191 results on '"Perl, Mario"'
Search Results
152. The immune response after fracture trauma is different in old compared to young patients
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Vester, Helen, Huber-Lang, Markus S, Kida, Qerim, Scola, Alexander, van Griensven, Martijn, Gebhard, Florian, Nüssler, Andreas K, and Perl, Mario
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Inflammation ,Ageing ,Research ,Immunoageing ,Immunology ,Apoptosis ,Trauma - Abstract
BACKGROUND: Despite significant medical progress and improved treatment, surgical procedures of proximal femur fractures in older patients are still associated with a high postoperative complication and mortality rate. Recently, several authors investigated the phenomenon of immunoageing, indicating differences in the ageing immune system. The aim of the present multi-center prospective clinical trial was to analyze differences in the posttraumatic immune response of old patients compared to young patients. METHODS: Blood was collected from young patients (70 y, n = 21) with proximal femur fractures (OF) upon clinical admission and within 6 hours after surgery, and two healthy age matched control groups (YH & OH). Serum TRAIL- and cytokine concentrations were analyzed via cytometric bead array, Fas-Ligand and TNF-Receptor-I via ELISA. CD15(+) magnetic bead-isolated neutrophils (PMN) were TUNEL stained. RESULTS: IL-6 was significantly increased only in OF after trauma and surgery whereas YF patient exhibited a marked decrease of TNF after trauma. Interestingly, a significant increase of GM-CSF serum levels was observed in YF only, whereas OF exhibited a decrease of systemic IFN-γ concentrations after trauma and after surgery. The healthy controls, old and young, had more or less similar inflammation levels. Moreover, TRAIL serum levels were diminished in OF after trauma and even further after surgery whereas in YF this was only observed after the surgical procedure. Fas-L concentrations were reduced only in YF after surgery or trauma. PMN apoptosis was significantly reduced only in YF, indicating activation of the innate immune system. DISCUSSION: In summary, our data suggest that the posttraumatic immune response is differently regulated in old and young trauma patients. The operative procedure further impacts these differences after trauma. Whether the decreased activation of PMNs and phagocytes along with the observed dysregulation of the posttraumatic inflammatory response contributes to the high perioperative mortality rate of the elderly suffering from a proximal femoral fracture requires further investigation.
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153. Weiterbildung und Fortbildung auf hohem Niveau!
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Perl, Mario and Münzberg, Matthias
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- 2014
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154. DECREASING NEUTROPHIL BUT NOT MONOCYTE APOPTOSIS IN VIVOIMPROVES SEPTIC SURVIVAL BY MODULATING INNATE IMMUNE FUNCTIONS
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Perl, Mario, Chung, Chun S., Perl, Ulrike, Rooijen, Nico V., Lomas-Neira, Joanne, Gregory, Stephen, and Ayala, Alfred
- Published
- 2006
155. Die Rolle des Anaphylatoxins C5 in der Pathogenese des Trauma-induzierten septischen akuten Lungenschadens
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Karbach, Michael, Perl, Mario, Huber-Lang, Markus, University of Zurich, and Karbach, Michael
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10216 Institute of Anesthesiology ,Respiratory distress syndrome, Adult ,Thoraxtrauma ,Brustkorbverletzung ,Complement C5 ,Komplement C5 ,610 Medicine & health ,Complement C5a ,Komplement C5a ,UZHDISS UZH Dissertations ,Sepsis ,Thoracic injuries ,ARDS ,ddc:610 ,DDC 610 / Medicine & health - Abstract
Inhibition der Wirkung des Anaphylatoxins C5a hat sich in der Vergangenheit benefiziell auf die Verläufe verschiedener tierexperimenteller akuter Lungenschaden (ALI)-Modelle ausgewirkt. Hierzu zählen die Immunkomplex-vermittelte ALI, Cecal Ligation and Puncture (CLP)-assoziierte ALI, sowie durch isoliertes Thoraxtrauma verursachte ALI. In vorliegender Arbeit wurde untersucht, inwiefern C5a in einem klinisch relevanten Double-hit Modell von Thoraxtrauma und polymikrobieller Sepsis die Inflammation in der Lunge sowie die Apoptose beeinträchtigt. Hierzu wurden C5–/– Mäuse einem stumpfen Thoraxtrauma ausgesetzt und 24 Stunden später eine polymikrobiellen Sepsis induziert oder eine korrespondierende Sham-Prozedur für die Kontrollgruppen durchgeführt. Die Proben wurden zum Zeitpunkt 12 Stunden nach CLP gewonnen. Als Zeichen einer abgeschwächten systemischen Entzündungsreaktion waren Keratinocyte chemoattractant (KC) und Monocyte Chemotattractant Protein-1 (MCP-1) im Plasma bei C5–/– Mäusen stark reduziert. Die Konzentrationen der proinflammatorischen Zytokine Interleukin-6 (IL-6), MCP-1 sowie Granulocyte colony stimulating factor (G-CSF) in der bronchoalveolären Lavage war bei C5-Defizienz jedoch deutlich erhöht. Ebenso konnte das Fehlen von C5 die Myeloperoxidase (MPO)-Aktivität in der Lunge als Indikator für die polymorphkernige neutrophile Granulozyten (PMN)-Migration in vorliegendem ALI-Modell nicht senken. In C5–/– Mäusen konnte zwar weniger aktive Caspase-3 im Lungengewebe nachgewiesen werden, dennoch war das Gesamtprotein in der BAL gegenüber Wildtyp deutlich erhöht. So konnte in vorliegender Arbeit gezeigt werden, dass in einem klinisch relevanten Double-Hit Modell der Thoraxtrauma-induzierten septischen akuten Lungenverletzung C5-Defizienz Apoptose in der Lunge positiv beeinflusst, insgesamt jedoch weder eine überschiessende Inflammation noch die Migration von PMN in die Lunge reduziert werden konnte.
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- 2020
156. Der intraoperative Keimnachweis bei der Revisionsoperation von primär als aseptisch eingestuften Pseudarthrosen an Femur und Tibia
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Hellinger, Lena, Perl, Mario, and Wittau, Mathias
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Pseudarthrose ,Tibia ,Gewebeprobe ,low-grade Infekt ,Schienbein ,aseptisch ,Keimnachweis ,Wundabstrich ,Tibial fractures ,Complications ,Pseudarthrosis ,Hip fractures ,ddc:610 ,DDC 610 / Medicine & health ,Oberschenkelknochen - Abstract
Die Behandlung aseptischer und septischer Pseudarthrosen folgt verschiedenen Behandlungskonzepten. Der Stellenwert eines intraoperativen Keimnachweises bei primär als aseptisch eingestuften Pseudarthrosen an Femur und Tibia ist aktuell unklar. In der vorliegenden Arbeit soll die Häufigkeit dieses akzidentiellen Keimnachweises sowie dessen Keimspektrum dargestellt, verschiedene mikrobiologische Nachweismethoden verglichen und die Auswirkungen des Keimnachweises auf das Outcome überprüft werden. Es wurde eine retrospektive Datenanalyse an 181 Patienten mit traumatisch bedingter, primär aseptisch eingestufter Femur- und Tibiaschaftpseudarthrose durchgeführt, welche initial an der Berufsgenossenschaftlichen Unfallklinik Murnau mittels einzeitiger Revisionsoperation behandelt wurden. Bei den Patienten wurden präoperativ erhobene Laborparameter (C-reaktives Protein (CRP), Leukozytenzahl), die mikrobiologische Diagnostik (Kurzzeitbebrütung, Langzeitbebrütung) und das Outcome (Anzahl der Revisionsoperationen, Zeit bis zur knöchernen Heilung, Lower extremity functional scale (LEFS)- Fragebogen und Short Form-12 (SF-12)- Fragebogen) erhoben und verglichen. Anhand der mikrobiologischen Diagnostik erfolgte postoperativ die Einteilung der Patienten in „septisch“ und „aseptisch“. Mittels deskriptiver und vergleichender Statistik erfolgte der Gruppenvergleich der Parameter und bei septischen Pseudarthrosen die Darstellung des Keimspektrums. Bei insgesamt 35,9 % (n= 65; Femur n= 34; Tibia n= 31) der Patienten wurde ein Keimnachweis erbracht. Die Langzeitbebrütung einer Gewebeprobe konnte diesen verlässlicher anzeigen als die Kurzzeitbebrütung eines Wundabstrichs (p
- Published
- 2019
157. Einfluss des Fas-Rezeptors auf die Pathogenese von Inflammation und Apoptose eines Thoraxtrauma-induzierten septischen akuten Lungenschadens
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Kellermann, Philipp, Perl, Mario, Huber-Lang, Markus, Weiß, Manfred, and Kleger, Alexander
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Inflammation ,Respiratory distress syndrome, adult ,Sepsis ,Entzündung ,Thoraxtrauma ,Brustkorbverletzung ,Fas-Rezeptor ,Apoptosis ,Thoracic injuries ,ARDS ,ddc:610 ,DDC 610 / Medicine & health - Abstract
Pulmonale Apoptose und Inflammation werden als zentrale Mechanismen bei der Pathogenese eines Acute Respiratory Distress Syndrome (ARDS) angesehen. Bei der Aktivierung beider Prozesse nimmt die Fas-Rezeptor-vermittelte Signalkaskade eine übergeordnete Rolle ein. Ziel dieser Studie war es daher den Einfluss der Fas-vermittelten Apoptose und Inflammation im Rahmen eines klinisch relevanten Double-Hit-Modells zu untersuchen. Hierfür wurde ein Wildtyp-Mausstamm (C57BL/6) und ein Stamm mit fehlerhafter Fas-Expression (B6.MRL-Faslpr/J (lpr)) einem stumpfen Thoraxtrauma und 12 Stunden später einer Sepsinduktion mittels zökaler Ligation und Punktion (Double-Hit) unterzogen. Dabei zeigte sich, dass in Fas-defizienten Tieren 12 und 24 Stunden nach Double-Hit die Zytokin- und Chemokinkonzentration im Plasma, BAL und Lungengewebe im Vergleich zu Wildtyp-Tieren vermindert war. Des Weiteren blieb in Fas-defizienten Tieren die pulmonale Apoptose, ein alveolärer Einstrom neutrophiler Granulozyten und proteinreicher Flüssigkeit als Zeichen einer Störung der alveolokapillären Integrität gegenüber Wildtyp-Tieren aus. Auch die histologische Untersuchung von Dünnschnittpräparaten der Lunge konnte einen protektiven Effekt der Fas-Defizienz nach einem Lungentrauma bestätigen. Daraus lässt sich schließen, dass die Fas-aktivierte Signalkaskade einen wesentlichen Einfluss bei der Entstehung des Thoraxtrauma-induzierten septischen akuten Lungenschadens hat. Eine ausbleibende Fas-Aktivierung hingegen milderte die Ausprägung eines experimentell-induzierten ARDS signifikant ab und könnte somit von therapeutischem Wert in zukünftigen Behandlungsstrategien dieser Erkrankung sein.
