U. C. Liener

Cardiopulmonary, histological, and inflammatory alterations after lung contusion in a novel mouse model of blunt chest trauma

Severe blunt chest trauma remains an important injury with high morbidity and mortality. However, the associated immunological alterations are poorly understood. Existing big animal models require large-scale settings, are often too expensive, and research products for immunological studies are limited. In this study we aimed to establish a new model of blunt, isolated and bilateral chest trauma in mice and to characterize its effects on physiological and inflammatory variables. Male C3H/HeN mice (n = 9–10/group) were anesthetized and a femoral artery was catheterized. The animals were subjected to trauma or sham procedure and monitored for 180 min. Blunt chest trauma was induced by a blast wave focused on the thorax. Trauma intensity was optimized by varying the exposure distance. Blood pressure, heart rate, respiratory rate, arterial blood gases and plasma cytokine levels were measured. Macroscopic and microscopic examinations were performed. In addition, outcome was evaluated in a 10-day survival study. Chest trauma caused a drop (P < 0.05) in blood pressure and heart rate, which partly recovered. Blood gases revealed hypoxemia and hypercarbia (P < 0.05) 180 min after trauma. There was marked damage to the lungs but none to abdominal organs. Histologically, the characteristic signs of a bilateral lung contusion with alveolar and intrabronchial hemorrhage were found. Plasma interleukin-6 and tumor necrosis factor &agr; were considerably increased after 180 min. Blunt chest trauma resulted in an early mortality of 10% without subsequent death. On the basis of these findings, this novel mouse model of blunt chest trauma appears suitable for detailed studies on immunological effects of lung contusion.

The role of C5a in the innate immune response after experimental blunt chest trauma.

The inflammatory response after severe blunt chest trauma often leads to acute lung injury and acute respiratory distress syndrome which are associated with high mortality rates. Whereas the role of innate immunity in acute lung injury has been broadly investigated, the immune response after blunt chest trauma is still poorly understood. Therefore, the role of complement and neutrophils was determined in bilateral lung injury induced by a single blast wave. The following time-points were investigated posttrauma: sham, 1, 6, 12, and 24 h. There was a time-dependent systemic activation of complement as determined by CH-50 and presence of C5a-dependent chemotactic plasma activity. Moreover, factor H, a complement regulatory protein, was increased systemically and locally after injury. Anti-C5a treatment immediately after trauma ameliorated these peaks. After an initial systemic leukopenic phase, a marked leukocytosis occurred. The latter was normalized by C5a blockade. In parallel, white blood cell count in bronchioalveolar lavage fluids was increased as a function of time and was significantly decreased by anti-C5a treatment. Trauma-induced lung injury was also associated with dramatic changes in neutrophil function, namely early enhanced chemotaxis and phagocytosis, followed by prolonged functional defects-all of which were ameliorated by anti-C5a treatment. Furthermore, blockade of C5a ameliorated the buildup of the proinflammatory cytokine TNF-&agr;, diminished the increase of cytokine-induced neutrophil chemoattractant 1, and altered the levels of the anti-inflammatory cytokine IL-10. These data suggest that blunt chest trauma leads to systemic activation of complement and robust C5a generation, which causes perturbations in defensive functions of neutrophils. Thus, C5a might represent a potential target for therapeutic immunomodulation to prevent immune dysfunctions post-trauma and thereby, perhaps, the progression to acute respiratory distress syndrome.

Chemokine activation within 24 hours after blunt accident trauma

Chemokines mediate the migration of leukocytes to sites of inflammation. Changes in the plasma concentration of interleukin (IL)-8 and macrophage inflammatory protein (MIP)-1&bgr; have not been investigated in the very early phase starting immediately after unintentional trauma. Enrolled in the study were 94 patients with multiple blunt injuries. Blood samples were collected at the scene of accident, then at regular intervals for 24 h. IL-8 and MIP-1&bgr; plasma levels were determined by commercial test kits. Patients were grouped according to trauma severity, pattern of injury, as well as survivors vs. nonsurvivors. Serious casualties [Injury Severity Score (ISS) ≧ 32] revealed a significant increase in IL-8 compared to only a slight elevation in individuals with an ISS < 32. Nonsurvivors showed a highly significant (P < 0.005) increase in IL-8 levels beginning immediately after admission. Trauma resulted in a modest activation of MIP-1&bgr; production without differences regarding trauma severity, pattern of injury, or survival. A very strong trauma stimulus is necessary to activate IL-8 production. In contrast to MIP-1&bgr;, IL-8 levels were significantly elevated in nonsurvivors compared to survivors. Therefore, IL-8 might be an early predictor of survival.

