihood of SSI was not significantly higher for operations in which gloves were punctured (odds ratio = 1.25; 95% confidence interval, 0.85 to 1.85; p = 0.263) Conclusion In the absence of antimicrobial prophylaxis glove perforation increases the risk of SSI. In addition to lowering the risk of glove leak by double gloving or routinely changing gloves in lengthy surgical procedures, the advantages of extending the indication of surgical antimicrobial prophylaxis in wound class 1 for further reduction of the incidence of SSI should be considered. Early versus delayed cholecystectomy in patients with biliary acute pancreatitis Christian A. Nebiker, Christian T. Hamel, Daniel Oertli, Christoph Kettelhack, Daniel M. Frey Department of Surgery, University Hospital of Basel, Switzerland Background In patients with biliary acute pancreatitis, cholecystectomy is mandatory to prevent further biliary events. However, timing of surgery remains a subject of ongoing debate. The objective of the present retrospective study was to compare the outcomes of early (within 2 weeks after onset of disease) versus delayed cholecystectomy in patients with biliary acute pancreatitis. Results There were no statistically significant differences regarding conversion rates to open surgery (2/32 vs. 2/67 or 6% versus 3%; p = 0.59), local (3% versus 4%; p = 1.00) or systemic complications (0 versus 3%; P = 1.00), and mean postoperative stay (4.7 days vs. 5.7 days; p = 0.40). However, a significantly higher rate of recurrent biliary pancreatitis was found in group B (0 versus 13.4%; p < 0.03). Methods Between January 2000 and December 2005, 112 patients underwent cholecystectomy because of biliary acute pancreatitis. Thirteen patients were excluded because of necrotisizing pancreatitis. Thirty-two were operated within 14 days (Group A), and 67 after a longer time period (Group B). Primary endpoint of the study was the rate of biliary complications prior to surgery. Conclusion Timing of cholecystectomy seems to have no clinically relevant effect on local or systemic complications, but delayed surgery may be associated with an increase of biliary complications in patients with non necrotisizing biliary acute pancreatitis. 19 Quality of surveillance after curative surgery for colon cancer A. Ochsner1, U. von Holzen4, C.T. Viehl1, R. Cecini2, U. Güller1, I. Langer3, U. Laffer2, D. Oertli1, M. Zuber4; Universitätsspital Basel, Departement Chirurgie; 2Spitalzentrum Biel, Chirurgische Klinik; 3Universitätsspital Lausanne, Service de Chirurgie Viscérale; 4Kantonsspital Olten, Chirurgische Klinik 1 Objective There is evidence that patients benefit from intensive surveillance after curative surgery for colon cancer. The Swiss Society of Gastroenterology regularly publishes the current Swiss recommendations for surveillance after curative resection for colorectal cancer. However, data on the actual surveillance performed in comparison to the recommendations are scarce. We therefore analysed the quality of surveillance of colon cancer patients according to the Swiss recommendations in the regions of BaselCity, Olten, and Biel. Methods The data used in this study are based on the follow up of patients enrolled in the Swiss multicenter trial “Sentinel Lymph Node Procedure in Colon Cancer”. All patients underwent curative surgery for colon cancer and provided written informed consent. Patients who deceased within 30 days after surgery, patients refusing surveillance, and patients who did not qualify for surveillance due to old age and severe comorbid conditions were excluded from this analysis. The parameters analysed were: measurements of carcinoembryonic antigen (CEA), diagnostic imaging (sonography [US] or computed tomography [CT]), and colonoscopy. All inpatient and outpatient files were reviewed and the treating physicians, gastroenterologists and patients received a questionnaire. In addition, all alive patients were contacted by phone at the time of follow up. We compared the actual surveillance during follow up to the surveillance recommended by the Swiss Society of Gastroenterology. We also compared the surveillance between subgroups of patients who did and did not undergo adjuvant chemotherapy. 20 Results Data of 129 patients (75 male, 54 female) were analysed.The median age was 72.7 years (range 27.392.2) and the median follow up was 33.5 months (5.6-74.7). Tumor stages according to UICC were: Stage I 18% (n=23), stage II 46% (n=59) and stage III 36% (n=47). Fourty-four (34.1%) patients were treated with adjuvant chemotherapy. Eleven patients (8.5%) died during follow up. The percentages of patients with optimal surveillance according to the recommendations of the Swiss Society of Gastroenterology were 32.8%, 31.7%, and 23.8% for measurements of CEA, for imaging with US/ CT, and for colonoscopy, respectively. For patients undergoing adjuvant chemotherapy the compliance with the current recommendations was clearly better (43.6%, 52.6%, and 40% for CEA, for US/CT, and for colonoscopy respectively) compared to patients who did not receive adjuvant chemotherapy. Conclusion The quality of surveillance according to the Swiss recommendations after curative surgery for colon cancer is poor. Further education regarding the potential benefits of surveillance after curative surgery for colon cancer is critical. Monitoring of cellular immune responses in whole blood: a simple, sensitive and accurate PCR based method Elke Schultz-Thater1, Paul Zajac1, Daniela Margelli2, Giulio C. Spagnoli1, Daniel M. Frey1,3 Institute for Surgical Research and Hospital Management ICFS, 2Department of Internal Medicine, 3Department of Surgery, University Hospital of Basel 1 Background Monitoring of cellular immune responses against tumor associated antigens (TAA) or micro organism derived antigens may require advanced cellular immunology skills and the application of time consuming protocols. Objective Real-time PCR (qRT-PCR) was applied as a simple and sensitive technique in order to characterize antigen specific cellular immune responsiveness in small samples of whole blood from patients or healthy donors following vaccinations or natural sensitization to specific antigens. Methods Defined antigens, in the form of peptides or commercial vaccine preparations at concentrations ranging between 1 and 5 µg/ml are added to 0.3 ml of heparinized peripheral blood. Samples are then centrifuged to bring cells in contact and cultured o/n at 37°. Four volumes of RNAlater (Ambion, Houston TX) are then added to provide RNA stabilization. Specimens can now be stored for over a week at 4°C or sent to another laboratory. Following RNA extraction and reverse transcription, cDNA is then amplified in the presence of primers and probes specific for defined cytokine genes, including those encoding IL-2, IFN-γ, IL-6, IL-10, TNF-α or MIP-1β. Antigen driven cytokine gene expression is evaluated in relationship to the expression of β-actin housekeeping gene. Results Cytokine gene expression and specific antibody titers were initially studied in donors (n=32) vaccinated against hepatitis B virus. Significant correlations between antigen stimulated expression of IL-2, MIP-1β, TNF-α and IFN-γ genes and specific antibody titers (p=0.0003, p=0.001, p=0.003 and p=0.015, respectively) were detected. In our hands, this technique demonstrates similar sensitivity than ELISPOT or intracellular staining with cytokine specific mAbs. In spiking experiments performed with different amount of specific cytotoxic T lymphocyte (CTL) for gp100 melanoma TAA, qRT-PCR was able to detect specific responses of 100 CTL added to 300ul of whole blood. Similarly, we were able to demonstrate EBV BMLF 1 or CMV pp65 specific responses in peripheral blood from seropositive healthy HLA-A0201+ donors stimulated with peptides. Conclusions In this study, real-time RT-PCR demonstrates a high sensitivity to detect antigen specific functional activities of lymphocytes in whole blood, suitable for the monitoring of immune responses against viral or tumor associated antigens. 21 Sentinel lymph node procedure in resectable colon cancer – Results from the prospective Swiss multicenter study Carsten T.Viehl1, Ulrich Guller1, Ramona Cecini2, Igor Langer1, Alex Ochsner1, Luigi Terracciano4, HansMartin Riehle5, Urban Laffer2, Daniel Oertli1, Markus Zuber3 Department of Surgery, University of Basel, Basel, Switzerland Department of Surgery, Spitalzentrum Biel, Biel, Switzerland 3 Department of Surgery, Kantonsspital Olten, Olten, Switzerland 4 Institute of Pathology, University of Basel, Basel, Switzerland 5 Viollier Histopathology/Cytology, Basel, Switzerland 1 2 Objective The value of sentinel lymph node (SLN) procedure in colon cancer patients remains a matter of debate. Therefore, the objective of this large prospective, multicenter trial was to evaluate the identification rate and accuracy of the SLN procedure for colon cancer patients; to analyze factors influencing the SLN procedure; and to assess the extent of upstaging due to the SLN procedure. Methods One hundred and seventy-four patients with biopsy proven, resectable colon cancer (stage I: n=32, stage II: n=78, stage III: n=64) underwent open colon resections at three different centers. In vivo SLN procedure was performed according to a standardized protocol: isosulfan 1% (median 2 ml, range 0.2-10 ml) was injected around the tumor, and blue staining lymph nodes were tagged and processed separately. Three levels of each SLN were stained with H&E and immunohistochemistry (IHC) with the pancytokeratin marker AE1/AE3. Groups were compared using the chi-square test, and Student’s t-test. Results SLN identification was successful in 155/174 patients (identification rate 89.1%). The accuracy of the procedure was 83.9%, sensitivity 55.4%, specificity 100.0%, and negative predictive value 79.8%. Identification rate (p=0.021), and sensitivity (p=0.043) significantly improved with center 22 experience.Additionally, successful SLN identification depended on the intraoperative identification of blue stained lymphatic vessels (p<0.001). Median number of sampled SLN was 3 (range 1-20), and median number of Non-SLN was 20 (range 1-57). Falsenegative results were significantly more frequent in pN1 compared to pN2 patients (p=0.004), and when fewer SLN were identified intraoperatively (p=0.026). In total, 4,000 lymph nodes were analyzed (562 SLN, and 3,438 Non-SLN). SLN were significantly more likely to contain tumor infiltrates than Non-SLN (p<0.001). Small nodal tumor infiltrates were found in SLN, due to the use of IHC, in 16 of 104 stage I and II patients considered node-negative in initial H&E analysis thus resulting in upstaging of 15.4% of these patients. Conclusions The sentinel lymph node procedure for resectable colon cancer has good identification and accuracy rates. However, several factors influence the success of the procedure and warrant attention. Most importantly, the SLN procedure results in upstaging of over 15% of stage I and II patients, who might therefore benefit from adjuvant chemotherapy. Anästhesie 23 Analgesic and antihyperalgesic properties of propofol and its solvent in a human pain model Bandschapp O1, Filitz J2, Urwyler A1, Koppert W2, Ruppen W1 1) 2) Department of Anaesthesia, University Hospital Basel, Switzerland Department of Anaesthesia University Hospital Erlangen, Germany Introduction Propofol has long been considered as non-analgesic. In a previous work of one of the authors, however, anaesthesia with propofol was associated with less postoperative pain and morphine consumption as compared to anaesthesia with isoflurane, while the group treated with the combination of isoflurane and intralipid (similar to the solvent of propofol) showed the highest pain scores (unpublished results). The current study was designed to investigate modulatory effects of propofol and a formulation similar to the solvent propofol (intralipid 10%) on pain perception and central sensitisation in healthy volunteers. Methods Fourteen healthy volunteers were included in this randomized, double-blind, and placebo-controlled study in a cross-over fashion design. Transcutaneous electrical stimulation (48.2 +/- 26.3 mA) induced spontaneous acute pain (numerical rating scale = 6 of 10) and stable areas of hyperalgesia and allodynia. Pain intensities and areas of hyperalgesia were assessed regularly before, during and after a 45min target-controlled infusion (2 microg/ml) of propofol, its solvent intralipid 10% and saline, respectively. 24 Results During administration, propofol significantly decreased pain scores and areas of hyperalgesia and allodynia as compared to intralipid 10% and saline (p<0.01). This difference disappeared shortly after cessation of the infusion. Thereafter, no group differences were observed in the NRS score and the areas of hyperalgesia or allodynia. Conclusion Propofol showed short-lasting analgesic properties during its administration. Sedative effects responsible for this analgesic properties were not completely ruled out. Intralipid was free of pain-modulatory action or pro-algetic effects in our experiments. Effects of anesthetics on chloride channel related myotonia O. Bandschapp*, C. Soule°, A. Urwyler*, P. Iaizzo°, T. Girard* * Departments of Anaesthesia and Biomedicine, University Hospital, Basel, Switzerland ° Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA Background Anesthetic choice for patients with muscular disorders is a matter of current debate. Thomsen’s disease and Becker type myotonia are myotonic muscle disorders originated from decreased chloride conductance. Chloride channels are essential for electrical stabilization of the membrane potential in skeletal muscle.Apart of case reports on the safe use of propofol in patients with such myotonia, literature on this topic remains scarce. The purpose of this study was to characterize the effects of propofol and volatile agents on myotonic muscle and to elucidate the possible mechanisms behind. Methods Vital rectus abdominis muscle preparations obtained from normal swine were investigated in in-vitro contracture test baths. Under 0.1 Hz supramaximal electrical stimulation the chloride channel blocker 9-AC was added. Thereafter the effects of increasing concentrations of propofol in intralipid (n=11), propofol in DMSO (n=10), intralipid alone (n=10), DMSO alone (n=10), halothane (n=8), isoflurane (n=8), sevoflurane (n=8), acetazolamide (n=10; as a voltage-gated chloride channel activator), lidocaine (n=10; as a voltage-gated sodium channel inhibitor), procainamide (n=10; as a voltage-gated sodium channel inhibitor) and caffeine (n=4; as a direct ryanodine receptor activator) on these myotonic muscle bundles were tested. Additionally, we tested the effects of propofol in intralipid on skeletal muscle in a chloride free environment (n=12). As a control, we used muscle bundles treated with 9-AC alone (n=19), those treated with chloride free buffer (n=12), as well as those with no treatment (n=30). Results Treatment with 9-AC or chloride free buffer lead to a myotonic reaction, as shown by an increased area under the curve.Treatment with propofol in intralipid, propofol in DMSO, lidocaine and procainamide reversed the myotonic reaction significantly, whereas the volatile agents and caffeine significantly increased the myotonic reaction. Acetazolamide, as well as the solvents intralipid and DMSO showed no effect. Propofol showed the same efficacy in resolving the myotonic reaction in a chloride free environment. There was no shifting in the dose-effect relation. Conclusion The active agent of propofol and not its solvent reverts pharmacologically induced myotonic reaction, possibly through its action on voltage-gated sodium channels.The fact that propofol resolved the myotonic reaction in a chloride free environment with the same efficacy as in normal Krebs-Ringersolution speaks against a major effect of propofol on voltage-gated chloride channels in our experiments. Volatile agents increased the myotonic reaction, possibly through their calcium releasing effect through ryanodine receptors. These data give experimental evidence as to why volatile agents may be dangerous for patients with myotonic syndromes.According to our experiments, particularly for patients with chloride channel myotonia, propofol seems to be the better choice. 25 Pathophysiology of Postoperative Delirium and Postoperative Cognitive Dysfunction The Role of Inflammation and Cerebral Perfusion Burkhart CS, Gamberini M, Möckli A, Monsch A, Strebel SP, Steiner LA Departement Anästhesie, Memory Clinic, Universitätsspital Basel Background Delirium and postoperative cognitive dysfunction (POCD) are important complications after major surgery with patients aged 65 or older being particularly at high risk of developing these problems. Delirium and POCD are associated with increased mortality, hospital stay and resource utilization. Furthermore POCD has an important long-term impact on independence, social interactions, and quality of life (1-3). The mechanisms leading to delirium and POCD are unclear and the role of cerebral perfusion in the development of delirium and POCD has not been characterized. Specifically, the role of cerebrovascular autoregulation, which should protect the brain against intraoperative hypoperfusion and hypoxia, has not been sufficiently characterized in elderly patients under general anaesthesia. Alternatively, the action of inflammatory cytokines on the brain may play an important role in the development of these complications. This project characterizes the relationships between delirium, POCD, perioperative inflammation, and cerebral perfusion in a group of patients with a moderate risk and a control group with a very low risk of developing delirium or POCD. Methods We are investigating two groups of patients undergoing elective major non-cardiac surgery under general anaesthesia with sevoflurane: Group 1: 20 patients aged 18 to 40, a control group with a very low risk of developing delirium or POCD. Group 2: 100 patients aged 65 or older, a group with moderate risk of developing delirium or POCD. Exclusion criteria are cardiac surgery, neurosurgery, any surgery precluding use of near-infrared spectroscopy (NIRS) or transcranial Doppler, history of cerebrovascular disease, a preoperative Mini Mental Score < 24 and long-term psychiatric medication. Group 2 has pre- and postoperative cognitive testing one week postoperatively. Cognitive function is assessed using the CERAD-Plus Neuropsychological Assessment Battery which provides demographically-adjusted (gender, age, education) standard scores. In both 26 groups C-reactive protein, IL-6, IL-8, IL-10, and TNF-A are monitored as markers of systemic inflammation. Intraoperative cerebral haemodynamics including an index of autoregulation are investigated with transcranial Doppler and NIRS in both groups. Cerebral haemodynamics and blood marker profiles are compared between groups and between patients with delirium, POCD or neither. Results So far 37 patients have been included in the study, 16 in Group 1 and 21 in Group 2. In Group 2, 4 patients in showed signs of POCD and 1 patient had delirium postoperatively. Laboratory analysis has not yet been performed. A preliminary analysis has not generated relevant differences between the two groups References 1. 2. 3. Newman S et al.: Postoperative cognitive dysfunction after noncardiac surgery. A systematic review. Anesthesiology 2007; 106: 572-90. Moller JT et al.: Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International study of post-operative cognitive dysfunction. Lancet, 1998; 351: 857-61. Monk TC et al.: Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 2008; 108:1830. Effect of intravenous lidocaine on laryngeal reflex responses in children anesthetized with sevoflurane T.O. Erb, B. von Ungern-Sternberg, K. Keller, F.J. Frei, Division of Anaesthesia, University Children‘s Hospital, Basel, Switzerland Introduction Laryngospasm with consecutive hypoxemia is common and often more severe in children than in adults. In order to reduce the incidence of laryngospasm,the administration of lidocaine has been advocated.1 However, its effectiveness in preventing or attenuating laryngospasm is controversial.2 This uncertainty is partially explained by the fact that the determination of the occurrence-based pure clinical signs can be difficult under study conditions and that the effect might be short lasting.3 Therefore, the purpose of the study was to evaluate respiratory responses to laryngeal irritation in a clinical model after administration of lidocaine in children anesthetized with sevoflurane and test whether these effects were transient. Methods Approval by the IRB, written parental informed consent. 40 children (3-7 years, 12 - 35 kg) scheduled for elective procedures. Premedication: Midazolam 0.3mg/kg. Following inhalational induction with sevoflurane 8%, a LMA was inserted. Maintenance of anaesthesia with 2.5% sevoflurane under spontaneous breathing. A fiberoptic bronchoscope was then inserted via the LMA and the tip was placed above the glottic opening. Video images were recorded simultaneously with respiratory parameters (tidal gas flow and airway pressure) and digitally stored. The laryngeal mucosa of each patient was stimulated 3 times: i) before, ii) 2 min, and iii) 10 min after i.v. ! administration of 2 mg/kg lidocaine by spraying the vocal cords with 0.25ml of distilled water via an epidural catheter placed through the endoscope’s suction channel. Evoked responses were classified into 4 categories3 (by a blinded reviewer): A) apnea with laryngospasm (complete closure of the glottis lasting >10s on the video images), B) expiration reflex, C) cough reflex, D) spasmodic panting. Statistical analyses were performed with the use of McNemar’s test. A P value <0.05 is considered statistically significant. Results Incidences of the various reflex responses are shown in the Figure. Conclusions The results of the present study demonstrated that the intravenous administration of 2mg/kg lidocaine resulted in a significant reduction of the incidence of laryngospasm. While this effect was traceable 2 min after the administration, this effect was already blunted after 10min. References 1. 2. 3. Baraka A. Anesth Analg 1978; 57:506 Leicht P. et al. Anesth Analg 1985; 64:1193 Tagaito Y. et al. Anesthesiology 1998; 88:1459 p<0.02 p<0.07 n.s. n.s. n.s. 27 Elevated BNP values does not allow for diagnosing cardiac dysfunction in young subjects Kasper J., Bolliger D, Seeberger M, Filipovic M. Department of Anesthesia, University Basel Introduction Elevated brain natriuretic peptide (BNP) levels are used for diagnosis of systolic and/or diastolic cardiac dysfunction in patients r 45 years [1]. Cut-off levels are established. However, nearly no data are available in younger subjects. The purpose of this study was to evaluate the range of BNP values in healthy young subjects. Methods Sixty-one patients (41 men and 20 women, range of age 18-48 years) free from cardiovascular or relevant concomitant disease and medication were studied. BNP was measured in awake, unpremedicated patients immediately before the transthoracic echocardiographic study was performed. Mean arterial pressure (MAP), heart rate (HR), and the following echocardiographic parameters were analysed: the fractional area change (FAC), the early diastolic mitral annulus velocities (E’) obtained by pulsed-wave (PW) Doppler tissue imaging, the transmitral early peak flow velocities (E) obtained by PW Doppler and the E/E’ ratio. BNP was reevaluated after one hour. Results BNP values ranged from <15 to 388 ng/l. Elevated BNP values (> 50 ng/l) were found in 20 (33%) patients; BNP levels suggestive for heart failure (> 100 ng/l) were found in four patients (7%). Echocardiographic signs of impaired systolic (FAC < 45%) and diastolic left ventricular function (E’ < 28 8.5 cm/s or E/E’ > 8) were present in one and two patients, respectively; all of them had BNP values < 50 ng/l. There was no correlation between BNP levels and FAC (R = 0.01, p = 0.93), E’ (R = 0.19, p = 0.16), or E/E’ (R = -0.06, p = 0.66). There were no differences in echocardiographic parameters between the groups with normal and elevated BNP levels (Mann-Whitney U test). Variation of BNP before and after echocardiography ranged from 0.0 to 15.5 ng/l. Discussion A high percentage of healthy young subjects had elevated BNP levels if cut-off values previously defined in an older patient population are applied. Due to a low pretest probability, BNP cut-off levels found in older patients are not useful for diagnosing diastolic and/or systolic heart failure in this young population without history of cardiac disease. Reference [1] Dong JS et al. JASE 2006; 19: 1017-25 Postoperative troponin T release is associated with 12-month mortality after on-pump cardiac surgery in adults G Lurati Buse1, C Brüni1, J Kasper1, M Grapow2, E Seeberger1, D Bolliger1, M Seeberger1, M Filipovic1 1 2 Anaesthesiology Department, University Hospital Basel Devision of cardiac surgery, University Hospital Basel Introduction Postoperative events are often neglected in risk stratification for patients undergoing cardiac surgery. We hypothesised that postoperative troponin T (TnT) release is associated with 12-month mortality after cardiac surgery. Methods After approval by the ethical committee and with patients’ written informed consent, we prospectively assessed the 12-month outcome of consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at our institution from January 2005 to September 2006. TnT values on the 1st and 2nd postoperative morning and baseline characteristics were documented and outcome information obtained by direct patient contact. All reported events were confirmed by the family physician or by hospitalisation charts. We calculated the TnT cut-off value by ROC-curve, and classified patients in 3 risk groups by Euroscore: low (Euroscore 0-2), moderate (Euroscore 3-5), and high risk (Euroscore r6).1 The crude odds ratio (OR) between TnT release and 12-month mortality was adjusted for risk groups by logistic regression. Results We included 764 patients; mean age was 66 years (±11.7); 73% were men. Isolated CABG was performed in 54%, valvular surgery in 29%, combined valvular and coronary surgery in 12%, and other procedures in 5%. Of the patients 21% were at low, 35% at moderate, and 44% at high risk. In the 723 patients (94.6%) with complete 12-month followup, we registered 56 deaths (7.7%). At the TnT cutoff level 0.80 µg/L, the crude OR (95% confidence interval) for the association between TnT and 12-month mortality was 3.75 (2.03-6.92). After adjustment for the Euroscore, the OR between postoperative TnT release and 12-month mortality was 3.55 (1.91-6.64). Discussion Troponin T release after cardiac surgery was a strong and independent predictor of 12-month mortality in adults undergoing cardiac surgery. 29 Paramedic based transmission of 12 lead-ECG in patients with an acute coronary syndrome reduces the “call-to-balloon-time” Marc Lüthya, Mathias Zürchera, Daniel Kellerb, Yves Meuryc, Wolfgang Ummenhofera, Stephan Marschd, Patrick Hunzikerd Department of Anaesthesia, University Hospital of Basel, Basel (UHBS), Switzerland Swiss Federal Institute of Technology Zurich (ETH), Switzerland, c Local Emergency Medical System (EMS), Basel, Switzerland d Clinic of Intensive Medicine, University Hospital Basel, Basel (UHBS), Switzerland a b Background Early reperfusion in patients with myocardial infarction has been shown to be a major determinant for preserved myocardial function and reduced mortality. Telemetric transmission of 12-lead ECG by paramedics gains time by shifting the indication for coronary intervention from the in-hospital emergency department to the out-of-hospital location of the patient. The aim of this prospective study was to test if telemetric transmission of a 12lead ECG performed by paramedics for patients with suspected acute coronary syndrome is feasible and reliable. A second aim was to control if involvement of the invasive cardiology decision maker in primary triage before transferring a patient by Emergency Medical System (EMS) improves selection of patients for direct admission to the cardiac catheterization lab. In addition, we tried to investigate if bypassing the emergency department reduces the “call-toballoon-time” and has a potential to improve patient outcome. Methods A 12-lead ECG transmission system (Zoll E-Series, Nokia 6210) linked to an ECG server developed at the Swiss federal institute of technology (ETH) was introduced in the local EMS. This allowed to link the existing algorithm for the management of patients with symptoms of an acute coronary syndrome (ACS): paramedic-based initial therapy with oxygen, nitroglycerine, aspirine and morphine i.v. with concomitant ECG transmission to the cath lab decision maker. All relevant time points from phone call to the EMS dispatch centre, start of the coronary angiography or angioplasty (PTCA) and the patient admission pathway were assessed, including “calltime”,“arriving on scene”,“sending ECG”,“departing from scene” and “arriving at hospital/cath lab”. Inhospital, start of PTCA and time of revascularisation (“balloon-time”) were recorded. 30 Results EMS personnel performed a 12-lead ECG in 210 patients suspected to have an ACS; 16 patients were excluded due to technical failures, age under 18 or impossibility to retrieve a patient’s chart. From the remaining 184 patients 66 (34.8%) underwent a coronary angiography during their hospitalisation; 21 (11.4%) were transported directly to the cath lab; 25 (13.6%) had a coronary angiography within 4 hours after the initial alarm phone call. Among these 25 patients, 9 who had a STEMI or a high possibility for it in their prehospital ECG were not primarily directed to the cath lab. Comparison of patients who were sent directly to the cath lab with the group of 9 STEMI patients transported to the emergency department first showed a significant decrease of the call-to-balloon-time (89.1p14.0min vs. 144.4p30.9min; p<0.005) and door-to-balloontime (48.4p13.0min vs. 100.7p25.0min; p<0.005). Conclusion A 12-lead prehospital ECG with immediate wireless transmission to the cardiologist on call is a feasible intervention for paramedics; technical failure should be reduced. Comparison of time intervals with a similar control group demonstrates a benefit of 55.3min for the call-to-balloon-time or 52.3min for door-to-balloon-time. Earlier arrival in the cath lab will probably save heart muscle (“Time is muscle”). A higher number of patients will be needed to test if patient outcomes can be improved. Correlation of SPECT-CT scans findings and diagnosticprognostic blockades of zygapophysial joint in patients with nonspecific low back pain Wilhelm Ruppen1), Esther Wettig1), Martin Kretschmar2), Stefan Schären3), Deniz Bilecen2), Augustinus Ludwig Jacob2), Armin Aeschbach1),Brugger Stefan1), Helmut Rasch4), Albert Urwyler1) Department of Anaesthesia, University Hospital Basel Department of Radiology, University Hospital Basel 3) Department of Orthopaedics, University Hospital Basel 4) Institute of Nuclear Medicine, University Hospital Basel 1) 2) Introduction Zygapophysial (facet) joints are the cause of 15 30% of the cases of nonspecific low back pain (1). Standard X-rays of the lumbar spine and CT- or MRscans are not able to reliably predict the origin of pain. As a consequence, clinicians worldwide have to perform test series of infiltrations with local anaesthetics of the ramus medialis of the dorsal spinal nerve (functional testing) to identify facet joints as the cause of nonspecific low back pain. Thus, several facet joint levels must each be tested during different sessions. It has recently become possible to examine facet joints using SPECT-CT scan. The great advantage of this method is the possibility to visualize a functional state of the facet joints, which is possibly more accurate than conventional radiological imaging (2-4). Thus, the aim of this study is to examine the correlation between hot spots in SPECT-CT-scans and the findings of diagnostic facet joint injections. Methods Thirty patients will be scheduled for a SPECT examination. The clinician, blinded to the infiltrate, will inject the rami mediales three times in a diagnostic prognostic manner: once with 0.5 ml lidocaine 1%, once with 0.5 ml bupivacaine 0.5% and once with 0.5 ml NaCl 0.9%. After each of the infiltrations the patient will receive a pain diary (Basler Schmerztagebuch) and will record his/her numeric rating pain score (NRS, scale from 0 to 10) every hour for 24 hours. After the infiltration test, the first part of the study is finished for the patient, and both (patient and clinician) are free in the choice of further therapy. Patients with an indication for radiofrequency therapy will be included in a follow-up programme. After 2 and 4 months this subset of patients will be interviewed by phone and a McQill questionnaire will be filled in. Importance of study In patients with nonspecific low back pain, conventional radiological findings are of minor importance as pathoanatomical morphological changes do not correlate with pain (up to now, pain is not “visible”). If SPECT-CT scans and diagnostic prognostic infiltrations would have a high positive and/or negative correlation for facet pain, things would become much easier. Not every patient would have to undergo several facet infiltrations with radiological emission doses for diagnostic purposes only. Literature 1 2 3 4 Schwarzer AC,Aprill CN, Derby R, Fortin J, Kine G, Bogduk N.The relative contributions of the disc and zygapophyseal joint in chronic low back pain. Spine 1994;19(7):801-6. Dolan AL, Ryan PJ, Arden NK, et al. The value of SPECT scans in identifying back pain likely to benefit from facet joint injection. Br J Rheumatol 1996;35(12):1269-73. Holder LE, Machin JL, Asdourian PL, Links JM, Sexton CC. Planar and high-resolution SPECT bone imaging in the diagnosis of facet syndrome. J Nucl Med 1995;36(1):3744. Pneumaticos SG, Chatziioannou SN, Hipp JA, Moore WH, Esses SI. Low back pain: prediction of short-term outcome of facet joint injection with bone scintigraphy. Radiology 2006;238(2):693-8. 31 Early intraosseous epinephrine increases coronary perfusion pressure comparable to late intravenous administration and improves 24h post-resuscitation neurological outcome in a swine model of prolonged ventricular fibrillation Mathias Zuercher1,5 MD; Karl B. Kern1,2 MD; Michael Loedl4, BS; Ronald W. Hilwig1 DVM, PhD; Robert A. Berg1,3 MD; Wolfgang Ummenhofer5 MD; Gordon A. Ewy1,2 MD University of Arizona Sarver Heart Center1, Departments of Medicine2, Pediatrics3, University of Arizona College of Medicine,Tucson, AZ, USA; Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Austria4; Department of Anaesthesia and Intensive Care, University Hospital, Basel, Switzerland5 BACKGROUND Epinephrine (Epi) improves coronary perfusion pressure (CPP) during CPR and enhances likelihood of successful defibrillation. Intravenous (IV) access is often delayed. AIM: To compare early intraosseous (IO) versus delayed IV administration of Epi or placebo on CPP, return of spontaneous circulation (ROSC) and 24-hour neurological outcome (24h-neuro) after prolonged ventricular fibrillation (VF). METHODS 30 pigs (34±3 kg) anesthetized with isoflurane and instrumented with micromanometer-tipped catheters in the right atrium and aorta. After 10 minutes of untreated VF, animals received 200 chest compressions (CC; 100/min) followed by one biphasic shock (150 J) and another 200 CC immediately postshock. Epi (0.045 mg/Kg) or placebo was administered at minute 1, 4, 6¼, 8½, 10¾ after starting CC until a perfusing rhythm or 6 unsuccessful defibrillations were attained. The rescuers were blinded to the drug administered. Animals were randomized into 32 3 groups: Group IO (B.I.G‘, WaisMed, Israel, tibia plateau; Epi at each time point); group IV (internal jugular vein; Epi only at time points 8½ and 10¾) and group placebo. Statistics: Student’s t test, MannWhitney U test and Fisher’s exact test. RESULTS CPPs 1 and 2 min after Epi administration were comparable (Fig. 1). ROSC was attained in 10/10 animals of the IO-*, in 9/10 of the IV-* and in 1/10 of the placebo-group. The number of animals with good 24h-neuro was 6/10 in the IO*, 3/10 in the IV-and 0/10 in the placebo-group. *p<0.05 vs placebo. CONCLUSIONS IO Epi administered earlier than IV results in comparable CPPs and improves 24-hour neurological outcome in a swine model of prolonged cardiac arrest. Resequencing Arrays for Pharmacogenetic Investigations in Anaesthesia Soledad Levano, Albert Urwyler, Thierry Girard Departments of Biomedicine and Anaesthesia, University of Basel. Introduction Anaesthesia is a clinical field, where knowledge about and diagnosis of pharmacogenetic diseases is of utmost importance. Two inherited pharmacogenetic diseases are of primary interest: malignant hyperthermia (MH) due to the potentially fatal consequences and butyrylcholinesterase (BCHE) deficiency due to its high incidence. Malignant Hyperthermia MH is an uncommon pharmacogenetic disorder of skeletal muscle triggered in predisposed individuals by exposure to commonly used anaesthetic agents such as volatile anaesthetics and/or the depolarising muscle relaxant succinylcholine. Presymptomatic diagnosis is essential to avoid an MH crisis. The primary locus of MH is the ryanodine receptor (RYR1). A second locus where MH causative mutations have been found is the alpha-1 subunit of the dihydropyridine receptor encoded by the CACNA1S gene. Butyrylcholinesterase deficiency The short duration of action of succinylcholine is due to rapid hydrolysis by the enzyme butyrylcholinesterase (BCHE). In patients with reduced BCHE activity the duration of action of succinylcholine may increase dramatically and prevent the patient from spontaneous ventilation for hours. Project and Methods Acquisition of the DNA sequence information in the above mentioned genes provides insight into the genetic heterogeneity of these diseases and consequently contributes to safer dosing of drugs and less invasive diagnosis of MH susceptibility. The goal of this project is to obtain the full coding sequence information of the most important genes involved in the above-mentioned diseases: RYR1, CACNA1S and BCHE. To reach this goal we plan to establish a sequencing array as a method, which is reliable, efficient and qualifies for high-throughput. This research project involves setting up PCR conditions and design of the Affymetrix custom DNA gene chip. The array will be evaluated for sensitivity and specificity. Conclusion The planned research will be helpful addressing the following issues: • Genotyping the BCHE gene in patients with suspicion of an inherited decreased BCHE activity • Genotyping RYR1 and CACNA1S in MH susceptible patients with unknown mutation status • Genotyping patients with MH suspicious clinical events • Determine the frequency variations in BCHE, RYR1 and/or CACNA1S • Identification of concomitant mutations in samples with a novel RYR1 mutation Knowledge of the complete sequence of RYR1 and/ or CACNA1S in patients potentially susceptible to MH is important for research and diagnostic investigations in this heterogeneous disease. Novel technologies, such as resequencing arrays allow for efficient genotyping of large genes and are therefore promising tools. Considering the invasive nature of the in vitro muscle contracture test and the limited number of MH testing centers, non-invasive diagnosis is of increasing importance. A fast and reliable sequencing method has a huge translational potential for diagnostic applications not only in perioperative medicine. 