- Published
- 2019
158. Die Rolle der Autophagie im traumainduzierten septischen Lungenschaden
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Meister, Anne, Perl, Mario, and Skrabal, Christian
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Respiratory distress syndrome, adult ,Autophagy ,Autophagie ,ARDS ,ddc:610 ,%22">Autophagie ,DDC 610 / Medicine & health - Abstract
Ausgelöst durch direkte (in der Lunge gelegene) oder indirekte (systemische) Ursachen, ist das akute Atemnotsyndrom (ARDS) ein schnell fortschreitender Prozess, der sich initial mit Dyspnoe, Tachykardie und Hypoxämie manifestiert. Aufgrund steigender Inzidenz und hoher Mortalität ist das ARDS eine klinisch hochrelevante Erkrankung. Zielsetzung dieser Arbeit war es daher, die Rolle der Autophagie im traumainduzierten septischen Lungenschaden näher zu untersuchen.
- Published
- 2018
159. Stellenwert des Knochenmarködems in der Diagnose eines ARCO Stadium 3 einer avaskulären Nekrose des Hüftkopfs
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Torka, Sebastian, Meier, Reinhard, and Perl, Mario
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Diagnosis, Differential ,Femur head necrosis ,Therapy ,Diagnostic imaging ,Methods ,Kernspintomografie ,ARCO 3 Stadium ,Avaskuläre Nekrose ,ddc:610 ,Ödem ,DDC 610 / Medicine & health ,Hüftkopfnekrose ,Knochenmarködem - Abstract
In der durchgeführten Arbeit wurde der Stellenwert des Knochenmarködems im Stadium III nach der Einteilung der Association de Recherché sur la Circulation Osseuse (ARCO) untersucht und die Hypothese aufgestellt, dass ein Knochenmarködem einen konkreten Hinweis für das Vorliegen einer subchondralen Fraktur darstellt. Hierfür wurden insgesamt n=37 Hüften von n=27 Patienten mit avaskulärer Hüftkopfnekrose in der Magnetresonanztomographie (MRT) in die Studie eingeschlossen. Die Patienten mussten zusätzlich ein Knochenmarködem in der MRT-Untersuchung, sowie eine Computertomographie (CT) der entsprechenden Hüfte vorweisen. Die Auswertung erfolgte durch zwei unabhängige Radiologen unter Verwendung der ARCO Klassifikation. Des Weiteren konnte bei n=14 Hüften, die im Verlauf eine Hüftprothese erhalten hatten, eine histopathologische Untersuchung durchgeführt werden. Die alleinige Beurteilung von MRT-Aufnahmen führte in nahezu 50% zu einem falsch-negatives Ergebnis (Stadium II statt Stadium III). Bei allen Patienten mit einem MR-tomographische nachweisbaren Knochenmarködem konnte auch anhand der CT-Untersuchung eine subchondrale Fraktur nachgewiesen werden. Dies bestätigte sich in allen Fällen einer histopathologischen Untersuchung. Die Hypothese, dass das Vorliegen eines Knochenmarködems einen konkreten Hinweis für das Vorliegen einer subchondralen Fraktur darstellt, ließ sich anhand der Studienergebnisse bestätigen.
- Published
- 2017
160. [Transtuberositary, Anterior Open Wedge High Tibial Osteotomy (TT-AOW-HTO) to Correct a Negative Slope].
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Harrer J, Ferner F, Lutter C, Petersen W, Perl M, and Simon M
- Abstract
Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.
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- 2024
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161. [Double-Level De-Rotational Osteotomy of the Knee].
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Ferner F, Lutter C, Perl M, and Harrer J
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- Humans, Tibia surgery, Tibia diagnostic imaging, Femur surgery, Femur abnormalities, Knee Joint surgery, Knee Joint diagnostic imaging, Bone Plates, Torsion Abnormality surgery, Torsion Abnormality diagnostic imaging, Joint Instability surgery, External Fixators, Osteotomy methods
- Abstract
Derotational osteotomies of the proximal tibia and distal femur are a common surgical treatment option in patients with a congenital or posttraumatic torsional deformity. Clinically, these patients present with isolated anterior knee pain alone or in in combination with patellofemoral instability. Since the combination of femoral and tibial deformity is common (quotation Cooke), a combined surgical treatment is needed for these cases. This includes high tibial derotational and a distal femoral osteotomy, stabilised by a plate respectively. The current video shows the technique of this combined osteotomy assisted by external fixateur and the tibial approach with tibialis anterior fasciectomy and neurolysis of the peroneal nerve., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
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- 2024
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162. [Treatment of Permanent Patellar Dislocation in Flexion by Patellar Osteotomy Combined with Modified Trochleoplasty and Tibial Tubercle Medialisation].
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Dickschas J, Schmeling A, Perl M, and Simon M
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- Humans, Female, Adolescent, Tibia surgery, Tibia diagnostic imaging, Treatment Outcome, Patellar Dislocation surgery, Patellar Dislocation diagnostic imaging, Osteotomy methods, Patella surgery, Patella diagnostic imaging
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Patellar dislocations in flexion, which occurs permanently with every movement, is the most serious manifestation of patellofemoral malalignment. Surgical approaches to correct this problem have been mostly unsuccessful. In a new therapeutic approach, the concave posterior surface of the patella, which slides on the hypoplastic lateral condyle as if guided by splints, is seen as the main pathology. The appropriate surgical strategy is trochleoplasty, combined with closed wedge patellar osteotomy, tuberosity medialisation, procedure for lengthening lateral retinaculum and MPFL plasty with the quadriceps tendon. In the case of a 13-year-old female patient presented here, this procedure leads to permanent stability in a symptom-free knee joint on both sides., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
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- 2024
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163. [The preventive flexion osteotomy at the head of the tibia].
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Reuter B, Perl M, and Dickschas J
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We present the case of a preventive tibial plateau flexion osteotomy in an adolescent patient who had a reduced posterior slope of the tibial plateau. The patient was asymptomatic and without instability at the time. However, magnetic resonance imaging (MRI) showed a dysmorphic posterior cruciate ligament, which was interpreted as an indication for osteotomy. This article demonstrates the surgical technique and postoperative outcome. The postoperative MRI shows a reorganization of the posterior cruciate ligament into a physiological ligament appearance., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme. All rights reserved.)