Induction of Apoptosis Following Blunt Chest Trauma

The cause for the high morbidity of blunt chest trauma is not fully understood. It is still unclear if and to what extent a second insult, e.g., apoptotic tissue damage initiated by the primary insult itself, may contribute to the development of serious complications. This study was done to elucidate whether a pulmonary contusion may induce programmed cell death. Sixty-four Wistar rats were evenly randomized to eight experimental groups: four sets were subjected to a standardized blast wave injury and sacrificed 6, 24, 48, and 72 h after the trauma; four groups served as controls for the same time points. Lung and liver samples were stained (H&E; TUNEL), and PMN infiltration was determined by myeloperoxidase (MPO) activity. Caspase 8 was analyzed by Western blot, and TNF-&agr; plasma levels by ELISA. Postmortem examination revealed bilateral pulmonary contusion in trauma animals with higher (P < 0.05) numbers of apoptotic cells in lung but not in liver tissue as early as 6 h after the injury. This amount gradually increased and reached a maximum after 48 h: 6.8 ± 1.1 apoptotic cells/hpf vs. 0.6 ± 0.06 in controls. Chest trauma caused an increased expression of active caspase 8 in lung but not in liver tissue at 48 and 72 h. TNF-&agr; plasma levels were not different. MPO activity in lung tissue of trauma animals increased (P < 0.05) after 6 h and peaked at 72 h. This study has provided the first evidence that apoptotic cell death in lung tissue is initiated following (experimental) pulmonary contusion. The exact mechanism remains, however, unclear and has to be elucidated further.

Blunt chest trauma induces delayed splenic immunosuppression.

Severe blunt chest trauma is frequently associated with multiple organ failure and sepsis. Posttraumatic immunosuppression seems to play a major role in their development. However, the immunologic alterations following pulmonary contusion are insufficiently elucidated. Specifically, it remains unknown whether immunocompetent cells located distant from the site of the impact are affected. We therefore aimed to characterize the influence of pulmonary contusion on lymphocytes and splenic macrophages. Male C3H/HeN mice (n = 8–10/group) were anesthetized and subjected to trauma or sham procedure. Blunt chest trauma was induced by a blast wave focused on the thorax. Two or 24 h later, splenocytes and splenic macrophages were isolated and stimulated for 48 h. The cytokine release (IFN-γ, IL-2, IL-3, IL-10, IL-12, IL-18) from splenocytes as well as from splenic macrophages (TNF-α, IL-10, IL-12, IL-18) and plasma levels of TNF-α and IL-6 were quantified by ELISA. The results indicate that at 2 h after blunt chest trauma, plasma TNF-α and IL-6 were markedly increased. At the same time, no differences in splenocyte cytokine production were detectable. However, at 24 h a significantly depressed cytokine release was observed in trauma animals. Furthermore, splenic macrophages showed a significantly decreased production of TNF-α, IL-10, and IL-12 at 24 h and markedly increased release of IL-18 at 2 h after trauma. These results indicate that blunt chest trauma causes severe immunodysfunction of lymphocytes and splenic macrophages. Thus, lung contusion as a localized type of trauma causes dysfunction of immunocompetent cell populations, which are located distant from the site of injury.