33 Investigations for Malignant Hyperthermia Susceptibility: An Update M. Singer1, J. Benthien2, S. Levano1, A. Matter1, A. Urwyler1, T. Girard1 1 2 Departments of Biomedicine and Anaesthesia, University Hospital of Basel. Department of Orthopedic Surgery, University Hospital of Basel. Introduction The only Swiss malignant hyperthermia (MH) investigations centre is affiliated to the Department of Anaesthesia, University Hospital Basel. Presymptomatic testing of MH susceptibility in individuals at risk, i.e. from MH families is essential in order to avoid potentially lethal episodes. Since 1986 the gold standard of MH testing, the in-vitro contracture test (IVCT), is performed on skeletal muscle bundles obtained by open muscle biopsies of the m. vastus medialis. In 2001 the presence of known causative mutations in the skeletal muscle type ryanodine receptor gene (RYR1) can be used to diagnose MH susceptibility. The European Malignant Hyperthermia Group (EMHG) has published guidelines for both methods, IVCT and molecular genetic testing. The aim of this abstract is to update on developments in testing for MH susceptibility. Methods IVCT was performed according to EMHG guidelines. Molecular genetic investigations were performed on genomic DNA and cDNA by PCR, dHPLC, PCR- 34 RFLP and automated sequencing. Investigations by IVCT and molecular genetics from 2000 until 07/2008 were analyzed. Numbers of 2008 were extrapolated for the full year. Results In the study period we investigated 476 patients, by IVCT and or molecular genetic methods. While the total number of MH investigations remained quite stable throughout the last 5 years, the proportion of molecular genetic diagnoses has increased. In 2007 we predicted the number of genetic diagnoses to exceed in-vitro contracture testing. This can be confirmed with the current data. Patient selection for genetic testing seems to be adequate, as the positive mutation rate of 50% in 2007 is to be expected in an autosomal dominant mode of inheritance. Conclusion The ongoing research in MH is reaching the defined goal to increase less invasive testing for MH susceptibility. It is still important to mention that due to the locus and allelic heterogeneity of MH, a negative molecular genetic result has to be followed by open muscle biopsy and IVCT. Both methods, molecular genetics and IVCT, will continue to be essential and complementary procedures for MH diagnosis. Loss of skeletal muscle strength by ablation of the sarcoplasmic reticulum protein JP45 Osvaldo Delbono*, Jinyu Xia†, Susan Treves†, Zhong-Min Wang*, Ramon Jimenez-Moreno*, Anthony M. Payne*, Laura Messi*, Alexandre Briguet°, Florian Schaerer°, Myuki Nishi#, Hiroshi Takeshima#, Francesco Zorzato† †Departments of Anaesthesia and Research, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland; #Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, U.S.A; ° Santhera Pharmaceuticals, Liestal, Switzerland; # Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; Skeletal muscle constitutes approximately 40% of body mass, and age-induced decrease of muscle mass and strength is a major cause for physical disability in the elderly. Activation of muscle contraction is initiated by membrane depolarisation during an action potential, which causes release of Ca2+ stored in the sarcoplasmic reticulum (SR) in a process called excitation-contraction coupling (ECC). ECC occurs via a highly sophisticated supramolecular signalling complex at the junction between the SR and the transverse tubules, which transduces the electrical signal into a transient increase of the myoplasmic calcium concentration. The core components of the ECC supramolecular complex are the dihydropyridine receptor (DHPR), ryanodine receptor (RyR), and calsequestrin which serve as voltage sensor, SR Ca2+ release channel, and SR Ca2+ storage protein, respectively. The ECC molecular machinery is complex, and the functional role of many of its protein components remains elusive. In this study we generated a mouse model to investigate the function of the JP45 sarcoplasmic reticulum protein, a component of the ECC signalling complex. Methods Ablation of mouse JP45 gene was carried out by homologous recombination of JP45 targetting vector into mouse SvJ129 embryonic stem cells. Screening of 700 neomicyn resistant ES clones by genomic southern blot analysis lead to the identification of 145 ES clones carrying mutant JP45 allele. ES cells carrying mutant JP45 allele were injected into C57BL6 blastocyst and chimera mice were identified by fur color. Chimera mice were backcrossed three times with C57BL6 to obtain JP45-/- mice. Muscle were analysed both in vivo and in vitro by running wheels and isometric force measurements with isolated muscles, respectively. Biochemical analysis was perfomed in isolated sarcoplasmic reticulum membranes. Cell electrophysiology and calcium measurement with fluorescent indicators were performed on enzymatically dissociated FDB fibers isolated from wild type and JP45 KO mice. Results Analysis of spontaneous motor activity with a running wheel revealed that dark phase running distance ran by the 3 and 6 months old JP-45 KO mice was significantly lower compared to wild type. In vitro EDL and soleus muscle mechanical property analysis showed slower twitch and tetanic absolute and specific force in JP-45 KO mice compared to wild-type, while muscle size, wet weight and cross sectional area of muscle fibers were not different. Isolated sarcotubular membranes from 3 month and 6 months old JP-45 KO mouse muscles exhibited reduced [H3]PN200-110 binding indicating down regulation of DHPR protein. SR Ca2+ release in voltage-clamped muscle fibers of JP-45 KO was significantly reduced compared to wild-type. Conclusion The decay of skeletal muscle strength is the major cause of poor physical performance in a large variety of individuals ranging from professional athletes to elderly people. Our data provides new insights into the molecular basis of skeletal muscle strength and suggests JP45 as an interesting molecular target for innovative strategies against the decay of skeletal muscle strength. References 1. 2. Delbono et al. Proc. Natl. Acad. Sci.104: 20108-20113. Anderson et al. J. Cell Sci. 119 : 2145-2155. 35 Recessive ryanodine receptor 1 mutation in a CCD patient affects RyR/Cav1.1 functional coupling Mirko Vukcevic, 2Farshid Ghassemi, 2Le Xu, 3Haiyan Zhou, 2Gerhard Meissner, 3Francesco Muntoni, 4Heinz Jungbluth, 2,5Francesco Zorzato and 2Susan Treves 1 Departments of Anaesthesia and Biomedical Research, Basel University Hospital, 4031 Basel, Switzerland. Departments of Biochemistry and Biophysics and Molecular and Cellular Physiology, University of North Carolina, Chapel Hill, NC 27599-7260, USA. 3The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London WC1N 1EH, U.K. 4Department of Paediatric Neurology, Neuromuscular Service, Evelina Children’s Hospital, St.Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, UK. 5Dipartimento di Medicina Sperimentale e Diagnostica, Universita` di Ferrara, 44100 Ferrara, Italy 1 2 Introduction The ryanodine receptor plays a crucial role in skeletal muscle excitation-contraction coupling by releasing calcium ions required for muscle contraction from the sarcoplasmic reticulum. At least three phenotypes associated with more than 100 RYR1 mutations have been identified to date; most commonly, dominant mutations have been found to cause central core disease and the malignant hyperthermia susceptibility trait, while some recessive mutations have been identified in some patients affected by multi-minicore disease. In the present report we investigated the functional effect of the c.7304G>T RYR1 substitution (leading to p.Arg2434Leu) identified in a patient affected by central core disease carrying the substitution at the homozygous state. 36 Methods We characterized Ca2+ homeostasis in myoD transduced myotubes from controls,the heterozygous parents and the homozygous proband expressing the endogenous mutation by Ca2+ imaging using the fluorescent Ca2+ indicator fura-2.We also expressed the recombinant mutated channel in heterologous cells and characterized its [3H]ryanodine binding and single channel properties. Results and Conclusions Our results show that the presence of the p.Arg2434Leu substitution either at the homozygous or heterozygous state, affects neither the resting [Ca2+], nor the sensitivity of the ryanodine receptor to pharmacological activators, but rather reduces KCl-induced Ca2+ release via the voltage sensing dihydropyridine receptor. METAP – a guideline to facilitate ethically appropriate decision making Meyer-Zehnder B (1,2), Albisser Schleger H (1), Mertz M (1), Pargger H (2), Reiter-Theil S (1) 1 Fachbereich Medizin- und Gesundheitsethik, Medizinische Fakultät Basel 2 Operative Intensivbehandlung (OIB), Departement Anästhesie, Universitätsspital Basel Background and Goal The project METAP (SNF Nr. 3200B0-113724/1) - modular ethical treatment allocation process - addresses the problem that vulnerable patient groups are facing particular risks of ethical relevance. It develops a medical ethical guideline focusing on problems of over-treatment (futility) and undertreatment. There is compelling evidence for these phenomena in the literature, including our own previous research (1-4). The goal of the project is to provide an ethically and empirically valid approach to structuring and facilitating difficult ethical decision making. consultation. METAP also provides checklists and other tools for practical use. All components of the manual are validated through a double review by an interdisciplinary group of ethical experts and a panel of clinical practitioners. The evaluation of the acceptance and practicability is carried out in a structured consensus-building process. Method No method exists for developing a medical ethical guideline. We describe a method derived from evidence-based medicine and clinical practice guideline development. Our approach includes literature reviews and providing recommendations resulting in a manual, a short version and procedural suggestions of ethical case discussion and Literature Outlook METAP is ready for pilot implementation on an intensive care and a geriatric care unit. The experiences and findings of this pilot will be integrated into the final version. 1. 2. 3. 4. Albisser Schleger H, Reiter-Theil S (2007) Ethik in der Medizin 19:103-119 Albisser Schleger H, Pargger H, Reiter-Theil S (2008) Z Palliativmed SAMW (2007) http://www.samw.ch/docs/Publikationen/d_ Rat_Kurzfassung.pdf Hurst SA et al (2008) J Med Ethics 34:241-246 37 Basel Starch Evaluation in Sepsis (BaSES) Trial Martin Siegemund, Hans Pargger, Luzius Steiner, Walter Weber, Christian Müller, Evelyne Häfliger, Evelyne Bucher, Patrick Hunziker, Stephan Marsch. Operative Intensivbehandlung, Klinik für Viszeralchirurgie, Medizinische Klinik und Klink für Intensivmedizin, Universitätsspital Basel Background Schwere Sepsis und septischer Schock sind bei einer Mortalität zwischen 20 und 40% die häufigste Todesursache auf Intensivstationen.In den vergangenen Jahren haben sich aber mehrere Therapieoptionen ergeben, welche eine Minderung der Mortalität erreichten. Neben einer frühen, empirischen Antibiotikatherapie und einer wenn immer möglichen chirurgischen Sanierung des Infektfokus, hat sich eine frühe aggressive Flüssigkeitstherapie sowie eine Beeinflussung der Mikrozirkulation durch aktiviertes Protein C als mortalitätssenkend erwiesen. Sepsis und septischer Schock führen durch eine relative und absolute Hypovolämie zu einer verminderten Füllung des Herzens und damit zu einer Senkung des Herzminutenvolumens, sowie durch eine Fehlverteilung des mikrozirkulären Blutflusses zu einer Störung der nutritiven Perfusion im Gewebe (8-10). Die absolute Hypovolämie wird durch eine Störung des kapillären Flüssigkeitsaustauschs (capillary leak) bedingt, welcher eine starke Zunahme der interstitiellen Flüssigkeit (Ödeme) nach sich zieht. Durch die bei der generalisierten Entzündungsreaktion freigesetzten Mediatoren besteht eine pathologische Vasodilatation welche ebenfalls zur Hypovolämie in der Sepsis beiträgt. Deshalb werden zur initialen Therapie der Sepsis meist große Mengen intravenöser kristalloider Infusionslösungen verabreicht. Dabei verbleibt nur ca. ¼ der verabreichten Infusion im Intravasalraum und die übrige kristalloide Flüssigkeit tritt in den Extravasalraum über, d.h. um das intravasale Volumen um einen Liter zu erhöhen müssen 4 Liter einer kristalloiden Flüssigkeit verabreicht werden. Diese dadurch entstehenden Gewebeödeme sind nicht selten die Ursache für eine verlängerte Verweildauer auf Intensivstationen, da diese zu einer Beeinträchtigung der respiratorischen, zentralnervösen und intestinalen Funktionen führen können. Hypothese Die Applikation des Hydroxyethylstärke Präparates Voluven® verkürzt die Liegedauer der Patienten auf der Intensivstation ohne nachteilige Effekte auf Nierenfunktion und Kosten. 38 Design Doppelblinde, Studie randomisierte monozentrische Setting Intensivstationen des Universitätsspitals Basel Patienten 240 konsekutive Patienten mit Sepsis, schwerer Sepsis oder septischem Schock Intervention Volumentherapie mit kristalloider NaCl 0,9% Lösung oder dem synthetischen, kolloidalen Hydroxyethylstärke Präparat Voluven® (Molekulargewicht 130 kDa; Substitutionsgrad 0.4) in den ersten fünf Tagen auf der Intensivstation Parameter Primärer Outcome-Parameter ist die Liegedauer auf der Intensivstation.Weiterhin werden Spitalliegedauer und Mortalität sowie die Behandlungskosten erfasst. Die Nierenfunktion wird anhand von Kreatinin, Harnstoff, Kreatinin-Clearance sowie fraktionierter Natrium und Harnstoffausscheidung überwacht. Der Einsatz von Nierenersatzverfahren wird erfasst. Statistik Mann-Whitney Test für nicht parametrische Daten wie Liegezeit auf der Intensivstation. Ungepaarter t-Test für Nierenfunktionsparameter. Vorläufige Ergebnisse Bisher konnten 180 konsekutive Patienten in die Studie eingeschlossen werden. Bisher ist die Rate an akuten Nierenversagen verglichen mit einem historischen Kontrollkollektiv nicht unterschiedlich. Bisher kam es zu keiner allergischen Reaktionen auf das verwendete Stärkepräparat. Nach dem Einschluss von weiteren 25 Patienten wird die Studie im Herbst 08 beendet. Die endgültigen Ergebnisse sollten Anfang 2009 vorliegen Succinylcholin versus Rocuronium für notfallmässige Intubationen auf der Intensivstation Martin Siegemund, Hans Pargger, Stephan Marsch Operative Intensivbehandlung und Klinik für Intensivmedizin, Universitätsspital Basel Einleitung Die Intubation eines schwer kranken Patienten auf einer Intensivstation ist ein Hochrisikoeingriff. Erstaunlicherweise gibt es in der Literatur sehr wenige Daten über diesen Eingriff und gar keine Evidenz-basierten Empfehlungen. Aufgrund eigener Erfahrungen rechnen wir mit einem erfolglosen ersten Intubationsversuch in ca. 15%, einer signifikanten hämodynamischen Verschlechterung von bis zu 50% und einer mit der Intubation assoziierten Reanimation in ca. 3%. Für die notfallmässige Intubation auf der Intensivstation stehen zwei Muskelrelaxantien zur Verfügung, Succinylcholin und Rocuronium. Succinylcholin ist ein depolarisierendes Muskelrelaxans und aus historischen Gründen das Muskelrelaxans der Wahl für Notfallintubationen. Eine nach modernen Kriterien durchgeführte Validierung von Succinylcholin als Muskelrelaxans in der Intensivmedizin fehlt. Succinylcholin hat einen raschen Wirkungseintritt und erlaubt damit eine rasche Intubation. Leider hat Succinylcholin potentiell schwerwiegende Nebenwirkungen wie Hyperkaliämie und Rhythmusstörungen und ist bei einer Reihe von Erkrankungen mit intensivmedizinischer Relevanz kontraindiziert. Als Alternative zum Succinylcholin bietet sich Rocuronium, ein nichtdepolarisierendes Muskelrelaxans mit kurzer Anschlagszeit, an. Allerdings ist die Anschlagszeit von Rocuronium länger als diejenige von Succinylcholin. Damit kann die Intubation nach Rocuronium erst später erfolgen als nach Succinylcholin. Ob dies bei schwer kranken Patienten klinisch relevant ist, ist unklar. Die vorliegende Studie vergleicht die Intubationsbedingungen nach Succinylcholin und Rocuronium bei notfallmässigen Intubationen auf der Intensivstation. Methode Die Indikation für eine notfallmässige Intubation wurde gemäss üblichen Kriterien durch einen Kaderarzt (Facharzt Intensivmedizin FMH) gestellt. Nach Einschluss in die Studie wurden die Patienten 1:1 für eines der beiden Relaxantien randomisiert (verschlossene Couverts, Blockrandomisierung nach Geschlecht). Bei Succinylcholin (Lystenon®, 1mg/kg/ KG i.v.). erfolgte die Intubation nach Abklingen der Faszikulationen resp. 45 Sekunden nach Applikation wenn keine Faszikulationen auftraten oder die Faszikulationen noch nicht abgeklungen waren. Die Intubation mit Rocuronium (Esmeron®, 0.6mg/ kg/KG i.v.) erfolgte 45 Sekunden nach Applikation. Mit Ausnahme der Wahl des Relaxans war die Intubationssequenz in beiden Gruppen identisch und beinhaltete eine Präoxygenierung von 3 Minuten, Cricoiddruck, und die Gabe von Fentanyl (2γ/kg/KG). Die Induktion erfolgte bei hämodynamisch stabilen Patienten (BD systolisch > 100 mmHg) mit Propofol (1.0 mg/kg/KG) und bei hämodynamisch instabilen Patienten mit Etomidate (0.3 mg/kg/KG). Ergebnisse Insgesamt wurden bisher 254 Patienten in die Studie eingeschlossen. Schweregrad (APACHE II) und Alter der Patienten war in beiden Gruppen gleich. Die Zeit bis zur erfolgreichen Intubation, sowie die Anzahl der Intubationsversuche waren in beiden Gruppen gleich gross. Es fanden sich keine signifikanten Unterschiede der Intubationsbedingungen. In der Gruppe mit Succinylcholin kam es häufiger zu Rhythmusstörungen sowie zu 7 Reanimationen. In der Gruppe mit Rocuronium wurden 2 Reanimationen druchgeführt. Schlussfolgerung Rocuronium ist eine mindestens gleichwertige Alternative zu Succinylcholin für Intubationen auf der Intensivstation. Ob das bessere Nebenwirkungsprofil von Rocuronium auf Dauer eine Senkung der Mortalität bei Intensivpatienten bewirkt, sollte in einer grösseren Studie überprüft werden. 39 Ileal and renal microcirculation during supramesenteric aortic cross clamping and reperfusion Martin Siegemund*,†, Jasper van Bommel*,‡, Wolfgang Studer†, Mat van Iterson*, Sandra Annaheim†, Michiel E. Stegenga*, Hans Pargger†, Can Ince* From the Department of Physiology*, Academic Medical Center, University of Amsterdam, Department of Anesthesiology‡, Erasmus Medical Center, University of Rotterdam both The Netherlands; and the Department of Anaesthesia and Intensive Care†, University Hospital, University of Basel, Switzerland Background Ischemia-reperfusion (I/R) is a severe multifactorial clinical syndrome and a good experimental model to study antigen-independent inflammation.1,2 Furthermore, ischemia-reperfusion frequently develops at some point during all forms of severe shock. Vascular dysfunction in ischemia-reperfusion is a consequence of changes in endothelial cells, affecting the integrity of barrier function, cytokine and adhesion molecule expression, and vascular tone. The bioavailability of nitric oxide, an important mediator of vasodilation, is decreased during the reperfusion period and results in impaired vasodilation of capillaries. Release of inflammatory mediators and increased expression of adhesion molecules in response to ischemia-reperfusion initiate inflammatory and coagulation reactions culminating in the occlusion of capillaries, known as the “no-reflow” phenomenon.2,3 During aortic cross clamping (ACC) and reperfusion, determination of microvascular oxygenation and blood flow of organs might provide insight into the effects of ischemia/ reperfusion injury on organ dysfunction and failure after aortic surgery. Methods Fifteen anesthetized pigs were randomized between an ACC group (n = 10), in which the aorta was clamped for 45 minutes above the superior mesenteric artery, and a time-matched control group (n = 5). Systemic, intestinal, and renal hemodynamic and oxygenation parameters were monitored for 4 hours of reperfusion. Microvascular oxygen partial pressure (µPO2) was measured in the renal cortex and the intestinal serosa and mucosa, using the Pd-porphyrin phosphorescence. The intestinal to arterial PCO2-gap was determined by air tonometry and the serosal microvascular flow by orthogonal polarization spectral imaging. 40 Results Regional blood flow as well as renal and intestinal µPO2 fell significantly during ACC, while the intestinal oxygen extraction and PCO2-gap increased. After initial hyperperfusion systemic as well as regional hemodynamic and oxygenation parameters reverted to baseline. µPO2 values and PCO2-gap were normal. After 4 hours of reperfusion renal cortex and serosal µPO2 decreased significantly compared to baseline, while the intestinal PCO2-gap increased (p < 0.05).The total number and flow quality of serosal microcirculatory vessels decreased significantly. Conclusions After 4 hours of reperfusion, microvascular oxygenation and blood flow in the serosa of the ileum and the kidney cortex decreased significantly. It is hypothesized that this may be due to ishemia/ reperfusion mediated denudation of the glycocalyx and redistribution of organ blood flow. References 1. 2. 3. Seal JB, Gewertz BL: Vascular dysfunction in ischemiareperfusion injury. Ann Vasc Surg 2005; 19: 572-84 Carden DL, Granger DN: Pathophysiology of ischaemiareperfusion injury. J Pathol 2000; 190: 255-66 Hassoun HT, Kone BC, Mercer DW, Moody FG,Weisbrodt NW, Moore FA: Post-injury multiple organ failure: the role of the gut. Shock 2001; 15: 1-10 Orthopädie - BZB 41 Interdisziplinäre und interprofessionelle Behandlung von geriatrischen Frakturpatienten im „Kompetenznetzwerk Altersfrakturen“ M. Pretto1, R.W. Kressig2, M. Frank3, D. Bareis4, R. Spirig1, M. Jakob, N. Suhm4 1. Abt. Klinische Pflegewissenschaft, 2. Akutgeriatrische Universitätsklinik (AGUK), 3. Geriatrisches Kompetenzzentrum FPS, 4. Behandlungszentrum Bewegungsapparat (BZB) Fragestellung Patienten mit Altersfraktur sind eine Herausforderung aufgrund der demographisch bedingten Häufigkeitszunahme, des komplexen Frakturmusters und vor allem wegen der Polymorbidität. Letztere bedingt das hohe Risiko für postoperative Komplikationen bei geriatrischen Frakturpatienten. In der klinischen Routine müssen diese Komplikationsrisiken frühzeitig erkannt und systematisch angegangen werden. Und um den weiteren Anstieg bei den Fallzahlen wenigstens zu begrenzen, soll der Frakturprävention in Zukunft eine noch größere Bedeutung beigemessen werden. Eine Lösungsstrategie, um den Traumatologen mit diesen Zusatzaufgaben nicht zu überfordern, sehen wir in mehr Interdisziplinarität und Interprofessionalität bei der Behandlung von geriatrischen Frakturpatienten. Im „Kompetenznetzwerk Altersfrakturen“ arbeiten AGUK,Abt. Klinische Pflegewissenschaft, FPS und das BZB gemeinsam an der Umsetzung dieses Konzepts. Unsere Hypothese ist,dass durch die Implementierung eines speziellen Behandlungspfads eine Verbesserung des Outcome und sozioökonomische Vorteile zu erreichen sind. Methodik und Patienten Mit dem Behandlungspfad „Altersfraktur“ wird ein standardisiertes Assessment angeboten, um verbesserungsfähige Zustände und Ansatzpunkte zur Prävention (Delir und Malnutrition, Sturz und Osteoporose) bei geriatrischen Frakturpatienten zu erkennen und zu behandeln.Aus Ressourcengründen ist die Maßnahme auf über 65-jährgie Patienten mit Femurfraktur beschränkt. Wir erfassten den Prozentsatz an Patienten mit Intervention bei Delir, Malnutrition oder Sturz und bei der Osteoporose speziell auch die Art der Intervention. Im Hinblick auf den noch ausstehenden Effektivitätsnachweis unserer Maßnahmen werden für alle Patienten jetzt schon ASA Score, Carlson-Morbiditätsindex (CCI), vorbestehende Medikation, Lebensumstände und Aktivitätsindex vor dem Unfall erhoben. 42 Resultate Vom 1.6.2007 bis 31.5.2008 wurden 204 Patienten mit einem Durchschnittsalter von 84 (SD 7.6) Jahren und mit durchschnittlich 2.1 relevanten Nebendiagnosen (CCI) entlang des Behandlungspfads geführt. Bei allen wurden vertiefte Assessments betreffend Osteoporose, Sturz, Delir und Malnutrition durchgeführt. Bei 89% der Patienten wurde in zumindest einer der vier Kategorien eine Intervention vorgeschlagen oder durchgeführt: In 30% im Hinblick auf ein drohendes oder manifestes Delir, in 26% bei Malnutrition, in 25% der Fälle im Hinblick auf das Sturzrisiko und in 72% der Fälle im Hinblick auf die Osteoporose. Die Osteoporosebasisprophylaxe (Calcium / Vitamin D) als quasi obligate Therapie bei diesem Patientengut fand sich in 18% der Patienten bei Eintritt und in 72% bei Austritt. In 49% der Patienten wurde eine DEXA indiziert und zumeist erst nach Austritt ausgeführt. Entsprechend blieb die Gabe von antiresorptiven Medikamenten (z.B. Bisphosphonate) nahezu konstant (9% bei Eintritt gegenüber 8% bei Austritt). Schlussfolgerung Der Behandlungspfad konnte im Hinblick auf die ausgewählten Präventionskategorien erfolgreich implementiert werden. Vor allem die Interventionsdaten bei Osteoporose belegen, dass für geriatrische Frakturpatienten ein hohes Potenzial für präventive Massnahmen gesehen wird. Andererseits kann die Anzahl von aufwändigen und für den Patienten z.T. belastenden Maßnahmen bei individueller Indikationsstellung beschränkt bleiben. Schlussendlich erhoffen wir uns durch unseren strukturierten, interdisziplinären und interprofessionellen Behandlungsansatz auch Prozessverbesserungen, um als Netzwerk für die geriatrischen Frakturpatienten und für die DRG noch besser vorbereitet zu sein.Ausser im regionalen Spitalverbund findet unser Konzept auch international Interesse: bislang wurden unsere Aktivitäten und der Behandlungspfad für drei Besuchergruppen mit mehr als 20 Teilnehmern vorgestellt. Morphology of 3D-printed porous HA scaffolds for bone augmentation Fabienne C. Fierz a,b, Felix Beckmann c, Marius Huser b, Stephan H. Irsen d, Barbara Leukers d, Frank Witte e, Özer Degistirici f, Adrian Andronache b, Michael Thie f, and Bert Müller a,b,g Biomaterials Science Center, University of Basel, 4031 Basel, Switzerland, b Computer Vision Laboratory, ETH Zürich, 8092 Zürich, Switzerland, c Institute of Materials Research, GKSS Research Center, 21502 Geesthacht, Germany, d Caesar Research Center, 53175 Bonn, Germany, e Laboratory for Biomechanics and Biomaterials, Department of Orthopaedic Surgery, Hannover Medical School, 30625 Hannover, Germany, f Dental Cell Biology, Caesar Research Center, 53175 Bonn, Germany, g Materials Science Institute, Dental School, University of Basel, 4056 Basel, Switzerland a Questions Tissue engineering based on interconnected porous ceramic scaffolds and autologous cells belongs to promising approaches for reconstructing larger bony defects. In designing the scaffold’s architecture, a high degree of porosity on different length scales needs to be accomplished The precise morphological characterization based on synchrotron radiationbased micro computed tomography (SRµCT) of the hydroxyapatite (HA) scaffolds is needed to gain dedicated feedback for improving the design and fabrication processes. The efficacy of the porous HA scaffolds has to be proven by cell experiments before any animal or clinical study can be initiated. Methods HA scaffolds in three different designs made layerby-layer based on nano-porous HA granules were fabricated using 3D-printing and sintering. Each scaffold was statically loaded with multipotent ectomesenchymal progenitor cells isolated from human tooth and cultured for 28 d. SRµCT measurements were performed at the beamline W2 (HASYLAB at DESY, Hamburg, Germany) with the pixel size of 3.7 µm using the photon energy of 30 keV. For 3D analysis, specific software packages were developed. Results The design of the scaffold follows the natural architecture of hollow bone: the periphery is rather compact to take the load-bearing function similar to the compacta, while the interior is porous like the spongiosa. The tomographic data allow representing any desired virtual cut through the scaffold to reveal the internal morphology such as the 1 mmwide central channel with axial orientation. The 3D analysis based on SRµCT data has revealed the importance of 3D data treatment [1]. For example, mean distances from pores to materials were overestimated by 33–50% in the 2D analysis with respect to the 3D analysis.The scaffolds contain 70% micrometer-wide pores that are interconnected. Using virtual spheres, which might be related to the cells migrating along the pores, the central channel remains accessible through the micro-pores for spheres with a diameter of up to (350±35) mm. For patient-specific implant planning, exact knowledge of the shrinking owing to the sintering process is crucial. Registering the tomograms with their 3D-printing matrices has yielded the almost isotropic shrinking of (27±2)%. This registration also allows comparing the design and tomographic data in a quantitative manner to extract the quality of the fabricated scaffolds. Histological analysis of the scaffolds seeded with osteogenic-stimulated progenitor cells has confirmed the suitability of the 3D-printed scaffolds for use in tissue engineering. Conclusions The preparation of scaffolds following biomimetic design rules belongs to key approaches for patientspecific implants.The large SRµCT data sets together with advanced computer tools for morphological analysis, yield vital feedback to improve the microarchitecture of scaffolds fabricated by any kind of biomaterial to be used for potential clinical applications. References [1] Fierz FC et al. The morphology of anisotropic 3D-printed hydroxyapatite scaffolds. Biomaterials 29 (2008) 3799– 3806 43 Nuclear magnetic resonance (NMR) spectroscopy: Implications in synovial fluid analysis Thomas Hügle1, Till Kühn2, Helena Kovaks2, Victor Valderrabano3 Rheumatologische Universitätsklinik, Felix-Platter-Spital, Basel Bruker Biospin AG, Fällanden 3 Orthopädische Universitätsklinik, Behandlungszentrum Bewegungsapparat, Universitätsspital Basel 1 2 Introduction Standard synovial fluid analysis includes cell count, polarizing microscopy, gram stain, and culture. Polarizing microscopy has a high specificity for detection of crystals, but the sensitivity is examiner dependent. For septic arthritis, gram stain of synovial fluid has a sensitivity of only 50-70% and culture needs 24-36 hours. Thus there is no rapid and accurate diagnostic test for synovial fluid analysis. The goal of this research project is the detection of molecules, microorganisms, crystals or other particles in synovial fluid by NMR technology and to differentiate between non-inflammatory and inflammatory arthritis. Furthermore, we try to identify synovial marker for the grade and prognostic of (osteo)arthritis. Methods Nuclear magnetic resonance (NMR) spectroscopy is a technique that identifies mixtures of chemicals in solution, tissue extracts, cell suspensions and whole tissues ex and in vivo. Induction decay is being detected during relaxation of previously magnetically excited nuclei. Consequently, application of Fourier transformation generates a (frequency dependent) chemical shift that depends on the chemical environment of the respective nucei and can be used for identification and determaination of chemical structures. Proton (1H) NMR is the most sentitive and widely used method. Usually 10-50 ul of a sample are needed for one analyisis and the duration is about 10-30 minutes. Principle component analyisis is performed to characterize a sample cohort. Results In this pilot study synovial fluid of 7 patients with septic arthritis, rheumatoid arthritis, crystal arthritis, osteoarthritis and undifferentiated arthritis were analysed. In all samples, a good quality of spectra, signal resolution and signal width were seen.The signal pattern were stable in experiments with different pH (Fig 1) or temperature values and over time (day 1,5,10 and 15). Different signal pattern were observed, (Fig 2). Conclusion These preliminary results show a good quality of NMR spectroscopy analysis in synovial fluid samples. Analysis of a larger sample cohort is planned to characterize the metabolic profile in different diseases. NMR results will then be correlated with clinical and radiological data. Undifferentiated ! Osteoarthritis CPPD Gout Septic Arthritis Osteoarthritis ! Fig 1. 44 Undifferentiated Fig 2. Frontal and lateral characteristics of the osseous configuration in chronic ankle instability Magerkurth O, Frigg A, Hintermann B, Dick W, Valderrabano V. Department of Radiology, University of Basel, Switzerland. Br J Sports Med. 2008 Jul 4. [Epub ahead of print] OBJECTIVE The osseous ankle configuration (tibiotalar sector, talar radius and height) has been discovered as intrinsic risk factor for chronic ankle instability (CAI). These measurements were done on lateral radiographs only. The aim of this study was to measure osseous characteristics in the frontal plane and further lateral values. DESIGN Case control study, Level III. SETTING: Radiological measurement of frontal and lateral radiographs by one independent, blinded radiologist using a digital DICOM/PACS system. PATIENTS: A group of 52 patients with CAI was compared to an age- and gender-matched control group of 52 healthy subjects. Main Outcome Measurements: In the frontal plane: the depth of the talar curvature (froCu), the lateral and medial malleolar length. In the lateral plane: the position of the center of rotation to the tibial axis (TibCOR) and the lateral tibial surface angle (TLS). RESULTS The froCu was deeper in patients with CAI (1.8+/1mm) than in healthy subjects (1.0+/-0.4mm; P<0.05). The TibCOR was more anterior in patients with CAI (2.4+/-1.9mm) than in healthy subjects (1.5+/2.2mm; P<0.05). The distance from the fibular tip to the center of rotation was smaller in patients with CAI (3.5+/-3.4mm) than in healthy subjects (6.5+/3.3mm; P<0.05). The TLS, the length of the lateral and medial ankle were not significantly different. CONCLUSIONS This study supports that the osseous joint configuration is an intrinsic risk factor for CAI. It could be shown that CAI is characterized by a deeper frontal curvature of the talus and a more anterior position of the talus to the tibia. 45 Cartilage stiffness and histological analysis of the human ankle joint cartilage Olaf Buettner1, André Leumann1,2, Magdalena Müller-Gerbl2, Victor Valderrabano1 1 Department of Orthopaedic Surgery, University Hospital of Basel, Basel, Switzerland 2 Institute of Anatomy, Department of Biomedicine, University of Basel, Basel, Switzerland Introduction, Aim, Hypotheses Specific cartilage distribution and biomechanical properties of the ankle joint is still not fully explored. Looking at general biomechanical data (highest load per surface area among all joints), it remains unexplained why the ankle joint is seldom affected by primary osteoarthritis (OA) and on the other hand osteochondral lesions represent a common injury to the talus. The Artscan200 device (©Oyscan, Helsinki, Finland) offers the possibility of intraoperative arthroscopic assessment of cartilage indentation stiffness as a biomechanical function. With this project, the authors plan a biomechanicalhistological study on 40 human fresh cadaver ankles aiming to collect a pool of physiological data on cartilage stiffness, thickness and specific composition of histological properties in all areas of the ankle joint. The hypotheses (H) of the current study are: (H1) The cartilage stiffness of the tibial plafond is different to the one of the talus and varies according to the localisation. (H2) The cartilage is thicker on the tibial plafond as on the talus. (H3) Composition and thickness distribution of the cartilage layers varies according to the localisation.This abstract will present the study design. Methods For this study 20 pairs of fresh cadaver ankle joints without macroscopic signs of ankle arthritis will be harvested from the pathologic department. The talar, tibial and fibular articular areas are divided into 17 areas according to the anatomic grid scheme 46 of Elias et al. (Foot Ankle Int 2007). Measurement of cartilage stiffness by the Artscan device will performed with the small indentation handle for thin cartilage (<1.5mm). In each area, minimally five valuable sample measurements are collected. The macroscopic cartilage degeneration is documented using the ICRS score. Mean cartilage thickness in all 17 areas will be measured by CT-Artrography by injection of the radio-opaque Iopamidol (Iopamiro® 300) into the restored joint space (by enwrapping in a plastic film). Histological evaluation with light microscopy is performed to describe distribution of cartilage layers and subchondral bone and to rule out underlying cartilage or bony pathology. Results Since this is an ongoing biomechanical histological study only early preliminary data are available at the moment. The results of this study will be shown at next year research day. Conclusions This biomechanical-histological study aims to provide a reliable biomechanical and histological map of human ankle cartilage with a device that allows intraoperative use in order to help the orthopaedic surgeon to choose the individual optimal treatment modality in cases of ankle OA or osteochondral lesions. This study is sponsored by the American Orthopaedic Foot an Ankle Society (AOFAS) research grant 2008. Added Value of SPECT-CT imaging in degenerative joint disease of the foot and ankle Geert Pagenstert1, André Leumann2, Helmut Rasch3, Jan Müller-Brandt3, Beat Hintermann1, Victor Valderrabano2 Dep. Orthopaedic Surgery Kantonsspital Liestal, 2Dep. Orthopaedic Surgery and 3Dep. Radiology and Nuclear Medicine University Hospital of Basel 1 Background Precise localisation of arthritic (OA) disease in foot and ankle is crucial for effective and selective surgical treatment. Single photon emission computed tomography – computer tomography (SPECT-CT) is a new diagnostic tool. It fuses the morphologic and biologic information of CT and bone-scans and levels its spatial resolutions. Consequently accuracy to localize increased szintigraphic uptake should be higher with SPECT-CT. Methods The intraobserver and interobserver reliabilites were determined by calculating the kappa values for the different anatomic areas, job experiences, medical specialties of five observers on the basis of multi-rater kappa. 20 patients with pain of uncertain origin at foot and ankle where evaluated clinically, with weight bearing x-rays, and with standard 3-phase whole body bone scintigraphy (99m-TcDPD) including a three dimensional SPECT-CT scan in the late phase with a thin slice SPECT-CT Scanner (Symbia T2, Siemens). The images were available as fused hybrid SPECT-CT images and as separate bone-scan, SPECT and CT images All patients had a complex history suspicious for degenerative joint disease. Results The average intraobserver reliability for the CT & bone-scan side-by-side was good (κ = 0.67; CI 0.60 to 0.76; p < 0.01) and for the SPECT-CT was perfect (κ = 0.86; CI 0.81 to 0.88; p < 0.01) and significant higher (p < 0.01). Comparing intraobserver reliability according to the medical specialty and to the level of training a significant difference between radiologist and orthopaedic residents was present for CT, bone-scan, and CT & bone-scan side-by-side (p < 0.01). Between orthopedic surgeons and residents a significant difference was found for bone-scan and CT & bone-scan side-by-side (p < 0.01) but not for CT and SPECT-CT (p > 0.05). No significant difference was found for any diagnostic method between radiologist and board certified orthopedic surgeons (p > 0.05). Each mean intraobserver reliability for the SPECT-CT was perfect (κ = 0.86; CI 0.81 to 0.88; p < 0.01).The mean value of multi-rater kappa interobserver reliability for the CT & bonescan side-by-side was 0.83 (CI 0.71 to 0.93; p < 0.01) (good agreement) and for SPECT-CT 0.92 (CI 0.73 to 1.00; p < 0.01) (perfect agreement). Comparing the of interobserver reliability according to anatomical regions of the foot all mean values for SPECTCT were found at very high level, the differences between the anatomic regions for SPECT-CT were not statistically significant (p > 0.05). However, comparing interobserver agreements of SPECTCT with CT & bone-scan side-by-side significant differences were found for the naviculocuneiforme and tarsometatarsal joints (p < 0.001). Conclusions Our data suggest that SPECT-CT has added value for orthopedic surgeons and radiologists in localizing active degenerative joint disease in foot and ankle in difficult patient settings with multiple arthritic joints. 