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- 2024
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164. The Surgical Treatment of a Bimalleolar Ankle Fracture - Tips and Tricks.
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Mayr J, Schramm S, Renner N, Perl M, and Palm HG
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The ankle fracture - the most common fracture of the lower extremities - is usually due to pro- and supination trauma and is commonly challenging for junior doctors of orthopaedics and traumatology. To accomplish sufficient surgical results, it is necessary to have surgical experience, not only because of the surrounding fragile soft tissue, but also due to the specific anatomical structures surrounding the ankle joint and the postsurgical biomechanical stress to osteosynthesis. In the following video, the most relevant steps of surgery as well as some useful tips and tricks are mentioned. The intention of the video is to convey to junior orthopaedic surgeons the most important surgical steps for their clinical daily routine., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)
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- 2024
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165. [The pararectus approach: surgical procedure for acetabular fractures].
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von Rüden C, Brand A, and Perl M
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- Humans, Aged, Acetabulum injuries, Treatment Outcome, Fracture Fixation, Internal methods, Fractures, Bone surgery, Spinal Fractures
- Abstract
Objective: The pararectus approach was rediscovered several years ago for pelvic surgery and described as an alternative approach especially for the treatment of acetabular fractures of the anterior column involving the quadrilateral plate., Indications: For optimal visualization of acetabular fractures involving the quadrilateral plate, fractures of the anterior wall and anterior column, anterior column/posterior hemitransverse fractures, and fractures with central impression of dome fragments, the pararectus approach has proven to be a useful access., Contraindications: The pararectus approach is not used for posterior column fractures, posterior wall fractures, combined posterior wall and posterior column fractures, transverse fractures with displaced posterior column or in combination with posterior wall fractures, and T‑fractures with displaced posterior column or in combination with posterior wall fractures., Surgical Technique: The entire pelvic ring, including the quadrilateral plate, can be accessed via the pararectus approach. The choice of the correct surgical window depends on the fracture location and the requirements of fracture reduction., Postoperative Management: In general, partial weight-bearing should be maintained for 6 weeks, although earlier weight-bearing release may be possible if necessary, depending on fracture pattern and osteosynthesis. Particularly in geriatric patients, partial weight-bearing is often not possible, so that early and often relatively uncontrolled full weight-bearing has to be accepted., Results: In a comparative gait analysis between patients following surgical stabilization of an isolated unilateral acetabular fracture through the pararectus approach and healthy subjects, sufficient stability and motion function of the pelvis and hip during walking was already evident in the early postoperative phase., (© 2023. The Author(s).)
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- 2023
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166. Radial head and neck fractures in children and adolescents.
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Kalbitz M, Lackner I, Perl M, and Pressmar J
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Background: Radial head and neck fractures are a rare entity in pediatric patients. Due to specific characteristics of the blood supply and remodeling potential, the correct diagnosis and initiation of appropriate therapy are crucial for the outcome. Therefore, the aim of this retrospective observational study was to present the outcome of a series of pediatric patients with radial head and neck fractures., Methods: In total, 67 pediatric and adolescent patients with a fracture of the proximal radius admitted to a Level I Trauma Center (Germany) between 2005 and 2017 were included in this retrospective observational study. Patients were stratified in accordance with the classification of Judet modified by Metaizeau and with the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF)., Results: AO-PCCF fracture type of proximal radius was age-dependent. Epiphyseal axis angle and displacement angle correlated significantly. Fractures treated with a K-wire or embrochage centromedullaire elastique stable (ECMES) presented higher displacement angles. The duration of callus formation was dependent on both the reduction technique and fracture displacement. The range of motion after complete fracture consolidation was dependent on the Metaizeau type and reduction technique but independent of the duration of immobilization and physical therapy., Conclusion and Clinical Relevance: Both the epiphyseal axis and displacement angle are suitable for measuring the initial fracture displacement in radiographs. Consolidation is dependent on the initial displacement and reduction technique. The mini-open approach leads to a worse reduction result, later callus formation, and a more restricted range of motion in terms of pronation. Furthermore, the range of motion at follow-up is independent of the duration of immobilization and physiotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Kalbitz, Lackner, Perl and Pressmar.)
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- 2023
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167. Biomechanical comparison of acetabular fracture fixation with stand-alone THA or in combination with plating.
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Wenzel L, Sandriesser S, Glowalla C, Gueorguiev B, Perl M, Stuby FM, Augat P, and Hungerer S
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- Acetabulum injuries, Acetabulum surgery, Biomechanical Phenomena, Fracture Fixation, Internal methods, Humans, Arthroplasty, Replacement, Hip methods, Fractures, Bone surgery, Hip Fractures surgery, Spinal Fractures surgery
- Abstract
Purpose: A common surgical treatment in anterior column acetabular fractures with preexisting osteoarthritis is THA, which is commonly combined with plate osteosynthesis. Implantation of a solitary revision cup cranially fixed to the os ilium is less common. The purpose of this study was to compare the stabilization of anterior column acetabular fractures fixed with a cranial socket revision cup with flange and iliac peg or with a suprapectineal plate osteosynthesis combined with an additional revision cup., Methods: In 20 human hemipelves, an anterior column fracture was stabilized by either a cranial socket revision cup with integrated flange (CF = Cup with Flange) or by a suprapectineal plate combined with a revision cup (CP = Cup and Plate). Each specimen was loaded under a stepwise increasing dynamic load protocol. Initial construct stiffness, interfragmentary movements along the fracture line, as well as femoral head movement in relation to the acetabulum were analyzed., Results: Both groups showed comparable initial construct stiffness (CP: 3180 ± 1162 N/mm and CF: 3754 ± 668 N/mm; p = 0.158). At an applied load of 1400 N, interfragmentary movements at the acetabular (p = 0.139) and the supraacetabular region (p = 0.051) revealed comparable displacement for both groups and remained below 1 mm. Femoral head movement in relation to the acetabulum also remained below 1 mm for both test groups (p = 0.260)., Conclusion: From a biomechanical point of view, both surgical approaches showed comparable fracture reduction in terms of initial construct stiffness and interfragmentary movement. The potential benefit of the less-invasive cranial socket revision cup has to be further investigated in clinical studies., (© 2022. The Author(s).)
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- 2022
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168. Early biomechanical outcome in patients with acetabular fractures treated using the pararectus approach: a gait and stair climb analysis study.
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Brand A, von Rüden C, Probst C, Wenzel L, Augat P, and Perl M
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- Adult, Biomechanical Phenomena, Gait, Humans, Knee Joint, Middle Aged, Treatment Outcome, Hip Fractures surgery, Spinal Fractures surgery
- Abstract
Purpose: Patients with surgically treated acetabular fractures using extensive dissection of hip muscles demonstrate an incomplete biomechanical recovery and limited joint mobility during movement. The purpose of this study was to evaluate the early biomechanical outcome in a series of patients with acetabular fractures treated using the less invasive anatomical pararectus approach., Methods: Eight patients (48 ± 14 years, BMI 25.8 ± 3 kg/m
2 ) were investigated 3.8 ± 1.3 months after surgery and compared to matched controls (49 ± 13 years, BMI 26 ± 2.8 kg/m2 ). Trunk and lower extremity kinematics and kinetics during gait and stair climb were calculated. SF-12 and the Merle d'Aubigné score were used for functional evaluation. Statistical analysis was conducted using Mann-Whitney test and Student's t test. Effect sizes were calculated using Cohen's d., Results: No group differences for lower extremity kinematics during walking and stair climbing were found. During walking, patients showed significant reductions (p < 0.05) of the vertical ground reaction force (8%) and knee and hip extension moments (29 and 27%). Ipsilateral trunk lean was significantly increased by 3.1° during stair descend while reductions of vertical ground reaction force were found for stair ascend (7%) and descend (20%). Hip extension moment was significantly reduced during stair descend by 37%. Patients revealed acceptable SF-12 physical and mental component outcomes and a good rating for the Merle d'Aubigné score (15.9 ± 1.7)., Conclusion: Patients showed some biomechanical restrictions that can be related to residual deficits in weight bearing capacity and strength of the hip muscles. In contrast, an immediate recovery of mobility was achieved by preserving lower extremity and pelvic movement. Therefore, the pararectus approach can serve as a viable strategy in the surgical treatment of acetabular fractures., Clinical Trial: Trial registration number DRKS00011308, 11/14/2016, prospectively registered., (© 2021. The Author(s).)- Published
- 2022
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169. Risk Factors for Failure in Conservatively Treated Osteoporotic Vertebral Fractures: A Systematic Review.