Inflammatory Alterations in a Novel Combination Model of Blunt Chest Trauma and Hemorrhagic Shock

BACKGROUND Chest trauma frequently occurs in severely injured patients and is often associated with hemorrhagic shock. Immune dysfunction contributes to the adverse outcome of multiple injuries. The aims of this study were to establish a combined model of lung contusion and hemorrhage and to evaluate the cardiopulmonary and immunologic response. METHODS Male mice were subjected to sham procedure, chest trauma, hemorrhage (35 mm Hg±5 mm Hg, 60 minutes), or the combination. Respiratory rate, heart rate, and blood pressure were monitored. Plasma, Kupffer cells, blood monocytes, splenocytes, and splenic macrophages were isolated after 20 hours. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, 10, 12, 18, and macrophage inflammatory protein-2 levels in plasma and culture supernatants were determined. RESULTS Heart rate and blood pressure dropped in all groups, and after chest trauma and the double hit, these values remained reduced until the end of observation. Blood pressure was lower after the double hit than after the single hits. Plasma and Kupffer cell TNF-α concentrations were increased after lung contusion but not further enhanced by subsequent hemorrhage. Peripheral blood mononuclear cell (PBMC) TNF-α and IL-6 release were suppressed after the combined insult. IL-18 concentrations were increased in PBMC supernatants after chest trauma and in splenic macrophage supernatants of all groups. CONCLUSIONS Although physiologic readouts were selectively altered in response to the single or double hits, the combination did not uniformly augment the changes in inflammation. Our results suggest that the leading insult regarding the immunologic response is lung contusion, supporting the concept that lung contusion represents an important prognostic factor in multiple injuries.

Entwicklung des Lernzielkatalogs „Muskuloskelettale Erkrankungen, Verletzungen und traumatische Notfälle“ für Orthopädie-Unfallchirurgie im Medizinstudium