47 Range of Motion of Standard and High-Flexion Posterior Cruciate Retaining Total Knee Prosthesis. A matched controlled study Geert Pagenstert1, Andreas Elsner1, Martin Bachmann1, Susanna Häfliger1, Beat Hintermann1, Victor Valderrabano2 Departments of Orthopaedic Surgery 1Kantonsspital Liestal and 2University Hospital Basel Introduction In total knee arthroplasty (TKA) there has been a shift of focus toward high-flexion TKA designs that meet patients’ needs and increasing demands. The purpose of this study was report on the early results of a new (European release August 2006) high flexion TKA design (Triathlon TKA, Stryker), and to compare the ranges of motion (ROM) associated with standard TKA (Duracon TKA, Stryker). Methods ROM was prospectively evaluated in the first consecutive 75 patients receiving the new highflexion TKA (higher posterior femoral condylar offset, mobile arc-fixed bearing tibial inlay, specific component sizing options) from a single surgeon. ROM was compared to an age, gender, and preoperative ROM, matched cohort (75 patients) which received the previous generation total knee design (Duracon) from two surgeons. All patients received all cemented, posterior cruciate retaining femoral and fixed bearing tibial implants over an anteromedial approach. Postoperative care and rehabilitation followed the same standard protocols at the same clinic. 48 Results The average preoperative ROM was 108°(range, 70 to 150°) for the Triathlon and 104°(range, 70 to 140°) for the Duracon cohort (p>0.05). At three months follow-up, postoperative ROM was in average 112° (range, 85° to 135°) for the Triathlon and 100° (range, 70° to 130°) for the Duracon cohort (p<0.001). At one year follow-up, the Triathlon cohort showed a significant higher ROM (average ROM, 125° (range, 85° to 145°)) as the Duracon cohort (average ROM, 106° (range, 70° to 130°)) (p<0.001). Conclusion The resulting average ROM of the Triathlon series exceeds the ROM of the previous generation knee design and suggests that flexion can be optimized by specific TKA designs. Sports and Recreation Activity of Ankle Osteoarthritis Patients Before and After Distal Tibia Osteotomy Pagenstert G1, Leumann A2, Hintermann B1, Valderrabano V2 Departments of Orthopaedic Surgery 1Kantonsspital Liestal and 2University Hospital Basel Background Physical activity in sports and work challenges ankle fusion and arthroplasty. Distal tibia osteotomy to unload ankle osteoarthritis (OA) has been proposed as treatment alternative for asymmetric ankle OA. However, participation in sports after this procedure has not been analyzed. Hypothesis Distal tibia osteotomy increases sports activity in patients with ankle OA. Sports activity correlates with ankle pain, function and alignment, but does not influence revision rate. Methods Series consisted of 35 consecutive patients with posttraumatic varus or valgus ankle OA (mean age 43 years; range, 23-68 years). Pain (visual analogue scale; VAS), ankle range of motion (ROM); function (American Orthopaedic Foot and Ankle Society (AOFAS) ankle score; Swiss symptom-related Ankle Activity Scale (SAAS); Sports Frequency Score (SFS), OA and tibiotalar alignment grade (Takakura score), and revision surgery were documented. The mean follow-up was 5 years (range, 3 to 10.5 years). Results The course of mean values from preoperative to follow-up were: VAS decreased (p=.0001) 4 points; ankle ROM increased (p=.001) 5°; AOFAS score increased (p=.0001) 46 points; SAAS increased (p=.0001) 42 points; SFS increased (p=.02) 0.5 grades; Takakura score decreased (p=.0001) 1.0 grades. Revision surgery was performed in 10 cases (29%). Three of these (9%) were revised to ankle arthroplasty. At follow-up: SAAS correlated with VAS, AOFAS score, Takakura score, and not with ROM or SFS. SFS did not correlate with other variables. Patients needing revision surgery had a higher (p=0.003) SFS than patients who needed no revision. Conclusion Distal tibia osteotomy increased sports activity of ankle OA patients. Improvement of ankle pain and function correlated with ability to perform activity without symptoms. However, sports frequency had no correlation to patients’ symptoms but showed higher revision rate. 49 DUAL-MODE DYNAMIC FUNCTIONAL STIFFNESS OF ARTICULAR CARTILAGE H. Ardura Garcia1,2, B. Goepfert1, A.U. Daniels1, D. Wirz1 1 2 Lab. for Orthopedic Biomechanics, Faculty of Medicine, Univ. of Basel, Basel, Switzerland. Biomedical Engineering Dept., Universidad Iberoamericana, Mexico City, Mexico. Elastic modulus, loss angle, and Poisson’s ratio Where Edyn = dynamic elastic modulus, ν = Poisson's determine how poro-viscoelastic materials or ratio, αmax = maximum displacement, Pαmax = force structures (e.g. cartilage) distribute and dissipate at maximum displacement, and R = indenter radius. loads. Also, these parameters are highly sensitive A value of ν = 0.44 was assumed. The loss angle φ to structural changes and thus have diagnostic was calculated directly from the time differences value. Nutrition processes in cartilage occur at between the maxima of the force and displacement slow loading rates which move water in and out. In curves. contrast, gait subjects hip, knee and ankle cartilage to RESULTS: Nutrition-mode (0.1Hz) and gait-mode impact loads, which severely limit water movement, stiffness, same specimen: n =8 in each mode. produce higher modulus values and lower loss S.D. Mean S.D. angles, indicating energy storage. We hypothesize Method Indenter Mean radius Edyn Edyn φ [°] φ [°] that evaluating cartilage in dual modes provides [mm] [MPa] [MPa] a more complete picture of functional stiffness. 8.2 0.9 15.7 2.2 Also, indentation testing minimizes specimen N-mode 1 preparation and is more functionally relevant [1]. G-mode 0.5 14.9 0.8 7.7 0.6 This study provides initial results. METHODS:The cartilage source was fresh, healthy ! knees harvested from young pigs (9 months old). Specimens were 7.6mm Ø osteochondral plugs from the lateral condyles. Each specimen was evaluated in both test modes, using a steel spherical tip indenter. “Nutritional” loading was accomplished with a Synergie 100 MTS® programmed to perform a series of single sinusoidal cycles at 0.1 Hz under ! displacement control to a depth of ~0.1 mm. “Gait” loading was accomplished with a single impact DISCUSSION & CONCLUSIONS: Precision micro-indentation (SIMI) device, mounted in a rigid of both test modes was acceptable (worst S.D.=14%). load frame. The SIMI indenter pendulum falls freely, Compared to N-mode, G-mode modulus was ~82% with impact force thus determined by mass and higher, and loss angle was ~51% lower. The data gravity. The mass and indenter dimensions used gave demonstrate the dependence of cartilage stiffness indentation depths of ~0.1 to 0.2 mm in healthy parameters on test mode, and support dual mode cartilage. An electromagnetic coil captures indenter tests to evaluate two aspects of cartilage function. motion data. The equivalent frequency of SIMI REFERENCES velocity at impact is 350Hz. All previous calculations of cartilage modulus from [1] R.K. Korhonen, et al (2002) J Biomech 35:909. [2] A. P. Kren, et al Determination of viscoelastic characteristics of indentation data are compromised by being based biological materials by SIMI (m.s. in preparation). [3] W. C. on a model which assumes cartilage is elastic [3]. Hayes (1972) et al. J Biomech 5:541 In the resultant indentation equation, modulus Funding: Deutsche Arthrose Hilfe (Saarlouis DE), values are inversely proportional to a correction Hardy & Otto Frey-Zünd Stiftung (Basel CH). factor, κ, which varies with both indenter-radius/ cartilage-thickness ratio and Poisson's ratio. Instead, we used the approach of Kren [2] which assumes viscoelasticity. The modulus is calculated from Edyn=(1-ν)[Pαmax / (R1/2αmax3/2)] 50 Die autologe matrixinduzierte Chondrogenese (AMIC®)- ein neues Verfahren zur Behandlung von Knorpeldefekten J.P. Benthien, M . Jakob Behandlungszentrum Bewegungsapparat, Universitätsspital Basel Fragestellung Für die Therapie von Knorpeldefekten im Kniegelenksbereich stehen verschiedene Methoden zur Verfügung, einen « golden standard « gibt es nicht. Mit dem AMIC®-Verfahren steht eine Möglichkeit zur Verfügung, unter Verwendung einer speziellen Kollagen I/III-Membran die Chondrogenese zu stimulieren. Können mit diesem Verfahren chondrale Defekte behandelt werden und gibt es einen klinisch messbaren Erfolg? Methodik Diese case control-Studie soll alle Fälle von AMIC® bei Knorpeldefekten im Kniegelenksbereich im Sinne einer Qualitätskontrolle an unserer Klinik erfassen und klinisch nachuntersuchen. 4 Fälle mit 6und 12-Monatsergebnissen konnten bisher erfasst werden. Schlussfolgerung Mit der autologen matrixinduzierten Chondrogenese (AMIC®) steht ein neues Verfahren zur Behandlung von osteochondralen Defekten zur Verfügung. Erste Ergebnisse an unserer Klinik zeigen, dass sie zur Behandlung von chondralen Defekten geeignet ist. Literatur 1. 2. 3. 4. Behrens P :Matrixgekoppelte Mikrofrakturierung.Ein neues Konzept zur Knorpeldefektbehandlung. Arthroskopie 2005 ; 18 : 193-197 Kramer J et al. : In vivo matrix-guided human mesenchymal stem cells. Cellular and Molecular Life Sciences 2006 ;63 : 616-626 Steadman J et al. : Microfracture to treat full-thickness chondral defects : surgical technique, rehabilitation and outcomes. Ergebnisse In allen Fällen ging in der 6- und 12-Monatskontrolle der Schmerzscore nach VAS deutlich zurück, der Bewegungsumfang der betroffenen Kniegelenke normalisierte sich. Insbesondere bei Retropatellardefekten, die sonst einer Behandlung schwer zugänglich sind, verbesserten sich Schmerzscore und Bewegungsumfang. 51 Effects of antimicrobial materials on microorganism growth kinetics can be determined by isothermal micronano calorimetry (IMNC) A.U. Daniels, D. Wirz, U. von Ah Laboratory for Orthopedic Biomechanics, Orthopedic Surgery Dept., Uni Basel Hospital Can IMNC accurately and efficiently determine the effects of antimicrobial materials on microorganism growth? Does our method offer advantages over standard methods? Previously, we have shown our simple IMNC method can rapidly detect, follow in real time, and quantify microorganism growth in culture. The heat production rate (W=J/s) measured at any time t is the aggregate cultured cell metabolic rate, and the amount of heat produced (J) between t1 and t2 is proportional to the number of cells produced. IMNC detects changes as low as 22 nJ/s-equivalent to a change of only ~104 in the number of active bacteria present. IMNC does not disturb the cultured specimens (cells, medium, solids). So, after IMNC data are obtained, specimens can be evaluated by any conventional means desired. METHODS: The IMNC instrument is equilibrated at a chosen temperature (e.g. 37ºC). Bacterial cultures of known types and concentrations (cfu/ ml) are prepared conventionally. Studies are done in sterile 4 ml glass ampoules. Typically, 2.97 ml of a growth medium (with or without an antimicrobial) are added, followed by 0.03 ml PBS containing 104 cfu of bacteria. The ampoule is then septum sealed. Measurements start ~60 minutes later--after the ampoule is lowered first into the equilibration position in one of the instrument’s calorimeters and then to the measurement position. The instrument used has 48 independent calorimeters, and can thus rapidly evaluate multiple culture variables and replicate specimens (TAM III-48, Waters/TA Inc., New Castle DE, USA). Heat is monitored for hours-even days--as needed. ! Fig. 1: E. coli/gentamicin Funding: Velux Found. (CH) 52 RESULTS: (A) Our IMNC method rapidly determines whether a sample contains methicillin-resistant or susceptible Staphylococcus aureus (MRSA or MSSA). The determination is made in ~ 4 hours vs. 24 hours by standard means. In addition IMNC provides the MIC (minimum inhibitory concentration) of the antibiotic used. (B) We expanded our approach to determine MICs of 10 different antibiotics for 5 different surgically important bacteria. IMNC was simple and accurate. Results correlated exactly with parallel standard assessments and reference values from the Clinical Laboratory Standards Institute (USA). At subinhibitory concentrations, growth curves (time histories of heat flow rate and aggregate heat) were reproducible for a given bacteria and medium and revealed their mechanisms: e.g., gentamicin only delays E. coli (Fig. 1) but choramphenicol reduces S. aureus growth rate (Fig. 2). (C) IMNC also reveals the antimicrobial action of Ag+ ions. The MIC (no growth at 24 hours) of AgNO3 was 8 mg/l for S. aureus. For an antimicrobial biomaterial (~1µm silica agglomerates containing silver particles 5-20 nm diam.) the MICs were much higher (e.g. 250 mg/l for silica-20% silver) because of reduced Ag+ available. IMNC also shows that subinhibitory concentrations of Ag+ only delay growth but have no effect on the growth rate (Fig 3). CONCLUSIONS: Answers to posed questions were “yes.” Results suggest IMNC is an important new microbiology tool. Our continuing studies include IMNC identification of microorganisms and IMNC evaluation of the dynamics of bacterial biofilm formation. ! ! Fig. 2: S. aureus/chloramphenicol Fig. 3: S. aureus/silica-20%Ag Muskelatrophie am Unterschenkel bei Arthrose des oberen Sprunggelenkes K. Dopke1, T. Egelhof2, T. Wischer3, W. Dick 4, V .Valderrabano4 Orthopädische Klinik, SRO AG, Langenthal, Schweiz Radiologische Klinik, Universitätsspital Basel, Schweiz 3 Abteilung für Radiologie, Merian Iselin Spital, Basel, Schweiz 4 Behandlungszentrum Bewegungsapparat, Universitätsspital Basel, Schweiz 1 2 Einleitung Bei posttraumatischer Arthrose zeigt sich klinisch häufig eine Differenz bei der Umfangsmessung der Unterschenkelmuskulatur im Seitenvergleich. Ziel dieser Arbeit ist es anhand der Magnetresonanztomographie (MRT) die Trophik und Gewebsqualität bei Arthrose des oberen Sprunggelenkes (OSG) zu untersuchen. Hypothetisch wurde eine selektive Atrophie und fettige Degeneration einzelner Muskelgruppen des Unterschenkels erwartet. Methodik Es wurden 21 Patienten (42 Unterschenkel;11 weiblich, 10 männlich; Altersdurchschnitt 54J., range 32-74J.) mit unilateraler posttraumatischer OSG - Arthrose erfasst. Einer ausführlicher Anamnese (vorangehende Traumata, Latenzzeit zur Arthroseausbildung) folgte eine klinische Untersuchung (Wadenumfang, AOFAS Hindfoot Score, Visual Analogue Scale (VAS)). Der radiologische Status wurde mittels konventionellem Röntgen (Standard belastete Aufnahmen OSG antero – posterior und seitlich) erfasst und der Ausprägungsgrad der Arthrose evaluiert (Athrosescore nach Morrey and Wiedeman). Anschliessend wurde eine MRI - Untersuchung beider Unterschenkel durchgeführt (T1 und T2 Gewichtung, Magnetom Avanto, Siemens Erlangen). Die Auswertung erfolgte am hochauflösendem Monitor (Totoku) unter Verwendung der E-Film Software. Dabei wurden der M. tibialis anterior, die Peronealmuskelgruppe, M. tibialis posterior, M. gastrocnemius medialis und lateralis sowie M. soleus identifiziert und die Muskelflächen quantitativ digital vermessen. Zusätzlich erfolgte die Vermessung der Dermisfettschicht. Ergebnisse In der klinischen Untersuchung war bei allen Patienten der Unterschenkelumfang der erkrankten Seite vermindert. Quantitativ zeigte sich im MRT überwiegend eine geringere Fläche der Unterschenkelmuskelgruppen im Vergleich zur gesunden Seite, signifikant war aber ausschliesslich der Unterschied beim M. soleus (p= 0,001). Bei dem Vergleich der Mittelwerte der Summe der Fläche der gesamten Unterschenkelmuskulatur der erkrankten Seite im Vergleich zur Gegenseite zeigte sich ebenfalls eine signifikante Flächenreduktion (p= 0,013). Bei der qualitativen Beurteilung der einzelnen Muskelgruppen im MRI war der M. soleus bei allen untersuchten Patienten eindeutig fettig degeneriert. Kein signifikanter Unterschied im Seitenvergleich war bei der Ausmessung der Dermisfettschicht nachweisbar. Schlussfolgerungen Bei Patienten mit OSG-Arthrose ist im Seitenvergleich der Unterschenkelumfang auf der erkrankten Seite signifikant vermindert. Die vorliegende Studie kann eindeutig aufzeigen, dass dies auf einer Muskelatrophie beruht. Es zeigen sich nachweislich in der Muskulatur der erkrankten Seite fettig degenerative Veränderungen, wobei hier der M. soleus einen besonderen Stellenwert einnimmt und als einziger Muskel am signifikantesten betroffen ist. Somit konnte ein Zusammenhang zwischen OSG-Arthrose und Muskelatrophie differenziert dargestellt und mit signifikanten Ergebnissen belegt werden. 53 Tantalum for Ankle- and Hindfoot-Reconstruction Analysis with Micro-CT Frigg A1,2, Dougall H1, Boyd S3, Nigg B3, Russell I1, Valderrabano V2 Department of Orthopaedic Surgery, University of Calgary, Canada Behandlungszentrum Bewegungsapparat, Universitätsspital Basel 3 Human Performance Laboratory, University of Calgary, Canada 1 2 Background For reconstruction of the ankle and hindfoot, a structural graft to fill a gap is often required.Autograft is associated with donor site morbidity in up to 48% of cases and its quantity is limited. Allograft carries potential risks of disease transmission, collapse and reduced healing potential. Trabecular metal (Tantalum) has been used successfully in spine, hip and knee surgery with the advantage of high primary stability, osteoconduction and absence of donor site morbidity. However its use in foot and ankle surgery has not yet been documented. Materials and Methods From 6/2006 to 11/2006 nine foot and ankle reconstructions were performed using Tantalum. Patients were followed clinically and radiologically with SF-36 and AOFAS-score over a mean followup of 1.7 (1.6-2.1) years. Ingrowth of bone into the Tantalum was analysed in vivo in selected patients using micro-CT. 54 Results All patients including revision cases, went on to radiological and clinical fusion after 3-4 months. Average Charlson co-morbidity score was 0.8 (0-5), SF-36 score 53 (31-82), AOFAS-score 73 (38-100). The micro-CT showed a condensation and ingrowth of trabecules into the Tantalum. Conclusion Tantalum is an excellent structural graft for ankleand hindfoot reconstruction. It exhibits a high fusion rate due to osteoconduction, high primary stability, has no donor site morbidity and saves operating time. Analysis of Muscular Coordination in Different Jumping Elements in Aerial Freestyle Skiing Beat Göpfert1, Cora Huber1,Anton Lüthi2, Dieter Wirz1 1 2 Lab. for Orthopaedic Biomechanics (LOB) CM&BE University Basel; Switzerland Swiss Federal Institute for Snow and Avalanche Research, Davos, Switzerland Aerial Freestyle Skiing is highly demanding on the coordinative skills of athletes. The increasing level in competitions demands jumps with a higher complexity and with additional acrobatic jumping elements. Therefore the improvement of proprioception and coordination of muscular skills is needed to be successful in international competitions. The goal of this study was to help to improve training methods in Aerial Freestyle Skiing. Methods The EMG of the M. tibialis anterior, M. gastrocnemius medialis, M. rectus femoris, M. semitendinosus, M. rectus abdominis, M. obliqus externus abdominis and M. erector spinae (left & right side) was recorded (SENIAM Standard) in Freestyle Aerial Skiing of 5 Swiss National Team members during 2 different jumps: a) Lay-Full (Double flip in the layout position with a full twist in the second flip) b) Lay-Tuck-Full (A triple flip, the first in the layout position, the second in the tuck position, and the third in the layout with a twist). The EMG-signals were afterwards analysed using Wavelet-Transformation (WT) (von Tscharner 2000). Results The WT-EMG-activation-pattern of all recorded muscles shows: a) The time for the muscle activation pattern decreases for the same jumping element with higher complexity of the jumps. In the 2 element jump the time per element is: Lay: 0.4s, Full 1.8s, and in the 3 element jump: Lay: 0.35s, Full 1.5s. b) The pre-activation of the leg muscles for the jumping element “Full” occurs in the preceding jumping element. Indicated by the circles in Fig. 1 Discussion The higher complexity of a “Lay-Tuck-Full” jump vs. “Lay-Full” jump can not only be compensated by a bigger kicker and therefore longer airborne time. It needs more precise and better coordinated muscular events in a shorter time. The muscular activation pattern of the same jumping element is similar but depending on the sequence of the jumping elements of the whole jump. The muscular activation of the leg muscles occurs in preceding jumping element of the element “Full” independent of the muscular activation of the trunk muscles. The actual measurement of the timing of the sequence of muscular events will allow the coaches and athletes a better understanding of the movements and allows an optimizing of the practice and therefore may lowering the risk of injuries. References Von Tscharner, V. (2000), Intensity analysis in time-frequency space of surface myoelectric signals by wavelets of specified resolution, J Electromyogr Kinesiol 10(6):433-45. Figure1: Muscle activation pattern in jump: Lay-Full and Lay-Tuck-Full 55 Adult-onset Still’s disease (AOSD) - a rare osteoarthritis entity for the orthopedic surgeon Dorian Hauke1 ,Franziska Saxer1 ,Alexander Tzankov 2, Victor Valderrabano1 University Hospital of Basel, Department of Orthopaedic and Trauma Surgery, Spitalstreet 21, 4031 Basel, Switzerland 2 University Hospital of Basel, Department of Pathology, Spitalstreet 21, 4031 Basel, Switzerland 1 AOSD is an inflammatory disorder characterized by spiking temperatures, arthralgia and a characteristic transient salmon-coloured rash. The etiology is unknown. There is only little information on the epidemiology, the incidence was estimated at 0.16 per 100000 without a gender predilection.There are two peaks, between 15 to 25 and 36 to 46 years, only rarely patients are older than 70 years.The diagnosis is reached when certain cardinal and secondary criteria can be met. Furthermore, other causes have to be excluded. Apart from these criteria, serum ferritin is a relevant diagnostic marker, which can be also used as parameter for therapeutic efficacy. The therapeutic options depend on the disease course and its clinical presentation. Typically, NSAID`s, glucocorticosteroids and immunosuppressants are used. Chronic illness can cause joint destruction and secondary amyloidosis, life threatening complications are rare. Case report A 59-year old woman presented with fever more than 39° C and clinical signs of omarthritis, general history was unremarkable.The right shoulder showed a painful restriction of movement without signs of imflammation. The laboratory results showed high inflammation markers and abnormal liver function tests. The x-ray was normal. Blood cultures were negative. After an aspiration (yellow and slightly cloudy fluid, microbiologic testing revealed a sterile leucocytosis) of the shoulder joint, we performed an shoulder arthroscopy, which showed regular intraarticular findings, subacromially there was a mild discharge of pus and moderate vascular injection. We carried out a subacromial debridement and an ample lavage. A synovial biopsy and subacromial samples revealed acute synovialitis in the histological examination, the microbiologal examinations were unremarkable. In view of persistent pain and static levels of inflammation markers, we performed a second look arthroscopy to perform a throughout lavage for reducing a potential septic arthritis and wash out cartilage damaging enzymes. Morphologically the arthroscopy showed a mild intraarticular synovialitis 56 and subacromially a considerable vascular injection. The biopsy again showed an acute synovialitis, while the bacteriologic analysis was again sterile. After excluding malignancies, infection and other rheumatoid disease our tentative diagnosis was an AOSD. This assumption was supported by a serum ferritin of 795ng/ ml. Oral prednison therapy with 40mg per day improved the clinical picture and the inflammation markers. Discharge of the patient in a good general condition. A final check three months later showed a symptom free patient and normal laboratory findings. We therefore assumed a favorable course with full remission. Discussion This case shows that a predominantly medical condition can be most relevant for the orthopedic surgeon and illustrates that the interdisciplinar approach is extremely important in the osteoarthritis diagnostic process. The diagnosis of AOSD was reached by exclusion of other conditions.The above mentioned criteria have at least partially to be met and can be of some assistance. With hindsight a second arthroscopy might have been avoided if we had thought of an AOSD as a differential diagnosis earlier. In the process of finding the empirically right diagnosis in this case, we excluded infections, rheumatologic disorders, solid and hematological malignancies step by step. The clinical presentation, as well as the pattern of laboratory findings, was at the end very typical for AOSD, although the patient lacked the characteristic rash, which might have given us a precious hint earlier.According to the mentioned criteria our patient presented with 6 listed criteria (3 primary, 3 secondary ones), the exclusion criteria were met as well. The final clue was given by the high serum ferritin and the therapeutic success of glucocorticosteroids, which led to full remission. To our best knowledge up to now no recurrences have been reported after initial success. Arthroscopic repair of massive rotator cuff tears: correlation of functional results with muscle atrophy, fatty infiltration and integrity of the cuff in a prospective, MRI controlled study Dorian Hauke 1, Sven Lichtenberg 2, Dennis Liem 3, Robert Varga 2, Petra Magosch 2 and Peter Habermeyer 2 University Hospital of Basel, Department of Orthopaedic and Trauma Surgery, Spitalstreet 21, 4031 Basel, Switzerland 2 ATOS-Clinic Heidelberg, Shoulder and Elbow Service, Bismarckstreet 9-15, 69115 Heidelberg, Germany 3 University Hospital of Muenster, Department of Orthopaedics, Albert Schweitzer Street 33, 48149 Muenster, Germany 1 Background Over the last decades there has been an impressing progress in the treatment of massive rotator cuff tears. The arthroscopic repair of rotator cuff tears from today shows good clinical results and a high patients` satisfaction. To our knowledge there were no studies, which have specifically assessed cuff integrity, muscle atrophy and fatty infiltration and their influence on the clinical outcome after arthroscopic repair of posterosuperior rotator cuff tears. Methods We evaluated twenty consecutive patients (average age 58.8 years) with massive posterosuperior rotator cuff tear. In all patients we performed an arthroscopic rotator cuff repair. After an average follow-up of 34.9 months, all patients were evaluated by a physical examination and a strength testing, which were graded to the Constant Score. Furthermore all patients unerwent a standardized MRI-examination. Evaluation criteria were cuff integrity, muscle atrophy and fatty infiltration. These findings were correlated to the clinical result and the appearance of retears. from pre- to postoperative (p = 0.012). Comparing the postoperative results of the intact and retorn tendon group there were no significant differences (p = 0.09). Regarding to the muscle atrophy of the supraspinatus there was no significant increase from pre- to postoperative in the retorn and intact tendon group (retear p = 0.08; intact p = 0.30). The fatty infiltration of the infraspinatus improved in both groups from pre- to postopertively significant (intact p = 0.027; retear p = 0.017). Fatty infiltration of the supraspinatus was only higher in the retear group (p = 0.026). The preoperative fatty infiltration of the supraspiantus was the only parameter, which showed a correlation to the retear rate (r = -0.519; p = 0.019). Regarding to the Constant Score there were no correlation between these preoperative values and the postoperative scores. Conclusion Arthroscopic repair of massive posterosuperior rotator cuff tears gives good clinical results and high patients` satisfaction. Our retear rate, clinical and structural results are comparable to open or miniopen techniques. Therefore it can be recommended as a good treatment option for this entity. Results The overall Constant Score improved significantly from preoperative 47.93 to postoperative 78.16 points after arthroscopic repair (p = 0.001).The retear rate was 40% (eight patients). In the retear group there were also a significant clinical improvement 57 Die Kraftmessung im Constant Murley Scores: Wie verlässlich und präzise messen wir überhaupt? Hirschmann MT1, Wind B1, Amsler F2, Regazzoni P3, Gross T4 Orthopaedic Surgery and Traumatology, Kantonsspital Bruderholz Amsler Consulting 3 Behandlungszentrum Bewegungsapparat, University Hospital of Basel University Hospital of Basel 4Trauma Unit, Department of Surgery Ospedale Civico, Via Tesserete, Lugano 1 2 Fragestellung Der Constant Murley Score ist eines der weltweit meist benutzten Instrumente zur Beurteilung der Schulterfunktion. Obwohl die Messung der Muskelkraft ein Viertel des Gesamtscores ausmacht, ist sie nur ungenau definiert und wird oft unterschiedlich gehandhabt. Methoden 33 gesunde Probanden (m:w=14:19; medianes Alter 31 Jahre) mit unauffälliger Schulteranamnese wurden standardisiert zu je zwei verschiedenen Zeitpunkten mit dem Isobex® Force Device bezüglich ihrer Schulterkraft untersucht. Der Einfluss verschiedener Arm- und Sitzpositionen (30°, 60°, 90° Abduktion des Armes mit oder ohne Stabilisierung des Rumpfes) auf die Kraftmessung wurde innerhalb 2 Wochen zwei Mal in zufälliger Reihenfolge getestet und die Intraobserver- Variabilität der Messungen bestimmt (p<0.05). Resultate Die mediane Schulterkraft (kg) lag abhängig von Arm-/Sitzposition und Händigkeit zwischen 5.6 und 10.6, wobei Frauen etwa die Hälfte der Kraft von Männern aufwiesen. Die Messwiederholung zeigte in allen Arm- und Sitzpositionen eine hohe Intraobserver- Reliabilität (Pearson r zwischen 0.73 und 0.93), mit der höchsten Genauigkeit in 90° Abduktion bei nicht stabilisiertem Rumpf. Die mittlere absolute Kraft in 30° Abduktion war 58 45% grösser als in 90° (dominante Seite 10.5±4.9 vs. 6.4±2.7; nicht-dominante Seite 9.5±4.1 vs. 5.8±2.8), zwischen 60° und 90° Abduktion betrug die relative Differenz 15%. Die Kraftmessungen in 30°, 60° und 90° Abduktion korrelierten signifikant untereinander (Pearson r > 0.89; p<0.001), sodass sich mittels Korrekturfaktoren die effektive Kraft in 90° Abduktion aus den Messungen in 30° oder 60° verlässlich extrapolieren liess. Der Vergleich von dominanter und nicht-dominanter Seite zeigte in 90° Abduktion einen 4%-igen Unterschied. Die Multiregressionsanalyse bestätigte den signifikanten Einfluss von Geschlecht (p<0.001) und Gewicht (p=0.017), nicht aber von Grösse, Armlänge und, aufgrund der homogenen Altersgruppe, Alter auf die Kraftmessung. Schlussfolgerungen Unterschiedliche Arm und Sitzpositionen beeinträchtigen die Präzision der Kraftmessung erheblich und sollten daher vermieden oder zumindest adäquat rechnerisch berücksichtigt werden. Sofern sich unsere Ergebnisse auch in Patientenkollektiven mit Schulterpathologien bestätigen, ist eine internationale Standardisierung des Kraftmessvorganges in Hinblick auf einen exakteren Vergleich klinischer Outcome-Angaben mittels des Constant Murley Scores zu fordern. Bestimmung der anterioren Beckenebene mittels Freihand-3D-Ultraschall für die Pfannenorientierung in der navigierten Hüfttotalprothetik Hirschmann MT1, Helfrich C 1, Schäfer T 1, Schwägli T2, Overhoff HM3, Friederich NF1 Kantonsspital Bruderholz, Klinik f. Orthop. Chirurgie & Traumatologie, Bruderholz, Schweiz, 2Smith & Nephew Orthopeadics AG Navigation, Aarau, Schweiz, 3Fachhochschule Gelsenkirchen, Fachbereich Physikalische Technik, Gelsenkirchen, Deutschland 1 Fragestellung Die anteriore Beckenebene, welche in der konventionellen Navigation durch perkutanes Abtasten von rechter/linker Spina iliaca anterior superior und der Symphyse bestimmt wird, findet in der navigierten Hüftprothetik als Referenzebene für die Pfannenorientierung weite Verwendung. Insbesondere bei adipösen Patienten mit ausgeprägtem Weichteilmantel kann es durch die Fehlbestimmung der Lage der Symphyse zu einem systematischen Abtastfehler mit nachfolgender Malorientierung der Beckenebene kommen. Methoden: Vom 01.01.2007 bis 31.12.2007 wurden in unserer Klinik die Becken von 20 Patienten mit primärer Coxarthrose vor Implantation einer Hüfttotalprothese mit einem Freihand-3D-Ultraschall System vermessen. (PiGalileo, Smith&Nephew, Aarau, CH; infrarot-optisches Messystem CamBar, Axios3D GmbH, Oldenburg, DE; linearer Schallkopf 5-10 MHz, EchoBlaster 128, Telemed, LT) vermessen. Die Bestimmung der anterioren Beckenebene erfolgte zum einen durch manuelles Abtasten der Referenzpunkte und zum anderen mit einer durch das Navigationssystem geführten Ultraschallbildaufzeichnung. Die Berechnung der Referenzpunkte aus dem Ultraschallvolumen erfolgte über Segmentierung von Knochenstrukturen aus den Ultraschallbildern und dem anschließenden Matching eines Beckenmodells. Die Genauigkeit des Ultraschall-basierenden Verfahrens konnte in einer vorangehenden Studie anhand von Kadaverversuchen auf +/-3° für die Winkel der Beckenorientierung (Inklination, Anteversion) bestimmt werden. Resultate Die mediane Bildakquisitions-Zeit war 12 Minuten (Spanne 7-20 Minuten). In 18 von 20 Patienten konnten plausible Datensätze mittels navigiertem Ultraschall akquiriert werden. Die abgetastete anteriore Beckenebene unterschied sich im Vergleich zu der mit dem Ultraschall erfassten Ebene vor allem in der Beckenkippung, resp. Rotation um die Transversalachse (8.5°+/-4.5°). In der Rotation um die um Longitudinal- (0.3°+/-1.7°), sowie um die Sagittalachse (0.6°+/-1.8°) wurden geringe Abweichungen festgestellt. Der vor allem auf der fehlbestimmten Beckenkippung beruhende Unterschied für die resultierende Anteversion der Pfanne war 6.0°+/-3.1° und für die Inklination 2.2°+/-1.4°. Zudem zeigte sich, dass Unterschiede >10° in der Beckenkippung tendenziell gehäuft in Patienten mit einem BMI>26 auftreten. Gerade bei adipösen Patienten gestaltete sich die Ultraschall Bilddatenaufzeichnung zum Teil schwierig und eine klare Darstellung der Knochenstrukturen und deren 3D-Aufzeichnung war nur unzureichend möglich. Schlussfolgerungen Die Ultraschall-unterstützte Navigation stellt in der Hüftprothetik eine vielversprechende Technik dar, mit der systematische Fehler der Orientierung der anterioren Beckenebene im Vergleich zur konventionellen Navigation mit manueller Abtastung, insbesondere bei adipösen Patienten, minimiert werden können. Die durch die Navigation geführte Ultraschall-Aufzeichnung erleichtert dem Operateur das Erfassen der richtigen Knochenstrukturen, bedingt aber immer noch eine hohe Lernkurve. Eine zusätzliche Verbesserung der Aufzeichnungstechnik und Benutzerführung ist nötig, um diese Technologie für einen breiteren Anwenderkreis nutzbar zu machen. 59 Mediane 5-Jahres-Ergebnisse nach winkelstabiler Plattenosteosynthese proximaler Humerusfrakturen Hirschmann MT1, Fallegger B1, Amsler F2, Regazzoni P3, Gross T4 Orthopaedic Surgery and Traumatology, Kantonsspital Bruderholz Amsler Consulting 3 Behandlungszentrum Bewegungsapparat, University Hospital of Basel 4 Trauma Unit, Department of Surgery Ospedale Civico, Via Tesserete, Lugano 1 2 Fragestellung Ziel der prospektiven Studie war die Erfassung mittelfristiger klinischer Ergebnisse nach winkelstabiler Plattenosteosynthese proximaler Humerusfrakturen, vor allem auch im Vergleich zu bereits früher erhobenen 1-Jahres- Ergebnissen. Methoden Von April 2001 bis August 2003 wurden in einem Universitätsspital 118 konsekutive Patienten aufgrund einer instabilen und/oder dislozierten proximalen Humerusfraktur mit einer winkelstabilen „proximal humeral interlocking“ Platte (PHILOS®, Synthes, Oberdorf, Schweiz) versorgt und prospektiv erfasst. 95 Patienten erfüllten die Einschlusskriterien der Untersuchung, wovon 31 während der Nachkontrollperiode verstarben, 4 nicht mehr kontaktierbar waren und 3 eine weitere Studienteilnahme verweigerten. Somit konnten 57 Patienten (=89% der Überlebenden; 11x 2-part, 23x 3-part- und 23x 4-part-Fraktur; m:w=15:42; Durchschnittsalter 65+14 Jahre) mit einem medianen Follow up von 5 Jahren klinisch nachuntersucht werden. Der Constant Murley und der DASH Score wurden erfasst, sowie subjektiv vom Patienten Schmerz, Zufriedenheit und Schwäche mittels Visual Analogue Score (VAS, 0-10) beurteilt. Resultate Während der Nachkontrollperiode verstorbene Patienten waren signifikant älter und hatten in der 6 Monatskontrolle einen schlechteren Constant Murley Score als die Überlebenden. Die subjektive Beurteilung durch die betroffenen Patienten mittels VAS bzgl. Schmerz, Zufriedenheit und Schwäche betrug 1.3±1.8, 9.0±1.6 und 2.3±2.1, 60 wobei sich eine signifikante Verbesserung von Schmerz und Zufriedenheit im Vergleich zu den 1-Jahresergebnissen zeigte (p<0.005, p<0.001). Der DASH Score verbesserte sich signifikant von 19+16 nach 12 Monaten auf 15+18 nach medianen 5 Jahren (paired t-test p<0.001), ebenso die Schulterkraft (6 Monate 5.4±3.7, 12 Monate 6.9±4.4, 5 Jahre 7.8±4.9; p<0.001). Absoluter und relativer Constant Murley Score verbesserten sich postoperativ signifikant (p<0.001) von 61±17 (77%±18%) nach 6 Monaten, über 69±17 (84%±18%) nach 12 Monaten bis zu 72±18 (88%±18) nach medianen 5 Jahren. 