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Scheyerer MJ, Spiegl UJA, Grueninger S, Hartmann F, Katscher S, Osterhoff G, Perl M, Pumberger M, Schmeiser G, Ullrich BW, and Schnake KJ
- Abstract
Study Design: Systematic review., Objectives: Osteoporosis is one of the most common diseases of the elderly, whereby vertebral body fractures are in many cases the first manifestation. Even today, the consequences for patients are underestimated. Therefore, early identification of therapy failures is essential. In this context, the aim of the present systematic review was to evaluate the current literature with respect to clinical and radiographic findings that might predict treatment failure., Methods: We conducted a comprehensive, systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) checklist and algorithm., Results: After the literature search, 724 potentially eligible investigations were identified. In total, 24 studies with 3044 participants and a mean follow-up of 11 months (range 6-27.5 months) were included. Patient-specific risk factors were age >73 years, bone mineral density with a t-score <-2.95, BMI >23 and a modified frailty index >2.5. The following radiological and fracture-specific risk factors could be identified: involvement of the posterior wall, initial height loss, midportion type fracture, development of an intravertebral cleft, fracture at the thoracolumbar junction, fracture involvement of both endplates, different morphological types of fractures, and specific MRI findings. Further, a correlation between sagittal spinal imbalance and treatment failure could be demonstrated., Conclusion: In conclusion, this systematic review identified various factors that predict treatment failure in conservatively treated osteoporotic fractures. In these cases, additional treatment options and surgical treatment strategies should be considered in addition to follow-up examinations.
- Published
- 2022
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170. The role of low-grade infection in the pathogenesis of apparently aseptic tibial shaft nonunion.
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Hackl S, Keppler L, von Rüden C, Friederichs J, Perl M, and Hierholzer C
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- Fracture Healing, Humans, Retrospective Studies, Treatment Outcome, Fractures, Open, Fractures, Ununited surgery, Tibial Fractures surgery
- Abstract
Purpose: Aim of this study was to determine the rate of low-grade infection in patients with primarily as aseptic categorized tibial shaft nonunion and lack of clinical signs of infection., Methods: In a retrospective study between 2006 and 2013, all patients who underwent revision surgery for treatment of tibial shaft nonunion without clinical evidence of infection were assessed. Bacterial cultures harvested during nonunion revision, C-reactive protein (CRP) and/or white blood cell (WBC) values at hospital admission, outcome, and epidemiological data were analyzed., Results: In 88 patients with tibial shaft nonunion without any clinical signs of infection, bacterial samples remained negative in 51 patients. In 37 patients, microbiological diagnostic studies after long-term culturing demonstrated positive bacterial cultures whereas after short-term culturing for 2 days only 17 positive cultures were observed. In 12 cases a mixed culture with 2.3 different bacteria on average was detected. Among patients with negative bacterial cultures bone healing was achieved after 13.2 months. Nonunion with positive bacterial cultures required 19 (range 2-42) months until osseous healing (p = 0.009). Furthermore, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing (2.9 ± 0.5 vs. 1.3 ± 0.1 additional procedure; (p = 0.003). Hematological studies carried out before surgical intervention did not demonstrate significant differences in CRP values (negative vs. positive cultures: 0.3 (range 0.3-2.8) mg/dl vs. 0.5 (range 0.3-5.7) mg/dl (p = 0.181) and in WBC values (negative vs. positive cultures: 7.4 (range 3.5-11.9) /nl vs. 7.3 (range 3.7-11.1) /nl (p = 0.723). Limitations of this study may include the varying amount of the at least four samples for microbiological diagnostics as well as the circumstance that for diagnosing low-grade infection swabs and tissue samples were included in this evaluation as being equivalent., Conclusion: The pathogenesis of nonunion may originate from low-grade infection even in patients without clinical signs of infection. In addition, nonunion with positive bacterial cultures require statistically more surgical revisions to achieve healing. Therefore, during any revision surgery, multiple bacterial samples are intended to be harvested for long-term culturing. Particularly, in tibial shaft nonunion following Gustilo-Anderson type III open fractures, low-grade infection should be suspected., Trial Registration Number: DRKS00014657., Date of Registration: 04/26/2018 retrospectively registered., (Copyright © 2021. Published by Elsevier Ltd.)
- Published
- 2021
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171. Complement Factor C5a Inhibits Apoptosis of Neutrophils-A Mechanism in Polytrauma?
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Ehrnthaller C, Braumüller S, Kellermann S, Gebhard F, Perl M, and Huber-Lang M
- Abstract
Life-threatening polytrauma results in early activation of the complement and apoptotic system, as well as leukocytes, ultimately leading to the clearance of damaged cells. However, little is known about interactions between the complement and apoptotic systems in PMN (polymorphonuclear neutrophils) after multiple injuries. PMN from polytrauma patients and healthy volunteers were obtained and assessed for apoptotic events along the post-traumatic time course. In vitro studies simulated complement activation by the exposure of PMN to C3a or C5a and addressed both the intrinsic and extrinsic apoptotic pathway. Specific blockade of the C5a-receptor 1 (C5aR1) on PMN was evaluated for efficacy to reverse complement-driven alterations. PMN from polytrauma patients exhibited significantly reduced apoptotic rates up to 10 days post trauma compared to healthy controls. Polytrauma-induced resistance was associated with significantly reduced Fas-ligand (FasL) and Fas-receptor (FasR) on PMN and in contrast, significantly enhanced FasL and FasR in serum. Simulation of systemic complement activation revealed for C5a, but not for C3a, a dose-dependent abrogation of PMN apoptosis in both intrinsic and extrinsic pathways. Furthermore, specific blockade of the C5aR1 reversed C5a-induced PMN resistance to apoptosis. The data suggest an important regulatory and putative mechanistic and therapeutic role of the C5a/C5aR1 interaction on PMN apoptosis after polytrauma.
- Published
- 2021
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172. [Minimally invasive stabilization of thoracolumbar osteoporotic fractures].
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Schnake KJ, Scheyerer MJ, Spiegl UJA, Perl M, Ullrich BW, Grüninger S, Osterhoff G, Katscher S, and Sprengel K
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- Bone Cements, Humans, Lumbar Vertebrae, Thoracic Vertebrae, Treatment Outcome, Kyphoplasty, Osteoporotic Fractures, Pedicle Screws, Spinal Fractures
- Abstract
Background: Minimally invasive stabilization of thoracolumbar osteoporotic fractures (OF) in neurologically intact patients is well established. Various posterior and anterior surgical techniques are available. The OF classification and OF score are helpful for defining the indications and choice of operative technique., Objective: This article gives an overview of the minimally invasive stabilization techniques, typical complications and outcome., Material and Methods: Selective literature search and description of surgical techniques and outcome., Results: Vertebral body augmentation alone can be indicated in painful but stable fractures of types OF 1 and OF 2 and to some extent for type OF 3. Kyphoplasty has proven to be an effective and safe procedure with a favorable clinical outcome. Unstable fractures and kyphotic deformities (types OF 3-5) should be percutaneously stabilized from posterior. The length of the pedicle screw construct depends on the extent of instability and deformity. Bone cement augmentation of the pedicle screws is indicated in severe osteoporosis but increases the complication rate. Restoration of stability of the anterior column can be achieved through additional vertebral body augmentation or rarely by anterior stabilization. Clinical and radiological short and mid-term results of the stabilization techniques are promising; however, the more invasive the surgery, the more complications occur., Conclusion: Minimally invasive stabilization techniques are safe and effective. The specific indications for the individual procedures are guided by the OF classification and the individual clinical situation of the patient.
- Published
- 2020
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173. The Pararectus Approach in Acetabular Surgery: Radiological and Clinical Outcome.