ZusammenfassungHintergrundMit der Entwicklung des gemeinsamen Faches Orthopädie-Unfallchirurgie bedarf es neben der Zusammenführung und Überarbeitung der Weiterbildungsinhalte des ärztlichen Nachwuchses auch der Erstellung eines für Deutschland einheitlichen Lernzielkatalogs, der die Grundlage der studentischen Lehre in der Orthopädie und Unfallchirurgie an den deutschen Fakultäten und Lehrkrankenhäusern bilden soll.Material und MethodeAusgehend vom Frankfurter Lernzielkatalog für Unfallchirurgie und dem Ulmer Lernzielkatalog für Orthopädie wurde von einer Expertenkommission der gemeinsame Katalog für das Fach Orthopädie und Unfallchirurgie entwickelt. Durch Vertreter beider Fächer erfolgte die Definition der Lernziele und anschließende Gliederung und Priorisierung in sog. Ebenen und Bereiche des kognitiven Wissens, Kompetenzstufen psychomotorischer Fertigkeiten (Skills) sowie emotionales Wissen und Kompetenz.ErgebnisInsgesamt wurden 283 Lernziele formuliert. Der „allgemeine Teil operativer Fachgebiete“ umfasst 120 Lernziele, die sich in 39 Items kognitiven Inhalts und 83 Skills unterteilen, 2 Lernziele beinhalten gleichzeitig sowohl Wissen als auch Skills. Der „spezielle Teil Orthopädie/Unfallchirurgie“ umfasst insgesamt 141 Lernziele unterteilt in 138 Lernziele mit Wissensinhalten sowie 6 Skills, 3 Lernziele beziehen sich auf Wissen sowie Skills. 22 Lerninhalte beziehen sich auf den Bereich „emotionales Wissen und Kompetenz“.SchlussfolgerungTrotz der erst jungen Verbindung der beiden Fächer Orthopädie und Unfallchirurgie konnte nicht nur eine „Themensammlung“, sondern ein gemeinsamer Lernzielkatalog für die studentische Lehre erarbeitet werden. Dieser hat nach der Verabschiedung durch die Ordinarienkonvente der Unfallchirurgen und Orthopäden bundesweiten Empfehlungscharakter. Mit der Konsentierung von Lernzielen sind die Weichen für eine zukunftorientierte moderne Lehre gestellt. Anhand der im Lernzielkatalog enthaltenen Empfehlungen zur Gewichtung der Inhalte, zur Verknüpfung mit anderen Fächern und zum Einsatz geeigneter Lehrmethoden, können die einzelnen Lernziele an den jeweiligen Fakultäten pragmatisch und unter Wahrung der Freiheit der Lehre umgesetzt werden.AbstractBackgroundThe development towards a combined speciality of orthopaedic and trauma surgery requires not only consolidation and revision of the postgraduate education training programme but also the development of a catalogue of learning objectives as a uniform basis for undergraduate medical training in the new speciality at German medical schools and teaching hospitals. Materials and methodsBased on the Frankfurt catalogue of learning objectives for trauma surgery and the Ulm catalogue of learning objectives for orthopaedics, a task force of experts developed a combined catalogue of learning objectives for the new speciality. Experts from both specialities classified the learning objectives into two levels of knowledge and four grades of skills competence, in addition to objectives for attitudes and social competence.ResultsThe section on general operative specialities contains 120 items classified into 39 learning objectives for knowledge and 83 for skills. Two learning objectives comprise both knowledge and skills. The section on orthopaedic and trauma surgery comprises 141 learning objectives, including six items for skills and 138 for knowledge, as well as three learning objectives for both knowledge and skills. In addition, 22 learning objectives deal with aspects of attitude and social competence.ConclusionAlthough this alliance of orthopaedics and trauma surgery is recent, the commission has developed not only a collection of topics but a joint catalogue of learning objectives for undergraduate training that can be used nationwide. This catalogue paves the way for modern education that looks to the future. The integrated recommendations for content prioritisation, links to other subjects and specialities, and the integration of didactic methods facilitate local implementation of the learning objectives without loss of academic freedom.BACKGROUND The development towards a combined speciality of orthopaedic and trauma surgery requires not only consolidation and revision of the postgraduate education training programme but also the development of a catalogue of learning objectives as a uniform basis for undergraduate medical training in the new speciality at German medical schools and teaching hospitals. MATERIALS AND METHODS Based on the Frankfurt catalogue of learning objectives for trauma surgery and the Ulm catalogue of learning objectives for orthopaedics, a task force of experts developed a combined catalogue of learning objectives for the new speciality. Experts from both specialities classified the learning objectives into two levels of knowledge and four grades of skills competence, in addition to objectives for attitudes and social competence. RESULTS The section on general operative specialities contains 120 items classified into 39 learning objectives for knowledge and 83 for skills. Two learning objectives comprise both knowledge and skills. The section on orthopaedic and trauma surgery comprises 141 learning objectives, including six items for skills and 138 for knowledge, as well as three learning objectives for both knowledge and skills. In addition, 22 learning objectives deal with aspects of attitude and social competence. CONCLUSION Although this alliance of orthopaedics and trauma surgery is recent, the commission has developed not only a collection of topics but a joint catalogue of learning objectives for undergraduate training that can be used nationwide. This catalogue paves the way for modern education that looks to the future. The integrated recommendations for content prioritisation, links to other subjects and specialities, and the integration of didactic methods facilitate local implementation of the learning objectives without loss of academic freedom.

Tibiocalcaneal fusion for the treatment of talar necrosis

SummaryBetween 1986 and 1996, 21 patients had a tibiocalcanear arthrodesis. Indications for surgery were in all cases either osteomyelitis or avascular necrosis of the talus. External stabilisation was used in 17 patients due to severe soft tissue damage or extensive infection of the talus, internal screw fixation was used in four patients. There were eight complications in seven patients, one patient had a below the knee amputation. The leg length discrepancies after resection of the talus was equalised in four cases with callus distraction using an Ilisarov ring fixator. Follow up evaluation was available in 18 patients after an average of 38 months (12–86 mo.). There were no infectious recurrenies during the follow up period and a solid fusion was achieved in all patients that were followed. According to a modified Kitaoka score, results were excellent and good in 12 of the 18patients. External stabilisation, especially the Ilisarov ring fixator is the primary method of treatment in cases with severe infection or soft tissue damage.ZusammenfassungAufgrund ausgedehnter septischer und aseptischer talarer Zerstörung erfolgte in 21 Fällen in den Jahren 1986–1996 eine tibiokalkaneare Arthrose. Mit externen Verfahren wurden bei bestehender Weichteil- oder Infektproblematik 17 Patienten behandelt. In 4 Fällen erfolgte eine Fusion mittels Schraubenosteosynthese, in weiteren 4 Fällen erfolgte der Ausgleich der Beinlänge mittels Kallusdistraktion. Bei 7 Patienten waren 8 Komplikationen zu verzeichnen, in 1 Fall mußte eine Unterschenkelamputation durchgeführt werden. Ein Extremitätenerhalt konnte somit in 20 von 21 Fällen erzielt werden. Nach durchschnittlich 38 (12–86) Monaten konnten 18 der 21 Patienten nachkontrolliert werden. Infektrezidive traten während des Nachuntersuchungszeitraums nicht auf. Bei allen nachuntersuchten Patienten bestand eine feste knöcherne Fusion. In einem, an die Bewertungskriterien der „American Orthopaedic Foot and Ankle Society“ angelehnten, klinischen Bewertungsscore erzielten 12 der 18 Patienten ein sehr gutes und gutes Ergebnis. Externe Stabilisationsverfahren, insbesondere der Ilisarov-Ringfixateur stellten bei der hohen Inzidenz von Infektsituationen das Verfahren der Wahl dar.