16/57 Patienten (29%) mussten sich einer Revisionsoperation (davon n=7 alleinige Metallentfernung) unterziehen, alle innerhalb der ersten 1.5 Jahre. Die Revisionsoperation verbesserte den Schmerzlevel in mehr als der Hälfte und die Beweglichkeit in 4/5 der Patienten). Die multivariable Regressionsanalyse nach im Mittel 5 Jahren zeigte eine signifikante Korrelation des absoluten Constant Murley Scores der verletzten Seite mit dem Alters der Patienten bei der Operation (p<0.007) sowie der Anzahl der Frakturfragmente nach CodmanNeer (p<0.020). Schlussfolgerungen Wie bereits bei den Frühresultaten so weisen unsere Patienten nach PHILOS- Versorgung am proximalen Humerus auch im mittelfristigen Verlauf überzeugende objektive und subjektive klinische Ergebnisse auf, meist selbst im Falle erforderlicher ReInterventionen und mit signifikanter Verbesserung bis 5 Jahre nach Operation. Longterm Outcome of Isolated Subtalar Arthrodesis with Two Screws Fixation Monika Horisberger, Andreas M. Müller, André Leumann, Arné Mehrkens, Olaf Buettner, Martin Wiewiorski, Victor Valderrabano Orthopaedic Department, University Hospital Basel Background Subtalar arthrodesis is the treatment of choice for pain relief and improved function in patients with isolated symptomatic subtalar disorders, e.g. osteoarthritis (OA). In the literature several surgical methods have been proposed to achieve successful subtalar fusion. In order to improve union rate, reduce revision surgery, and increase patient satisfaction a two-screw, two-plane fixation has been used in our clinic. The presented study aims to explore longterm outcome after isolated subtalar fusion with two screws fixation; in particular to examine b) pain relief, b) functional outcome, and c) radiological evaluation as c1) achievement of stable fusion, c2) hindfoot alignment, c3) adjacent joint degeneration over time. Methods Between 1995 and 2005 54 isolated unilateral subtalar arthrodesis (54 patients; 38 male, 16 females) have been performed at our institution with a two screw technique. The average age of the patients was 45.4 years (range, 19.5-80.7). All patients were retrospectively evaluated for detailed reason for subtalar arthrodesis, operation technique, complications, and revision surgery. At an average follow-up of 6.7 years (range, 2.8-13.1) all patients were evaluated clinically including the AOFAS hindfoot score, visual analogue scale for pain (VAS), SF-36, range of motion (ROM), and ability to participate in daily life acitivities and in sports. X-rays were obtained to assess hindfoot alignment and osteoarthritis grade of adjacent joints. Dynamic pedobarography was used to compare plantar pressure distribution of the healthy and the arthrodesis foot. Results The reason for the isolated subtalar arthrodesis were posttraumatic OA in 38 cases, talocalcaneal coalition in 5 cases, residual of congenital clumbfoot in three cases, postinfectious in two cases, related to a posterior tibial tendon disfunction in two cases, primary osteoarthritis in 2 cases, and chronical ligament instability and rheumatoid arthritis in one case, respectively. Follow-up examination is still conducted. Final results are awaited within the next year. Conclusion This study is expected to show that subtalar fusion with two screws is a reliable option for pain relief and a good quality of life in isolated subtalar osteoarthritis of various etiologies. Moreover, the study will answer questions about longterm effects, i.e. adjacent joint degeneration. 61 Spherical separation detects the effect of endurance and sprint training in the wavelet transformed EMG spectra Cora Huber1, Beat Göpfert1, Dieter Wirz1, Reinald Brunner2, Vinzenz von Tscharner3 1 Lab. for Orthopaedic Biomechanics (LOB), CM&BE, University Basel, Switzerland 2 Laboratory for Gait Analysis, University Children’s Hospital Basel (UKBB), Switzerland 3 Human Performance Lab. (HPL), University Calgary, Canada The type of training, endurance vs. speed, affects muscular properties like volume and fiber type ratio. The frequency distribution of the EMG spectra is depending on the proportion of the fibre type ratio, as Wakeling showed in fishes [Wakeling, 2002]. The purpose of this study was to show that the wavelet transformed EMG spectra [von Tscharner, 2000] of two groups of runners can be separated. It was hypothesised that sprint trained athletes show a different wavelet-transformed EMG spectra than endurance trained athletes under the same loadingcondition. Methods During extension of the knee on an isokinetic dynamometer (Cybex) the bilateral EMG (SENIAMStandard) of the M. Vastus lateralis and M. Vastus medialis were recorded of 7 volunteer female endurance and 8 volunteer female sprint trained athletes.Additional the kinematics using a goniometer and the torque acting in the knee respectively in the Cybex moment axes was recorded during the 2 test conditions (condition 1: <40°/s and < 26Nm; condition 2: >100°/s and <26Nm). The EMG, angle, torque-data were synchronously sampled at a rate of 2520 Hz. The analysis of the EMG was done with a wavelet transformation following a sphere separation of the EMG mean power spectra. A sphere separation is an analysis of the whole EMG spectra to detect the two groups by there different muscle properties. The statistical analysis was done by a binominal distribution a) Discussion The result of the sphere separation shows its capability to separate a cohort of athletes trained individually according to there training regime by the EMG wavelet spectra with a non-invasive technique. The conclusion of this study is that the EMG wavelet spectra of an individual muscle allow a specific training regime to reach a desired goal. This is essential in sport activities and in rehabilitation to get an optimal result. References 1. 2. Von Tscharner, V. (2000), Intensity analysis in timefrequency space of surface myoelectric signals by wavelets of specified resolution, J Electromyogr Kinesiol 10(6):43345. Wakeling, J. (2002), Determining patterns of motor recruitment during locomotion, J Exp Biol 205:359-69 b) sprint trained Figure 1: Spherical separation of a) condition 1 and b) condition 2 of endurance (cross) and sprint (circle) trained athletes. sprint trained endurance trained endurance trained ! 62 Results Figure 1 displays the distribution of the endurance (cross) and sprint (circle) trained athletes using the spherical separation analysis. The diagonal line represents the separation line and in this analysis the angle bisector of quadrant. The results of this study show that in condition 1 13 of 15 athletes and in condition 2 11 of 15 athletes could be statistically significant separated. (p<0.05) ! Klinische, radiologische und biomechanische Analyse von Talonavicular-Arthrodesen Sandra Kölblin, André Leumann, Martin Wiewiorski, Thomas Egelhof,Victor Valderrabano Orthopädische Universitätsklinik, Behandlungszentrum Bewegungsapparat, Universitätsspital Basel, Basel, Schweiz Hintergrund Bei Arthrose des Talonaviculargelenks oder medialer Rückfußinstabilität ist die Talonavicular (TN)-Arthrodese eine anerkannte Therapieform. Nachteile sind eine begrenzte Fehlstellungskorrektur im Rückfuß, sowie eine Pseudarthroserate bis zu 64%. Hauptursache möglicher Langzeitschmerzen sind Anschlussarthrosen benachbarter Gelenke. Ziel dieser Studie ist die Erfassung von Langzeitergebnissen nach TN-Arthrodesen in Bezug auf sekundäre Degeneration benachbarter Gelenke und den Einfluss auf das Gangbild postinterventionell. Methoden Eingeschlossen wurden Patienten, die in den letzten 2-12 Jahren eine Arthrodese des TN-Gelenks erhielten. Die klinische Untersuchung erfolgte mit dem AOFAS-Hindfoot-Score. Prä- und postoperative Fußschmerzen wurden mit der Visuellen Analogskala (VAS 0-10), die Lebensqualität mit dem ShortForm 36 (SF-36) erfasst. Die radiologische Arthrosegradierung erfolgte nach Morrey und Wiedemann (Grad 0-3). Das Abrollverhalten wurde mit Hilfe der dynamischen Baropedographie (EMED, Novel, München) ermittelt. zustimmen. Der AOFAS betrug im Schnitt 60,1 Pkt (Min. 8, Max. 100, SD 23,9). Ein postoperativerVAS von 5 (SD 3,0) zeigte eine signifikante Schmerzreduktion (präop. 7,3; SD 2,6). 4 Re-Arthrodesen (19%) wegen Pseudarthrose und 1 Infekt (4,8%) postop. konnten in dieser Kohorte verzeichnet werden. Röntgenund Baropedographische Ergebnisse werden am Forschungstag dargestellt. Schlußfolgerung Die Ergebnisse korrelieren mit den in der Literatur beschriebenen,welche trotz radiologischem Nachweis von Anschlussarthrosen und einer veränderten Fußfunktion, eine subjektive Patientenzufriedenheit zwischen 86 und 100% beinhalten. Im Hinblick auf die große Patientenzufriedenheit kann diese Therapie bei isoliertem Befall des Talonavicular-Gelenks empfohlen werden. Auf der möglichst anatomischen Wiederherstellung des Rückfussalignements sollte ein besonderes Augenmerk liegen. Resultate Von 44 Patienten konnten 21 (14 Frauen, 7 Männer; Alter: 42-83 J; Durchschnittsalter 58,7 Jahre) nachuntersucht werden. Die mittlere Nachbeobachtungszeit betrug 5 Jahre. Mit der Operation waren 66,7% zufrieden und 33,3% unzufrieden. 71,4% würden dieser Operation erneut 63 Chronische Achillessehnenossifikation – Fallbericht und Diskussion therapeutischer Optionen André Leumann, Claudio Rosso, Victor Valderrabano Orthopädische Universitätsklinik, Behandlungszentrum Bewegungsapparat, Universitätsspital Basel, Basel, Schweiz Fragestellung Die Ossifikation bei chronischer Achillestendinose stellt den Endpunkt in der Pathogenese der Sehnendegeneration dar, führend zu einer Funktionsunfähigkeit der Sehne, persistierenden Schmerzen sowie der Gefahr einer chronischen Ruptur. Methodik Anhand eines eindrücklichen Fallberichts soll das Ausmass der Befunde gezeigt,mögliche therapeutische Optionen diskutiert und die gewählte Behandlung dargestellt werden. Dabei werden intraoperative Bilder, Histologie und die operative Rekonstruktion präsentiert. Ergebnisse Der 59 jährige Patient zeigt bei Status nach Achillessehnenverlängerungs-Operation in der Kindheit bei Klumpfuss eine degenerative Achillessehnentendinose mit einer vollständigen Ossifikation über 10 cm Länge. Bei klinischer Funktionslosigkeit der Sehne mit einer fixierten Spitzfussstellung, starken Belastungsschmerzen und der Gefahr einer chronischen Ruptur wurde nach Ausschöpfung der konservativen Therapiemassnahmen eine operative Revision notwendig. Dabei wurde das degenerative, ossifizierte Gewebe vollständig entfernt. Die Achillessehnenrekonstruktion zur Überbrückung 64 von 10cm sowie Verstärkung des restlichen Gewebes wurde mit einer Kombination von Umkehrplastik, Plantaris longus-, Semitendinosus- und Gracilis-Sehne durchgeführt.Alternative Rekonstruktionsmethoden wären: Y-Plastik, Hallucis longus-Sehne. Die Y-Plastik ist nur zur Überbrückung von 2-4cm geeignet. Die Hallucis longus wurde zurVermeidung einer weiteren Push-off Schwäche des Fusses nicht verwendet. Schlussfolgerung Die Ossifikation der Achillessehne stellt einen schweren Verlauf einer chronisch degenerativen Tendinose dar. Der vorliegende Fall stellt eine rekordverdächtige Ossifikation über eine Länge von 10cm dar. Nach Ausschöpfung der konservativen Therapien ist eine operative Revision indiziert. Die Rekonstruktion einer solchen Entität stellt stets eine anspruchsvolle Chirurgie dar, wobei je nach Ausmass verschiedene Techniken zur Anwendung kommen können. Analysis of the subchondral bone plate density of the talus by means of CT-Osteoabsorptiometry (CT-OAM) Leumann A1,2, Müller-Gerbl M2, Büttner O1, Dick W1, Valderrabano V1 1 2 Orthopädische Universitätsklinik, Behandlungszentrum Bewegungsapparat, Universitätsspital Basel Anatomisches Institut, Departement Biomedizin, Universität Basel Introduction The subchondral bone plate plays an important role in the joint homeostasis: it links bone and cartilage together to the osteochondral unit. It has been shown by Müller-Gerbl (Adv Anat Embryol Cell Biol 1998) that the density distribution of the subchondral bone plate is a precise indicator for the long-term biomechanical loading of a joint. Structural changes of the joint like degenerative diseases (e.g. posttraumatic osteoarthritis) are found to happen in the subchondral bone plate earlier than in cartilage or bone. With CT-Osteoabsorptiometry one has a tool to precisely display the subchondral bone plate density distribution. The aim of the study was to determine the exact subchondral bone plate density distribution of the talus as a base for comparison to pathologic, mainly degenerative, morbidities. Methods 20 human ankles of 10 fresh cadavers (mean age: 75 years; range 34-89) without ankle pathologies or macroscopic degenerative changes have been explanted and analyzed by a CT scan. Analysis for subchondral bone density have been performed with the Analyze® Software (Mayo Clinic, Rochester, USA). Analyses of results consisted of qualitative and quantitative comparison according to the subdivision of the talar dome as shown by Elias et al. (Foot Ankle Int 2006). Results Qualitative comparison showed a very high symmetrical subchondral bone plate configuration between left and right talus. Of these, two different types of distribution patterns were found: One density maxium joints (40%) and two density maxima joints (60%), with a maximum medial and a maximum lateral. Density maxima were found anteromedially in 50%, mediomedial in 30%, and anterolateral and mediolateral in 15% respectively. Quantitative comparison showed subchondral bone plate density values between 123,9 and 230,0 Houndsfield units with large variabilities between different specimens. Discussion The CT-OAM can be seen as valuable diagnostic tool to visualize the effect of joint biomechanics on joint biology.The present study provides the first mapping of the subchondral bone plate density distribution of the physiologic talus. According to the data, different joint loading patterns exist on the talus, either a one maximum loading (antero- or mediomedial) or a two maxima loading pattern (medial and lateral). These data are of great importance for comparison and interpretation of early degenerations of the subchondral bone plate (as subchondral sclerosis) as well as on pathologies affecting the osteochondral unit (e.g. osteochondral lesion, posttraumatic osteoarthritis, ankle joint malalignement). 65 SPECT-CT: a new imaging diagnostic tool for osteochondral lesions (OCL) of the talus – comparison to MRI Leumann André MD*, Pagenstert Geert I. MDç, Plaass Christian MD*, Rasch Helmut MD+, Egelhof Thomas MD°, Hintermann Beat MDç, Valderrabano Victor MD PhD* From the Departments of *Orthopaedic Surgery, °Radiology and +Nuclear Medicine, University Hospital of Basel, Basel and the çOrthopaedic Department, Cantonal Hospital of Liestal, Liestal, Switzerland Introduction Magnet resonance imaging (MRI) is the gold-standard of non-invasive diagnostics in osteochondral lesions (OCL) of the talus. Single photon emission computed tomography – computed tomography (SPECT-CT) shows additional, high-resolutioned information of osteoblastic activity and bony morphology.The study aimed for evaluating the influence of this additional information on decision-making for the treatment in OCL of the talus. Methods MRI and SPECT-CT of 26 patients (average age: 32y) were analyzed separately by 3 blinded, independent orthopaedic foot and ankle surgeons experienced in treating OCL and working with MRI and SPECTCT for clinical information content and treatment decision-making. 66 Results By the SPECT-CT, a change in treatment was documented in 46 of 78 decisions (59%) in comparison to the MRI. Following treatment decisions were chosen most often: Retrograde drilling: 64 (41.0%); microfracture and antegrade drilling: 28 (17.9%); osteochondral autologous transplantation (mosaicplasty): 23 (14.8%); excision and debridement: 16 (10.3%); others: 25 (16.0%). However, overall distribution of therapies remained unchanged. Discussion The additional information provided by the SPECTCT influences the decision-making for the treatment of OCL significantly. No study reported on SPECTCT in OCL yet. SPECT-CT may become important in diagnostics and treatment decision-making in OCL. Midand Long-term Results of Medial Malleolar Osteotomy for Treatment of Medial Talus Osteochondral Lesions Antonios Konstantinidis, André Leumann, Olaf Buettner, Monika Horisberger, Kai-Uwe Steuber, Victor Valderrabano Department of Orthopaedic Surgery, University Hospital of Basel, Basel, Switzerland Introduction, Aim, Hypotheses: Medial malleolar osteotomy is an established surgical technique for efficient exposure to medial talar dome osteochondral lesions (OCL). However, there is concern about its mid- and long- term results. Complication rate, grade of secondary osteoarthritis (OA), and necessity and effectiveness of hardware removal have not been well documented yet. The hypotheses of the present study are: (H1) through complete exposure to the surgical talar site improved treatment of the talar pathology was possible and patients reached an increased functional outcome compared to preoperative level; (H2) Hardware removal provides pain relief for posteoperative medial ligament painful syndrome due to screw head irritation; (H3) medial malleolar osteotomy may cause secondary OA in the articular surface of the medial malleolus which is, however, low-grade and almost never symptomatic. Results Mean follow-up time was 5.3 years (range, 2-22 years). All osteotomies were healed uneventfully within 9 weeks. In 9 patients (60%) the osteosynthesis material had to be removed after a mean of 8 months (range, 4-14 months) due to deltoid irritation and provided significant pain relief. In 5 patients (33%) signs of OA were found in the edge of the medial malleolus. Functional outcome will be available after clinical follow-up examinations which will be undertaken until the end of September. Conclusions Medial malleolar osteotomy allows a complete exposure to symptomatic medial OCL, thus leading to long-term functional outcome improvement. The complication rate is low and includes treatable screw head irritation on the medial ligament complex and certain rate of asymptomatic secondary OA. Methods According to inclusion and exclusion criteria, 15 patients (mean age, 39 years; range, 19–59 years) with a medial malleolar osteotomy due to OCL of the medial talus were evaluated.The clinical outcome was assessed using VAS (visual analogue scale, 0-10) pain score, American Orthopaedic Foot & Ankle Society (AOFAS) ankle score, and short-version SF36 life quality score. Preoperative and postoperative radiological findings of the medial malleolus were analyzed, whereas OA grade was measured according to the scale of Morrey and Wiedemann. Time and clinical course of osteosynthesis material removal was evaluated. 67 Prospektive klinische Evaluation einer Methode zur intraoperativen Messung der Knochenfestigkeit – erste Ergebnisse aus der Pilotstudie Andreas Marc Müller 1, Michael Hirschmann 2 , Norbert Suhm 1 1 Behandlunsgzentrum Bewegungsapparat, Universitätsspital Basel 2 Orthopädische Klinik, Kantonsspital Bruderholz Einleitung Frakturtyp und Frakturreposition, Implantatlage und Knochenqualität bestimmen die Versagensquote von Osteosynthesen am proximalen Femur. Während die ersten drei Faktoren prä- oder intraoperativ fluoroskopisch beurteilt werden können, ist eine Aussage über die Knochenfestigkeit auf Basis einer DEXA nur verzögert und sehr eingeschränkt möglich. Dabei käme diesem Parameter bei der Wahl des Stabilisationsverfahrens und des Implantates, bei der Ausführung der Nachbehandlung und nicht zuletzt auch aus abrechnungstechnischen Überlegungen (Kodierung als Patient mit Osteoporose) eine wachsende Bedeutung zu. Das Ziel dieser Studie war eine im Labor bereits validierte Methode zur intraoperativen Messung der Knochenfestigkeit auf ihre klinische Anwendbarkeit hin zu prüfen. Es wurden diesbezüglich die Parameter Komplikationshäufigkeit und zusätzlicher personeller und zeitlicher Aufwand betrachtet. Um die Korrelation der Messung mit dem Knochenmineralgehalt und postoperativem Osteosyntheseversagen zu prüfen ist eine multizentrische Evaluation der Methode geplant. Methoden Von Januar bis Dezember 2007 wurden 31 konsekutive Patienten älter als 40 Jahre (19 Frauen, 12 Männer, mittleres Alter 63.5 Jahre) mit 24 pertrochantären (13 AO31A1, 8 A31A2, 3 AO 31A3 ) und 7 lateralen Schenkelhalsfrakturen eingeschlossen, die mit DHS versorgt werden konnten. Ausgeschlossen wurden Patienten mit pathologischen Frakturen und lokalen Infektionen, sowie Fälle, bei denen intraoperativ keine korrekte Reposition und Implantatlage erzielt werden konnte. Intraoperativ wurde vor Einbringen der DHS eine kannülierte mechanische Messsonde über den liegenden Zieldraht an den Ort der späteren Schraubenlage eingebracht und das Durchdrehmoment durch Rotation um die Längsachse der Sonde gemessen. Weiterhin wurden der dazu notwendige intraoperative Zeit und Personalaufwand sowie allfällig auftretende Komplikationen dokumentiert. 68 Resultate Die intraoperative Knochenfestigkeitsmessung konnte bei allen Patienten vom Operateur selbst ohne wesentliche Komplikationen ausgeführt werden. In fünf Fällen wurde der Zieldraht versehentlich mit der Messonde entfernt. Dieser konnte in allen Fällen problemlos wieder repositioniert werden. Die Messung dauerte im Durchschnitt 2.8 ± 1.6min (2.8 ± 1.5% der totalen Operationszeit). Bisher zeigt das intraoperative maximale Drehmoment eine enge Korrelation mit der BMD des Schenkelhalses (R=0.8), es konnte aber noch kein Osteosyntheseversagen im Sinne einer Sekundärdislokation oder Schraubendurchbruches durch den Femurkopf beobachtet werden. Schlussfolgerung Die Drehmoment basierte intraoperative Knochenfestigkeitsmessung ist eine sichere, der DHS Osteosynthese von proximalen Femurfrakturen integrierbare Methode, die aktuell eine Tendenz zu einer Korrelation mit dem Knochenmineralgehalt aufweist und möglicherweise ein Oteosyntheseversagen aufgrund schlechter Knochenfestigkeit voraussagen kann. Ihre Wertigkeit wird in einer Multizenterstudie weiter evaluiert werden. Wavelet-EMG-analysis of the co-contraction of the leg muscles in fencing during a flèche attack Corina Nüesch1,3, Beat Göpfert1, Marcel Fischer1,2, Julien Frere1,4, Dieter Wirz1,2, Niklaus Friederich2 Lab. for Orthopaedic Biomechanics (LOB), CM&BE, University Basel, Switzerland; Dept. for Orthopaedic Surgery, Kantonsspital Bruderholz, Switzerland 3 Institute for Biomechanics, ETH Zurich, Switzerland 4 Centre d’Etude des Transformations des APS (CETAPS), Université de Rouen, France; 1 2 Fencing is highly demanding on the coordinative skills of athletes. The timing of the muscular activation during a flèche attack is one factor of a successful touch during an attack in a fencing bout [Williams, 2000]. The goal of this study was to analyze the muscular activation sequences of the main leg muscles during flèche attacks and to help to improve training methods in fencing. Methods Kinematics of the whole body [Romkes, 2007] (VICON MX, 240 Hz), ground reaction force during the push-off phase (Kistler, 6000 Hz) and EMG data (Biovision, 6000 Hz, SENIAM-Standard) of the M. Tibials anterior, (TA), M. Gastrocnemius medialis (GM), M. Vastus medialis (VM), M. Rectus femoris (RM), M. Semitendinosus (HAM) of both legs and of the M. Vastus lateralis (VL) of the front leg was recorded of 7 volunteer male expert fencers. The data of 10 trials/subject were averaged using EMG Wavelet-Transformation (WT-EMG) [von Tscharner, 2000]. The test setup simulates a competition situation. The subject was doing small vertical bouncing jumps on the 2 force plates. The start for flèche attack was given by a visual signal at the target. The distance between the force plate and the target was 2.5 m. The beginning of the forward movement of the center of mass was set as movement start (t = 0 sec). Results The results in the WT-EMG-activation-pattern show (see Fig 1) that a co-contraction of the rear leg occurs at the beginning of the flèche attack and prior to the landing after hitting the target. The cocontraction of the front leg takes place during the airborne phase of the flèche attack in the upper leg muscles. Discussion The first co-contraction of the rear leg after take-off and the one of the upper leg is needed to keep the whole leg in its desired position during the airborne phase of the flèche attack. While the second cocontraction of the rear leg prior to landing is a muscular pre-activation which is needed to control angular position of the joint and to absorb the impact force of the landing on the rear foot after hitting the target. The pre-activation which is known form running [von Tscharner, 2003], can be seen also in the landing after flèche attack. In parallel the co-contraction is part of strategy of positing and stiffening up the joint. The pre-activation and cocontraction are essential for optimizing the joint loading and preventing injuries. References 1. 2. 3. 4. Romkes et al. (2007), Evaluating upper body movements during gait in healthy children and children with diplegic cerebral palsy; J Pediatr Orthop B, 18(3); 175-180 Von Tscharner, V. (2000), Intensity analysis in timefrequency space of surface myoelectric signals by wavelets of specified resolution, J Electromyogr Kinesiol 10(6):43345. Von Tscharner et al. (2003), Gender dependent EMGs of runners resolved by time/frequency and principal pattern analysis.J Electromyogr Kinesiol. 13(3):253-72. Williams et al. (2000), Response amendment in fencing: differences between elite and novice subjects. Percept Mot Skills. 91(1):131-142. Fig. 1 WT-EMG-activation pattern 69 The Effect of Restricted Knee Extension on Gait in Healthy Subjects Jacqueline Romkes, Christine Seppi, Reinald Brunner Laboratory for Movement Analysis, University Children’s Hospital Basle (UKBB) Clinical Morphology & Biomedical Engineering (CMBE) Introduction In patients with cerebral palsy, spasticity and muscle weakness lead to gait deviations. If both legs are affected, crouch gait with excessive knee and hip flexion is a frequent problem. Crouch gait in children should be subjected to treatment, as knee and hip flexion angles tend to increase with age due to increasing body weight, ultimately resulting in the loss of independent walking [McNee et al., 2004]. Several factors are known to contribute to crouch gait. In order to look at the effects of crouch gait without any interfering factors, healthy subjects walking in crouch can be used as a model [Van der Krogt et al., 2007]. The purpose of this study was to determine the effect of restricted knee extension during gait in healthy individuals and its influence on muscle activity. Discussion The main goal of this study was to investigate changes in gait and muscle activity as a result of restricted knee extension. Restricting healthy subjects in their knee extension during gait resulted in substantial deviations from normal gait with compensatory adjustments observed at all levels. It also puts a significant higher demand on muscle activation in order to stay upright. With alterations in pelvic and thorax position towards anterior, the relative angle between these segments in the sagittal plane, however, did not change.The data give us insight into the changes occurring as a result of imposing a single factor that is known to influence crouch gait. Methods Nine healthy adult female subjects underwent a 3D instrumented gait analysis to collect whole body kinematics, lower body kinetics, and surface electromyograms (SEMG) of selected leg muscles. First the subjects walked with 30° restricted knee extension bilaterally by applying a taping technique (Fig. 1A). Then the tape was cut and after at least 10 minutes of rest, recordings continued for normal gait (Fig. 1B). The markers and electrodes stayed unchanged between conditions. For each subject and condition data of 5 gait cycles were analysed and averaged. The SEMGs were analysed using a wavelet analysis technique [Von Tscharner, 2000]. Results The gait pattern with restricted knee extension of 30° resulted in increased anterior thorax and pelvic tilt, hip and knee flexion, and ankle dorsiflexion compared to normal. Peak knee flexion in swing and spine tilt (relative movement between pelvis and thorax), however, stayed unchanged. The duration of muscle activity over the gait cycle and the normalized amplitude of the SEMGs increased for the majority of muscles investigated with the restricted knee extension gait pattern. Exceptions were for the tibialis anterior, in which the duration of activation did not change between conditions, and for the gastrocnemius medialis where the normalized amplitude decreased with restricted knee extension. 70 Figure 1. Testing conditions with A) restricted knee extension and B) normal. References 1. 2. 3. McNee et al, Gait Posture 20:S81, 2004. Van der Krogt et al, Gait Posture 26:532-8, 2007. Von Tscharner, J Electromyogr Kinesiol 10:433-45, 2000. TIME-FREQUENCY ANALYSIS OF LEG MUSCLES DURING GAIT IN PATIENTS WITH DIPLEGIC CEREBRAL PALSY Jacqueline Romkes and Reinald Brunner Laboratory for Movement Analysis, University Children’s Hospital Basle (UKBB) Clinical Morphology & Biomedical Engineering (CMBE) INTRODUCTION Some main characteristics of patients with cerebral palsy (CP) are spasticity, movement disorders, and muscle weakness.In the past,surface electromyograms (SEMGs) during gait provided valuable information with respect to on- and offset timing of muscles, the frequency content, and the amplitude. However, only one aspect could be examined in isolation. The introduction of a SEMG-specific non-linearly scaled wavelet analysis provided a simultaneous intensity, time, and frequency analysis. The objective of this study was to investigate the SEMGs over the gait cycle in patients with diplegic CP using a wavelet analysis technique. METHODS Surface EMGs were collected of the gastrocnemius medialis (GM), tibialis anterior (TA), rectus femoris (RF), and semitendinosis (ST) muscles during gait. For each subject, data of 12 gait cycles were analyzed (foot-strike to foot-strike) to retrieve the timefrequency content using a wavelet analysis technique [Von Tscharner, 2000]. Data of 12 children with diplegic CP and 11 healthy children were compared. Clinical assessment included rating spasticity (modified Ashworth scale), rating manual muscle force, and examining passive range of motion. RESULTS Mean frequency over the entire gait cycle was significantly higher for the CP children compared to healthy children for all muscles (GM: 149±30 Hz vs. 95±9 Hz; TA: 133±25 Hz vs. 105±18 Hz; RF: 114±16 Hz vs. 78±7 Hz; ST: 120±20 Hz vs. 86±14 Hz). DISCUSSION AND CONCLUSIONS This study showed that a group of children with diplegic CP activate their muscles at higher frequencies during gait than healthy children (Figure 1). Factors affecting the frequency in a wavelet spectrum can be muscle weakness, the shape of the motor unit action potential, and the conduction velocity. These factors depend on the fibers used by the muscles and may thus indicate the new distribution or types that resulted from the disease. Treatment interventions may change this distribution and wavelet analysis may be used to monitor the effect. Wavelet analysis could potentially be a method for studying treatment intervention, help with the assessment of motor function, or give insight into the neuro-muscular mechanisms of CP. Figure 1: Raw SEMG (top graphs) and the same data analyzed with a wavelet analysis (bottom graphs) for 1 patient with diplegic CP and 1 healthy child. ! 71 Calf Muscle Atrophy after Achilles Tendon Rupture – A Clinical-Radiological-Biomechanical Multicenter Study Rosso Claudio1, Majewski Martin1, Heisterbach Patricia1, Egelhof Thomas2, Polzer Caroline1, Regazzoni Pietro1,Valderrabano Victor1 1 Orthopaedic Department, University Hospital Basel, 2 Radiology Institute, University Hospital of Basel Background, Aims & Hypotheses Tendon ruptures are a frequent problem in sports and may have severe consequences for the athlete. Surgical treatment of acute Achilles tendon (AT) rupture is known to be superior to conservative treatment. Compared to minimal-invasive techniques, advantageously, the open reconstruction allows an anatomical reconstruction (attachment of Soleus muscle, multilevel ruptures). Regardless type of therapy, the problem of secondary long-term muscle atrophy and weakness remains. Having no literature on the topic, the authors believe that tendon length adjusted after treatment may influence the amount of volume of attached muscles, i.e. tendon overlength causing muscle atrophy. Therefore, the aim of the present research is to MR-radiologically measure calf muscle volume and tendon length in patients with a long-term followup after treated unilateral AT rupture in order to prove the supposed relationship between AT length and muscle atrophy. Further, a correlation between these radiological variables and biomechanical parameters will be performed in order to proof the best treatment type. The hypotheses are: (H1) there is a negative correlation between ratio of the length of the AT (L) and muscle volumes (V) of the posterior calf on the affected (L2,V2) compared to the healthy side (L0,V0), i.e. L0:L2 correlates negatively with V0:V2; (H2) there is a positive correlation between muscle volume (atrophy) and maximal plantar flexion torque (weakness); (H3) there is less muscle atrophy after surgical than conservative treatment; (H3) open reconstruction shows less muscle atrophy than percutaneous/mini-invasive reconstruction. 72 Patients and Methods Multicenter case-control study with data collection of the Orthopedic Department of the University Hospital Basel, the Rennbahn-Clinic, Muttenz, and the Crossklinik, Basel. The cohort consists on patients aged 20-55 years with a minimum followup of 3 years after unitlateral AT rupture treated conservatively, surgically minimal-invasive, and open. Clinical parameters (collected by an independent orthopaedic surgeon): age, gender, weight, height, Body Mass Index (BMI), thigh/knee/ankle alignment and range of motion, maximal calf circumference, thigh circumference, SF-36 (quality of life), date of operation, date of follow-up examination, complications, pain (VAS), sports type, ARTS (Achilles Tendon Total Rupture Score), Valderrabano Sport Score. Radiological variables (measured by an independent radiologist) on the basis of the MRI of both calves: a) quantitative parameters: muscle volume of the gastrocnemius medialis and lateralis (separate) and soleus muscle of both calves, crosssectional area of the above mentioned muscles, length of the AT and b) qualitative parameters: degree of tendon morphology as well as tendon sheath fluid, fatty atrophy of the muscle (scored none to +++).The length of the AT will be measured from its insertion until the thickness of 1 mm in the sagittal plane. Biomechanical variables: maximal plantar flexion torque and dynamic pedobarography will be measured by an independent biomechanist. Relevance One of the long term problems of AT reconstructions is calf muscle atrophy and consequently reduced muscle force, which may be, according to the authors, driven by the AT length. This makes AT rupture a challenge for the athlete and the treating orthopedic surgeons. In this interdisciplinary study, the authors would like to bring more evidence to the still etiologically unknown muscle atrophy after AT rupture repair and to come up with a proposal for the best AT rupture treatment. Preoperative Botulinum Toxin To Avoid Poor Surgical Results of Muscle Lengthening in Patients With Cerebral Palsy Rutz E. MD, Hofmann E. MS, Brunner R. MD Pediatric orthopeadics University Children’s Hospital Basle UKBB, Switzerland Introduction Botulinum toxin is a standard antispastic therapy. We reviewed our botulinum toxin test injections performed to identify CP patients who benefit from muscle lengthening surgery. Patients/Materials and Methods We performed a retrospective analysis of all consecutive CP patients having single or multilevel botulinum toxin test injections for planning surgery and gait analysis (preoperatively, 6 and 12 weeks after the test injection) at our institution from 1999 to 2008. A total of 110 patients had 112 test trials (2 patients had 2 test trials of botulinum toxin). Sixtyseven boys and 43 girls with a mean age of 14.4 years (range, 8–53) were included. All patients suffered from cerebral palsy (42 hemiplegia, 39 spastic diplegia, 27 quadriplegia, 2 atactic CP).The botulinum toxin injection was controlled by ultrasound in all cases. The average dosage was 50 U of botulinum toxin per muscle. Loss of joint control (excessive ankle dorsiflexion, loss of knee extension and/or increase of anterior pelvic tilt) was considered as deteriorating parameters and consequentely surgery addressing the respective muscle groups was omitted. in other muscles (1 tibialis anterior, 1 tibialis anterior, tibialis posterior and rectus femoris muscles). Seventyfive patients showed an improvement or no deterioration of the gait pattern. Nine patients with improvement rejected surgery and here the 12 week assessment in the gait lab was not carried out. In 3 patients no effect of the botulinum toxin was seen. Sixtyfive patients had surgery and postoperative no deteriorations were observed. Ten patients agreed to the proposed operation and are now on our waiting list for surgery. Conclusions Muscle tendon lengthening always carries a danger of muscle weakness. In our series of consecutive patients with cerebral palsy (CP) considered for surgical muscle lengthening 21% showed a deterioration in gait after preoperative botulinum toxin test injections. In these patients muscle lengthening surgery was not performed. In none of the remaining 79% of patients gait function deteriorated after surgery. Preoperative botulinum toxin test injection is a reliable tool to avoid poor surgical outcome of muscle lengthening surgery in patients with CP. Results Twentythree patients (= 21%; 8 hemiplegia, 8 quadriplegia, 6 spastic diplegia, 1 atactic CP) showed a deterioration of the gait pattern after the botulinum toxin test injection. Five of these patients had botulinum toxin injections in the hamstrings and the gastrocs, 7 in the hamstrings only, 5 in the gastrocs only, 4 patients in all heads of the triceps surae and 2 73 Total hip arthroplasty after hip joint arthrodesis Erich Rutz, MD 1,2 , Dirk Schäfer, MD +, Victor Valderrabano, MD, PhD 2 1 2 Pediatric Orthopeadic Department, University Children’s Hospital Basle, UKBB, Switzerland Orthopeadic Department, University Hospital Basle, Switzerland INTRODUCTION Back and chronic groin pain are typical secondary degeneration symptoms after hip arthrodesis. Take down of hip arthrodesis and implantation of a total hip arthroplasty (THA) is believed to be a promising treatment option. Only few reports are available in the literature. METHODS Twenty-two hip arthrodesis patients (15 males, 7 females; average age 32.5 years (range 2 – 61 y)) underwent THA between 1980-2000 after spontaneous or surgical fusion of the hip joint. The primary indications for the arthrodesis-THA conversions were low back pain (n = 10), hip problems (n= 7), knee pain (n = 4) and one pertrochanteric fracture of an ancylosed hip joint. 74 RESULTS At the mean follow-up of 13.2 years (range, 2 – 19 y), the Harris hip score averaged 84.9 points (range, 70.1 – 99 pts). Eleven patients (52.4 %) were pain free, 7 (33.3%) had pain reduction, and 3 (14.3%) felt no improvement of pain. One patient has died and one could only be asked by phone. All patients (100%) confirmed that they would undergo desarthrodesis surgery again. Trendelenburg sign was negative in 12 (57.2 %), mildly positive in 7 (33.3 %), and severe positive in 2 patients (9.5%). Aseptic loosening of 2 stems (1 cemented, 1 cementless; 9.5 %) and 2 deep infections (9.5 %) required revision surgery. CONCLUSION THA is a promising option for treatment of secondary longterm hip arthrodesis sequelae. However, full function with complete pain relief and negative Trendelenburg sign might be not reached in all cases. Intertrochantere Korrekturosteotomien mit der LCPPädiatrie-Hüftplatte Erich Rutz, Reinald Brunner Kinderorthopädische Universitätsklinik, Universitäts-Kinderspital beider Basel (UKBB) Einleitung Bei Patienten mit schwerer Osteoporose kann die Fixation bei intertrochanteren Korrekturosteotomien mit der Klingenplatte schwierig sein. In diesen Fällen können winkelstabile Implantate (locking compression plates) sehr nützlich sein. Wir berichten über unsere ersten Erfahrungen mit der LCP-Pädiatrie-Hüftplatte. Material und Methodik Es wurden alle Patienten prospektiv erfasst, die bei schwerer Osteoporose eine Korrekturosteotomie am proximalen Femur im Zeitraum von Januar 2007 bis Feburar 2008 erhalten haben. Insgesamt wurden in 22 Operationen 30 Platten implantiert. Total wurden 18 Patienten operiert (16x rechts, 14x links). Das Durchschnittsalter bei der Operation betrug: 12.5 Jahre (4-20 J). Alle Patienten haben eine neuromuskuläre Erkrankung (16x Zerbralparese, 2x MMC, 1x andere). Nur 5 Patienten vom Kollektiv sind gehfähig. Fällen wurde ein Beckenbeingips angelegt, 3x ein Abduktionsbrace und die 5 gehfähigen Patienten konnten alle voll belasten. Die durchschnittliche Varisation betrug 25.2° (15-35°); in total 27 Fällen. Die durchschnittliche Derotation betrug 27.4° (15-50°); in total 23 Fällen. In 5 Fällen war eine extendierende Osteotomie indiziert, durschnittlich 39.0° (20-90°). Die durchschnittliche Nachkontrollzeit betrug 8.8 Monate (1-13 Mte). Es zeigten sich bis jetzt keine Infektionen und keine Korrekturverluste. Schlussfolgerungen Die LCP-Pädiatrie-Hüftplatte ist unserer Meinung nach eine hervorragende Indikation bei nicht gehfähigen Patienten mit schwerer Osteoporose. Die Operation ist technisch anspruchsvoll. Ergebnisse Die durchschnittliche Operationszeit betrug 65.3 Min (40-120 Min). Bei 13 Fällen wurden die Grossfragmentplatten (Dimension 5.0) und bei 17 Fällen die Kleinfragmentplatten (Dimension 3.5) implantiert. Der durchschnittliche Blutverlust betrug 186.3 ml (50-450 ml). 