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Wenzel L, von Rüden C, Thannheimer A, Becker J, Brand A, Augat P, and Perl M
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- Acetabulum diagnostic imaging, Acetabulum surgery, Adolescent, Adult, Aged, Aged, 80 and over, Female, Fracture Fixation, Internal, Humans, Male, Middle Aged, Radiography, Retrospective Studies, Treatment Outcome, Young Adult, Fractures, Bone diagnostic imaging, Hip Fractures
- Abstract
Objectives: To evaluate radiological fracture reduction and clinical results using the pararectus approach in complex acetabular fractures involving the anterior column., Design: Retrospective database analysis of prospectively collected data., Setting: Level 1 trauma center., Patients/participants: 61 patients (48 male and 13 female) with a median age of 55 (range 17-91) years were included. According to the chosen surgical approach, they were divided into 2 groups. The P-group included 43 patients, among them 32 male and 11 female patients with a median age of 55 (range 17-90) years. Eighteen patients [16 male, 2 female; median age: 53 (range 23-91) years] were treated through the ilioinguinal approach (I-group)., Intervention: Anterior surgical procedures through the pararectus or the ilioinguinal approach., Main Outcome Measured: Reduction results were rated according to the modified Matta criteria using a measurement protocol of hip joint gaps and steps in computed tomography scans. Operation time, complications, and clinical outcomes median one year postoperatively were compared., Results: In the pararectus group reduction was anatomical in 21 out of 40 analyzed patients (52.5%), imperfect in 11 patients (27.5%), and poor in 8 patients (20%). The mean joint step reduction was 3.7 mm, and the mean joint gap reduction was 12.1 mm. In the ilioinguinal group reduction was anatomical in 9 out of 18 patients (50%), imperfect in 4 patients (22%), and poor in 5 patients (28%). The mean joint step reduction was 1 mm, and the mean joint gap reduction was 7 mm. Operation time was significantly shorter in the P-group (mean: 49 minutes; P < 0.001)., Conclusions: This study indicates that acetabular fracture reduction using the pararectus approach is at least comparable with the ilioinguinal approach independent of patients' age. A relevant advantage of the pararectus approach was seen in a significantly shorter operation time., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
- Published
- 2020
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174. The pararectus approach for internal fixation of acetabular fractures involving the anterior column: evaluating the functional outcome.
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von Rüden C, Wenzel L, Becker J, Thannheimer A, Augat P, Woltmann A, Bühren V, and Perl M
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- Adolescent, Adult, Aged, Aged, 80 and over, Bone Plates, Female, Fracture Fixation, Internal methods, Humans, Male, Middle Aged, Open Fracture Reduction, Operative Time, Postoperative Period, Retrospective Studies, Trauma Centers, Treatment Outcome, Young Adult, Acetabulum surgery, Hip Fractures surgery
- Abstract
Introduction: Aim of this retrospective analysis of prospectively collected data was to evaluate the functional mid-term outcome two years after open reduction and internal fixation of acetabular fractures involving the anterior column with affection of the quadrilateral plate using the pararectus approach on a large cohort., Method: Fifty-two patients (12 female, 40 male) with a median age of 55 (range 18-90) years and displaced acetabular fractures involving the anterior column were surgically treated in a single level I trauma centre between July 2012 and February 2016 using the pararectus approach. Thirty-four patients (8 female and 26 male) with a median age of 58 (range 20-85) years were available for complete clinical follow-up at regular intervals, finally 24 months post-operatively. Functional outcome was evaluated according to modified Merle d'Aubigné score, Lower Extremity Functional Scale, WOMAC, and SF-36., Results: Range of time between trauma and surgical treatment was three (range 0-19) days. Operation time was 140 (range 60-240) minutes, and duration of hospital treatment was 19 (range 7-38) days. Functional results in 34 patients available for final follow-up demonstrated 68 points (median; range 39-80) according to the Lower Extremity Functional Scale, 6% according to the WOMAC (mean; SD ± 14.5%), and 69% (mean; SD ± 20.1%) according to the SF-36. The modified Merle d'Aubigné score was excellent in 22 patients, good in eight patients, and fair in four patients., Discussion/conclusion: Based on the good to excellent functional mid-term follow-up results of this study, the pararectus approach can be recommended as sufficient alternative single access to address displaced acetabular fractures involving the anterior column, independent of patients' age.
- Published
- 2019
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175. Alcohol Binge Reduces Systemic Leukocyte Activation and Pulmonary PMN Infiltration After Blunt Chest Trauma and Hemorrhagic Shock.
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Franz N, Dieteren S, Köhler K, Mörs K, Sturm R, Marzi I, Perl M, Relja B, and Wagner N
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- Animals, Apoptosis drug effects, Disease Models, Animal, Ethanol therapeutic use, Female, Inflammation drug therapy, Leukocytes drug effects, Lung pathology, Rats, Rats, Inbred Lew, Thoracic Injuries pathology, Wounds, Nonpenetrating, Binge Drinking, Ethanol pharmacology, Lymphocyte Activation drug effects, Neutrophil Infiltration drug effects, Shock, Hemorrhagic drug therapy, Thoracic Injuries drug therapy
- Abstract
Blunt chest (thoracic) trauma (TxT) and hemorrhagic shock (HS)-induced local and systemic inflammation with increased neutrophil activity often result in an impaired organ function. Next to increasing the trauma risk, binge drinking causes anti-inflammatory effects due to immunomodulatory properties of alcohol (ethanol, EtOH). The impact of clinically relevant acute binge drinking scenario on local and systemic inflammatory changes, notably regarding the activity and longevity of leukocytes, has been analyzed in a combinatory trauma model of TxT + H/R. Twenty-four female Lewis rats (190-240 g) received alcohol (5 g/kg, 30%) or saline gavage. Two hours after alcohol gavage, TxT with subsequent HS (60 min) and resuscitation (TxT + H/R) were induced. Sham-operated animals underwent surgical procedures. Bronchoalveolar lavage fluid (BAL), lung tissue, and blood were harvested 2 h after resuscitation. Pulmonary infiltration with PMN, IL-6 gene expression, systemic PMN activation, neutrophil and monocyte apoptosis (caspase-3/7), and pyroptosis/inflammasome activation (caspase-1) were evaluated. Lung damage was evaluated by hematoxylin-eosin (H/E) staining and determination of the total protein content in BAL (ANOVA, p < 0.05 was significant). TxT + H/R-induced increases in IL-6, PMN infiltration and BAL-protein concentration were significantly reduced by EtOH; however, histological morphology changes after trauma remained unaltered by EtOH. TxT + H/R-induced systemic leukocyte activation (increased CD11b and CD31, reduced CD62L expression) as well as inflammasome activation in monocytes were significantly diminished by EtOH. Apoptosis was prolonged only in PMN after TxT + H/R and was further prolonged by EtOH, an effect that was observed in sham animals as a trend as well. Acute EtOH exposure inhibits the activation of circulating leukocytes after trauma compared to controls. These EtOH-driven systemic changes may be associated with reduced infiltration with PMN after trauma as well as reduced local tissue inflammation.
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- 2019
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176. Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1.
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Relja B, Wagner N, Franz N, Dieteren S, Mörs K, Schmidt J, Marzi I, and Perl M
- Subjects
- Animals, Disease Models, Animal, Gene Expression Regulation, HMGB1 Protein metabolism, Humans, Lung physiology, NF-kappa B metabolism, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Rats, Rats, Inbred Lew, Signal Transduction drug effects, Tumor Necrosis Factor-alpha metabolism, Acute Lung Injury drug therapy, Anti-Inflammatory Agents therapeutic use, Lung drug effects, Pyruvates therapeutic use, Shock, Hemorrhagic diet therapy, Thoracic Injuries drug therapy
- Abstract
Objective: After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R., Methods: Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses., Results: EP significantly improved pO
2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections., Conclusions: Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism., (Copyright © 2017 Elsevier GmbH. All rights reserved.)- Published
- 2018
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177. [Polytrauma Management - Treatment of Severely Injured Patients in ER and OR].
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von Rüden C, Bühren V, and Perl M
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- Advanced Trauma Life Support Care, Air Ambulances, Algorithms, Early Medical Intervention, Emergency Medical Services, Germany, Humans, Imaging, Three-Dimensional, Interdisciplinary Communication, Intersectoral Collaboration, Male, Middle Aged, Multidetector Computed Tomography, Multiple Trauma classification, Multiple Trauma diagnosis, Multiple Trauma mortality, Shock, Traumatic classification, Shock, Traumatic diagnosis, Shock, Traumatic mortality, Shock, Traumatic therapy, Survival Rate, Tomography, Spiral Computed, Trauma Centers, Ultrasonography, Emergency Service, Hospital, Multiple Trauma therapy, Operating Rooms
- Abstract
The adequate treatment of severely injured patients is challenging and can only be successfully executed when it starts at the accident site and is continued in all treatment phases including the early rehabilitation phase. Treatment should be performed by an interdisciplinary team guided by a trauma surgeon in order to adequately manage the severe injuries some of which are life-threatening. Treatment of polytrauma patients is a key task of certified trauma centers and must follow standardized guidelines. For a successful therapy of severely injured patients lifetime training at regular intervals in well-established polytrauma concepts is a mandatory requirement., Competing Interests: Interessenkonflikt: Die Autoren geben an, dass keine Interessenkonflikte vorliegen., (Georg Thieme Verlag KG Stuttgart · New York.)
- Published
- 2017
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178. Acute Alcohol Binge Deteriorates Metabolic and Respiratory Compensation Capability After Blunt Chest Trauma Followed by Hemorrhagic Shock-A New Research Model.