Die Korrektur posttraumatischer diaphysärer Fehlstellungen an der unteren Extremität

Summary. Post-traumatic deformities do occur as a result of disturbed fracture healing with loss of bone stock, necrosis of fragments or the development of pseudarthrosis resulting in malunion or progressive malalignment. In the majority of the cases these disturbances can be related to technical problems of primary fracture treatment like insufficient reduction or implant failure. On the other hand, complex deformities with involvement of the adjacent joints may also be a result of injuries of the growth plate in childhood. In some cases primary correction is impossible because of critical conditions of the bone and the soft tissue envelope in the center of deformation. If a secondary correction is indicated, knowledge of all reconstructive techniques is essential to choose the appropriate method and carry out successful and exact correction of malalignment of the affected limb after detailed planning.Zusammenfassung. Fehlstellungen nach Extremitätentraumen können als Folge von Frakturheilungsstörungen auftreten, welche zu Knochensinterungen und Pseudarthrosen mit zunehmender Achsabweichung und Verkürzung führen. Daneben führen Verletzungen im Kindesalter unter Beteiligung der Wachstumsfugen zu komplexen Fehlern, die nicht zuletzt auch das angrenzende Gelenk in seiner Kontur mit betreffen können. Nicht selten liegen die Ursachen auch in technischen Fehlern der Frakturerstversorgung, insbesondere Instabilität der Osteosynthese oder ungenügende Reposition, die je nach angewandtem Stabilisationsverfahren zu typischen Fehlstellungen führen. Bei komplizierten Frakturheilungsverläufen mit kritischer lokaler Weichteil- und Knochensituation kann – trotz rechtzeitigen Erkennens einer sich abzeichnenden Fehlstellung – deren frühzeitige Korrektur sich aus eben den lokalen Gründen verbieten. Auch bei der Spätkorrektur solcher Fehlstellungen mit initial lokaler Knochen- und Weichteilproblematik müssen alle Verfahren der Rekonstruktion beherrscht werden, um – nach exakter planerischer Analyse – unter Berücksichtigung der Komplexität und der lokalen Situation die Auswahl des jeweils optimalen Korrekturverfahrens zu treffen

Trauma severity-dependent changes in AT III activity.

Trauma may cause a relevant reduction in antithrombin (AT) III activity, which is associated with adverse events. The very early changes in AT III activity after accident trauma are still unclear and possible relations with Interleukin (IL)-6, which is known to interact with AT III, have not been investigated so far. Upon approval of the IRB/IEC, 30 patients were enrolled with multiple injuries (ISS 9-75). Groups were performed according to injury severity, IL-6 concentration, and survivors versus non-survivors. Blood samples were collected at the scene of accident then at 2, 4, 6, 12, and 24 h and at day 3, 5, 10 and 15. No patient received AT III concentrates. In all groups a reduction in AT III activity occurred, which was most pronounced in very severe injuries. The activity re-increased spontaneously and steadily in all groups regardless of the IL-6 concentration. There was no clear impact of the AT III activity on survival.