10x wurde eine offene Hüftgelenksrekonstruktion und 9x wurden zusätzliche Weichteileingriffe durchgeführt. In 7 75 Suprakondyläre Femur- Korrekturosteotomien mit einer modifizierten LCP-Pädiatrie-Hüftplatte Erich Rutz, Reinald Brunner Kinderorthopädische Universitätsklinik, Universitäts-Kinderspital beider Basel (UKBB) Einleitung Bei Patienten mit noch offenenWachstumsfugen ist es oft schwierig eine suprakondyläre Femurosteotomie genügend weit distal durchzuführen. Daher wurde die LCP-Pädiatrie-Hüftplatte modifiziert, so dass die winkelstabilen Schrauben distal 90° zur Platte eingebracht werden können. Wir berichten über unsere ersten Erfahrungen mit dieser modifizierten LCP-Pädiatrie-Hüftplatte. Material und Methodik Es wurden alle Patienten prospektiv erfasst, die eine suprakondyläre Femurosteotomie im Zeitraum von März 2007 bis März 2008 erhalten haben. Insgesamt wurden bei 17 Patienten 28 Platten über einen Subvastus Zugang implantiert. 16x rechts und 12x links. Das Durchschnittsalter bei der Operation betrug: 15.4 Jahre (4-27 J). Alle Patienten haben eine neuromuskuläre Erkrankung (13x Zerebralparese, 2x MMC, 2x andere). Eine Patientin ist nicht gehfähig. Ergebnisse Die durchschnittliche Operationszeit betrug 69.3 Min (30-110 Min). Bei 24 Fällen wurden die Grossfragmentplatten (Dimension 4.5) und bei 4 Fällen die Kleinfragment-platten (Dimension 3.5) implantiert. Der durchschnittliche Blutverlust betrug 121.4 ml (50-250 ml). 18x wurde eine Verkürzung des Ligamentums patellae und 26x wurden zusätzliche Weichteileingriffe durchgeführt.Die durchschnittliche Extension betrug 23.8° (10-50°); in total 21 Fällen. Die durchschnittliche Aussenrotation betrug 19.1° 76 (5-50°); in total 22 Fällen. Die durchschnittliche Innenrotation betrug 21.7° (15-30°); in total 6 Fällen. In 6 Fällen wurde zudem noch eine Achsenkorrektur durchgeführt: 1x 5° valgisierend, 5x varisierend (durchschnittlich 9.0° (5-10°)). Eine Verkürzung wurde 4x vorgenommen (durchschnittlich 15mm (5-40mm)). Die durchschnittliche Nachkontroll-zeit beträgt 9.1 Monate (1-12 Mte). In 2 Fällen zeigten sich Komplikationen: 1x Schraubenlockerung, 1x Korrekturverlust (starke Spasmen); 2 Revisionsoperationen. Schlussfolgerungen Diese modifizierte LCP-Pädiatrie-Hüftplatte ermöglich unserer Meinung nach eine ausgezeichnete 3D Korrektur am distalen Femur bei noch offenen Wachstumsfugen. High tibial closing wedge osteotomy in middle-aged patients. A 10 year experience Kai Sprengel, Andreas Schmid°,Victor Valderrabano#, Christian Flamme* Department of Orthopedic and Trauma Surgery, Diako Hospital Bremen, Germany; °Surgical Clinic, Triemli Municipal Hospital Zürich, Switzerland; #Department of Orthopedic Surgery, University Hospital Basel, Switzerland; *Department of Orthopedic and Trauma Surgery, Asklepios Hospital Harburg, Germany Introduction Middle-aged patients with moderate medial tibiofemoral gonarthritis are considered being the ideal candidates for a high tibial osteotomy. We present data from our patients, which have been followed prospectively for 10 years. Methods All patients over 40 years, which were operated on for medial tibiofemoral gonarthritis using lateral closing wedge osteotomy from 04/1994 until 03/1995 were assessed and followed prospectively. The osteotomy in all patients was stabilized using 1/3-tubular plate according to the technique described by Weber. 49 patients were operated on during this period of time, out of which 22 (45 %) could be re-assessed after 10 years. 27 patients were lost to follow-up (15 deaths unrelated to the procedure). Results 22 patients were eligible for 10 years follow-up. 9 patients were asymptomatic, 6 patients had mild symptoms of gonarthritis and did not require medical treatment. 7 patients received knee replacement surgery. In multivariate analysis we found no significant influence of factors such as age, gender, profession, body-mass-index and degree of gonarthritis. Furthermore, the tibiofemoral angle, neither pre- nor postoperatively was no significant predictive factor for the outcome after 10 years. In tendency, we observed less favourable results in younger patients, whereas patients with moderate to mild gonarthritis showed better outcome. The group of patients which received secondary arthroplasty showed a higher degree of varus deformity preoperatively. HSS-Score was 51.4 points preoperatively, 76.4 points 6 months postoperatively and 70.1 points after 10 years, respectively. KSSScores were 24.0 / 42.1 preoperatively, 71.8 / 71.8 after 6 months and 79.5 / 33.3 after 10 years, respectively. Conclusions These results 10 years after high tibial closing wedge osteotomy for medial gonarthritis are similar to current literature. Patients who did not require secondary arthroplasty show good results. Patients with a higher degree of gonarthritis and a higher degree of varus deformity, as well as younger patients seem to be less satisfied in long term. Body-massindex was not identified as an independent risk factor for unfavourable outcome. We conclude that good results can be obtained in patients with less severe arthritis und a moderate level of preoperative varus deformity. 77 Position of the patella after high tibial closing wedge osteotomy Kai Sprengel, Andreas Schmid°,Victor Valderrabano#, Christian Flamme* Department of Orthopedic and Trauma Surgery, Diako Hospital Bremen, Germany; °Surgical Clinic, Triemli Municipal Hospital Zürich, Switzerland; #Department of Orthopedic Surgery, University Hospital Basel, Switzerland; *Department of Orthopedic and Trauma Surgery, Asklepios Hospital Harburg, Germany Introduction Various results have been discussed in the literature concerning the position of the patella after high tibial osteotomy. We present data from our clinics, which was prospectively collected and analyzed regarding this controversy. Methods Data from all patients over the age of 40 years, which received a lateral closing wedge osteotomy for medial gonarthritis were collected prospectively. All osteotomies were stabilized with tension-plate fixation according to Weber. Early active mobilization with limited weight bearing was allowed in all patients. In total, 49 patients were operated on, wherefrom 5 were lost to follow-up. Therefore, 44 patients (90%) could be re-examined and analyzed after 6 months. For analysis of the patella high we could use data of 33 patients (67%). Results The mean Insall-Salvati-Index was 0.77 (+/-0.17) preoperatively and 0.82 (+/-0.15) postoperatively (p=0.109). In 19 patients, this index increased after surgery, in 14 patients it decreased respectively. In 20 patients this index was below 0.82 before surgery, in 18 patients it was below 0.82 after surgery. The mean Blackburne-Peel-Index was 0.98(+/-0.13) preoperatively and 0.98 (+/-0.18) postoperatively (p=0.659). In 17 patients this index increased after 78 surgery, in 15 patients it decreased, respectively. We did not observe any patient with an index below 0.54. However, 10 patients had an index above 1.06 preoperatively and 11 patients postoperatively. According to the Insall-Salvati-Index, we would have to diagnose a patella baja preoperatively and a normal height of the patella postoperatively. In our series, 20 patients would qualify for a patella baja before surgery and 18 patients after surgery. According to the Blackburne-Peel-Index, the mean scores are within the normal range. Therefore, no malpositioning of the patella was present. 10 patients were diagnosed with patella alta before surgery, 11 patients after surgery, respectively. Conclusion There is no direct influence on the position of the patella by high tibial closing wedge osteotomy. According to the literature, the main risk factor is postoperative immobilization. However, the appropriateness of the scoring-systems has to be critically scrutinized, because reference points of these assessments are altered by the osteotomy. Osteotomy of the fibula in high tibial closing wedge osteotomy Kai Sprengel, Andreas Schmid°,Victor Valderrabano#, Christian Flamme* Department of Orthopedic and Trauma Surgery, Diako Hospital Bremen, Germany; °Surgical Clinic, Triemli Municipal Hospital Zürich, Switzerland; #Department of Orthopedic Surgery, University Hospital Basel, Switzerland; *Department of Orthopedic and Trauma Surgery, Asklepios Hospital Harburg, Germany Introduction As it has previously been described by Jackson, the osteotomy of the fibula is regarded as a major risk factor for a lesion of the peroneal nerve in closing wedge osteotomy of the tibia. Therefore it was presumed, that the osteotomy of the fibula should be done as distally as possible. However, distal osteotomy of the fibula is associated with an increased risk of non-union. We present data from our clinics, which was prospectively collected and analyzed regarding this controversy. Methods Data from all patients over the age of 40 years, which received a lateral closing wedge osteotomy for medial gonarthrosis were collected prospectively. All osteotomies were stabilized with tension-plate fixation according to Weber. Early mobilization with limited weight bearing was allowed in all patients. In total, 49 patients were operated on, wherefrom 5 were lost to follow-up. Therefore, 44 patients (90%) could be re-examined and analyzed after 6 months. For analysis of the osteotomy of the fibula we could use data of 42 patients (86%). Results The median level of the osteotomy of the fibula was 9.4 cm (+/- 2.2) below the tip of the fibula. In 28 cases (67%), the osteotomy was between 7 and 12 cm below the tip of the fibula, in 7 cases (17%) it was above 7 cm and in another 7 cases (17%) below 12 cm. In 11 cases, a lesion of the peroneal nerve was found. 10 of these patients have received an osteotomy 7 to 12 cm below the tip of the fibula. The distance between the two planes of the osteotomy was found to decrease from 0.7 cm (+/- 0.6) postoperatively to 0.4 (+/- 0.5) after 6 months. In 9 patients there was radiological evidence of callous bone healing, in 21 patients there was mineralized callus, whereas in 10 patients no evident reaction was found. In subgroup analysis we found in patients with mineralized callus a distance between the planes of the osteotomy of 0.4 cm (+/- 0.3), decreasing to 0.1 cm (+/- 0.2) after 6 months. In patients with evidence of callous bone healing, this distance was found to be 1.0 cm (+/- 0.6) postoperatively and 0.7 cm (+/0.5) after 6 months, respectively. In patients with no evidence of bone healing, this distance was found to be 1.0 cm (+/-0.5) and 0.7 cm (+/-0.4), respectively. The distance of the plane of osteotomy corresponds to the risk of delayed- or non-union (p<0.001) whereas the level of the osteotomy of the fibula does not (p=0.410). Conclusion To avoid lesions of the peroneal nerve, the osteotomy of the fibula should be done at least 12 cm below the tip of the fibula. According to our data there is no increased risk of non-union. However, the risk of non-union is markedly increased, if the distance of the two planes of the osteotomy is over 1 cm. 79 CT-guided Robotically-assisted Retrograde Drilling of Osteochondral Lesions Victor Valderrabano1, Martin Wiewiorski1,André Leumann1, Olaf Büttner1, Martin Kretzschmar2, Helmut Rasch3, Tanja Markus4, Severine Dziergwa4, Deniz Bilecen4, Augustinus Ludwig Jacob4 Orthopaedic Department, University Hospital Basel, Switzerland Institute of Radiology, University Hospital Basel, Switzerland 3 Institute of Nuclear Medicine, University Hospital Basel, Switzerland 4 Institute of Interventional Radiology, University Hospital Basel, Switzerland 1 2 Introduction Disadvantages of arthroscopically guided surgical techniques for treatment of osteochondral lesions (OCL) of the ankle joint are disruption of viable articular cartilage and insufficient addressing of the subchondral bone.For certain lesion locations,like the posteromedial talus, feasibility is often compromised. The INNOMOTION robotic assistance device proved its value for precise musculoskeletal interventions, such as facet joint and sacroiliac joint infiltrations. We present our first experience with CT-guided robotically-assisted retrograde drilling of osteochondral lesions of the ankle joint and evaluate its feasibility, precision and potential use as a routine operative treatment. Methods 8 patients diagnosed with OCL of the talus (4) and the distal tibia (4) were included. MRI revealed an intact cartilaginous cover in all cases. Surgery was performed with the INNOMOTION robotic assistance device (Innomedic, Herxheim, Germany) mounted on the table of a CT scanner. The robotdevice was referenced to the coordinate system of the CT-scanner. Drill trajectory and depth were planned within acquired CT images. A guiding sleeve for the Kirschner-Wire (K-Wire) was attached to the holding device on the application module and positioned automatically according to the planned trajectory. A 2.5 mm K-Wire was advanced through the guiding-sleeve up to the calculated drilling depth. A cannulated drill was placed over the wire and 80 advanced into the lesion. The lesion was curetted and filled with DBM - paste and patient spongiosa. CT-control scans were performed to determine the position of the instruments and to document the exact localization of the deposit. Results Technically successful CT-guided robot-assisted retrograde drilling was performed in all cases without intra- and postoperative complications. No intervention abort or conversion to arthroscopically guided technique or arthrotomy was necessary. CTcontrol scans confirmed exact initial placement of the guiding wire within the centre of the OCL, precise drill bit positioning and successful retrograde filling of the bored cavity. Discussion The first clinical cases demonstrated CT-guided robot-assisted intervention to be a feasible and safe method for retrograde drilling of OCL of the ankle. Precise assistance by the INNOMOTIONrobot combined with the superior ability of the CT to visualize skeletal anatomy greatly improves the accuracy of drilling with exact and reliable addressing of OCL without damage to overlying cartilage. Further studies need to evaluate the outcome of this new operative technique and to compare it to conventional retrograde drilling. Origin of Pain in Osteochondral Lesions Victor Valderrabano1, Martin Wiewiorski1, Monika Horisberger1, Olaf Buettner1, André Leumann1, Martin Kretzschmar2, Helmut Rasch3, Deniz Bilecen4, Augustinus Ludwig Jacob4 Orthopaedic Department, University Hospital Basel, Switzerland Institute of Radiology, University Hospital Basel, Switzerland 3 Institute of Nuclear Medicine, University Hospital Basel, Switzerland 4 Institute of Interventional Radiology, University Hospital Basel, Switzerland 1 2 Introduction Pain is the key symptom of patients and athletes suffering of osteochondral lesion (OCL) of the ankle. However, the origin of the pain and its inducing and modulating mechanisms remain controversial. Cartilage is aneural and unlikely causing pain. Contrary, subchondral bone and soft tissues (capsule, ligaments, tendons,…) show rich nociceptive innervations. Routine radiographic imaging of OCL fails to visualize the pain inducing structure. SPECTCT is a new hybrid imaging technique allowing perfect overlay of functional and anatomical images. In OCL, SPECT-CT identifies the exact location of an OCL and determines the spatial extent of pathological bone remodeling. We conducted a study to evaluate the correlation between pathological uptake within an OCL and pain experienced by the patients. Methods 15 patients (7 female, 8 male; mean age 39, range 20-61 years) were assessed for unilateral OCL of the talus (13 joints) or distal tibia (2 joints). Plain radiographs, MRI and SPECT-CT were conducted. Pain status was measured by visual analogue scale (VAS). All patients underwent CT-guided ankle joint injection with local anesthetics and iodine contrast medium. Exact location of the deposit was documented. VAS score was assessed immediately post-infiltration and compared to pre-interventional VAS score. Pain relief was defined as a reduction of VAS score of more than 50% of the pre-intervention score immediately after infiltration. Results All infiltrations were technically successful. Preinterventional VAS score was 5.3 (range 2 - 10; SD 2.33). Post-interventional VAS score was 1.1 (range 2 - 4; SD 1.45). This difference was statistically significant (p < 0.01). Conclusion The results of our study show a highly significant correlation between pain in OCL and pathological uptake seen on SPECT-CT, indicating subchondral bone as a major contributor to pain in this disease. Hybrid SPECT-CT technique is a new and powerful approach for the diagnosis, staging, and therefore treatment quality of OCL. 81 Early results of a New Retrograde Lower Leg/Hindfoot Arthrodesis Nail – A prospective Study Victor Valderrabano1, Monika Horisberger1, Andreas M. Müller1, Arne Mehrkens1, André Leumann1, KaiUwe Steuber1 Orthopaedic Department, University Hospital Basel 1 Background Tibiotalocalcaneal (TTC) arthrodesis is used as salvage procedure to treat disabling distal lower leg, ankle, and hindfoot conditions that are refractory to other forms of treatment. Tibiotalocalcaneal arthrodesis is performed with a variety of techniques, including several different designs of arthrodesis nails. The new hindfoot arthrodesis nail (HAN; Synthes Switzerland) has been developed to minimise the risk for plantar neurovascular lesion at the calcaneal insertion site of the nail. The aim of the present prospective study is to evaluate our first experiences with the HAN nail; in particular to assess a) achievement of stable fusion, b) hindfoot alignment, c) numbers of complications, and d) possible technical problems with this new device. Results The reason for the TTC-Arthrodesis were posttraumatic OA in five cases, posttraumatic OA in combination with an intraarticular infection in one case; and in combination with a neuropathy in three cases; neurological diseases in four cases, salvage procedure after total ankle replacement in one case and after arthrodesis in one case. Preoperatively, the VAS for pain was 7.4 (range, 0-10), the AOFAS hindfoot score was 18.8 (range, 0-50). Radiographically, 7 patients showed a varus alignement, 6 patients a physiological alignment, and 2 patients a valgus alignement. Implantation of the nail was possible in all cases; no complications arose so far. The one year follow-up of the first cases will be finished in the end of the year 2008. Methods Since the beginning of the study in 2007 we could include 15 cases (14 patients; 7 male, 8 females) in the study.The average age of the patients was 64.2 years (range, 36-85). Pre- and postoperatively at 6 month and one year the patients were/will be evaluated clinically including the AOFAS hindfoot score, visual analogue scale for pain (VAS), range of motion (ROM), ankle stability, and ability to participate in daily life acitivities and in sports. Preoperative x-rays were obtained to assess hindfoot alignment and osteoarthritis grade. Postoperative x-rays were used to assess alignment, time to fusion, and integrity of the HAN. Conclusion TTC-Arthrodesis is a good salvage procedure for severe entities of the distal lower leg, ankle, and hindfoot. HAN provides in such cases good intramedullary fixation and physiological alignment allowing patients a satisfactory pain reduction, stability, and mobility. 82 Analysis of a New Hemostatic and Analgetic Bioresorbable Putty for Bone Surgery Victor Valderrabano1, Andreas M. Müller1, Lars Walz2, Susanne Müller2, Arne Mehrkens1 1 2 Orthopaedic Department, University Hospital of Basel, University of Basel, Switzerland Clinical Trial Unit, University Hospital of Basel, University of Basel, Switzerland Background & Aim Orthostat is an absorbable bone hemostat (cleared by the US-FDA) intended for use in the management of bleeding from the cut surface of bone. It is a sterile, hand-moldable, biocompatible and absorbable putty which is applied to a bleeding bone site and acts as a mechanical tamponade to stop bleeding. In Orthostat-L, the putty is additionally ”loaded” with a locally acting analgesic (lidocaine), which will be released over a certain time and may be useful in the management of post-operative pain. The purpose of the present clinical study was to gather preliminary data for the safety and efficacy of Orthostat-L in reducing pain from the Iliac Crest Bone Graft (ICBG) harvest site following autograft bone harvest for use in foot and ankle procedures. Methods Fourteen subjects who met all study inclusion/ exclusion criteria were treated with either Orthostat-L (n=7) or Orthostat (n=7). A standard tricortical bone was harvested in volume no larger than 6 cm3 (3x1x2cm). The surgeon applied at least 2 grams but no more than 6 grams of the assigned putty to the ICBG harvest site. Time to hemostasis and total blood loss from the harvest site was recorded. Subjects were provided with Patient Controlled Analgesia (PCA) for management of their postoperative pelvis pain for the first 3 days after surgery. Regional nerve blocks were administered for the control of foot pain. Efficacy (pain evaluation) was monitored every 4 hours post surgery using a 100 mm Visual Analog Scale for the first 72 hours after surgery. Serial blood draws were performed at baseline and at 2, 4, 8, 12, 24, 48, and 72 hours. Subjects were medically followed at 14 and 30 days after surgery. Results The serum levels of lidocaine reached a peak at 4-8h after application. At 48h after application there was no difference between the two groups (Fig. 1). With Orthostat-L there was a clear trend of substantial pain reduction at harvest site over the first 24h postoperatively compared to the Orthostat group (Fig. 2). There were no significant differences in size of graft, amount putty used, time to hemostasis or blood loss between the two groups. No devicerelated unexpected adverse events were recorded. Conclusions Orthostat-L demonstrated a trend towards better hip pain VAS scores for the immediate 24 hour period following ICBG harvest than the placebo treatment.This preliminary study demonstrated that further clinical studies of Orthostat-L are warranted to demonstrate that the device is a safe and effective treatment for postoperative bone pain following orthopedic surgery procedures. ! ! ! Orthostat-L Orthostat Figure 1. Serum Lidocaine Levels Figure 2. Pelvis Pain VAS Scores 83 Swiss Prospective Randomized Study on Use of Orthobiologics in a Subtalar Arthrodesis Model Victor Valderrrabano 1, Ernst-Wilhelm Radü 2 , Andreas Müller1 , Arne Mehrkens 1, Marcel Jakob 1, Ivan Martin 3, Norman Espinosa 4 , Lars Walz5 , Christiane Pauli Magnus 5 Department of Orthopaedic Surgery, University Hospital Basel 1 , Department of Radiology, University Hospital Basel 2,Tissue Engineering Laboratory, University Hospital Basel 3 Balgrist Orthopedic Department Zürich 4, Clinical Trial Unit, University Hospital of Basel 5 Introduction Isolated subtalar arthrodesis has widely been used for the treatment of many hindfoot pathologies including rheumatoid, primary and posttraumatic osteoarthritis of the talocalcaneal joint, calcaneal fractures, talocalcaneal coalition and adult flatfoot deformity. In principle, the rest of the talocalcaneal cartilage is removed, joint surfaces are prepared, and the joint is fused in its physiologic position by screw fixation. Subtalar arthrodesis has been demonstrated to relieve pain and improve limb function in the above mentioned pathologies, but it is still associated with a clinically relevant number of delayed and even non-unions, ranging from 13-40%, particularly marked among diabetics and smokers. Any delay of bony union prevents the patient’s return to work and leads to relevant socioeconomic costs. Today, there is a debate whether the application of osteoinductive substances such as autologous bone and demineralised bone matrix (DBM) may accelerate and secure bony union in addition to simple cartilage removal and screw fixation. Moreover, it is unclear if autologous bone as the gold standard osteoinducing product – but associated with donor site morbiditymay even be more effective in this respect than DBM but costly alternative. Here, we intend to compare in a randomized controlled trial the time to union in subtalar arthrodesis either performed by simple isolated fusion, or additionally supported by the application of autologous cancellous bone or DBM respectively. Methods In participating centers (orthopaedic departments of the university hospitals of Basel and Zürich) patients undergoing subtalar arthrodesis older than 20 years of sound mind and sufficient compliance, not suffering from neuromuscular diseases will be randomized after informed consent to three different treatment groups. In group 1, isolated subtalar arthrodesis will be performed following a specific intraoperative protocol. In group 2 and 3 the arthrodesis will be enhanced by the addition of autologous cancellous 84 bone and DBM, respectively. Patients will be followed up for 6 weeks, 3, 6 and 12 months. On each follow up visit, CT scans will be performed to assess the extent of bony union defined as the percentage of the subtalar joint space completely filled with bony tissue. Additionally, hindfoot function and patient’s quality of life will be recorded using the AOFAS and SF 36 score respectively as well as the patient’s capacity to return to work and sports. Results will be recorded in a web based data base. A power calculation will be perfoemed using the results of pilot study performed at the University Hospital of Basel. A Swiss National Fund application will be targeted. Conclusion With the present study we will try to show the most effective technique of arthrodesis of the subtalar joint which may justify the additional morbity or higher cost of the operation. These results may also be the basis for general evidence based recommendations in foot and ankle arthrodesis-surgery in the best interest of the patient (morbidity) and society (primary and secondary costs). 99mTc-DPD-SPECT-CT for Localization of Symptomatic Osteoarthritic Joints Martin Wiewiorski1, Martin Kretzschmar2, Helmut Rasch3, Deniz Bilecen4, Augustinus Ludwig Jacob4 , Victor Valderrabano1 Orthopaedic Department, University Hospital Basel, Switzerland Institute of Radiology, University Hospital Basel, Switzerland 3 Institute of Nuclear Medicine, University Hospital Basel, Switzerland 4 Institute of Interventional Radiology, University Hospital Basel, Switzerland 1 2 Introduction Osteoarthritis (OA) is a common disease with increasing prevalence and rising socioeconomic burden. Of all symptoms accompanying OA, pain is the most disabling and frequent and the major reason why patients affected seek medical help. The determination of the origin of chronic foot OA pain is challenging since clinical examination of the foot faces a complex anatomy with several joints, osseous, and non-osseous structures contributing to the symptoms. For OA noninvasive imaging methods like plain radiograph, CT or MRI underestimate the degree of degenerative changes and show a poor correlation with pain degree. Studies using functional imaging based on the detection of activated osteoblasts with 99mTcDicarboxypropandiphosphate (DPD) to indicate painful facet joints in the lower spine show promising results, but so far no evaluation for chronic OA pain conditions in foot joints has been conducted and the diagnostic potential was limited due to poor spatial resolution of the scintigraphic assessment. Single Photon Emission Computed Tomography – Computed Tomography (SPECT-CT) is a new hybrid technique combining metabolic information with an exact anatomical localization. We hypothesised that diagnostic infiltration with a local anaesthetic of a painful hindfoot or midfoot joint showing 99mTcDPD-uptake in SPECT-CT, leads to a positive OA pain response. Methods 26 patients with chronic OA pain and radiological signs of OA in a hindfoot or midfoot joint (27 feet) were included. Plain radiography was performed to detect degenerative changes and to rule out pathologies different from OA. Pain status was measured by Visual Analogue Scale (VAS). AOFAS hindfoot/midfoot score and SF-36-score were documented. . All patients received a 99mTc-DPD SPECT-CT (Symbia T2, Siemens). The localisation of 99mTc-DPD-uptake and consequently the site of infiltration were defined. The infiltration was performed with a local anaesthetic (bupivacaine) and iodine solution under CT-guidance with exact documentation of the contrast media deposit by CT. Pain status was assessed directly post-infiltration. Pain relief in responders was defined as reduction of VAS-score > 50% immediately after infiltration, partial response as reduction of < 50%. Results Infiltration was performed in 26 hindfoot joints and 5 midfoot as indicated by 99mTc-DPD-uptake in SPECT-CT. Subsequent CT control scans showing contrast media depot confirmed exact successful infiltration in all indicated joints. In 22 patients an immediate significant (p<0.01) postinterventional pain reduction of VAS more than 50% was observed. Mean VAS before infiltration was 5.77 (range 2-10; SD 2.22) and 0.82 (range 0-4; SD 1.26) immediately after infiltration. Two patients showed a partial response and one patient showed no pain resolution after infiltration. Conclusion The results show a significant correlation of uptake and pain resolution after infiltration allowing precise identification of OA hindfoot joints as pain inducing foci. Non-invasive SPECT-CT offers good prediction of outcome after infiltration improving the localisation of the pain inducing pathology, thus aiding in pre-operative planning and avoiding unnecessary interventions, as diagnostic infiltrations, with its possible risks and side effects. 85 90° Peel Off Test for Measuring Osteochondral Bonding in Tissue-engineered Constructs Wirz D1, Buergin V1, Francioli S 2, Barbero A2 , Martin I2 , Goepfert B1, Daniels AU1 1 2 Laboratory for Orthopaedic Biomechanics, University of Basel Faculty of Medicine Institute for Surgical Research and Hospital Management, University Hospital Basel Introduction Osteochondral and chondral joint lesions affect many patients. A promising future treatment of osteochondral and chondral articular defects may be the implantation of tissue-engineered osteochondral constructs in an affected joint. An important issue in construct development is the early-stage integration between the osseous and cartilage layers of the twocomponent scaffolds used. The aim of this work was to develop a test which accurately measures the mechanical integration of the two layers. A 90° peel off test was developed. As shown (Fig. 1), other peel test modes are possible. However the ‘t-peel’ mode is not practical when one layer is stiff or brittle (as here). Also, compared to 90º, the 180º mode is more likely to damage or rupture a delicate upper layer and obscure peel test results. Material and Methods The peel off tests were developed and performed on a small-scale mechanical testing machine (MTS Synergie 100, MTS Systems, Inc. Eden Prairie, Minnesota, USA) with an 2 N load cell. Low forces were anticipated, and a low-force paper-paper adhesion system (Post-It Notes®, 3M, USA) was used in methods development (Fig. 2.). The crosshead was raised at 1 mm/s and the resultant force and displacement were registered. Parameters assessed were maximum peel off force, N, and total peel energy, J (area under force/distance curve, AUC). ! Fig. 1: Peel off test modes (a) 90°(used here), (b) 180º, (c) t-peel 86 Results Development tests (paper-glass adhesion) showed that the method provides consistent results down to peel off forces as low as 0.05 N (Fig. 2). Preliminary tests were performed with two-layer osteochondral constructs consisting of a spongiosa block with a collagen I/III porcine collagen sponge on top. After static culture of 4 weeks, the spongiosa layer was attached to a glass plate with cyanoacrylate glue. The edge of the collagen sponge was grasped with a small clamp attached to the crosshead of the MTS. After 4 weeks of culture, the constructs had a median maximum peel-off force of 0.53 N and a median peel-off energy of 0.005 J. Conclusion The 90° peel off test is an appropriate method to measure the early-stage mechanical integration of the two layers of osteochondral constructs. Reference: [1] Buergin V., 90° Peel off tests of tissue engineered osteochondral constructs: A new method to determine the osteochondral integration. Dissertation, Laboratory for Orthopaedic Biomechanics, University of Basel Faculty of Medicine, in Preparation Fig. 2: Maximum force and total peel off energy of 10 sticky notes experiments ! ! Fig. 3: two-layer construct during a 90º peel-off test Handchirurgie 87 Clinical results after Sauvé-Kapandji Operation of the arthritic distal radioulnar joint Jens Schulze, Sabina Lang, Urs Genewein, Hans Troeger Musculoskeletal Center, Division of Handsurgery, University Hospital Basel, Switzerland Objective The Karpandji-Sauvé procedure has been developed as a salvage procedure for the treatment of painful arthrosis of the distal radioulnar joint (DRUJ). This operation is performed as soon as the anatomical reconstruction of the DRUJ is not possible. Our retrospective study aimed to evaluate objective (e.g. strength, ROM) and subjective measures (pain, satisfaction) after a long term interval and to compare these with the results obtained by others. Methods In this retrospective analysis 45 of 51 patients (20 female, 25 male; mean age: 48 years) were examined clinically and by X-ray. Reasons to perform KarpandjiSauvé procedure included posttraumatic situations (37 distal radius fractures, 4 lower arm fractures, and 2 wrist luxations) and primary DRUJ arthrosis in 2 cases. Patients with rheumatoid polyarthritis (5 pt.) and Madelung’s deformity (1 pt.) had been excluded due to co-existing problematic that could bias the analysis.The mean observation interval was 7.2 years (14 months-11 years). The grip strength assessment was performed using JAMAR dynamometer (TEC, New Jersey, U.S.A) in comparison to the contralateral site. The ROM of the wrist was evaluated with a goniometer and neutral-null method compared to the preoperative status. The pain was assessed using a visual-analog scale (VAS; 0=pain free, 4=maximal pain). The results were then summarized using the modified Mayo-Wrist score according to Krimmer. Additionally, we assessed patient satisfaction and work load in their original profession. 88 Results Eighty four percent of our patients reported a significant decrease in pain (p<0.05). The ROM in terms of pronation (59° vs. 81°) and suppination (52° vs. 82°) improved significantly (p<0.001). The mean strength related to the contralateral site increased significantly from 34% to 65% (p<0.05). All arthrodeses were completely integrated without any ulna dislocation. The Krimmer score revealed that the postoperative results were very good in 10 of 45 patients, good in 26 of 45, satisfactory in 6 of 45, and bad in 3 of 45 patients. Conclusion The results of our study show that the preoperative relevant pain was significantly reduced by this operation leading to a significant improvement in the pronation/suppination of the wrist and an increase in grip strength followed by a high percentage of patients satisfied. The majority of them went back to work soon and would undergo this procedure again if necessary. Therefore, to be successful with Karpandji-Sauvé procedure a very strong patient selection is necessary. Herzchirurgie 89 Quantitative Proteomanalyse in einem Tiermodell der Hypertonie-induzierten Herzinsuffizienz Thomas Grussenmeyer1, Ivan Lefkovits1, Silvia Meili-Butz2, Thomas Dieterle2, Thierry Carrel1,3, Friedrich Eckstein1. Herzchirurgie, Universitätsspital Basel CardioBiologyLaboratories, Dept. Biomedizin, Universitässpital Basel 3 Herz-u. Gefässchirurgie, Universitätsspital Bern 1 2 Fragestellung Pathologische Prozesse wie Herzinsuffizienz gehen mit vielfältigen und komplexen Veränderungen im Expressionsmuster von Proteinen einher. Mittels proteomischer Untersuchungmethoden sollen diese präzise und sensitiv erfasst werden. Ein einfaches und reproduzierbares Tiermodell für die Herzinsuffizienz sind salzsensitive Dahlratten. Durch Fütterung mit einer Hochsalzdiät entwickeln diese Tiere nach wenigen Tagen eine Hypertonie, die wenige Wochen später linksventrikuläre Hypertrophie und Herzinsuffizienz zur Folge hat. Da es sich um Inzuchttiere handelt, ist die Krankheitsentwicklung sehr reproduzierbar. Somit ist in diesem Tiermodell ein direkter Vergleich unterschiedlicher Krankheitsstadien möglich. Die Analyse von Proteomen mittels zweidimensionaler Gelelektrophorese beruht auf der Visualisierung der separierten Proteinspezies. Dafür stehen Färbemethoden mit unterschiedlicher Sensitivität aber auch unterschiedlicher Reproduzierbarkeit zur Verfügung. Um das Potential der Silberfärbung für die Quantifizierung von Herzproteinen auszuloten, untersuchten wir Reproduzierbarkeit und Lineartität dieser Methode. Methoden Proteinextrakte von tiefgefrorenen linksventrikulärem Muskelgewebeproben wurden durch Solubilisierung in 7M Urea, 2M Thiourea, 4% CHPAS, 20mMDTT, 2%Ampholine gewonnen und durch 2-dimensionale Gelelektrophorese (ISODALT) separariert. Proteinspezies wurden durch Silberfärbung (Vorumprotokoll) visualisiert, per Flachbettscanner digitalisiert und mittels PDQuest Image-Analyse-Software quantifiziert. Statistische Verfahren wurden mit PDQuest und mit Excel durchgeführt. Resultate Durch Scatter- und Verteilungsanalysen (quantil/ quantity-plot) zeigte sich für das Herzproteom, dass Beladungen von 20µg bis 200µg Gesamtproteinextrakt 90 zu durchschnittlich 482 bis 1204 detektierbaren und quantifizierbaren Proteinspezies pro Gel führen. Dagegen führten Beladungen mit 650µg Protein zwar zu mehr detektierten Proteinen (durchschnittlich 1325), diese waren aber nur unzureichend quantifizierbar. Weiterhin verglichen wir unterschiedliche Normalisierungsmethoden, um Gel-zu-GelFärbevariationen auszugleichen (Gesamtfärbung, Median, Durchschnitt des interquartilen Bereichs) und entwickelten einVerfahren, bei dem Gelsegmente separat normalisiert werden. Durch Anwendung dieser letzteren Methode konnten experimentelle Variationen besser ausgeglichen werden und somit eine grössere Zahl von Proteinspezies mit signifikanten Expressionsveränderungen identifiziert werden. Schlussfolgerung Die Determinierung von optimaler Gelbeladung, sowie die Auswahl einer geeigneten Normalisierungsmethode führt zu verbesserten und umfangreicheren Resultaten in der Proteomanalyse. Rapamycin impairs endothelial cell function in human arteries Martin T. R. Grapow, David C. Reineke, Moritz A. Konerding, Thomas Grussenmeyer, Peter Matt, Thierry P. Carrel, Else Mueller-Schweinitzer, Friedrich S. Eckstein Department of Cardiac Surgery, University Hospital Basel, Switzerland, Department of Biomedicine, University Basel, Switzerland,Department of Cardiovascular Surgery, University Hospital Berne, Switzerland, Department of Anatomy, Johannes Gutenberg-University Mainz, Germany Background Evidence has accumulated that treatment with rapamycin negatively impacts endothelial function in human coronary arteries. Recently rapamycin has been shown to inhibit mTORC2 which was previously believed to be rapamycin-insensitive. Prolonged treatment with rapamycin reduces the levels of mTORC2 below those needed to maintain AKT/PKB signalling, a key protein in the regulation of cell function and survival. Since AKT/PKB plays a pivotal role in activation of eNOS our goal was confirm this pathway in human internal thoracic arteries (ITA) in vitro. Methods Vascular reactivity of ITA rings (44 patients) undergoing elective coronary artery bypass surgery was investigated using the organ bath technique. After incubation with rapamycin (solvent control, 0.1, 1 and 10 µmol rapamycin) for 20 h, rings were challenged with the contractile agonist noradrenaline (NA, 1µM) and the relaxant compound acetylcholine (ACH, 1µM). Morphological analysis was performed on 12 of these rings from 4 patients by scanning electron microscopy (SEM). Evaluation followed by two independent observers in blinded fashion. For measurement of NO release an assay using DAF-FM diacetate was employed. Results No differences were obtained in contractile response to NA between the groups. Comparison of the ACH-induced relaxation revealed a concentration dependent decrease, being significant for groups being incubated with 1 and 10µmol rapamycin (in % of control: 1 µmol 66 ±7, p<0.01; 10 µmol 36 ±7, p<0.001; solvent control 112 ±17 n.s.). During evaluation of the SEM specimens the examinators were not able to differentiate between controls and samples exposed for 20h to rapamycin. In all groups of ITA rings the endothelial layer was well preserved. Preliminary results of NO measurement revealed considerably decreased NO-release in rapamycinincubated rings compared with the controls. Conclusion Our results confirm the modification by rapamycin of the above described signal-transduction pathway with inhibition of mTORC2/AKT/PKB. We demonstrated that incubation of human ITA with rapamycin affects negatively both the endotheliumdependent vasorelaxant responses and NO release in a concentration dependend manner in vitro without inducing morphological changes. 