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Wagner N, Franz N, Dieteren S, Perl M, Mörs K, Marzi I, and Relja B
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- Acidosis blood, Acidosis chemically induced, Acute Disease, Animals, Arterial Pressure drug effects, Binge Drinking complications, Binge Drinking metabolism, Blood Gas Analysis, Central Nervous System Depressants blood, Disease Models, Animal, Ethanol blood, Female, Hydrogen-Ion Concentration, Rats, Rats, Inbred Lew, Resuscitation, Shock, Hemorrhagic complications, Shock, Hemorrhagic metabolism, Thoracic Injuries complications, Thoracic Injuries metabolism, Wounds, Nonpenetrating complications, Wounds, Nonpenetrating metabolism, Binge Drinking physiopathology, Respiratory Mechanics drug effects, Shock, Hemorrhagic physiopathology, Thoracic Injuries physiopathology, Wounds, Nonpenetrating physiopathology
- Abstract
Background: The clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock with resuscitation (H/R) in alcohol-intoxicated rats., Methods: Depending on group allocation, 12 (subacute) or 2 (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol [EtOH]) or saline (NaCl) followed by TxT, hemorrhagic shock (35 ± 3 mm Hg), and resuscitation (TxT + H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined., Results: Subacute and acute EtOH group exhibited lower baseline mean arterial blood pressure values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed-out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups, a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO
2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group., Conclusions: This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality., (Copyright © 2017 by the Research Society on Alcoholism.)- Published
- 2017
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179. [Young doctors wanted - but how many? : Current data on the number of aspiring specialist doctors in orthopedics and trauma surgery in Germany].
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Münzberg M, Sotow B, Hoffmann R, Kladny B, Perl M, Stange R, and Mutschler M
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- Adult, Female, Germany, Humans, Male, Sex Distribution, Young Adult, Career Choice, Health Workforce statistics & numerical data, Internship and Residency statistics & numerical data, Needs Assessment statistics & numerical data, Orthopedics, Personnel Staffing and Scheduling statistics & numerical data, Traumatology
- Abstract
There is an ongoing discussion about demographic change, a possible lack of young doctors and its impact on the healthcare system in Germany. Up to now, no valid data has been available on the exact numbers of residents in orthopedics and trauma surgery. Therefore, the aim of this study was to determine the actual number of residents in Germany in 2013/2014. We generated a database with all eligible providers of postgraduate training in orthopedics and trauma surgery in Germany. All of these were asked to fill out a questionnaire about the number of trainees, their gender and year of training. We achieved an 80% response rate (1509 questionnaires). Within these institutions, 4310 residents are trained. For Germany, this means an estimated number of about 5300 residents in the year 2013/2014. Ninety percent of postgraduate training is performed within a hospital and one-third of the residents are female. Looking at the expected number of doctors who will retire within the next five years, there seems to be enough young doctors to fill the gap. However, by 2040, an increased demand for othopedic and trauma surgeons is experted. Thus, we recommend centrally analyzing and coordinating the demand of residents in orthopedics and trauma surgery in Germany.
- Published
- 2017
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180. Divergent Effects of Neutrophils on Fas-Induced Pulmonary Inflammation, Apoptosis, and Lung Damage.
- Author
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Bruns B, Hönle T, Kellermann P, Ayala A, and Perl M
- Subjects
- Animals, Apoptosis physiology, Bronchoalveolar Lavage Fluid, Chemokine CCL2 metabolism, Enzyme-Linked Immunosorbent Assay, Fas Ligand Protein metabolism, In Situ Nick-End Labeling, Inflammation metabolism, Interleukin-6 metabolism, Lung cytology, Lung metabolism, Male, Mice, Mice, Inbred C57BL, p38 Mitogen-Activated Protein Kinases metabolism, Neutrophils metabolism, Pneumonia metabolism, fas Receptor metabolism
- Abstract
Pulmonary Fas activation is essential in the pathogenesis of the acute respiratory distress syndrome. It remains unclear whether Fas-induced lung injury is dependent on neutrophils or mainly triggered by epithelial cell apoptosis. The contribution of lung epithelial cells (LEC) and alveolar macrophages (AM) remains elusive.Mice were neutrophil reduced prior to intratracheal instillation of Fas-activating (Jo2) or isotype antibody for 6 or 18 h. LEC and AM were incubated with Jo2 and in the presence of nuclear factor kappa B, p-38 mitogen activated protein kinase (p38MAPK), or extracellular signal regulating kinase 1/2 (ERK1/2) inhibitors. Cytokines were assessed by cytometric bead array or ELISA. Apoptosis was quantified via active caspase-3 Western blotting and Terminal Deoxynucleotide Transferase dUTP Nick End Labeling (TUNEL). Lung injury was assessed by bronchoalveolar lavage fluid (BALF) protein concentration and lung histology.KC, IL-6, and MCP-1 were markedly increased in lung, plasma, and BALF 18 h after Jo2 in the presence of neutrophils; in neutrophil-reduced mice lungs, MCP-1, but not KC or IL-6, was even further enhanced. Six hours after Jo2, BALF protein was markedly increased only in the presence of neutrophils. Apoptosis remained unaffected by neutrophil reduction. AM released MCP-1 and underwent apoptosis at lower concentrations of Jo2 than LEC. Inhibition of p38MAPK significantly increased, while inhibition of ERK1/2 reduced AM and LEC apoptosis.In conclusion, neutrophils are a necessary component of Fas-induced lung damage, while not affecting lung apoptosis directly per se. LEC display higher resistance to Fas-triggered inflammation and apoptosis than AM.
- Published
- 2017
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181. Pre- or post-treatment with ethanol and ethyl pyruvate results in distinct anti-inflammatory responses of human lung epithelial cells triggered by interleukin-6.
- Author
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Relja B, Omid N, Schaible A, Perl M, Meier S, Oppermann E, Lehnert M, and Marzi I
- Subjects
- Cell Adhesion drug effects, Cell Line, Tumor, Cell Survival drug effects, Enzyme-Linked Immunosorbent Assay, Humans, Intercellular Adhesion Molecule-1 metabolism, Interleukin-6 analysis, Interleukin-8 analysis, Interleukin-8 metabolism, Leukocytes, Mononuclear cytology, Leukocytes, Mononuclear immunology, Lung Neoplasms metabolism, Lung Neoplasms pathology, Neutrophils cytology, Neutrophils immunology, Ethanol pharmacology, Gene Expression Regulation, Neoplastic drug effects, Interleukin-6 pharmacology, Pyruvates pharmacology
- Abstract
Increased local and systemic levels of interleukin (IL)-6 are associated with inflammatory processes, including neutrophil infiltration of the alveolar space, resulting in lung injury. Our previous study demonstrated the beneficial anti-inflammatory effects of acute exposure to ethanol (EtOH) in an acute in vivo model of inflammation. However, due to its side-effects, EtOH is not used clinically. In the present study, the effects of EtOH and ethyl pyruvate (EtP) as an alternative anti-inflammatory drug prior to and following application of an IL-6 stimulus on cultured A549 lung epithelial cells were compared, and it was hypothesized that treatment with EtOH and EtP reduces the inflammatory potential of the A549 cells. Time- and dose-dependent release of IL-8 from the A549 cells was observed following stimulation with IL-6. The release of IL-8 from the A549 cells was assessed following treatment with EtP (2.5-10 mM), sodium pyruvate (NaP; 10 mM) or EtOH (85-170 mM) for 1, 24 or 72 h, prior to and following IL-6 stimulation. The adhesion capacities of neutrophils to the treated A549 cells, and the expression levels of cluster of differentiation (CD)54 by the epithelial cells were measured. Treatment of the A549 cells with either EtOH or EtP significantly reduced the IL-6-induced release of IL-8. This effect was observed in the pre- and post-stimulatory conditions, which is of therapeutic importance. Similar data was revealed regarding the IL-6-induced neutrophil adhesion to the treated A549 cells, in which pre- and post-treatment with EtOH or EtP decreased the adhesion capacity, however, the results were dependent on the duration of incubation. Incubation durations of 1 and 24 h decreased the adhesion rates of neutrophils to the stimulated A549 cells, however, the reduction was only significant at 72 h post-treatment. The expression of CD54 was reduced only following treatment for 24 h with either EtOH or EtP, prior to IL-6 stimulation. Therefore, EtOH and EtP reduced the inflammatory response of lung epithelial cells, and the potential of EtP to mimic EtOH was observed in the pre- and post-treatment conditions.
- Published
- 2015
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182. Accuracy of screw placement and radiation dose in navigated dorsal instrumentation of the cervical spine: a prospective cohort study.
