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