91 TGF-beta Is A Promising Biomarker For Monitoring The Aortic Root Dilatation And Losartan Therapy In Marfan Syndrome Peter Matt12; Jennifer Habashi1; Tammy Holm1; Qin Fu1; Florian Schoenhoff1; Friedrich Eckstein2; David Huso3; Jennifer Van Eyk1; Harry Dietz1 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Univ Hosp, Basel, Switzerland Objectives Aortic root dilatation is the main cause of morbidity and mortality in Marfan syndrome (MFS), a disorder caused by mutations in the gene encoding fibrillin-1 and consequent dysregulation of TGF-beta signaling. The aim of this study was to discover a serological biomarker for the aortic root dilatation in a mouse model of MFS, that was also responsive to losartan therapy. Methods Serum samples from mice heterozygous for a fibrillin-1 missense mutation (C1039G/+) and wild-type mice treated with losartan or placebo were obtained at 10 weeks, 6 months and 10 months of age.Total (acid activated) TGF-beta 1 serum concentrations were measured by ELISA. Echo measurements of the aortic root were obtained from a parasternal long axis view at 10 months of age. Results Mean TGF-beta serum concentrations were higher in C1039G/+ mice compared to wild-type mice (p=0.01; 80.0 ng/ml (n=5) vs. 58.3 ng/ml (n=4) at 10 weeks, 117.4 ng/ml (n=11) vs. 87.0 ng/ml (n=6) at 6 months, 137.5 ng/ml (n=3) vs. 103.0 ng/ml (n=2) at 10 months, respectively). Losartan-treated C1039G/+ mice had significantly lower mean TGF-beta serum levels compared to C1039G/+ mice with placebo (p=0.007; 92.9 ng/ml (n=5) vs. 117.4 ng/ml (n=11) at 92 6 months, 101.2 ng/ml (n=13) vs. 137.5 ng/ml (n=3) at 10 months, respectively). Mean TGF-beta serum concentrations in losartan-treated C1039G/+ mice and wild-type mice with placebo were not significant different (p=0.3; 92.9 ng/ml (n=5) vs. 87.0 ng/ml (n=6) at 6 months, 101.2 ng/ml (n=13) vs. 103.0 ng/ ml (n=2) at 10 months, respectively). Echo analyses revealed significantly smaller mean aortic root diameters in 10 months old wild-type and losartantreated C1039G/+ mice compared to age-matched C1039G/+ mice with placebo (p=0.001; 1.94 mm (n=2) and 2.06 mm (n=13) vs. 2.4 mm (n=3), respectively). Conclusions TGF-beta serum levels are higher in C1039G/+ mice compared to wild-type mice. Losartan treatment of C1039G/+ mice reduces TGF-beta serum concentrations and aortic root diameters towards wild-type levels. Serum TGF-beta is a promising biomarker for prognostication and monitoring the therapeutic response to losartan therapy in Marfan syndrome. A New Mouse Model of Acute Aortic Dissection Type A in Marfan Syndrome Peter Matt12; Jennifer Habashi1; James Black1; Friedrich Eckstein2, Martin Grapow2; Florian Rueter2; David Huso1; Jennifer Van Eyk1; Harry Dietz1 1 Johns Hopkins Univ, Baltimore, MD, USA; 2 Univ Hosp, Basel, Switzerland Objectives Acute Aortic Dissection Type A is the main cause of death in patients with Marfan Syndrome (MFS). We developed a procedure to surgically induce an acute aortic dissection type A in a mouse model of MFS. Methods Ten fibrillin-1 deficient (Fbn1C1039G/+) and ten wild-type mice at 8 months of age were intubated, ventilated and the aorta exposed via a hemisternotomy. We hypothesized that an aortic dissection type A could be induced in fibrillin-1 deficient or wild-type mice by either injecting autologous blood in the aortic wall or by performing a clamp injury. Autologous blood was collected before and after induction of the aortic lesion from the right femoral vein. The mice were sacrificed 30 minutes after aortic surgery. Results Transthoracic echocardiography of the aortic root performed prior to surgery showed significantly larger diameters in Fbn1C1039G/+ mice compared to the wild-type (p<0.0001). Aortic clamp injury compared to injection of autologous blood led in Fbn1C1039G/+ and wild-type mice to a highly reproducible visible aortic wall hematoma, and large intimal tears. In contrast, injection of autologous blood into the aortic wall was difficult and led to less reproducible wall hematoma and small intimal tears. After aortic clamp injury hematoxylin-eosin stained histological sections revealed a dissection of the medial layer in all Fbn1C1039G/+ mice but not in wild-type mice (p<0.001). Wild-types showed only transmural wall lesions. Aortic dissections in Fbn1C1039G/+ mice were limited to the ascending aorta. Elastin-stained histological sections revealed a significantly higher elastic fiber fragmentation and disarray in Fbn1C1039G/+ aortas compared to wildtype mice (p<0.001). All mice survived 30 minutes after inducing the aortic lesion. Conclusions We present a highly reproducible and in the shortterm non-lethal mouse model of a surgically induced acute aortic dissection type A in MFS. This model may provide new insights into this life-threatening disease, which may lead to novel diagnostic and therapeutic strategies. 93 Activated Rho/Rho kinase and modified calcium sensitivity in cryopreserved human saphenous veins Else Müller-Schweinitzer a,b*, David C. Reineke c, Erika Glusa d, Anthony B. Ebeigbe e,Martin T. R. Grapow a,b , Thierry P. Carrel a,b,c, Friedrich S. Ecksteina,b Division of Cardiac Surgery, University Hospital, CH-4031 Basel, Switzerland, Department of Biomedicine, University Hospital, CH-4031 Basel, Switzerland c Department of Cardiovascular Surgery, University Hospital, CH-3010 Bern, SwitzerlanddInstitute for Pharmacy, Friedrich Schiller-University Jena, D-07743 Jena, Germany, eDepartment of Pharmacology & Toxicology, University of Benin, Benin, Nigeria a b Background We have shown previously that cryopreservation of human internal mammary arteries activates protein kinase C and enhances intracellular Ca2+ [Ca2+]i. We now present evidence that in human saphenous veins (HSV) cryoinjury is associated with activation of the Rho/Rho kinase signaling pathways and enhanced [Ca2+]i. Methods HSV were investigated in vitro either unfrozen within 12 h after removal or after storage at -196° C in a cryomedium containing 1.8 M dimethyl sulfoxide and 0.1 M sucrose as cryoprotectant additives. Results Cryostorage diminished responses to receptormediated contractile agonists such as noradrenaline, 5-HT and endothelin-1 by up to 30% whereas responses to KCl were attenuated by about 50%. Concentration-response curves for CaCl2 on unfrozen and cryopreserved HSV revealed similar inhibitory activities of both blocking 1,4-dihydropyridine derivatives nifedipine and the (-)-(R) enantiomer of SDZ 202-791 whereas the Ca2+ channel activating (+)-(S) enantiomer of SDZ 202-791 was 10 times less effective at enhancing 94 contractions to CaCl2 when tested after cryostorage. These functional effects were reflected by changes in [Ca2+]i as demonstrated by fluorescence of Fluo3AM loaded veins. The diminished activity of (+)-(S) SDZ 202-791 in cryopreserved HSV was reversed partially when the potassium channel opener pinacidil (1 µM) was present during the freezing/ thawing process. Blockade of Rho kinase by HA-1077 proved to be significantly more effective at attenuating contractile responses to both endothelin-1 and KCl after cryostorage. Conclusions Data suggested that cryopreservation modified [Ca2+]i of venous smooth muscle cells (1) through depolarization-induced changes in Ca2+ influx and (2) through activation of Rho kinase signaling pathways. ICSF 95 Dose-dependent angiogenic effects of VEGF164 and PDGF-BB co-delivery R. Gianni-Barrera, P. Fueglistaler, T. Wolff, H. Misteli, L. Gürke, M. Heberer and A. Banfi Cell and Gene Therapy ICFS, Gefässchirurgie USB Introduction The delivery of angiogenic growth factors to restore blood flow in ischemic tissues (therapeutic angiogenesis) is being investigated as a treatment strategy for both peripheral artery disease and cardiac ischemia.Vascular Endothelia Growth Factor (VEGF) is the most potent angiogenic factor and it has been tested in several clinical trials, but it also can induce aberrant vasculature and angioma growth, that can call into question its therapeutic utility. We have previously shown that a discrete threshold exists in VEGF expression level, determining whether normal or aberrant angiogenesis is induced (Ozawa et al 2004).We recently found that this threshold is not an intrinsic property ofVEGF dose, but it rather depends on the balance between angiogenic stimulation by VEGF and vascular maturation by Platelet Derived Growth Factor-BB (PDGF-BB)-mediated pericyte recruitment (Banfi et al. manuscript submitted). In this project, we investigate how PDGF-BB co-delivery can modulate the dose-dependent effects of VEGF. In particular we test the hypotheses that PDGF-BB codelivery: 1) can increase efficacy of low, and already safe,VEGF doses; 2) can increase the safety of high VEGF levels (avoid angioma growth). Methods Monoclonal populations of retrovirally transduced mouse myoblasts, which stably secrete clearly defined amounts of VEGF or VEGF and PDGF-BB were cultured in vitro. The myoblasts were implanted into the posterior auricular muscle and into the tibialis anterior and gastrocnemius muscle of SCID mice, where they fuse with each other or with surrounding host myofibers, providing a well-localized source of transgene expression. Whole-mounts of the posterior layer of the ear were analyzed histologically for 3-dimensional vessel architecture. Leg muscle sections were analyzed by immunofluorescence staining for endothelial, pericyte and smooth muscle markers to assess vessel maturation. 96 Results We found that at low microenvironmental VEGF levels (~10ng/106cells/day) the VEGF effects are not affected by PDGF-BB. At intermediate and high VEGF levels (30-60 or 100-150 ng/106cells/day) the effects of PDGF-BB co-delivery in the ear and in leg muscle was very different: In the leg muscles it led to a network of normal and stable capillaries at 4 weeks and 6 months but no hemangioma growth, which was always found with VEGF alone in the high level range. On the other hand, implantation in the mainly subcutaneous tissue of the ear frequently caused the growth of macroscopically visible soft tissue tumors that were not highly vascularized, as well as the formation of unorganized bundles of homogeneous capillaries, quite distinct from the aberrant angiogenesis induced by VEGF alone. Both effects occurred only in areas where the injected myoblasts failed to fuse with resident myocytes, such as in subcutaneous tissue. Immunofluorescence staining of the tumor revealed that the proliferating cells were LacZ negative and NG2 positive, suggesting that they did not originate from the implanted myoblasts, but rather from local fibroblasts. As expected, high levels of VEGF alone always led to the formation of cavernous vessels or hemangiomas, which were never observed with PDGF-BB co-delivery, even at the highest VEGF levels. Conclusion PDGF-BB co-expression fundamentally modulates the dose-response of VEGF, always leading to homogeneous normal capillary formation in skeletal muscle, despite extremely high VEGF expression levels. This suggests that delivery methods with heterogeneous expression levels, such as adenoviral gene therapy, which have failed in clinical trials of VEGF delivery alone, ,could yield safe and efficient angiogenesis with VEGF and PDGF-BB co-expression in skeletal muscle. Furthermore, our results underscore the tissue-specificity of angiogenic responses and the importance to perform preclinical studies in the tissue which is targeted for clinical therapy. Recombinant vaccinia virus expressing CD40 ligand enhances the expansion of CD8+ T cells with a memory phenotype Chantal FEDER-MENGUS, Walter P. WEBER, Nermin RAAFAT, Elke SCHULTZ-THATER, Michel ADAMINA, Daniel OERTLI, Michael HEBERER, Giulio C. SPAGNOLI and Paul ZAJAC. Institute für Chirurgische Forschung und Spitalmanagement (ICFS), University Hospital, Basel, Switzerland. Objective: We and others have shown in vitro (Marti, 1997; Zajac, 1998) and in vivo (Hodge, 1999), that coexpression of costimulatory molecules enhances immunogenic capacities of recombinant Vaccinia virus (rVV) encoding tumor associated antigens (TAA). Furthermore, rVV encoding melanoma TAA, CD80 and CD86 was used in a phase I/II clinical trial (Spagnoli, 2002; Zajac, 2003) resulting in enhanced specific response to TAA after vaccination. Nevertheless, this response is not sustained over time. In order to study the capacity of these vectors to provide signals relevant in the generation/ maintenance of T cell response against TAA, we tested a rVV expressing CD40 ligand (CD154rVV). CD154 plays a role in activation of helper-dependent immune responses, is expressed on activated CD4+ T cells, binds to CD40 on APCs leading to APC activation and to an increase in their antigen presentation and immunomodulatory capacities (IL12, IL-15) (Feder-Mengus, 2005). CD154 plays also a role in generation of T cell memory (Borrow, 1996; Bourgeois, 2003). CD154rVV may reproduce these mechanisms and thereby optimize CTL generation and help to maintain immune response overtime. cells. Activation of total and CM CD8+ T cells was enhanced upon priming with CD154rVV as compared to ControlVV as demonstrated by enhanced IL-2 and IFN-G gene expression, and increased IFN-G protein expression. Percentage of dividing cells with CM phenotype upon CD154rVV triggering was also observed. Among many signals, VV infection is triggering IL15 gene expression in APC. In CD154rVV infected cultures, this gene was expressed to a higher extent. Conclusions Taken together, these data indicate that stimulation of CD8+ T cells with CD154rVV increases expansion of T cells with CM phenotype as compared to ControlVV. Such rVV might help to bypass the requirement for helper cells, thus qualifying as a relevant reagent in the generation of CD8+ T cell responses, and to maintain immune response overtime during vaccination process in cancer immunotherapy. Methods Phenotypic characterization of CD8+ T cells cultured with infected monocytes as APC was performed by antibody staining and FACS analysis. Gene expression was evaluated by qRT-PCR. Results CD154rVV enhances APC capacity to stimulate specific T cell responses (Feder-Mengus, 2005). Phenotype of total and Ag specific CD8+ T cells primed in presence of CD154rVV infected APC showed an increase in CD8+ T cells with Central Memory (CM) phenotype (CD45RA+CCR7+) mainly as compared to ControlVV. More marked differences were observed for Ag specific CD8+ T 97 Impaired responsiveness to homeostatic cytokines and CD8+ T cells exhaustion in prostatic diseases Chantal Feder-Mengus, Clémentine Le Magnen, Robin Ruszat, Alexander Bachmann, Michael Heberer, Giulio Spagnoli and Stephen Wyler. Institute für Chirurgische Forschung und Spitalmanagement (ICFS), University Hospital, Basel, Switzerland. Objective Prostate cancer (PCA) is a leading cause of cancer death in men. Impairments of immune responsiveness may favour tumour development, possibly due to decreased immune surveillance against transformed cells. Underlying immunosuppressive mechanisms in benign prostate hyperplasia (BPH) and PCA patients are not fully clarified. We analyzed homeostatic proliferation of CD8+ T cells upon stimulation with common receptor G chain IL-2, IL-7 and IL15 cytokines in PCA as compared to BPH patients. CD8 T cells exhaustion was assessed by evaluating Program death-1 (PD-1) receptor and its ligand PDL1 expression in PBMC and tissues from PCA and BPH patients. Materials and methods 23 BPH and 36 PCA patients were enrolled. PBMC from patients were cultured for 9 days with or without homeostatic cytokines and T cell proliferation was evaluated by CFSE dilution (flow cytometry). PD-1 and PD-Ll expression in peripheral blood or tissue infiltrating CD8+ T cells was assessed by flow cytometry. Results CD8 T cells from BPH and PCA patients (n=17 and n=21, respectively) showed a significantly decreased responsiveness to IL-7 and IL-15 homeostatic cytokines as compared to healthy donors (n=9) (p=0.021 and p=0.015, respectively), whereas response to IL-2 was similar. A trend towards a lower response to IL-15 in PCA as compared to BPH patients was also detectable (p=0.149). Notably, culture in media containing sera from either BPH or PCA patients did not affect the proliferative 98 capabilities of IL-7 or IL-15 stimulated CD8+ cells from healthy donors. Urged by these findings, we addressed the expression of PD-1 on CD8+ T cells from BPH and PCA patients. We found a highly significant (p=0.003) increase in the percentage of PD-1 expressing peripheral blood CD8+ cells in a subgroup of PCA patients (40±9%; n=4/15) as compared to other PCA patients (5.3±4%; n=11/15) or BPH patients (12±3%; n=6). In contrast, PD-L1 expression on peripheral blood CD8+ T cells was similar in BPH and PCA patients and in healthy donors. CD8+ cells infiltrating BPH or PCA tissues were then studied. In either case we found that a large majority of CD8+ lymphocytes (90±12% for BPH, n=4 and 82±23%, n=3 for PCA) expressed PD-1, whereas PD-L1 was expressed in 61±37% and 76±25% of CD8+ T cells in BPH and PCA, respectively. Conclusions Taken together these data indicate that both BPH and PCA patients display a decreased responsiveness to IL-7 and IL-15 homeostatic cytokines. Furthermore, and most interestingly, PD-1 and its ligand PD-L1 are highly expressed in BPH and PCA infiltrating CD8+ T cells. Notably in a subgroup of PCA patients high percentages of peripheral blood CD8+ lymphocytes expressed PD-1, thus raising the issue of the role of T cells exhaustion in PCA. Controlled angiogenesis by FACS-purified engineered myoblasts that homogeneously express specific levels of VEGF – Optimization of sorting parameters P. Fueglistaler, T. Wolff, H. Misteli, R. Gianni-Barrera, L. Gürke, M. Heberer, A. Banfi Cell and Gene Therapy ICFS, Gefässchirurgie USB Introduction Therapeutic angiogenesis is a promising strategy for the treatment of end stage peripheral artery or coronary artery disease. Delivering vascular endothelial growth factor (VEGF) by intramuscular injection of in vitro engineered myoblasts might prove to be superior to conventional gene delivery systems because it leads to prolonged VEGF-expression, which has been shown to be necessary for the formation of stable vessels. However, high levels of VEGF induce uncontrolled vessel growth and we have shown that even small numbers of myoblasts secreting high levels of VEGF are sufficient to cause aberrant vessels. When transducing a population of myoblasts with a retroviral vector carrying VEGF, it is not possible to precisely control the VEGF level of each infected cell. We have developed a system in which the gene for VEGF is linked to the gene of a biologically inactive cell surface marker (truncated CD8) through an Internal Ribosomal Entry Site sequence (IRES). The VEGF level of each cell is thus proportional to the expression of CD8, so that the cells can be rapidly purified for desired VEGF levels by FACS.We have shown that in clones of transduced myoblasts, where all cells produce identical levels of VEGF, VEGF production correlates tightly with CD8 expression as determined by FACS. We have also shown that, based on the fluorescence intensity of a given “reference clone” producing a desired VEGF level, it is possible to purify cells expressing similar VEGF levels from a heterogeneous population. Angiogenesis induced by the purified population was very similar to that induced by the reference clone (Misteli et al. manuscript in preparation). The aim of the present project is to investigate how sorting parameters such as size of the gate and number of successive rounds of sorting influence the purity of the sorted populations and to define optimal settings to reliably avoid uncontrolled vessel growth. Methods Primary mouse myoblasts were infected with a retrovirus carrying the gene construct VEGFIRES-trCD8, generating a population expressing heterogeneous VEGF and CD8 levels. Cells with a fluorescence intensity corresponding to that of a “reference clone” with a know VEGF level of 34 ng of VEGF/106 cells/day were FACS-sorted from the heterogenous transduced population. Sorting was performed either with a FACS gate corresponding to the total fluorescence range of the reference clone (“wide gate”) or to 25% of it (“narrow gate”). These populations were further sorted for a 2nd or 3rd round using identical parameters. The resulting 6 different populations were injected into the posterior auricular muscle of SCID mice and the induced vasculature was analyzed after 4 weeks and 3 months by whole mount microscopy Results At 4 weeks there were no aberrant vessels in mice treated with the “narrow gate” cells whereas 4/9 animals in the “large gate” group showed at least 1 aberrant vessel (usually only 1 per animal). This incidence was reduced to 1/4 by performing 3 sorting rounds. At 3 months there were 2/7 animals in the “narrow gate” group that showed traces of enlarged bulbous vessels, which did not grow beyond microscopic size and had normal vessel architecture, whereas 1/6 animals in the “wide gate” group developed frankly abnormal vessels. All the animals injected with unsorted cells showed widespread aberrant vessels after 4 weeks and had to be euthanized after 6 weeks because of progressive hemangioma growth. Conclusion These results confirm that our FACS-based technology allows the rapid purification of cells producing desired transgene levels without cloning. We found that the crucial parameter to obtain completely purified populations is gate size rather than multiple sorting rounds.These optimized sorting parameters will be used in pre-clinical studies to test the efficacy and safety of this concept in ischemia, in order to ultimately develop a novel treatment strategy for peripheral artery disease. 99 Nutzenpotential workflowgestützter Kodierung am Beispiel der Handchirurgie Urs Genewein, MD, MME, Behandlungszentrum Bewegungsapparat, USB Fragestellung Realisierung eines Workflows zur zeitnahen FreitextDiagnosekodierung innerhalb eines elektronischen Klinikinformationssystems (KIS). Quantifizierung der Güte und des Nutzens der resultierenden strukturierten Daten in real-time Verfügbarkeit während des Spitalaufenthaltes. Einleitung Mindestens in der Deutsch-Schweiz werden derzeit die Diagnose- und Problemlisten meist im Freitext erfasst und erst nach dem Spitalaustritt zwecks offiziellen Statistiken (BfS) oder DRG-Abrechnung kodiert und somit strukturiert. Um decision support aber auch Steuerungs-möglichkeiten durch ein KIS realisieren zu können,muss zwingend auf strukturierte Daten zurückgegriffen werden. Strukturierte Daten (z.b. ICD 10 Codes / CHOP) bieten eine solide Beurteilungsbasis für prozessrelevante Abläufe, sind aber nicht in der Lage, die Informations-vielfalt und Vielschichtigkeit von Freitexten zu ersetzen. In einer elektronischen Patienten-akte können medizinische Prozesse, wie z.B. die Medikation nur sinnvoll von Experten-systemen hinterfragt werden, wenn auf strukturierte Diagnosedaten zurückgegriffen werden kann. Methode Projekt A: Unter Laborbedingungen werden die ärztlichen Diagnosen im Freitext in der Diagnoseliste des Klinikinformationssystemes erfasst. Das semantische Codiertool Semfinder (Semfinder AG) liesst die Felder der Diagnoseliste im Hintergrund aus und liefert strukturierte ICD-10 Codes zu den erfassten Diagnosen. Kann kein valider Code generiert werden, muss der User Zusatzangaben einfügen. Jede Änderung der Diagnoseliste führt zu einer erneuten automatisierten Codierung im Hintergrund. 100 40 randomisierte Patientenakten der Handchirurgie mit insgesamt 130 Diagnosen (Haupt- und Nebendiagnosen) wurden retrospektiv analysiert. Dazu wurden die durch das professionelle Kodierteam generierten ICD-10 Codes verglichen mit den durch Semfinder-generierten Codes. Ausgeschlossen wurden Kodierungen, welche ausserhalb der professionellen Kodierung erfasst wurden. Nicht berücksichtigt wurde die Kodierung von Interventionen (keine Unterstützung der CHOP-Kodierung in Semfinder). Resultate Projekt A: Von 130 Diagnosen wurden durch das Kodierteam 18 (13 %) nicht kodiert, durch Semfinder konnten 4 (3%) aufgrund eines unspezifischen Textes nicht kodiert werden. Die vollständige und richtige Kodierung im Hintergrund ohne Zusatzangaben durch User erfolgte bei 91 Diagnosen (70 %), in 19% erfolgt die Kodierung mit einer, in 11 % mit zwei Rückfragen.. Sämtliche Rückfragen führten zu einem validen Code. Schlussfolgerungen Der getestete Workflow ist in der Lage, zeitgerecht strukturierte Daten aus Freitext zu generieren, ohne einen relevanten Mehraufwand für die dokumentierenden Ärzte zu implementieren. Er dient als Basis, decision support oder DRG-Berechnungen durchzuführen. Der Primärprozess kann somit durch Informationsvermittlung gesteuert werden, bedingt aber eine tiefe Integration desWorkflows in sämtliche relevante Umsysteme des KIS. Im Laborversuch zeigt sich, dass insbesondere die Integration eines OnlineDRG-Groupers zu einem erheblichen Mehrwert für ärztliches Handeln führt: neben einer Konzentration auf ärztliche Kernkompentenzen kann eine optimale Primärkodierung, eine Kostenersparnis und relevante Erlössicherheit erreicht werden. IL-17 favours the expansion of IL-17-producing CD4+ T cells by amplifying LPS-triggered cytokine-production by monocytes/macrophages X.S. Huber, C. Feder-Mengus, D.M. Frey, R.A. Droeser, M. Heberer, G.C. Spagnoli, G. Iezzi Institute of Surgical Research and Hospital Management (ICFS) Objective IL-17 producing CD4+ T cells represent a newly described lymphocyte subset (such as Th1, Th2 or Treg) involved in the pathogenesis of autoimmune diseases and host defence. Indeed, IL-17 gene expression is increased in Rheumatoid Arthritis, Multiple Sclerosis and Inflammatory Bowel Disease. On the other hand, the induction of immune responses against self tumor associated antigens might take advantage of the expansion of IL-17 producing T cells. Recent papers have clarified the requirements for the expansion of human Th17 cells in vitro. IL-1B and IL-23 have been found to be of major importance for the polarization and/or expansion of human IL17-producing CD4+ T helper cells. Here, we analyzed the conditions favouring the production of these cytokines by monocyte/ macrophages and their effects on the generation of Th17 T cells. Methods Expression of IL-17 receptor was tested by flow cytometry. CD14+ monocytes isolated by magnetic beads were stimulated with recombinant IL-17 and or lipopolysaccharide (LPS) and expression of surface markers and cytokine genes or cytokine secretion was evaluated by flow-cytometry, quantitative realtime PCR and ELISA, respectively. CD4+ T cells producing IL-17 were enumerated by intracellular staining. Results IL-17 receptor expression in lymphocytes was negligible on CD4+ T cells and limited to a subset of <20% of CD8+ T cells. In contrast, virtually all CD14+ monocytes expressed IL-17 receptor. However, culture in the presence of GM-CSF and IL-4 or IFN-α, promoting the generation of dendritic cells (DC) led to a complete disappearance of IL-17 receptor.These data posed the question of functional effects of IL-17 on monocytes. Incubation of CD14+ monocytes in the presence of 10-100 ng/ml IL-17 did not induce modulation of the expression of HLA-class I or II determinants, CD80, CD83, CD86 or CCR5 chemokine receptor. However, in the presence of 50-100 ng/ml concentrations of IL-17, secretion of IL-1β by monocytes stimulated with LPS (1-1000 ng/ml) was significantly (2X) increased as compared to cultures performed in the absence of IL-17. Finally, stimulation of CD4+ T cells with allogenic monocytes pre-incubated in the presence of LPS (1 µg/ml) and IL-17 (100 ng/ml) led to the expansion of a number of IL-17 producing CD4+ cells significantly higher as compared to cultures performed in the presence of LPS alone. In particular, significantly higher percentages of memory CD4+/CD45RAcells producing IL-17 alone or together with IFN-γ were detectable (19±0.19 vs. 12.2±0.87, p=0.003) in these conditions. Conclusions Our data indicate that IL-17 amplifies the expansion of IL-17 producing CD4+ T cells. These effects are mediated by monocyte activation. Thus the interaction between IL-17 and monocytes might represent a target for therapeutic intervention in inflammatory bowel disease or, alternatively, for the induction of immune responses against tumor associated antigens. 101 Characterization of putative cancer stem cells in colorectal carcinoma cell lines M.G. Muraro, C. Giovenzana, X.S. Huber, R. Droeser, L. Tornillo, I. Zlobec, M. Heberer, D.M. Frey, G.C. Spagnoli, D. Oertli and G. Iezzi. Institute of Surgical Research and Hospital Management (ICFS) Objectives Cancer initiating cell subpopulations, also known as cancer stem cells (CSC), have been identified in several malignancies, based on the expression of specific surface markers. Phenotypic characteristics of CSC derived from colorectal cancers (CRC) are still debated. Indeed, their low frequency in clinical specimens, precludes a comprehensive phenotypic and functional analysis. We have investigated expression of several surface molecules previously reported as potential CSC markers, including CD133, CD166 and CD44, on established CRC cell lines.Their correlation with CSC functional features, including ability to grow in spheroids, clonogenic capacity and aldehyde-deydrogenase (ALDH) 1 activity in vitro, and tumorigenicity in vivo was also assessed. Methods Colo201, Colo205, HCT116, LS174, LS180, SW480 cell lines were analyzed for surface markers expression by flow cytometry. The ability to growth in spheroids was assessed upon culture on polyHema-coated plastic surfaces and spinner flasks. Clonogenic capacity was tested by limiting dilution analysis. Tumorigenicity was evaluated upon subcutaneous injection of tumor cells in NOD/SCID mice. 102 Results CD133 expression was detected on a large majority (up to 90%) of HCT116 and LS174 cells,concomitantly with CD166 expression. In contrast, Colo201, Colo205 and LS180 were almost completely negative for CD133 but homogeneously expressed CD166. Finally, SW480 was negative for both markers. All cell lines expressed CD44 molecule, although to different extents. CD133 expression positively correlated with the capacity to form spheroids/aggregates upon culture on polyHema-treated flasks or spinner flasks. In contrast, CD166 rather than CD133 expression correlated with high clonogenicity and ALDH1 activity in vitro. Most importantly, CD166, but not CD133 expression correlated with the tumor initiating capacity of cancer cells. The prognostic relevance of CD166 expression in clinical specimens of CRC is currently under investigation. Conclusions Expression of putative CSC markers is heterogeneous in CRC cell lines and may correlate with defined functional features. Thus, specific CRC cell lines might serve as model for a precise identification of CSC. Feasibility of cell-based therapeutic angiogenesis by FACS-purification of VEGF-expressing human myoblasts E. Mujagic, A. Patel, T. Wolff, R. Giannì-Barrera, L. Gürke, M. Heberer, A. Banfi Cell and Gene Therapy ICFS, Gefässchirurgie USB Introduction Therapeutic angiogenesis is a promising strategy for the treatment of end-stage peripheral artery or coronary artery disease. Delivering vascular endothelial growth factor (VEGF) to skeletal muscle by injection of in vitro engineered myoblasts leads to prolonged VEGF expression, which has been shown to be necessary for the formation of stable vessels. However, high levels of VEGF induce uncontrolled vessel growth and we have shown that even small numbers of myoblasts secreting high levels of VEGF are sufficient to cause aberrant vessels. Therefore, we have developed a FACS-based method to rapidly purify myoblasts expressing specific levels of VEGF based on their expression of a cell-surface reporter molecule (truncated CD8a) and have shown that the purified myoblasts induce controlled normal and stable angiogenesis in non-ischemic mouse muscle (Misteli et al, manuscript in preparation) as well as in a rat model of chronic hindlimb ischemia (Wolff et al, manuscript in preparation).The aim of the present project is to determine the feasibility of achieving controlled expression of humanVEGF in vivo by rapid FACS-purification of transduced human primary myoblasts, in order to translate our previous proofof-concept results towards a clinical application. Therefore we determined their expansion potential and maintenance of differentiation ability in vitro, and how these may be affected by transduction. Methods Human primary myoblasts were isolated under GMP conditions from a biopsy obtained from the internal oblique abdominal muscle in a patient undergoing kidney transplantation after informed consent. At passage 2, when the isolation was complete, pure myoblasts were transduced with the retroviral vector pAMFG-hVICD8, carrying the human genes for VEGF and the FACS-quantifiable cell surface marker truncated CD8a. The maintenance of proliferative and differentiation potential in vitro was determined during expansion over 11 passages. Aliquots of cells from every passage were cultured in differentiation medium for 10 days and then immunostained for expression of sarcomeric actin (SA). Differentiation efficiency was measured as the percentage of nuclei included in SA+ myotubes. Results Untransduced human myoblasts could be expanded over 25 doublings (passage 9) with a doubling time of less than 1.5 days. During passages 10 and 11 proliferation decreased significantly and cultures reached senescence. In vitro myogenic differentiation was maintained at least until passage 8 and assays of the last 3 passages are ongoing. After 5 rounds of infection with the hVICD8 retrovirus 54% of primary human myoblasts were succesfully transduced and expressed CD8 by FACS. In vitro expansion and differentiation experiments of the transduced population are ongoing. Clonal populations of transduced human myoblasts are being isolated by FACS-sorting single cells in collagen-coated 96-wells. Because in each of these clones all cells express the same level of VEGF and amount of surface CD8, they will provide the reference values to purify the cells expressing a desired VEGF level from the heterogeneous transduced myoblasts. Conclusions We could show that untransduced human myoblasts can be safely expanded over 25 doublings.As the initial yield from the biopsy was around 106 myoblasts, this degree of expansion would yield over 30 billion cells (25 doublings=32x106-fold expansion). The current estimate of the number of cells necessary for clinical delivery into human muscles is 1-5 billion. In order to achieve this number of myoblasts expressing a desired therapeutic VEGF level after FACS purification, it can be calculated that it will be necessary to recover 3-15% of initially-isolated cells after transduction and sorting. Since the transduction efficiency was over 50%, this aim should be achievable with our FACS-based technology. The completion of these experiments will provide a definitive evaluation of feasibility for a clinical application. 