- Author
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Kraus M, von dem Berge S, Perl M, Krischak G, and Weckbach S
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- Adult, Aged, Aged, 80 and over, Cervical Vertebrae diagnostic imaging, Cohort Studies, Female, Humans, Imaging, Three-Dimensional, Male, Middle Aged, Operative Time, Prospective Studies, Radiation Dosage, Radiography, Spinal Fractures diagnostic imaging, Bone Screws, Cervical Vertebrae injuries, Cervical Vertebrae surgery, Spinal Fractures surgery, Spinal Fusion methods, Surgery, Computer-Assisted methods
- Abstract
Background: Dorsal cervical spinal fusion is a challenging procedure in fracture fixation. There is limited information in the literature about computer navigation using lateral mass screws in cases of spinal trauma., Methods: Retrospective analysis of a prospective database covering an 8 year period. All patients who received a dorsal spinal fusion due to a fracture of the cervical spine were included. Outcome parameters were screw accuracy, duration of surgery, the radiation emitted and intra-/postoperative complications., Results: Sixteen patients, who received 67 screws (44 navigated vs 23 conventionally inserted screws) were included. Three-dimensional (3D)-based computer navigation prolonged the duration of surgery but helped to reduce the radiation emitted and led to significantly increased accuracy of screw positioning., Conclusion: Computer navigation can increase the accuracy of lateral mass screws in spinal trauma. It prolongs the surgical procedure but reduces the emission of radiation significantly., (Copyright © 2013 John Wiley & Sons, Ltd.)
- Published
- 2014
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183. Cathepsin D is released after severe tissue trauma in vivo and is capable of generating C5a in vitro.
- Author
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Huber-Lang M, Denk S, Fulda S, Erler E, Kalbitz M, Weckbach S, Schneider EM, Weiss M, Kanse SM, and Perl M
- Subjects
- Biocatalysis drug effects, Blotting, Western, Cathepsin D antagonists & inhibitors, Cathepsin D blood, Chemotaxis, Leukocyte, Complement Activation, Enzyme-Linked Immunosorbent Assay, Humans, Neutrophils cytology, Neutrophils metabolism, Pepstatins pharmacology, Protease Inhibitors pharmacology, Time Factors, Wounds and Injuries blood, Wounds and Injuries enzymology, Cathepsin D metabolism, Complement C5 metabolism, Complement C5a metabolism, Wounds and Injuries metabolism
- Abstract
In response to severe tissue trauma several danger sensing and signalling cascades are activated, including the complement and the apoptosis systems. In polytrauma patients, both the early activation of the complement cascade with an excessive generation of the potent anaphylatoxin C5a and the induction of apoptosis have been shown to modulate the post-traumatic immune response. However, little is known about a direct interaction between the complement and apoptosis systems after severe tissue trauma. Therefore the focus of the present study was to elucidate the interplay between the central complement component C5 and the pro-apoptotic aspartic protease cathepsin D. In vivo, the cathepsin D plasma concentration of multiple injured patients was markedly increased when compared to healthy volunteers. In vitro incubation of C5 with cathepsin D resulted in a concentration- and time-dependent generation of C5a, which was inhibited by the aspartate protease inhibitor pepstatin A. Immunoblotting and sequencing analysis indicated that the C5 cleavage product represents the native form of human C5a, also exhibiting chemotactic activity for human neutrophils. In conclusion, these data show for the first time that cathepsin D is increased in plasma early after severe tissue injury. Furthermore, the results provide in vitro evidence of cleavage of C5 by an aspartic protease with subsequent generation of functional C5a, which represents a new path of complement activation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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184. Granzyme B: a new crossroad of complement and apoptosis.
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Perl M, Denk S, Kalbitz M, and Huber-Lang M
- Subjects
- Humans, Apoptosis immunology, Complement System Proteins immunology, Granzymes immunology, Multiple Trauma immunology, Signal Transduction immunology
- Abstract
In response to severe tissue trauma, several "molecular danger" sensing and signaling pathways are activated, especially the complement and the apoptosis cascade. Although possible crossroads between both systems have been proposed, little is known about the underlying molecular interactions. In this study a new interaction interface is presented for C3a and C5a generation by the pro-apoptotic factor granzyme B. In vitro incubation of the central human complement components C3 and C5 with the serine protease granzyme B resulted in a concentration-dependent production of the anaphylatoxins C3a and C5a. The so generated anaphylatoxin C5a was chemotactic active for isolated human neutrophils. In a translational approach, intracellular granzyme B concentration in leukocytes was determined early after severe tissue trauma. In comparison to healthy volunteers, multiple injured patients (less than one hour after trauma, Injury Severity Score > 18, n = 5) presented a significant increase in granzmye B levels in neutrophils and lymphocytes. Thus, tissue trauma is associated with early activation of both, the complement and apoptosis system. The present data suggest a new form of interaction between the complement and the apoptosis system on the level of granzyme B that is capable to generate C3a and C5a independently of the established complement proteases.
- Published
- 2012
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185. Is the function of alveolar macrophages altered following blunt chest trauma?
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Liener UC, Perl M, Huber-Lang MS, Seitz DH, Brückner UB, Gebhard F, and Knöferl MW
- Subjects
- Animals, Chemotaxis, Disease Models, Animal, Macrophages, Alveolar metabolism, Male, Phagocytosis, Rats, Rats, Wistar, Respiratory Burst, Wounds, Nonpenetrating immunology, Cytokines immunology, Macrophages, Alveolar immunology, Thoracic Injuries immunology
- Abstract
Purpose: The purpose of this study was to characterize the local pulmonary inflammatory environment and to elucidate alterations of alveolar macrophage (AMØ) functions after blunt chest trauma., Methods: Wistar rats were subjected to blunt chest trauma. AMØ were isolated, stimulated, and cultured. Bronchoalveolar lavage (BAL) was collected. Cytokines/chemokines were quantified in the BAL and in AMØ supernatants via ELISA. AMØ phagocytic and chemotactic activity and respiratory burst capacity were assessed., Results: Following chest trauma, a significant increase of IL-1β (at 6 and 24 h) and IL-6 (at 24 h) in BAL was observed, whereas IL-10 and TNF-α concentrations were not altered. MIP-2 and CINC were substantially increased as early as 6 h and PGE2 early at 10 min, whereas BAL MCP-1 was not elevated until 24 h after trauma. MIP-2 release by AMØ isolated form trauma animals was markedly increased as early as 10 min after injury. IL-1β and IL-10 exhibited a late increase at 24 h. AMØ TNF-α release was increased at 6 h. At 6 or 24 h, AMØ from trauma animals incorporated significantly more opsonized latex beads than their sham controls, and their chemotactic activity was substantially enhanced at 24 h. AMØ oxidative burst capacity remained largely unchanged., Conclusions: Already very early after chest trauma, inflammatory mediators are present in the intraalveolar compartment. Additionally, AMØ are primed to release cytokines and chemokines. Blunt chest trauma also changes the phagocytic and chemotactic activity of AMØ. These functional changes of AMØ might enable them to better ward off potential pathogens in the course after trauma.
- Published
- 2011
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186. Epithelial cell apoptosis and neutrophil recruitment in acute lung injury-a unifying hypothesis? What we have learned from small interfering RNAs.
- Author
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Perl M, Lomas-Neira J, Chung CS, and Ayala A
- Subjects
- Animals, Humans, Models, Biological, RNA, Small Interfering therapeutic use, Respiratory Distress Syndrome etiology, Respiratory Distress Syndrome therapy, Apoptosis physiology, Epithelial Cells pathology, Neutrophil Infiltration physiology, RNA, Small Interfering physiology, Respiratory Distress Syndrome immunology, Respiratory Distress Syndrome pathology
- Abstract
In spite of protective ventilatory strategies, Acute Lung Injury (ALI) remains associated with high morbidity and mortality. One reason for the lack of therapeutic options might be that ALI is a co-morbid event associated with a diverse family of diseases and, thus, may be the result of distinct pathological processes. Among them, activated neutrophil- (PMN-) induced tissue injury and epithelial cell apoptosis mediated lung damage represent two potentially important candidate pathomechanisms that have been put forward. Several approaches have been undertaken to test these hypotheses, with substantial success in the treatment of experimental forms of ALI. With this in mind, we will summarize these two current hypotheses of ALI briefly, emphasizing the role of apoptosis in regulating PMN and/or lung epithelial cell responses. In addition, the contribution that Fas-mediated inflammation may play as a potential biological link between lung cell apoptosis and PMN recruitment will be considered, as well as the in vivo application of small interfering RNA (siRNA) as a novel approach to the inhibition of ALI and its therapeutic implications.