103 Modulation of immunogenicity of viral cancer vaccine Dr. Nermin RAAFAT, Prof. Giulio SPAGNOLI, Prof. Michael HEBERER and Dr. Paul ZAJAC. I.C.F.S, Immuno-oncology, Dept. Biomedicine, University Hospital Basel Although many reports have highlighted the potential of poxviral vectors as recombinant vaccines, their immunogenicity can also be a major drawback. Indeed, immunodominant vectorspecific CTL response could limit the effectiveness of recombinant poxviruses especially in cancer immunotherapeutic strategies which often require multiple rounds of vaccine stimulations. To balance this effect, powerful heterologous prime-boost strategies or immuno-modulation of vector specific responses are required. Objective We aim at decreasing CTL response against Vaccinia Virus by diminishing the viral epitope MHC class-I restricted presentation from infected cells without affecting the presentation of recombinant TAA epitopes encoded by minigenes or MHC class-II presentation of viral entities. This approach should simultaneously decrease epitope competition and the CD8 anti-vector responses. Hypothesis - Design: ICP47 protein (encoded by US12 gene from HSV-I) has been shown to interact with Transporter of Antigen Processing (TAP) protein thereby inhibiting peptide transport to the Endoplasmic Reticulum. This peptide blockade prevents MHC-I loading and surface presentation. We anticipated that in antigen presenting cell infected with recombinant vaccinia virus expressing US12 gene, the generation of epitopes derived from viral proteins should be blocked. In contrast, recombinant ER-targeted vaccine epitopes should not be affected and their overall immunogenicity may be increased. Methods Herpesvirus US12 gene was introduced into Vaccinia virus wild type as well as the rVV expressing the ERMart27-35, a melanoma associated HLA-A2 restricted epitope. Effect on MHC-class I and other surface molecules from infected cells (using non replicating 104 virus) was characterized by antibody staining and FACS analysis. Human T-lymphocyte were stimulated in vitro with autologous CD14+ cells infected with US12rVV, M-US12- rVV or control virus. Proliferation of specific CD8+ and CD4+ for viral proteins and the recombinant epitope were monitored by MHCmultimer and IFNg intracellular staining. Results • US12-rVV demonstrated MHC class-I downregulation. • Kinetic analysis of MHC class-I downregulation indicated that this effect become most visible after 16-24h of infection. • In HLA-A2 positive cell lines , HLA-A2 downregulation with US12-rVV was partially compensated by presence of ER-Mart peptide in M-US12-rVV • The absence of effect of US12-rVV on other surface molecules CD44, CD80 and MHC class II demonstrates that ICP47 effect is specific for MHC class-I molecule. • Preliminary tests seem to confirm that CD8+ responses against viral epitopes (processed from vaccinia vector) are diminished when primed with US12-rVV. Conclusion Recombinant vaccine expressing the HSV-US12 gene confirmed a diminished class-I recognition of native proteins from the viral vector. While helperclass-II properties should be conserved, this type of vector could thereby have a stronger immunogenic potential toward the recombinant ER-targeted class-I epitope. Such reagent could become of high relevance especially in multiple-boost vaccine protocol required in cancer immunotherapy Adenoviral co-delivery of VEGF164 and PDGF-BB for therapeutic angiogenesis S. Reginato, R. Gianni-Barrera, T. Wolff, L. Gürke, M. Heberer and A. Banfi Cell and Gene Therapy ICFS, Gefässchirurgie USB Introduction The delivery of growth factors to restore blood flow (therapeutic angiogenesis) is an attractive and widely investigated strategy for the treatment of peripheral artery disease, cardiac ischemia and other ischemic conditions. Vascular endothelial growth factor (VEGF) is the best studied angiogenic factor and several clinical trials have employed it for therapeutic angiogenesis in cardiac or limb ischemia using a variety of delivery methods. Although phase I studies have demonstrated safety, placebocontrolled phase II studies have not shown significant efficacy. In particular, VEGF164 gene delivery appears to have a very narrow therapeutic window in vivo, with low doses being inefficient and higher levels inducing progressive growth of hemangiomas. We have recently shown that a discrete threshold exists in VEGF expression level, determining whether normal or aberrant angiogenesis is induced, which depends strictly on the amount of VEGF produced in the microenvironment around each cell, as VEGF remains tightly localized in the extracellular matrix (Ozawa et al 2004). This helps explain the disappointing results of VEGF gene therapy trials, as no gene delivery system can control the distribution of VEGF expression levels in vivo (Banfi et al. 2005). Furthermore, we recently found that this threshold is not an intrinsic property of VEGF dose, but it rather depends on the balance between angiogenic stimulation by VEGF and vascular maturation by Platelet Derived Growth Factor-BB (PDGF-BB)mediated pericyte recruitment. Coordinated coexpression ofVEGF and PDGF-BB in a fixed ratio from myoblasts transduced with a bicistronic retrovirus induced homogeneous normal angiogenesis, despite heterogeneous VEGF expression levels (Banfi et al. manuscript submitted). distribution of VEGF levels, and that delivery of a bicistronic adenoviral vector could therefore induce the formation of normal, stable and mature new vessels in skeletal muscle, despite the generation of heterogeneous expression levels. Methods Adenoviral vectors are presently employed in 26% of all gene therapy clinical trials. Because of their immunogenicity, they allow a short duration of transgene expression (10-20 days). While this is a disadvantage if the objective is the permanent replacement of a defective gene, a self-limiting expression is desirable in therapeutic angiogenesis, since the production of angiogenic growth factors for long periods increases the risk of toxic effects. Adenoviral vectors have been constructed, carrying the cDNA for VEGF164 (V), PDGFb (P) or both linked together through an Internal Ribosomal Entry Site (IRES), to ensure coordinated levels of expression (VIP for VEGF-IRES-PDGF). The vectors will be injected in skeletal muscle of immunocompetent mice at increasing titers. The morphology, maturation and stability of newly formed vasculature will be analyzed by whole-mount hystology and immunofluorescent staining.The evolution and stability of the angiogenic response will be correlated to the clearance of the adenoviral genomes and the induced cellular and humoral immune response. Conclusion These experiments will provide fundamental information to develop an convenient, off-theshelf adenoviral gene therapy delivery system, that should lead to safe and efficient angiogenesis in the treatment of various ischemic conditions. Hypotesis We hypothesize that VEGF and PDGF-BB coordinated co-expression may overcome the requirement for control of the microenvironmental 105 Safety and efficacy of controlled VEGF expression in chronic hind limb ischemia T. Wolff, E. Mujagic, P. Fueglistaler, R. Gianni-Barrera, L. Gürke, M. Heberer, A. Banfi Cell and Gene Therapy ICFS, Gefässchirurgie USB Introduction Therapeutic angiogenesis is a promising strategy for the treatment of end stage peripheral artery or coronary artery disease. Delivering vascular endothelial growth factor (VEGF) by intramuscular injection of in vitro engineered myoblasts might prove to be superior to conventional gene delivery systems because it leads to prolonged VEGFexpression, which has been shown to be necessary for the formation of stable vessels. However, high levels of VEGF induce uncontrolled vessel growth and we have shown that even small numbers of myoblasts secreting high levels of VEGF are sufficient to cause aberrant vessels. We have developed a FACS-based method to rapidly purify myoblasts expressing specific levels of VEGF and have shown that the purified myoblasts induce controlled and stable angiogenesis in non-ischemic tissue (Misteli et al, manuscript in preparation). The present study aims to determine whether VEGF delivery by FACSsorted myoblasts is safe when applied in ischemic tissue, where endogenous angiogenic stimuli are activated and secondarily, if it can lead to improved perfusion. Methods Chronic ischemia in the hind limb of nude rats was induced by bilateral ligation of the femoral artery. One week later, VEGF-engineered myoblasts were injected into the adductor and quadriceps muscles (12 injections of 1 Mio cells per leg). Six groups were compared: FACS-purified myoblasts producing 50ng of VEGF/Mio cells/day, unsorted myoblasts with very heterogeneous VEGF levels but producing an average of also 50ng/Mio cells/day, myoblasts from a clone homogeneously expressing 50ng/Mio cells/day, negative control cells, vehicle alone and non-ligated animals. In 82 rats (n=10-15 / group) blood flow in individual leg muscles was measured by injection of radioactive microspheres (15 µm diameter) in the aortic arch four weeks after injection. Withdrawing blood from the tail artery at a fixed rate allowed for absolute blood flow measurements. Maximal blood flow was determined while the rat was running on a treadmill at two different running speeds. Equal blood flow at both speeds confirmed that 106 maximal conductance of the collateral network had been reached. Histological assessment (H&E and immunostaining for endothelial, smooth muscle and pericyte markers) after 1 and 3 months (n=4/group/ time-point) was used to quantify angiogenesis, assess the morphology of the induced vessels and evaluate the appearance of aberrant vessels or vascular tumors. Results Maximal blood flow in the calf muscle was reduced from 176 ml/100g/min before ligation to 39 ml/100g/ min 1wk after ligation with a modest spontaneous recovery to 73 ml/100g/min in the BSA treated animals 5wk after ligation, proving that femoral artery ligation in the nude rat leads to a chronic state of ischemia. Implantation of all cell populations did not further increase global flow at 5 weeks. However, immunostaining of the thigh muscle at the site of cell injection showed a significantly increased number of normal capillaries in the animals treated with sorted cells and cells from the clone. On the other hand, aberrant angioma structures were induced by the unsorted heterogeneous myoblasts and no angiogenesis was induced in control groups. Precise quantification of histologically visible vessel growth is currently being completed. Only rare and small areas of transgenic muscle fibres around the needle tracts of the injection were observed, suggesting that the engraftment rate of injected myoblasts was very low. Conclusion Intramuscular injection of FACS-purified myoblasts secreting specific levels ofVEGF was safe in chronically ischemic muscle, as it completely avoided vascular tumor growth, and efficiently induced controlled normal angiogenesis in the areas of engraftment. However, the number of cells injected was greatly insufficient, leading to the failure to improve global blood flow distal to the site of myoblast injection. Determination of the appropriate number of cells to be injected to achieve efficacy will be a critical parameter for the success of clinical trials with cellbased VEGF delivery for therapeutic angiogenesis. ARE ANKLE CHONDROCYTES FROM DAMAGED FRAGMENTS A SUITABLE CELL SOURCE FOR TISSUE ENGINEERING-BASED CARTILAGE REPAIR? Candrian C.1;2*, Miot S.1, Wolf F1. Bonacina E.1, Valderrabano V.1 , Dickinson S.3, Wirz D. 4, Jakob M. 1, Daniels A.U. 4, Heberer M.1, Martin I.1, Barbero A.1 Institute for Surgical Research and Hospital Management, University Hospital Basel Department of Surgery, Ospedale Regionale di Lugano, Lugano 3 Department of Cellular and Molecular Medicine, University of Bristol /School of Medical Sciences, University of Walk 4 Laboratory for Orthopaedic Biomechanics, University of Basel Faculty of Medicine 1 2 Objective Chondrocytes harvested from the detached fragments of osteochondral lesions of ankle joints (Damaged Ankle Cartilage Fragments, DACF) have been recently shown to proliferate well and to reexpress to a certain extent cartilage specific proteins during 3D culture. Thus, they have been proposed as a useful cell source for autologous chondrocyte implantation in the ankle joint defects. With the goal of assessing whether DACF represent a good source for tissue engineering based cartilage repair approach in the talus, we aimed our study at characterizing the post-expansion cartilage-forming capacity of DACF. Chondrocytes derived from normal ankle cartilage (NAC) were used as control cells. Design DACF were obtained from 6 patients (mean age: 35 years, range 23-43 years) undergoing surgery, while NAC were retrieved from 10 autopsies (mean age: 55, range: 32-79 years). The quality of the harvested tissues was assessed histologically (Safranin O) and immunohistochemically (type I and II collagens). Chondrocytes isolated from the tissues were expanded in monolayer for two passages and then cultured in hyaluronan meshes (Hyaff®-11, FAB, Italy) for 14 or 28 days. Resulting tissues were assessed histologically, biochemically (glycosaminoglycanGAG, DNA and type II collagen) and biomechanically. Statistical differences were assessed with the twotailed Wilcoxon tests. Results DACF contained statistically significant lower amounts of GAG (5.3-fold) and type II collagen (1.5-fold) but higher amounts of type I collagen (6.2-fold) as compared to NAC. Histological and immuhistochemical assessments confirmed the biochemical results. DACF were less cellular compared to NAC, as evidenced by a three-fold lower DNA content in the tissues and by a twofold reduction in cell yield after enzymatic digestion of the biopsies. However, chondrocytes isolated from DACF proliferated at a higher rate (1.2-fold), possibly suggesting a more fibroblastic characteristic. Following 14 days of culture in Hyaff®-11, tissues generated by both cell sources were faintly stained for Safranin O, contained similar amounts of GAG and type II collagen and had similar biomechanical properties.After 28 days of culture, tissues generated by NAC chondrocytes where more intensely stained for Safranin O, contained higher amounts of GAG (1.9-fold) and exhibited superior biomechanical properties (1.7-fold and 3.3-fold equilibrium modulus and dynamic pulsatile modulus, respectively). Conclusions Our results indicate that chondrocytes isolated from the DACF (detached osteochondral fragments) exhibit inferior cartilage forming capacity as compared to chondrocytes from normal ankle cartilage tissues. The inferior tissue forming capacity of chondrocytes isolated from DACF probably results from environmental changes occurring within the cartilage fragment during and after trauma/disease and might limit their efficacy in tissue engineeringbased cartilage repair of the talus. 107 FGF-2 selects and maintains a population of in vitro self-renewing, highly potent, non-adherent mesenchymal progenitors Di Maggio N., Banfi A., Schaeren S., Heberer M., Martin I. Institute for Surgical Research and Hospital Management, University Hospital Basel Objective Bone marrow stromal cells (BMSC) rapidly lose their differentiation potential during in vitro culture. Therefore it is desirable to maximize the yield of clonogenic cells in order to limit their expansion. In this regard, we investigated whether the nonadherent fraction of bone marrow cells, which is normally discarded after three days of culture, contains fibroblastic colony forming units (CFU-f) and, if so, how their proliferative and differentiation potential compares to early-adhering BMSC. Methods The non-adherent fraction of fresh bone marrow cultures was collected during the medium changes on different days and serially replated in new dishes.The presence of mesenchymal progenitors in suspension cultures was assessed by colonogenicity (CFU-f) assays. The cell proliferation rate was determined from the diameters of the formed colonies, while the cell differentiation capacity was assessed by exposing cells to stimuli known to induce adipogenic, chondrogenic and osteogenic phenotypes. Results A non-adherent clonogenic population was always present in bone marrow cultures, which could be maintained and even increased over at least 4 serial replating steps (Replate1=17.5p3.0 %,Replate2=44.9p14.5%, Replate3=72.3p21.7%, Replate4=109.4p34.5% of the number of colonies generated in the primary plate). The colonies produced in the first, second and third replating were significantly larger than the primary colonies 108 (replate1=10.7p2.7 mm, replate2=8.8p1.5 mm and replate3=7.5p0.7 mm vs primary plate=5.5p1.0 mm diameter, t-test p<0.05). Furthermore, the progeny of non-adherent progenitors replated after three days proliferated faster (15.7p1.2 vs 11.8p1.2 doublings in 14 days) and differentiated better in multiple lineages compared to the early-adherent population. Interestingly this phenomenon could only be observed in the presence of FGF-2, suggesting that this factor has a role in maintaining and regenerating the clonogenicity of this class of progenitors. Conclusions These results indicate that non-adherent clonogenic cells exist in bone marrow stroma. These cells can originate adherent colonies while regenerating themselves and maintaining their clonogenic potential, over several rounds of serial replating and under the control of FGF-2, suggesting a self-renewal step. Ongoing studies are aimed at identifying strategies to exploit the growth and differentiation capacity of this cell population for tissue regeneration. Platelet lysate as a serum substitute for 2D-static and 3D-perfusion culture of human stromal-vascular fraction cells of adipose tissue Andreas Marc Müller 1, Michael Davenport 1, Sophie Verrier 2, Mauro Alini 2, Chiara Bocelli-Tyndall 1,3, Michael Heberer 1, Ivan Martin 1 and Arnaud Scherberich 1 Tissue Engineering, Institute for Surgical Research and Hospital Management, University Hospital Basel Biomaterials & Tissue Engineering,AO Research Institute, Davos 3 University Dept of Rheumatology, Felix Platter Spital, Burgfelderstrasse 101, 4012 Basel 1 2 Introduction We recently demonstrated that direct perfusion through ceramic scaffolds of human freshly isolated stromal vascular fraction (SVF) cells obtained from adipose tissue establishes a 3D culture system for osteoprogenitor and endothelial cells and generates osteogenic-vasculogenic constructs. Towards the development of clinically compliant culture conditions for SVF cells, the present study investigated whether platelet lysate (PL) from platelet rich plasma could be used as a substitute to fetal bovine serum (FBS) and FGF-2, currently key components of standard media for the expansion of SVF cells. Methods SVF cells were isolated from lipoaspirates obtained from thigh and/or abdominal adipose tissue of 16 healthy donors (mean age: 47+/- 23 y, mean BMI 22.2 +/-2.7 kg/m2) during routine dermolipectomy. SVF cells were then grown in 2D layers over serial passages as well as in 3D cultures under direct perfusion for five days using α-MEM medium either supplemented with 10% FBS and 5 ng/ml FGF2, or with 5% PL. For each 2D passage, SVF cells were characterized with respect to proliferation rate, frequency of clonogenic cells (defined by CFU-f assays) and expression of mesenchymal and endothelial surface markers (detected in cytoflurometric analysis). Constructs cultured in 3D were implanted in the subcutaneous tissue of nude mice for eight weeks. Upon explantation, constructs were analysed histologically for bone tissue formation and immunohistochemically using antibodies against human CD34 for the presence of blood vessels of human (and not mouse) origin. Results In 2D cultures, α-MEM+PL failed to support the growth of SVF cells and resulted in growth arrest quickly after the first passage (doublings per day in p1: 0.14 ± 0.15, in p2: 0.07 ± 0.05 and no proliferation during p3). At the same time, SVF cells cultured with FBS+FGF-2 proliferated steadily with 0.5 doubling/day in average. SVF cells cultured in 3D for 5 days inside ceramic scaffolds under perfusion and subcutaneously implanted in nude mice for 8 weeks demonstrated bone formation with both medium types, but de novo formation of human blood vessels by SVF cells occurred only in the presence of FBS and FGF-2 and not with PL. This was unexpected, since the proportion of endothelial progenitors, characterized as CD34+/CD31+ cells, was significantly higher using PL as compared to FBS+FGF-2 supplements (33 % vs. 3% respectively). Conclusion These results indicate that PL could be a viable serum substitute for the generation of osteogenic grafts in 3D perfusion cultures, but not for prolongued 2D cell expansion. Moreover, they demonstrate that FBS and FGF-2 are required for the maintenance of vasculogenic cells fractions in 3D cultures of SVF under perfusion. 109 Towards an in-vitro 3D multi-cell co-culture model of bone tissue Papadimitropoulos, A. Mehrkens, M. Heberer, A. Scherberich and I. Martin Institute for Surgical Research and Hospital Management, University Hospital Basel Objective The ultimate goal of this work is to generate a 3D osteoblastic-osteoclastic-endothelial multi-cell coculture system, as an in vitro model to mimic the process of bone matrix deposition and remodelling. Here, we investigate the feasibility to generate the three cell lineages using human adipose tissue derived cells (AT) and CD14+ monocytes from peripheral blood (PBM). Material and methods AT with or without PBM were seeded and cultured on 3D ceramic scaffolds using a perfusion bioreactor in the presence of Machrophage Colony Stimulating Factor and Receptor Activator for Nuclear Factor κB-Ligand for 19 days. Cell phenotypes were assessed by cytofluorimetry and Tartrate Resistant Acid Phosphatase (TRAP) staining. To assess the functionality of the cells, constructs were subcutaneously implanted in nude mice and the formation of bone tissue and human blood vessels was histologically and immunohistochemically assessed. 110 Results Cytofluorimetry analysis demonstrated the presence of endothelial (1.2% of CD34+/CD31+), osteoclastic (13% CD14+/CD31+) and osteoblastic (22% STRO1-/ALP+) cell lineages in constructs generated in vitro by AT and PBM. Osteoclastic cells (TRAP+) attached to the scaffolds were detected only in the presence of PBM. In vivo, human cellderived blood vessel and sporadic bone formation were found in both groups. The presence of humanderived osteoclasts is currently being investigated. Conclusions The study indicates that AT and PBM cells, in a 3D dynamic environment, can be used to establish an in vitro co-culture model of osteoblastic,osteoclastic and endothelial lineage cells, retaining their functionality following in vivo implantation. Ongoing experiments will investigate the potential use of this model for testing the effect of drugs or mechanical forces on the regulation of bone homeostasis. Bioreactor based engineering of large-scale engineered cartilage grafts for joint resurfacing Santoro, R; 2Brans, G; 3Olivares, D; 3Lacroix, D; 4 Wirz, D; 1Jakob, M; 1Martin, I; 1Wendt, D 1 Institute for Surgical Research and Hospital Management, University Hospital Basel Applikon Biotechnology BV, The Netherlands. 3 Institute of Bioengineering of Catalonia, Technical University of Catalonia, Spain 4 Laboratory for Orthopaedic Biomechanics, University of Basel Faculty of Medicine 1 2 Objective While Carticel® and Hyalograft-C® have been well established in the clinic for the treatment of traumatic focal cartilage defects, no tissue engineered product is currently available to treat large defects associated with advanced diseases such as osteoarthritis. We have developed a large-scale perfusion bioreactor to engineer human cartilage grafts of clinically relevant size, with dimensions sufficient for uni-compartmental resurfacing of a human knee. Engineering grafts of such size poses a significant challenge, requiring a 100-fold scale-up of constructs typically generated for basic research. Material and methods Human chondrocytes were seeded into Hyaff-11 meshes (50mm φ x 4mm thick; Fidia Advanced Biopolymers, Italy) for 16 hours in a perfusion bioreactor system. Cell-seeded meshes were either harvested and stained to assess the distribution of cells seeded throughout the scaffold or were further perfusion cultured in the bioreactor for two weeks to generate a cartilaginous graft. Engineered tissue constructs were assessed histologically, biochemically, and mechanically. Results Staining of cell-seeded meshes showed that cells were uniformly distributed throughout the volume of the large-scale scaffold. Following two weeks of perfusion culture, engineered constructs stained faintly positive for Safranin-O (i.e., for glycosaminoglycans; “GAG”), contained 0.12±0.2% GAG per wet weight of tissue, and had a pulsatile dynamic modulus of 1.6±0.1MPa. Conclusions We developed a perfusion bioreactor to scale-up engineered human cartilage grafts to a size with clinical relevance for the treatment of advanced joint diseases such as osteoarthritis. Constructs engineered in the bioreactor were found to have comparable histological staining patterns, similar GAG contents, and similar mechanical properties to cartilage constructs previously engineered in a dramatically smaller size (7.9cm3 vs. 0.057cm3). Ongoing efforts are aimed at integrating the bioreactor into an automated and closed system for safe, standardized, and GMP compliant manufacturing of large-scale engineered cartilage grafts. 111 ENGINEERING OSTECHONDRAL TISSUES WITH HUMAN ARTICULAR CHONDROCYTES AND CLINICALLY USED BIOMATERIALS Scotti C.1, Wolf F.1, Wirz D.2, Schaefer D.J.1,3, Candrian C.1,4, Valderrabano V. 5, Heberer M.1, Daniels A.U. 2, Martin I.1, Barbero A.1 Institute for Surgical Research and Hospital Management, University Hospital Basel Laboratory for Orthopaedic Biomechanics, University of Basel Faculty of Medicine 3 Department of Plastic, Reconstructive and Aesthetic Surgery, University Hospital Basel 4 Department of Surgery, Ospedale Regionale di Lugano, Lugano 5 Department of Orthopaedic Surgery, University Hospital Basel 1 2 Introduction To engineer in vitro functional ostechondral (OC) composites of clinically relevant size using human articular chondrocytes (HAC) and biomimetic scaffolds currently used in clinical practice. Since a strong integration between the two layers of the construct is of key importance for an efficient repair of cartilage defects based on the implantation of engineered OC grafts, special efforts were dedicated to define an easy, repeatable and precise method to quantitatively assess the mechanical strength of integration (“90°-peel-off” test). Design HAC isolated from 3 different individuals were expanded in monolayer and then seeded onto a collagen I/III sponge (Chondro-Gide®, Geistlich, 11 mm of diameter) in a fibrin solution (Tisseel®, Baxter) at a density of 70x106 cells/cm3. The bony scaffolds (Tutobone®, Tutogen, 11 mm of diameter) were wetted in thrombin solution (Tisseel®, Baxter) and then combined to the cell-seeded sponges manually, using a custom-made silicon mould. The generated composites were then assessed immediately after the polymerization (group 1) or after culture for 2 weeks (group 2) or 4 weeks (group 3) in a defined chondrogenic medium. Assessments consisted of standard histological analysis of undecalcified samples, biochemical quantification of GAG and DNA contents in the cartilage phase, and measure of the 90°-peel-off force and energy between the two layers of the osteochondral composites. Results Histological assessment of OC composites from group 2 indicated that HAC were mainly located at the interface of the two scaffolds, had a general fibroblastic appearance and accumulated a loose matrix negative for Safranin O. In OC composites 112 from group 3, chondrocytes at the interface displayed a more round morphology and accumulated a denser Safranin O positive matrix among the trabeculae of the Tutobone®. The cartilage layer remained thin during the OC culture, in this layer only few HAC could be detected. 90°-peel-off test of OC composites showed a significant increase of the integration force with culture time. Median values were: 0.17N, 0.26N and 0.52N respectively for group 1, group 2 and group 3 OC composites. A similar trend was observed for the measured integration energy. Importantly, such measurements were highly repeatable and precise among different replicate samples. Biochemical analyses of the delaminated cartilaginous layers after “90°-peeloff” test demonstrated (i) a low DNA content (corresponding to less then 5% of the initial seeded cell) in both group 2 and 3 groups confirming that the majority of the cells where confined at the cartilage/ bony layer interface and (ii) a slight increase in GAG contents (1.2-fold) from group 2 to group 3. Conclusions Our study indicates that osteochondral composites, consisting of a cartilaginous layer well integrated with a subchondral material, can be generated using human articular chondrocytes and biomimetic scaffolds currently used in clinical practice. Additionally, the measure of the 90°-peel-off force between the two layers can permit to reproducibly quantify the integration of the two layers. Further studies are planned in order to improve the quality and the thickness of the cartilage layer, while maintaining strong integration with the bone layer. From primary chondrocytes to engineered grafts: Streamlined bioreactor-based engineering of human cartilage tissue Tonnarelli, B; Jakob, M; Martin, I; and Wendt, D. Institute for Surgical Research and Hospital Management, University Hospital Basel Objective In the attempt to streamline tissue engineering processes for cartilage regeneration, we firstly assessed whether freshly isolated human articular chondrocytes (HAC) could proliferate directly into a three dimensional (3D) Hyaff-11 mesh to overcome the conventional monolayer cell expansion. Upon proliferation within a closed perfusion bioreactor system, we evaluated the feasibility to prime chondrogenic differentiation in 3D expanded cells. Methods Freshly isolated HAC were seeded at 300.000 cells/cm2 into Hyaff-11 non woven meshes (Fidia Advanced Biopolymers, Italy), corresponding to the available cell yield in a conventional autologous chondrocyte implant procedure. Cell seeding and cultivation were performed in a closed perfusion bioreactor system, respectively at 1mm/sec and 100µm/sec; constructs were firstly cultured for two weeks in proliferating medium supplemented with Transforming growth factor β1, TGF β1, and fibroblastic growth factor 2, FGF2 to sustain proliferation and sequentially perfused for further two weeks with differentiating medium containing growth factors as TGF β1, ascorbic acid and insulin to support chondrogenic differentiation. Samples were evaluated histologically and biochemically to assess GAG and DNA contents. Results As far as proliferation is concerned, HAC underwent approximately 4 cell doublings in 7 days, and then reached 4.75 cell doublings after 2 weeks. During this initial proliferation phase, GAG content was negligible. On the contrary, during the subsequent 2 weeks under differentiating conditions, cellular expansion continued to only a limited extent while GAG started to be deposited: constructs displayed slightly positive safranin-o staining and contained 0.25±0.05% GAG per wet weight. Conclusions The study indicates the feasibility of cellular proliferation directly in 3D and shows promising outcomes to generate a cartilaginous graft in a simplified and streamlined process within a closed bioreactor system, totally bypassing the conventional 2D cell expansion phase. Ongoing investigations aim at optimizing culture conditions towards the development of a fully automated, standardized, and cost effective cartilage tissue engineering manufacturing system. 113 Konzept zur Produktivitätsmessung von Krankenhäusern Arlett Prengel, Michael Heberer Forschungsgruppe Spitalmanagement, ICFS Einleitung Zur Standortbestimmung im Wettbewerb im Gesundheitswesen erhält auch die Messung der Leistungsfähigkeit von Krankenhäusern immer mehr Bedeutung. Bisherige Produktivitätskennzahlen berücksichtigen nur den Output der medizinischen Leistung und dort auch meist nur die stationären Leistungen. Dieser Output wird überwiegend auf das Personal bezogen, z.B. Entlassungen pro Mitarbeiter oder Fälle pro Arzt. Dies ist insbesondere deshalb als unzureichend zu betrachten, da 1. die Leistungen eines Krankenhauses nicht nur durch die Mitarbeiter, sondern auch durch die verwendeten Betriebsmittel und Materialien beeinflusst werden, und 2. das Krankenhaus ein Dienstleistungsunternehmen darstellt, welches neben der medizinischen Leistung weitere Kernleistungen in Form von Vorhalteleistungen, Forschung und Lehre erbringt. Forschungsziel Das Ziel der Untersuchungen ist die Bildung einer die Gesamtleistung eines Krankenhauses widerspiegelnde Produktivitätskennzahl, die zum Vergleich von Krankenhäusern mit unterschiedlicher Ausprägung der Kernleistungen angewendet werden kann. Methode Es wurde ein theoretisch-konzeptionelles Vorgehen gewählt, bei dem neben den Erkenntnissen zur Produktivitätsmessung in Sachleistungsunternehmen die Ergebnisse zur Outputmessung von Krankenhäusern miteinander verbunden werden sollen. Ergebnisse Um mit der Produktivitätskennzahl das Gesamtbild des Krankenhauses wiedergeben zu können, müssen sowohl im Input als auch im Output die gesamten Einsätze und Leistungen berücksichtigt werden. Der Gesamtinput umfasst neben den Arbeitskräften auch die Betriebsmittel und Werkstoffe. Die Zusammenfassung der Inputfaktoren Produktivität des KH = 114 erfolgt auf der Basis ihrer Aufwendungen. Zur Bestimmung des Outputs des gesamten Krankenhauses muss neben dem Output der medizinischen Leistung, der Output der Forschung, der Lehre, der Vorhalteleistungen und der Zusatzleistungen berücksichtigt werden. Der Output der medizinischen Leistung kann durch deren Umsatz abgebildet werden. Dabei werden die erbrachten Leistungen mittels Punktwerten (ambulant) bzw. Relativgewichten (stationär) erfasst und monetär bewertet. Vorhalteleistungen sind Leistungen zur Bereitstellung bedarfsdeckungsorientierter Betriebsbereitschaft. Diese werden zur Versorgungssicherheit der Bevölkerung vereinbart. Für die Bereitstellung dieser Leistung erhalten die Krankenhäuser eine Subvention, welche als Outputgröße herangezogen werden kann.Die Bestimmung des Outputs der Forschung ist um einiges schwieriger. Er setzt sich aus eingeworbenen Drittmitteln und Patenten zusammen. Basis dafür sind veröffentlichte Artikel. Der Output der Forschung beträgt aus monetärer Sicht die Summer der Erträge aus Drittmitteln und Patenten. Die Lehre eines Krankenhauses setzt sich aus der Aus-,Weiterund Fortbildung zusammen. Auch diese Leistungen sind Bestandteil des Gesamtoutputs eines Krankenhauses. Krankenhäuser mit dem Auftrag der Lehre erhalten dafür eine „Aufwandsentschädigung“. Diese Bezahlung der Lehre kann als Outputgröße herangezogen werden. Die Summe der Erträge der Kernleistungen und der Zusatzleistungen eines Krankenhauses bildet nun die Gesamtleistung des Krankenhauses ab und kann auf den Gesamtinput bezogen werden Schlussfolgerungen Durch die Berücksichtigung aller Kernleistungen und des gesamten Inputs eines Krankenhauses wurde eine Kennzahl gebildet, welche die Produktivität des Gesamtunternehmens Krankenhaus widerspiegelt. Mittels dieser Produktivitätskennzahl können Krankenhäuser auf einer hohen Aggregationsebene miteinander verglichen werden. Zur Steuerung eines Krankenhauses muss allerdings aufTeilproduktivitätskennzahlen zurückgegriffen werden. Diese können durch die Differenzierung im Input, im Output oder der Unternehmenseinheiten gebildet werden. 3 Erträge (EMedizin + EVorhaltung + EForschung + ELehre + EZusatzleistungen) 3 Aufwendungen (AArbeitskräfte + ABetriebsmittel +AWerkstoffe) Kiefer- und Gesichtschirurgie 115 Oculodynamic MRI- a helpful tool for maxillofacial surgeons? B.-I. Berg1, 2, C. Kunz1, 2, K. Schwenzer-Zimmerer1, 2, E.W. Radü3, C. Kober4, K. Scheffler5, C. Buitrago-Téllez6 and A. Palmowski-Wolfe Hightech Research Center of Cranio-Maxillofacial Surgery, University Hospital Basel, Switzerland Dept. of Cranio-Maxillofacial Surgery, University Hospital Basel, Switzerland 3 Dept. of Neuroradiology, University Hospital Basel, Switzerland 4 Faculty of Life Sciences, HAW Hamburg, Germany 5 MR Physics, University Hospital Basel, Switzerland 6 Radiological Center Aarau Zofingen, Spitalzofingen AG, Switzerland 7 Dept. of Neurosurgery, University Hospital Basel, Switzerland 1 2 Objective In this study near real time MRI, a technique for the recording of eye movements was qualitatively evaluated and quantitatively compared with clinical testing. Materials and Methods Eye movements of 22 patients were tracked in the horizontal and vertical plane. In all cases, diplopia was the inclusion criteria. A standard 1.5 T MRI with a TrueFISP sequence (180ms/image, 1.3x1.3 mm spatial resolution) was used.The average slice thickness was 5 mm.The average acquisition time for one sequence was about 10 sec. The eye movement was assessed in two planes (sagittal and axial). Three independent physicians graded the visibility of extraocular muscles qualitatively throughout the movement. For the clinical evaluation, maximal monocular horizontal and vertical excursions measured in mm according to Kestenbaum with a see-through ruler held over the patient’s eye were compared to the angel of the largest possible eye movements in the MRI sequence ( in degrees measured on print-outs) by using the Pearson test. 116 Results A distinction could be made between mechanical adhesions from entrapment and paralytic eye movement disorders. Three independent assessors graded the MRI quality (from 1= not visualized to 5 = very good quality, continuous visualization). According to the plane examined, visualization was better for the horizontal and vertical rectus muscles than for the superior and inferior oblique. Complete visualization throughout the axial or sagittal sequence varied between about 10% and 90% respectively. MRIs with complete visualization were compared to the clinical measurements. Positive correlations were found between the angles measured in the MRI and complete movement of the right eye, between complete movement of the left eye as well as for the upwards-downwards movement of the right eye. Conclusion The oculodynamic MRI promises to be a helpful tool for the maxillofacial surgeon and ophthalmologist. With a good correlation to clinical findings, the oculodynamic MRI can record and visualize normal versus pathologic ocular movements. Its potential application is particularly in the setting of preoperative planning of posttraumatic diplopia or periorbital tumors with secondary ocular motility disorders. Capturing infant faces with cleft lip in the operation theatre using the T-Scan¡ B.-I. Berg 1,2, A.A. Müller 1,2, B. Williger1,2, P. Jürgens1,2, A. Ringenbach 3 , E. Schkommodau 3, K. SchwenzerZimmerer 1,2 Hightech Research Center of Cranio-Maxillofacial Surgery, University Basel, Switzerland Dept. of Cranio-Maxillofacial Surgery, University Hospital Basel, Switzerland 3 Institute for Medical und Analytic Technologies, FHNW, Muttenz, Switzerland 1 2 In cleft surgery it is desirable to gain an as precise as possible 3D documentation of the pre-operative situation, of the treatment results and follow up. Different devices for the capturing and digitising of the facial surface are available and suitable for compliant patients. Examples are white-lightscanners, linear laser-scanners, photogrammetric devices and the holographic camera. A contact free acquirement is needed otherwise the soft tissue is displaced and an accurate reproducibility is unfeasible. A high resolution (in the range of sub millimetre) is necessary as well as a user friendly technical system which can be used by medical staff (e.g. in the operation theatre).The T-Scan¡ (Fa. Steinbichler, Neubeuern, Germany) is a handheld, flexible scanning system. In contrast to the other methods undercut regions are accessible due to the hand-held use of the T-Scan¡ and simultaneous registration by a tracking camera system. Material and Method The facial surface is captured by a visible laser beam (670 nm, laser class 2) and measured with high scanning frequencies. The laser beam is linearly orientated by a polygon mirror. The measurement distance is calculated using the triangulation principle. The scanning device has 29 infrared markers. Three of these markers have to be determined for the exact spatial position using an optical tracking system. For the assessment of the T-Scans¡ infants (average age 3 months) with cleft lips received in general anaesthesia two scans before the surgical procedure, two scans straight after the operation and another two scans 7 days later when the sutures were removed. Plaster cast masks were also produced for the determination of the reproducibility of the scanning system in object acquisition.The masks were also scanned.The datasets were optimized, registered and statistically evaluated.The variance was taken as a measurement feature for the accuracy. Results Datasets with a resolution in the range of less than a millimetre were acquired. The mean accuracy of the plaster masks comparison was less than 0.05 mm. The scans from breathing children (in general anaesthesia) showed a mean accuracy of less than 0.09 mm. The scanning device was in the operation theatre with extra effort comparable to systematic photo- and video-documentation. The plaster cast could be captured without any lost of data. The children had to be scanned several times using changing angles of incidence in complex areas to gain undercutting parts facial surface. The measuring time for one face was in the range of 15 seconds. Discussion and Outlook The feasibility of a handheld triangulation scanner offers a new opportunity in the operation theatre. It is also useable as a follow-up tool. The capturing of three dimensional datasets in the range of less than a millimetre was possible in aggravating circumstances (breathing patient, small operation theatre). However the relative long input time and therefore motion artefacts will result in wider deviations when using this system for scanning awake patients. Another disadvantage is the lack of coloured texture. Compared with other scanning devices a major advantage is the possibility to scan undercut complex regions in detail. Cleft lip and the nose/ear regions are captured in a very precise way. Different perspectives for the use of the t-scanning device could be the three dimensional Cephalometry or in navigation as tool for soft tissue tracking. 117 Neurobiologische Parameter bei Kindern vor und nach dem Lippen-Kiefer-Gaumenspaltverschluss – eine longitudinale Querschnittsstudie Andreas Müller1,2, Serge Brand3, Edith Holsboer-Trachsler3, Robert Sader2,4, Hans-Florian Zeilhofer1,2, Katja Schwenzer-Zimmerer1,2 Klinik für Wiederherstellende Chirurgie, Kiefer- und Gesichtschirurgie, Universitätsspital Basel, Spitalstrasse 21, 4031 Basel 2) Hightech-Forschungs-Zentrum der Kiefer- und Gesichtschirurgie, Universität Basel, Schanzenstrasse 46, CH-4031 Basel 3) Universitäre Psychiatrische Kliniken Basel, Kinder- und Jugendpsychiatrie, Wilhelm Klein Strasse 27, CH-4025 Basel 4) Klinik für Mund-, Kiefer- und Plastische Gesichtschirurgie, Klinikum der J.W. Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main 1) Fragestellung Cortisolausschüttung, Schlaf, Stresslage des Kindes und Stresslage der Eltern stehen in enger wechselseitiger Abhängigkeit. Wir untersuchen anhand dieser Parameter die physischen- und psychischen Auswirkungen welche durch den Hospitalistions- und Operationsstress im Rahmen der Erstoperation mit ca. 4 Monaten verursacht wird. Methoden Die Studiengruppe umfasst 25 Kinder mit einer LKGSpalte und eine alters- und geschlechtsangeglichene Gruppe von 25 unauffälligen Kindern. Eine Woche vor bis eine Woche nach der Operation tragen die Kinder einen Actimeter, zur Erfassung der körperlich aktiven und inaktiven Phasen. Zu mehreren Zeitpunkten vor, während und nach der Operation wird der Cortisolspiegel im Speichel ermittelt. Die körperliche, kognitive, emotionale und soziale Entwicklung des Kindes wird mit Hilfe validierter psychologischer Fragebogen ermittelt, ebenso der 118 momentane psychische Zustand der Eltern. Die Datenerhebung wird 6 und 12 Monate nach der Operation wiederholt. Resultate Wir präsentieren die Resultate der ersten 10 Studienpatienten bezüglich der Actigraphie, des Schlafmuster und der psychologischen Erhebungen des Kindes und der Eltern rund um die Operation. Erste Resultate zeigen, dass die Schlafdauer der Kinder unmittelbar vor der Operation abnimmt und die Einschlaflatenz zunimmt. Vorläufige Schlussfolgerungen Die Schlafmuster der Mütter und ihrer Kleinstkinder vor und nach dem Lippen-KieferGaumenspaltverschluss lassen die Vermutung zu, dass die psychische Belastung der Mütter auf die Psyche der Kleinstkinder direkt übertragen wird. Diesem Aspekt ist während der perioperativen Führung und Betreuung der Eltern speziell Rechnung zu tragen. Dank: Gottfried und Julia Bangerter-Rhyner-Stiftung Kinderchirurgie 119 Subureteral Endoscopic Injection Using Stabilized NonAnimal Hyaluronic Acid/Dextranomer Gel (Deflux®) as First Line Treatment of Vesicoureteral Reflux (VUR) in Children Haecker FM1, Dörfler M1, von Rotz M1, Rudin C2, Mayr J1 Department of Pediatric Surgery, 2Department of Pediatric Nephrology; University Children’s Hospital, Basle, Switzerland 1 Purpose Endoscopic correction of vesicoureteral reflux (VUR) has become an established alternative to long-term antibiotic prophylaxis and ureteral reimplantation. At our institution, the procedure is used since 1988. A number of tissue augmenting substances have been used, and since 2002 we are using hyaluronic acid/dextranomer (Deflux®) as first line treatment. The aim of the study was to assess the data of patients treated with Deflux® and compare them to the results of a former study, including 82 patients treated with collagen injection. Methods Retrospective study of the charts of 79 children with VUR grade II-V, also including children presenting with additional malformations such as duplex ureter, posterior urethral valves (PUV), diverticulum or neurogenic bladder. All patients underwent subureteral Deflux®-injection. Outcome was verified with voiding cysto-urethrography (VCU) 3 months (all patients) and 12 months (22 patients) after operation. Results From January 2002 to August 2007, 79 children (56 girls, 23 boys) with a total of 125 ureters underwent subureteral Deflux®-injection. 59 patients presented bilateral VUR. Additional malformations were duplex ureters in 16 patients, PUV in 4 patients, diverticulum in 3 patients, neurogenic bladder in 2 patients and 120 ectopic orifice in 1 patient. VUR grade was II in 34 ureters, III in 52 ureters, IV in 32 ureters and V in 7 ureters, respectively. VCU 3 months after infection therapy demonstrated no VUR in 56 patients (71%) and diminished VUR grade in additional 13 patients (total 87.3%). After a second injection therapy (21 patients), the postoperative VCU was negative in 16 children. Due to persistent VUR, 2 children underwent a third Deflux®-injection with success. Serious complications were not noted. Conclusion Subureteral Deflux®-injection is a safe method for treatment of VUR, even for high-grade reflux. It demonstrates minimal morbidity and low complication rate. The success rate is higher compared to the treatment using collagen injection. Using a differentiated injection technique (HIT), the results are even similar to these of ureteral reimplantation. Die Saugglocke nach E. Klobe zur konservativen Therapie der Trichterbrust: eine alternative Therapie? Frank-Martin Häcker, Jozef Bielek, Johannes Mayr Kinderchirurgie, Universitäts-Kinderspital beider Basel, Postfach, CH-4005 Basel Die Trichterbrust ist mit einer Inzidenz von ca. 1 : 300 die häufigste Thoraxwanddeformität. Bei erfolgloser konservativer Behandlung mit intensiver Physiotherapie kommt die operative Korrektur zur Anwendung, in früheren Jahren insbesondere die Verfahren nach Ravitch sowie heutzutage die minimal invasive Korrektur nach Nuss (MIRPE). Eine mögliche Alternative oder auch eine Ergänzung zu MIRPE, stellt die Vakuumtherapie mittels Saugglocke nach E. Klobe dar. Unter Berücksichtigung des individuellen Patientenalters stehen derzeit 3 verschiedene Grössen sowie ein für adoleszente und erwachsene Patientinnen konzipiertes Model zur Verfügung. Die Saugglocke wird direkt auf den Brustkorb aufgelegt. Mittels Handpumpe wird ein Vakuum von ca. 15% unter Atmospherendruck erzeugt. Während der Steigerung des ausgeübten Unterdruckes zeigt sich zumeist sofort eine spürbare Anhebung des Trichters. Die tägliche Anwendungsdauer sollte bei mindestens zweimal 30 Minuten liegen, kann aber individuell bis zu mehreren Stunden täglich gesteigert werden. Seitens des Herstellers wird ein Anwendungszeitraum von durchschnittlich 12-18 Monaten empfohlen. Derzeit befinden sich 72 Patienten (10 weiblich, 62 männlich) im Alter von 3 bis 52 Jahren (Durchschnitt 17.2 Jahre) in unserer Behandlung. Nach durchschnittlich 18 Monaten konnte bei 7 Patienten die regelmässige Anwendung der Saugglocke erfolgreich abgeschlossen werden. 4 Patienten haben die Vakuumtherapie vorzeitig abgebrochen und sich einer operativen Korrektur (MIRPE) unterzogen. Zu Langzeitresultaten mehr als 2 Jahre nach Behandlungsabschluss kann derzeit noch keine verwertbare Aussage gemacht werden. Die bisher erzielten Resultate zeigen jedoch einen beeindruckenden Erfolg. Dies soll neben Prinzipien und Technik der Anwendung diskutiert werden. 121 FAST RECOVERY FOLLOWING ENDOSCOPIC STENTING FOR PANCREATIC DUCT INJURY M. Köhler1, D Siabalis1, FM Häcker1, L Degen2, J Mayr1. Department of Paediatric Surgery, University Children´s Hospital (UKBB), Basle Department of Gastroenterology, University Hospital, Basle 1 2 Aim The management of paediatric pancreatic trauma remains controversial. In patients with ductal disruption some authors recommend early surgery in order to decrease duration of parenteral nutrition and prevent pseudocyst formation. We followed a minimally invasive approach for the same goals but aiming also for a shorter postoperative course and hospital stay. Methods We report two cases (6 and 7 years respectively) presenting to our hospital with increasing abdominal pain following a handlebar injury. Further investigations with ultrasonography and CT scan showed signs of pancreatic duct lesions with beginning pseudocyst formation. Patients were immediately started on TPN and Octreotide.As soon as the overseas ordered Pigtail stents (5 Fr diameter, 7cm length) had arrived, ERCP was performed and placement of the pigtail stent beyond the site of duct lesion could be achieved. 122 Results One day after stent placement the patients were asymptomatic. They started on clear fluids shortly after the procedure followed by build-up of oral nutrition the following day. Patients were discharged 7 and 2 days respectively following stenting and controlled with regular ultrasounds. In the first patient, the initial pseudocyst was disappeared after 3 weeks. The second patient had no pseudocyst detectable on ultrasonography on day 2. In patient 1 the stent was removed as day surgery after 4 weeks. On follow-up 4 months after stent removal abdominal ultrasound showed normal pancreas with no signs of fluid collection. In patient 2 stent removal is still pending. Conclusion In our cases, minimal invasive stenting of the pancreatic duct was feasible, abbreviated the natural course of complicated pancreatic duct injury and shortened the hospital stay as well as the duration on parenteral nutrition. Neurochirurgie 123 The influence of blood on energy metabolism, brain edema, histological damage and functional outcome after evacuation of acute subdural hematoma in rats H. Baechli1, M. Behzad2, A. Heimannr2, H.-G. Buchholz3, O. Kempski2, B. Alessandri2 Clinic of Neurosurgery, University Hospital and Children`s University Hospital Basel (UKBB), Switzerland Institute for Neurosurgical Pathophysiology, Johannes Gutenberg University Mainz, Germany 3 Clinic of Nuclear Medicine, University Hospital Mainz, Germany 1 2 Objective Acute subdural haematoma (ASDH) are the most lethal of all brain injuries. The role of blood constituents on the pathophysiology of ASDH is still unclear. In former studies we could show that blood itself produce a broader damage than volume alone. The aim of this study is to examine if this effect is due to early changes in energy metabolism. Methods Male Sprague-Dawley rats were infused subdurally with either 300µl autologous venous blood or paraffin oil. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF) were monitored during 1 hour after injury. Brain edema and histological damage were assessed 2, 24, 48 and 96 hours after injury. Additionally we studied glucose metabolism using (18-F)-deoxyglucose (FDG) in an animal PET (Focus 120) at 2 hours and 11th day after surgery. A lateral and medial cortical region of interest was defined and the ratio of ipsito contra lateral FDG metabolism was calculated for each animal and region. 124 Results Infusion of blood or paraffin oil increased ICP to 46.4±2.6 and 42.9±1.5 mmHg, dropped CPP by 34.6±2.2 and 32.4±2.7 mmHg and CBF by 70.8±4.1 and 66.5±2.8% (n=19 vs. 23; n.s.) Cortical glucose metabolism at 2 hours postinjury was drastically decreased for blood- but not for paraffin-treated animals (n=6/group), whereas brain water content was not affected in both groups at this time point (n=10/group). At later time points, brain edema and histological damage was significantly more pronounced following blood infusion (main differences occurred with a delay of 24 hours). Blood also induced a stronger activation of microglia. In addition, neurological score (10±2.0 vs. 2.0±1.3) and lesion volume (34.7±8.7 vs. 15.8±2.6 mm3) was more severely affected by blood in comparison to the same volume of paraffin at day 11 after injury (n=10/group, p<0.05). Conclusion Blood causes more severe brain damage than volume alone suggesting an important role of blood constituents on pathomechanisms. Except for glucose metabolism, markers for injury severity such as ICP, CPP or CBF were not sensitive enough to distinguish between blood and volume effects in the acute period after injury. Role of dopaminergic transmission in extinction of conditioned fear in the prefrontal cortex of mice H. Bächli1, C.K. Thöringer2, N. Edlbergmeier2, C. Flachskamm2, C.T. Wotjak2 Clinic of Neurosurgery, University Hospital Basel and Children`s University Hospital Basel (UKBB), Switzerland Max Planck Institute of Psychiatry, Munich, Germany (all authors contributed equally to the study) 1 2 Objective Many of the most common psychiatric diseases are emotional disorders and related to the brain’s fear system. More than 50% of mental problems are accounted for anxiety disorders, including phobias, panic attacks, posttraumatic stress disorder, obsessive compulsive disorder and generalized anxiety. The aetiology of such complex disorders, which tendency is growing, is poorly understood and their biological basis remains unclear. Most research has focussed on fear conditioning in animal studies and try to explore how animals learn to fear specific stimuli within the environment. But little is known about the exact functioning of the neuromodulatory system. In previous studies we could show that the dopaminergic system in the prefrontal cortex (PFC) of different mice strains is essentially involved in fear memory. The present study was designed to elucidate the role of dopamine (DA) in extinction of conditioned fear with the ultimate goal of better understanding some of the mechanisms underlying affective dysregulation in human patients Methods We conditioned male Balb C mice with a single tone-shock pairing at day 0, followed by systemic administration of selective DA receptor D1R (SCH23390; 1mg/kg) and D2R antagonists (Sulpirid; 5mg/kg) prior to extinction training at day 1 and 2. On day 3 we tested extinction retention in a drugfree state. In a second step we measured the DA release and its metabolites in the prefrontal cortex with microdialysis during conditioning and extinction training. In a third experiment we locally injected the D1R and D2R antagonists directly into the prefrontal cortex prior to extinction on day 1 and 2 and tested 24h later for extinction retention. Results 1. The D1 receptor antagonist SCH23390 facilitated extinction learning, whereas the D2R (Sulpirid) attenuated long-term extinction. 2. We noticed a strong increase in DA release during conditioning and extinction, which was only partially related to behavioural performance 3. SCH23390 failed to affect fear conditioning and Sulpirid attenuated fear conditioning. Conclusion Our studies demonstrate bidirectional modulated DA effects on extinction of conditioned fear. Within the mPFC, the dopaminergic system is phasically activated during extinction training and seems to promote fear extinction via D2R. 125 Neoadjuvant Targeting of Glioblastome Multiforme with Radiolabelled Substance P – Results from a Phase I Study D. Cordier1, S. Kneifel2, F. Forrer2, Martin Sailer1, J.C. Reubi 3, H. Mäcke2, J. Müller-Brand2, A. Merlo 1 Division of Neurosurgery, University Hospitals, Basel; 2Institute of Nuclear Medicine, University Hospitals, Basel; 3 Institute of Pathology, University of Berne 1 Objective Neoadjuvant therapy as an established strategy in oncology has so far not been implemented into the therapeutic algorithm of glioblastoma multiforme (GBM). The usually rapid initiation of surgical treatment in these fast growing tumors aims at the avoidance of increasing and thus symptomatic intracranial pressure. In a previous study, we could show that local intratumoral injection of radiolabelled substance P in recurrent high grade glioma substantially inhibited further growth and led to radionecrotic transformation of the tumor. Subsequently, we evaluated feasibility and toxicity of this new therapeutic modality in the neoadjuvant setting for GBM as primary and the extent of resection and functional outcome as secondary endpoints. Methods After stereotaxic biopsy and diagnosis of GBM, ten patients were included in a prospective nonrandomized study. Treatment consisted in repetitive local injections of radiolabelled substance P into the tumor, followed by surgical resection. The chemical synthesis, the radiolabelling protocol and local injection of the peptidic vector [90Yttrium]-DOTAGASubstance P has been described previously. 126 Results Neoadjuvant injection of [90Yttrium]-DOTAGAsubstance P could be shown to be feasible without clinical or radiological signs of decompensating intracranial pressure. The prolonged application of corticosteroids in the current study protocol was identified as the main risk factor for potential side effects. Nine patients improved or at least stabilized in their functional status. Neoadjuvant local irradiation of these tumors allowed to achieve a high extent of resection (median 98%), which may be of prognostic importance. Conclusion Neoadjuvant therapy of GBM using locally injected radiolabelled substance P is feasible and of low toxicity. Furthermore, this modality markedly improves the extent of resection in subsequent surgery and may therefore improve therapeutic outcome. Bipallidal Stimulation Improves Glottal Closure in the Dysphonia of Parkinson’s Disease: Case Report with Videographic Documentation Ethan Taub1, Adrian Merlo1, Peter Fuhr2 und Claudio Storck3 Neurochirurgie, 2Neurologie und 3Hals-Nasen-Ohren-Chirurgie UHBS 1 Introduction The patient, a 75-year-old retired otorhinolaryngologist, underwent bilateral globus pallidus stimulation for the treatment of medically intractable, akinesia-dominant Parkinson’s disease. Dysphonia with a markedly weak voice was a prominent symptom. Methods Deep brain stimulation (DBS) electrodes were implanted into the globus pallidus bilaterally in the awake patient with both anatomical and functional target localization (fused MRI/CT, intraoperative microelectrode recording and stimulation). Postoperatively, laryngeal videostroboscopy and quantitative measurement of objective voice parameters (loudness, mean phonation time, and voice handicap index) were performed with the bilateral pallidal stimulation turned off and on to document improvement of the patient’s voice. Results The patient’s appendicular motor function and facial expression were markedly improved by DBS. With regard to his voice, videostroboscopy with the stimulation turned off showed a laryngeal tremor and total glottal insufficiency. When the stimulation was turned on, the tremor was no longer evident and glottal closure was fully normal (complete). The objective voice parameters were also markedly improved. Conclusions Laryngeal videostroboscopy and voice parameter measurement can be used to document the response of dysphonia to deep brain stimulation for Parkinson’s disease. 127 A New Assessment Tool for Evaluation of Normal Pressure Hydrocephalus (NPH): Quantitative Volumetric CSF Drainage Wasner M.G. Neurosurgical Clinic, University Hospital, Basel, Switzerland Objective Therapy of choice in patients with clinical and neuroradiological signs of NPH is ventriculoperitoneal (VP-) shunting. The available shunt systems are partial pressure valves. The opening pressure of the valve is important to prevent overor underdrainage. In a pilot study we determine preoperatively the individually adapted CSF volume reduction (ml/h) in optimal regression of NPH symptoms. The aim was to correlate the flow rate with the pressure stage of the valve. Methods 10 patients with suspected NPH underwent preoperatively external volumetric controlled CSF drainage (LiquoGuard®, MöllerMedical) with staged drainage of 5ml/h to 20ml/h over 5 days. Before, during and after external CSF drainage, repetitive neuropsychological testing and a standardized gait analysis have been performed. In patients with confirmed NPH-diagnosis a proGAV (020/+25cm H2O) VP-shunt was implanted. In case of symptomatic improvement at 5ml/h CSF flow the pressure valve was set to 15cm H2O. In the follow up gait analysis, minimental test, urodynamic and CCT were repeated. 128 Results 2 of 10 patients showed no decrease of symptoms during open drainage. 8 patients received a VP shunt and exhibited a satisfactory reduction of NPH symptoms. No overdrainage was noted. Ataxia was reduced in 8 of 8 patients, disturbance of memory was reduced in 6 of 8 patients. Conclusion Preoperative volumetric drainage is a new assessment tool for NPH diagnostic workup and allows determining the optimal pressure stage of the shunt system. Plastische, rekonstruktive und ästhetische Chirurgie 129 Tissue Engineered Autologous 3D-Arthroplasty of the First Carpo-Metacarpal Joint in Thumb Basal Joint Osteoarthritis Marina Barandun a, Magdalena Müller-Gerbl b, Thomas Egelhof c, Victor Valderrabano d, Marcel Jakob d, Michael Heberer e, Ivan Martin e, Dirk J. Schaefer a Department of Plastic, Reconstructive and Aesthetic Surgery; b Institute of Anatomy; c Institute of Radiology; d Department of Orthopaedics and Traumatology; e Department of Research, Tissue Engineering a Aims The objective of this project is to define a tissue engineered autologous arthroplasty of the first carpo-metacarpal (CMC I)-joint in end-stage osteoarthritis (OA). Thereby, the defective joint surfaces are replaced by a tissue engineered osteochondral graft while the ligaments are left in place (or reconstructed where necessary), hence providing an anatomical reconstruction of the joint surfaces while maintaining stability and mobility of the joint. Methods To define the anatomical morphometry of the normal CMC I-joint, anatomical studies of ligaments, joint surfaces and thickness of cartilage are performed as well as 3D-CT measurings of the bone and MRI to determine the thickness of the cartilage. To define the anatomical morphometry of the altered CMC I-joint in end-stage OA, radiological (3DCT, Spect-CT, MRI) and clinical (range of motion, force, ligament stability) studies are performed. For the tissue engineering of autologous cartilage a biopsy of cartilage (e.g. nasal septum) is processed by in vitro breeding on a membrane and fixing on 3D-Tutoplast. These osteochondral grafts are first implanted in cadaveric hands, in a second stage in patients with endstage OA of the CMC I-joint. The assessment of osteointegration and biomechanics of the reconstructed joint will again be performed by radiological and clinical studies. 130 Results The project will be started in 2009; progress reports and results will follow. Discussion In the hand, the CMC I-joint is the second most commonly involved site of primary OA.The functional disability secondary to painful, weakened pinch and grip is significant. The etiology of OA involves biochemical and biomechanical factors, which are not yet fully understood. Therapeutic options in the CMC I-joint include nonoperative treatment in early stages as well as operative treatment in later stages such as ligament reconstruction, osteotomy, arthrodesis, implant arthroplasties and trapezium excision, tendon interposition and ligament reconstruction. However, all of these treatment options still cannot reconstruct an anatomically and biochemically normal joint. When thinking about an alternative treatment for OA, where anatomy and biomechanics of the joint remain unchanged, engineered autologous tissue replacement seems to represent the method of choice. The CMC I-joint is a small and easily accessible joint with rather small joint forces compared to the joints of the lower extremity. Therefore, it is an ideal model for tissue engineered autologous 3D-arthroplasty in end-stage OA. Effekt von Stammzellen bei chronischen Wunden am Modell des Dekubitalulkus. Eine Pilotstudie zur Machbarkeit, Verträglichkeit und möglichen Wirkung Savic M1, Zweifel M1, Scheufler O1, Kalbermatten D1, Schmid D1, Gratwohl A2, Halter J2, Dirnhofer S3, Baumberger M4, Schaefer DJ1, Pierer G1 Abteilung für Plastische, Rekonstruktive und Ästhetische Chirurgie, Universitätsspital Basel Abteilung für Hämatologie, Universitätsspital Basel 3 Institut für Pathologie, Universitätsspital Basel 4 Schweizer Paraplegiker Zentrum Nottwil 1 2 Fragestellung/Ziel der Studie Überprüfung der Eignung des sakralen Dekubitalulkus als klinisches Modell einer chronischen Wunde für die Behandlung mit Stammzellen. Negative Effekte der Stammzellapplikation sollen mit der gewählten Methodik ausgeschlossen werden können. Überprüfung der Objektivierbarkeit einer möglichen Wirkung der Stammzellapplikation. Methodik Patienten Drei para-/tetraplegische Patienten, die wegen eines sakralen Dekubitalulkus des Stadiums III-IV nach Daniel und Seiler im Schweizer Paraplegikerzentrum Nottwil hospitalisiert waren,wurden mit Stammzellen behandelt. Stammzellgewinnung/ Wundvorbereitung Als Stammzellen wurden autologe hämatopoetische (CD 34+) Knochenmarkstammzellen verwendet. Nach Punktion des Knochenmarkes erfolgte das Wunddébridement standardisiert in „PseudoTumor“ Technik. Stammzelltherapie Zwei Tage nach Débridement wurde die linke Hälfte der Wunde mit Stammzellsuspension infiltriert während die rechte Hälfte als Kontrolle mit isotoner Kochsalzlösung isovolumetrisch behandelt wurde. Débridement nach Stammzellbehandlung Der Wundrand wurde 3 Wochen nach Applikation der Stammzellsuspension vollständig exzidiert. Anschliessend erfolgte der definitive Defektverschluss mittels Lappenplastik. Auswertung Die Auswertung erfolgte mittels digitaler Forografie, Volumetrie (VI-910 NON-CONTACT 3-D DIGITIZER, MINOLTA), laborchemisch und bioptisch. Resultate Bei allen behandelten Pat. konnten die applizierten Stammzellen mittels Immunhistochemie (CD 34+ Marker) objektiviert werden. Histologisch zeigte sich in dem gewählten Zeitraum keine meta-/ dysplastische Differenzierung des Gewebes. Systemische Reaktionen konnten klinisch und laborchemisch ausgeschlossen werden. Mittels 3-D Laser Scanners wurde nach 3 Wochen eine gesteigerte Wundkontraktion der behandelten Seite objektiviert. Schlussfolgerung Der sakrale Dekubitus bei plegischen Patienten eignet sich als definiertes klinisches Modell für chronische Wunden zur Untersuchung der Behandlung von chronischen Wunden mit autologen hämatopoetischen Stammzellen aufgrund seiner Lage und Beschaffenheit, sowie der schmerzfreien Gewinnung von Gewebeproben. Eine gute Verträglichkeit ist gegeben, wobei Langzeitresultate fehlen. Erste Hinweise deuten auf einen positiven Effekt der Applikation von Stammzellen in sakrale Dekubitalulzera in Bezug auf beschleunigte Wundkontraktion, Granulation und gesteigerte Gewebequalität. 131 Vascularized tissue engineered bone flaps Dirk J Schaefer1, C. Jaquiéry2, R Verstappen1, D. Schmid1, A. Scherberich, M. 3 Heberer3, I Martin3 Abteilung Plastische, Rekonstruktive und Ästhetische Chirurgie Abteilung Mund-Kieferchirurgie Klinik für Wiederherstellende Chirurgie 3 Institut für chirurgische Forschung und Spitalmanagement 1 2 Fragestellung In Vorversuchen konnte gezeigt werden, dass zellbeladene Knochenkonstrukte durch Kombination von Tissue engineering Methoden und mikrochirurgischen Lappentechniken im ektopen Kaninchenmodell extrinsisch vaskularisiert werden können. Ziel dieser weiterführenden Untersuchung ist,ob diese präfabrizierten Lappen einen segmentalen Knochendefekt kritischer Grösse rekonstruieren können. In einer in vitro und in vivo Vorstudie wurde das Tiermodell etabliert. Resultate In vitro konnte das Besiedlungsverfahren der porösen HA-Zylinder durch Immobilisation der Stammzellen im Konstrukt optimiert werden. In vivo gelang die extrinsische Prävaskularisation der Konstrukte durch Verwendung eines Panniculus carnosus Faszienlappens. Die präfabrizierten Knochenlappen konnten in den Humerusdefekt unter Erhalt der Vaskularisation eingebracht werden. Winkelstabile Plattenosteosynthesen sind zur stabilen Osteosynthese unter funktionellem Erhalt des N. radialis notwendig. Methoden 24 New Zealand Kaninchen in 3 Gruppen zu 8 Tieren werden durch Knochenmarkaspiration Bone Marrow Stem Cells (BMSC) entnommen, welche in vitro für 3 Wochen expandiert und in Fibrinogen gelöst auf 9x5 mm Engipore Hydroxylapatit-Zylinder (HA) appliziert werden. Die zellbeladenen Zylinder werden in einen Panniculus carnosus Faszienlappen eingenäht. In Gruppe 1 (n=8) wird der präfabrizierte Lappen erst 4 Wochen ektop zur Prävaskularisation implantiert und in einem zweiten Eingriff anschliessend in einen 9 mm langen segmentalen Humerusdefekt eingesetzt. In Gruppe 2 (n=(8) wird der Lappen direkt in den Defekt eingesetzt. Gruppe 3 ist die Kontrollgruppe. Nach 8 Wochen erfolgen Röntgenkontrollen und histologische Untersuchung der Knochenpräparate. Schlussfolgerungen Durch Kombination von Knochen Tissue engineering und mikrochirurgischen Lappentechniken gelingt die ektope Vaskularisation von Knochenlappen. Der Nachweis, dass diese präfabrizierten Lappen einen segmentalen Knochendefekt rekonstruieren können steht noch aus. Aus diesem Grund wurde dieses Tiermodell optimiert und zur Durchführung der Hauptuntersuchung etabliert. 132 Urologie 133 Vergleich zwischen rechts- und linksseitiger retroperitoneoskopoischer Lebendnierenspende nach 179 Operationen N. Ebinger Mundorff, S. Wyler, C. Abe, T. Gasser, A. Bachmann Universitätsspital Basel, Departement Urologie Hintergrund Seit 2001 ist die Retroperitoneoskopie Universitätsspital Basel der Standardzugang Lebendnierenspende. Mit einer Erfahrung von Operationen vergleichen wir die Ergebnisse rechts- und linksseitigen Spenden. am zur 179 der Methoden Von November 2001 bis Juni 2008 wurden 179 Spender (f=122, m=57; l=137, r=42) operiert. Das Alter lag bei 53 (27-79) Jahren und der BMI betrug 25.5 (17.3-44.5) kg/m2. Die Spender wurden in der üblichen überstreckten Seitenlagenlagerung retroperitoneoskopisch operiert. Eine Operation wurde aufgrund drei vorhandener Arterien handassistiert ausgeführt. Ergebnisse Die Operationsdauer betrug 146 (55-300) min. (l=148 [55-300], r=141 [90-240]), die warme Ischämiezeit betrug 134 (30-280) sek. (l=132 [30280], r=139 [60-280]). Der Blutverlust lag bei 160 (0-600)ml (l=158 [0-600], r=167 [0-500]) und der stationäre Aufenthalt bei 11 (4-29) Tagen (l=11 [5-29], r=10 [4-14]). Die Konversionsrate lag bei 1.2% (n=1 aufgrund Aortenverletzung während linksseitiger Operation; n=1 aufgrund zwei Venen und einer zusätzlichen Arterie bei rechtsseitiger Operation mit intraoperativem Wechsel von retroperitoneoskopisch rechts auf offen links). Kleine intraoperative Zwischenfälle traten bei 4.5%(n=8) auf (l=5.1% [n=7], r=2.4% [n=1]). 134 Geringe postoperative Komplikationen wurden bei 15.6% (n=28) beobachtet (l=17.5% [n=24], r=9.5% [n=4]). Die Re-Operationsrate betrug 2.8% (n=5) (l=3.6% [n=5], r=0% [n=0]). Die Gründe waren eine Blutung aus der A.iliaca ext., persistierende Schmerzen aufgrund einer verbliebenen Nadel nach Zwerchfellnaht und drei Chyloretroperitonei. Bei den linksseitigen Spenden bestanden zu 15.3% (n=21) Gefässabnormalitäten, bei 3.0% (n=4) entstanden dadurch Probleme. Bei den rechtsseitigen Spenden bestanden bei 4.8% (n=2) Gefässabnormalitäten, bei 2.4% (n=1) entstanden Probleme. Bei nur einem Patienten waren die Probleme schwerwiegend und hatten einen Seitenwechsel und eine Konversion zur offenen Operation zur Folge. Insgesamt zeigte sich im Vergleich links zu rechts ausser bei der stationären Aufenthaltsdauer kein statistisch signifikanter Unterschied. Schlussfolgerung Die perioperativen Daten unterstreichen die Sicherheit der retroperitoneoskopischen Spendernephrektomie. Die perioperativen Daten der rechtsseitigen Operationen sind keinesfalls schlechter als die der linksseitigen. Daher sollte weder bei der Indikation zur rechtsseitigen Spende, noch bei bestehenden Gefässabnormalitäten einer offenen Operation der Vorzug gegeben werden. Greenlight Laser Vaporisation der Prostata – Erfahrungen und Langzeitergebnisse nach 500 Eingriffen M. Rieken, S. Wyler, C. Abe, G. Bonkat, T. Gasser, A. Bachmann Urologische Universitätsklinik Basel - Liestal Hintergrund: Die Greenlight Laservaporisation der Prostata (PVP) zur Behandlung von Miktionsbeschwerden bei Prostatavergrösserung hat sich mittlerweile als eine Alternative zur TURP etabliert. Trotz ermutigender kurzfristiger Ergebnisse sind bisher nur wenig Langzeitergebnisse bezüglich Dauerhaftigkeit und Komplikationen nach PVP verfügbar. Wir präsentieren Erfahrungen und Langzeitergebnisse nach 500 Eingriffen an einem Zentrum. Material und Methoden Perioperative Parameter, intra- und postoperative Komplikationen sowie postoperative Ergebnisse wie Internationaler Prostata Symptom Score (IPSS), Lebensqualität (QoL), maximale Harnflussrate (Qmax) und Restharn (Vres) von 500 Patienten mit Miktionsbeschwerden infolge Prostatavergrösserung, welche zwischen September 2002 und April 2007 eine 80W PVP erhalten hatten wurden analysiert. Ergebnisse Das mediane Follow-up betrug 30,6±16,6 Monate (5,2-60,6). Das mediane Patientenalter bei Operation lag bei 71,4±9,6 Jahren (46-96) mit einem medianen Prostatavolumen von 56,1±25,3 ml (10-180). Die mediane Operationszeit war 66,4±26,8 min (10- 160), die mediane applizierte Energie betrug 206±94 kJ (2,4-619).Trotz laufender oraler Antikoagulation in 45% der Patienten wurden keine schwerwiegenden intraoperativen Komplikationen beobachtet. Die mediane Katheterliegenzeit und postoperative Hospitalisationszeit war 1,8±1,2 (0-10) und 3,7±2,9 (0-35) Tage. Der mediane IPSS und QoL nach 3 Jahren waren 8,0±6,2 und 1,3±1,3, Qmax 18,4±8,0 ml/s und Vres 28±42ml. Die Reoperationsrate lag bei 6,8%, ein lokalisiertes Prostatakarzinom wurde während des Follow-up bei 6 Patienten diagnostiziert. Schlussfolgerungen Die PVP ist eine sichere und effiziente operative Therapieoption bei Miktionsbeschwerden infolge Prostatavergrösserung. Patienten unter oraler Antikoagulation können sicher operiert werden. Die deutliche Verbesserung von Symtomen und Miktionsparametern ist von langfristiger Dauer, die Reoperationsrate ist vergleichbar mit der konventionellen TUR-Prostata. 135 Index Symbols 3D Modell Tissue engineering 111 A Achillessehne Ossifikation 65 Ruptur 73 Adipositas 16 Adrenalin 33 AMIC 52 Analgesie Lidocain 84 Propofol 25 Anästhetika Myotonie 26 Angiogenese Myoblasten 100, 104 VEGF und PDGF-BB 97, 106 Angst 126 Aorta Klemmung 41 Marfan 93, 94 Arthritis radioulnares Gelenk 89 Arthrodese Fuss 64 Langzeitresultate 62 Orthobiologie 85 retrograder Nagel 83 Hüftprothesen 75 Arthroplastie 131 Arthrose 54 Atrophie Arthrose d. Sprunggelenkes 54 Rotatorenmanschette 58 Augmentation Knochen 44 Ausdauertraining EMG 63 B BASES 39 Biomarker TGF-beta 93 Bioreaktor Knochen 111 Knorpel 112, 114 Blockade, vagal 16 BNP 29 Botulinustoxin 74 C CD8 98, 99, 100, 102, 104, 105 Central core disease 37 Cerebralparese 72, 74 Cholezystektomie 20 Chondrozyten 52, 108, 112, 113, 114 136 CT Osteoabsorptiometrie 66 Spect 32, 48, 67, 82, 86, 131 D Darmdurchblutung 41 Defekte, Knorpel 52 Deflux 121 Dekubitus 132 Delirium 27 Dopamin 126 E EKG 31 EMG 63, 70 Endothel 92 Ethik 38 F Fechten 70 Fibulaosteosynthese 80 Fraktur 43, 61, 69 Fuss Analgesie 84 Arthrodese 62, 64, 83, 85 Atrophie 54 Instabilität 46 Knochendichte 66 Knorpel 47 Osteoarthritis 50, 86 Osteochondrose 68 Rekonstruktion 55 SPECT-CT 48, 67 G Gangbild 71, 72 Gehirn 125, 129 Gen-Chip 34 Geriatrie 43 Glioblastom 127 Glottis 128 Gonarthrose 78, 79, 80 H Hämatom, subdural 125 Hämostase 84 Handschuhe 19 Hernie, inguinal 15 Herzchirurgie Mortalität 30 Herzinsuffizient Proteom 91 Herzkatheter ‘call-to-balloon-time’ 31 Hüftplatte Korrekturosteotomie 76, 77 Hüftprothesen 60, 75 Humerus 61 Hyaluronsäure vesikuloureteraler Reflux 121 Hyperalgesie Propofol 25 Hyperthermie, maligne 34, 35, 37 Hyrdozephalus 129 I Immunogentität Modulation 105 Infektion Handschuhe 19 Kalorimetrie 53 Inguinalhernie 15 Instabilität, Knöchel 46 K Kalorimetrie 53 kardiale Dysfunktion 29 Karzinom Glioblastom 127 Kolon 21, 23 Stammzellen 103 Prostata 99, 136 Knie Gangbild 71 Prothese 49 Knöchel Instabilität 46 Knorpel 47 Osteoarthritis 50 SPECT-CT 48 Tantalum 55 Knorpel 47, 51, 52. s. Chondrozyten Kodierung 101 Kognitive Dysfunktion 27 Kolonkarzinom 21, 23, 103 Koordination, Skelettmuskel 56 Korrekturosteotomie Hüftplatte 76, 77 Kryopreservation Venen 95 L Larynx 28 Laser Vaporisation Prostata 136 Leber 17 Lichtenstein 15 Lidocain 28, 84 Lippen-,Kiefer,Gaumenspalten 118, 119 Lymphknoten Sentinel 21, 23 M Maligne Hyperthermie 34, 35, 37 Marfan 93, 94 Mesh plug 15 METAP Ethik 38 Micro-CT 55 Mikrozirkulation 41 Mortalität 30, 39 MRI Gesicht 117 Spektroskopie 45 Talus 67 Mutation 34, 35, 37 Myoblasten 97, 100, 104, 106, 107 Myotonie 26 N Neoadjuvante Therapie 127 Neurostimulation Parkinson 128 Niere Mikrozirkulation 41 Transplantation 135 vesikuloureteraler Reflux 121 NMR 45 O Okulodynamik 117 Osteoarthritis Arthroplastie 131 SPECT-CT 86 Still’s disease 57 Osteochondrose 81, 82 Osteosynthese 69 Humerus 61 Talus 68 Osteotomie Gonarthrose 78 Malleolar 68 P Pankreas biliäre Pankreatitis 20 Trauma 123 Parkinson Neurostimulation 128 PDGF-BB Angiogenese 97, 106 Perfusion Mikrozirkulation 41 zerebral 27 Pharmakogenetik 34, 35 Propofol Analgesie und Hyperalgesie 25 Chloridkanäle 26 Prostatakarzinom 99, 136 Proteom Herzinsuffizient 91 R Radioulnares Gelenk 89 Rapamycin 92 Reanimation 33, 40 Rocuronium 40 137 Rotatorenmanschette 58 Rückenschmerzen SPECT-CT 32 rVaccina Virus 98 S Saugglocke 122 Schmerz Osteochondrose 82 Propofol 25 Sepsis 39 Sevofluran 28 Skelettmuskel Atrophie Achillessehnenruptur 73 Arthrose 54 Rotatorenmanschette 58 CCD 37 Chloridkanal 26 Gangbild Cerebralparese 72 JP-45 36 Koordination 56 Kraft JP-45 36 Murley Scores 59 Myotonie 26 SPECT-CT. s. CT: Spect Spektroskopie Magent Resonanz 45 Sport 50, 73 Stammzellen Dekubitus 132 FGF-2 Selektion 109 Knochen 133 Kolonkarzinom 103 Stärkeinfusionen 39 Stent Pankreas 123 Still’s disease 57 Succinylcholin 34, 40 Synovia NMR 45 T Talonavicular Arthrodese 64 Talus CT-Osteoabsorptiometrie 66 osteochondrale Läsionen 68 MRI, SPECT-CT 67 Tantalum 55 Thrombozytenlysat 110 Tibia Osteotomie Fibulaosteosynthese 80 Gonarthrose 78 Knöchel osteoarthritis 50 Patellaposition 79 Tissue engineering 87 3D Modell 111 Arthroplastie 131 Bioreaktor Knorpel 112, 114 Chondrozyten 108 Knochenlappen 133 Knorpel 113 Thrombozytenlysat 110 Training 63 Transplantation Niere 135 Trauma Pankreas 123 Zytokine 18 Trichterbrust 122 Troponin-T 30 T-Scan 118 T-Zellen. s. CD8 U Ultraschall Pfannenorientierung 60 V Vagaler Block 16 VBLOC 16 VEGF Angiogenese 97, 100, 106 Ischämie 107 Venen Kryopreservation 95 vesikuloureteraler Reflux Hyaluronsäure 121 Virusvakzine Immunogentität 105 W Workflow Kodierung 101 Z Zerebrale Perfusion Delirium und kognitive Dysfunktion 27 zygapophyisches Gelenk SPECT-CT 32 Zytokine 22 Prostatakarzinom 99 Trauma 18