- Published
- 2008
- Full Text
- View/download PDF
187. Hydrodynamic delivery of siRNA in a mouse model of sepsis.
- Author
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Wesche-Soldato DE, Lomas-Neira J, Perl M, Chung CS, and Ayala A
- Subjects
- Animals, Disease Models, Animal, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, RNA, Small Interfering genetics, Gene Transfer Techniques, Genetic Therapy methods, RNA, Small Interfering metabolism, Sepsis therapy
- Abstract
The use of siRNA in vivo as well as in animal models has become more widespread in recent years, leading to further questions as to the best mode of delivery that will achieve optimal knockdown. While the exact mechanism of siRNA uptake at a cellular level has yet to be fully elucidated, various delivery techniques are being researched, including the use of viral vectors of shRNA, liposome encapsulations, and hydrodynamic delivery of naked siRNA. We describe the use of hydrodynamic administration as a technique to deliver, in vivo, naked siRNA constructs into experimental animals as a method of transient gene knockdown. This method may prove useful in situations where knockout animals do not exist, or to determine the effect of gene knockdown at specific time points during an experiment.
- Published
- 2008
- Full Text
- View/download PDF
188. Beneficial versus detrimental effects of neutrophils are determined by the nature of the insult.
- Author
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Perl M, Chung CS, Perl U, Biffl WL, Cioffi WG, and Ayala A
- Subjects
- Analysis of Variance, Animals, Bronchoalveolar Lavage Fluid chemistry, Cecum injuries, Cell Survival, Chemokines immunology, Cytokines immunology, Enzyme-Linked Immunosorbent Assay, Ligation, Lipopolysaccharides pharmacology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neutrophil Activation physiology, Punctures, Respiratory Distress Syndrome pathology, Sepsis immunology, Systemic Inflammatory Response Syndrome immunology, Neutrophils immunology, Respiratory Distress Syndrome immunology, Shock, Hemorrhagic immunology
- Abstract
Background: Neutrophils are thought to play pivotal roles in eliminating pathogens, and they have also been implicated in end organ dysfunction associated with systemic inflammatory response syndrome (SIRS). Because modulating neutrophil survival and function has been proposed as a therapy for sepsis, it remains critical to determine under which circumstances modulating neutrophil function is efficacious. The aim of this study was to investigate whether sustaining the presence of neutrophils activated by hemorrhagic shock (HEM) would be disadvantageous during subsequent sepsis, ie, inflammation plus infection, or systemic inflammation without infection., Study Design: Transgenic mice, overexpressing the antiapoptotic protein Bcl-2 in a myeloid restricted fashion (Bcl-2(my)), and controls (C57) were subjected to HEM, followed 24 hours thereafter either by cecal ligation and puncture to induce sepsis, or by intraperitoneal injection of lipopolysaccharide to induce SIRS. Lung injury was assessed by bronchoalveolar lavage fluid protein and histology. Lung, plasma, and liver cytokines were quantified through CBA or ELISA., Results: In sepsis, Bcl-2(my) had increased lung neutrophil and lower lung bacteria counts compared with C57. This translated into a marked early survival benefit for Bcl-2(my). There were no differences between Bcl-2(my) and C57 with respect to the degree of lung injury or lung and plasma cytokines. In contrast, in SIRS, Bcl-2(my) exhibited markedly increased acute lung injury and lung and plasma cytokines when compared with C57. Bcl-2(my) also had a profound survival disadvantage., Conclusions: Whether effects of prolonged survival of hemorrhage-primed neutrophils are beneficial or detrimental is determined by the nature of the second insult. During sepsis, prolonging neutrophil survival is beneficial, enhancing antimicrobial activity. Alternatively, during inflammation without infection, increased organ damage by long-lived neutrophils is detrimental.
- Published
- 2007
- Full Text
- View/download PDF
189. Role of Programmed Cell Death in the Immunopathogenesis of Sepsis.
- Author
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Perl M, Chung CS, Swan R, and Ayala A
- Abstract
Apoptosis is an important mechanism during the immunopathogenesis of sepsis. Early programmed cell death of lymphocytes substantially impairs innate and adaptive immunity reducing the capacity to ward off the invading pathogen. Apoptosis of parenchymal cells (e.g. in the lung, liver and gut) may also promote organ failure and death. Several experimental therapeutic strategies have now been developed to beneficially influence these mechanisms; however, their potential clinical benefit is yet to be evaluated.
- Published
- 2007
- Full Text
- View/download PDF
190. Blockade of apoptosis as a rational therapeutic strategy for the treatment of sepsis.
- Author
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Ayala A, Wesche-Soldato DE, Perl M, Lomas-Neira JL, Swan R, and Chung CS
- Subjects
- Animals, Humans, Sepsis metabolism, Sepsis pathology, Signal Transduction physiology, Apoptosis, Sepsis therapy
- Abstract
Over time it has become clear that, much like other organ systems, the function and responsiveness of the immune system is impaired during the course of sepsis and that this is a precipitous event in the decline of the critically ill patient/animal. One hypothesis put forward to explain the development of septic immune dysfunction is that it is a pathological result of increased immune cell apoptosis. Alternatively, it has been proposed that the clearance of increased numbers of apoptotic cells may actively drive immune suppression through the cells that handle them. Here we review the data from studies involving septic animals and patients, which indicate that loss of immune cells, as well as non-immune cells, in some cases, is a result of dysregulated apoptosis. Subsequently, we will consider the cell death pathways, i.e. 'extrinsic' and/or 'intrinsic', which are activated and what cell populations may orchestrate this dysfunctional apoptotic process, immune and/or non-immune. Finally, we will discuss potentially novel therapeutic targets, such as caspases, death receptor family members (e.g. tumour necrosis factor, Fas) and pro-/anti apoptotic Bcl-family members, and approaches such as caspase inhibitors, the use of fusion proteins, peptidomimetics and siRNA, which might be considered for the treatment of the septic patient.
- Published
- 2007
- Full Text
- View/download PDF
191. Role of alveolar macrophage and migrating neutrophils in hemorrhage-induced priming for ALI subsequent to septic challenge.
- Author
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Lomas-Neira J, Chung CS, Perl M, Gregory S, Biffl W, and Ayala A
- Subjects
- Acute Disease, Animals, Bronchoalveolar Lavage Fluid chemistry, Chemokines antagonists & inhibitors, Endothelial Cells metabolism, Esterases metabolism, Hemorrhage pathology, Intercellular Adhesion Molecule-1 metabolism, Interleukin-10 metabolism, Lung enzymology, Lung metabolism, Male, Mice, Mice, Inbred C3H, Neutropenia metabolism, Neutropenia physiopathology, Neutrophils enzymology, Peroxidase metabolism, Pneumonia prevention & control, Proteins metabolism, Tumor Necrosis Factor-alpha antagonists & inhibitors, Hemorrhage complications, Hemorrhage physiopathology, Lung Diseases etiology, Macrophages, Alveolar pathology, Neutrophil Infiltration, Sepsis complications
- Abstract
Acute lung injury (ALI) is identified with the targeting/sequestration of polymorphonuclear leukocytes (PMN) to the lung. Instrumental to PMN targeting are chemokines [e.g., macrophage inflammatory protein-2 (MIP-2), keratinocyte-derived chemokine (KC), etc.] produced by macrophage, PMN, and other resident pulmonary cells. However, the relative contribution of resident pulmonary macrophages as opposed to PMN in inducing ALI is poorly understood. We therefore hypothesize that depletion of peripheral blood PMN and/or the oblation of a macrophage-mediated PMN chemokine signal (via macrophage deficiency) will reduce the inflammation and ALI observed in mice following hemorrhage (Hem) and subsequent sepsis (CLP) in our murine model of ALI. To examine this we pretreated mice with either 500 microg anti-mouse Gr1 antibody/animal (to deplete PMN) or subjected mice deficient in mature macrophage (B6C3Fe-a/a-CsF1op) to Hem (90 min at 35 +/- 5 mmHg) followed by resuscitation. Twenty-four hours post-Hem, mice were subjected to CLP and killed 24 h later, and lung tissue samples were collected. Our data showed that in the absence of either peripheral blood PMN or mature tissue macrophages there was a suppression of IL-6, KC, and MIP-2 levels in lung tissue from Hem/CLP mice as well as a reduction in PMN influx to the lung and lung injury (bronchoalveolar lavage fluid protein). In contrast, lung tissue IL-10 and TNF-alpha levels were suppressed in the macrophage-deficient Hem/CLP mice compared with PMN-depleted Hem/CLP mice. Together, these data suggest that both the PMN and the macrophage are required to induce inflammation seen here, however, macrophage not PMN regulate the release of IL-10, independent of local changes in TNF.
- Published
- 2006
- Full Text
- View/download PDF
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