Refine
Year of publication
Document Type
- Article (61)
- Conference Proceeding (6)
Keywords
- polytrauma (7)
- inflammation (5)
- Inflammation (4)
- Trauma (4)
- trauma (4)
- Biomarker (3)
- BMC (2)
- Bone defect (2)
- CC16 (2)
- Cell therapy (2)
Institute
- Case report-delayed splenic rupture in combination with medial femoral neck fracture after low energy trauma. Development of hemorrhagic shock 5 days after hip prosthesis due to a rare cause (2016)
- A 79 year old female patient was admitted to our emergency department with a fracture of the right medial femoral neck six days after a fall on her right side and a cemented hemiprosthesis was implanted. Five days later, she developed a hemorrhagic shock and was diagnosed with a delayed splenic rupture and the spleen was resected. Histopathological examination showed a delayed rupture of an otherwise normal spleen without signs of an underlying pathology. The outcome was fatal: In the postoperative course she developed pneumonia, three weeks later she succumbed due to multiple organ failure. Even careful reevaluation of the case did not provide any clues to expect an injury of the spleen according to trauma mechanism. This case shows that delayed splenic rupture of a normal spleen may occur even after a low energy trauma. Injury of the spleen should therefore always be considered, even with an uncharacteristic anamnesis. Physical examination after trauma should therefore always include a careful clinical evaluation. The clinical threshold for a FAST examination should be low. The coincidence of a femoral neck fracture and a splenic rupture after a low energy trauma has not been reported before.
- 11,12 and 14,15 epoxyeicosatrienoic acid rescue deteriorated wound healing in ischemia (2019)
- Introduction: Epoxyeicosatrienoic acids (EETs) are able to enhance angiogenesis and regulate inflammation that is especially important in wound healing under ischemic conditions. Thus, we evaluated the effect of local EET application on ischemic wounds in mice. Methods: Ischemia was induced by cautherization of two of the three supplying vessels to the mouse ear. Wounding was performed on the ear three days later. Wounds were treated either with 11,12 or 14,15 EET and compared to untreated control and normal wounds. Epithelialization was measured every second day. VEGF, TNF-α, TGF-β, matrix metalloproteinases (MMP), tissue inhibitors of metalloproteinases (TIMP), Ki67, and SDF-1α were evaluated immunohistochemically in wounds on day 3, 6, and 9. Results: Ischemia delayed wound closure (12.8 days ± 1.9 standard deviation (SD) for ischemia and 8.0 days ± 0.94 SD for control). 11,12 and14,15 EET application ameliorated deteriorated wound healing on ischemic ears (7.6 ± 1.3 SD for 11,12 EET and 9.2 ± 1.4 SD for 14,15 EET). Ischemia did not change VEGF, TNF-α, TGF-β, SDF-1α, TIMP, MMP7 or MMP9 level significantly compared to control. Local application of 11,12 as well as 14,15 EET induced a significant elevation of VEGF, TGF-β, and SDF-1α expression as well as proliferation during the whole phase of wound healing compared to control and ischemia alone. Conclusion: In summary, EET improve impaired wound healing caused by ischemia as they enhance neovascularization and alter inflammatory response in wounds. Thus elevating lipid mediator level as 11,12 and 14,15 EET in wounds might be a successful strategy for amelioration of deranged wound healing under ischemia.
- Differential relevance of NF-κB and JNK in the pathophysiology of hemorrhage/resususcitation-induced liver injury after chronic ethanol feeding (2015)
- Background: Chronic ethanol (EtOH) abuse worsens pathophysiological derangements after hemorrhagic shock and resuscitation (H/R) that induce hepatic injury and strong inflammatory changes via JNK and NF-κB activation. Inhibiting JNK with a cell-penetrating, protease-resistant peptide D-JNKI-1 after H/R in mice with healthy livers ameliorated these effects. Here, we studied if JNK inhibition by D-JNKI-1 in chronically EtOH-fed mice after hemorrhagic shock prior to the onset of resuscitation also confers protection. Methods: Male mice were fed a Lieber-DeCarli diet containing EtOH or an isocaloric control (ctrl) diet for 4 weeks. Animals were hemorrhaged for 90 min (32 ± 2 mm Hg) and randomly received either D-JNKI-1 (11 mg/kg, intraperitoneally, i. p.) or sterile saline as vehicle (veh) immediately before the onset of resuscitation. Sham animals underwent surgical procedures without H/R and were either D-JNKI-1 or veh treated. Two hours after resuscitation, blood samples and liver tissue were harvested. Results: H/R induced hepatic injury with increased systemic interleukin (IL)-6 levels, and enhanced local gene expression of NF-κB-controlled genes such as intercellular adhesion molecule (ICAM)-1 and matrix metallopeptidase (MMP)9. c-Jun and NF-κB phosphorylation were increased after H/R. These effects were further increased in EtOH-fed mice after H/R. D-JNKI-1 application inhibited the proinflammatory changes and reduced significantly hepatic injury after H/R in ctrl-fed mice. Moreover, D-JNKI-1 reduces in ctrl-fed mice the H/R-induced c-Jun and NF-κB phosphorylation. However, in chronically EtOH-fed mice, JNK inhibition did not prevent the H/R-induced hepatic damage and proinflammatory changes nor c-Jun and NF-κB phosphorylation after H/R. Conclusions: These results indicate, that JNK inhibition is protective only in not pre-harmed liver after H/R. In contrast, the pronounced H/R-induced liver damage in mice being chronically fed with ethanol cannot be prevented by JNK inhibition after H/R and seems to be under the control of NF-κB.
- Decreased inflammatory responses of human lung epithelial cells after ethanol exposure are mimicked by ethyl pyruvate (2014)
- Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM), sodium pyruvate (NaP, 10 mM), or EtOH (85–170 mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.
- Objektiv strukturierte Bewertung einer Hautnaht am Modell : ist die direkte Beobachtung der video-basierten Beobachtung überlegen? ; Poster (2006)
- Poster Einleitung: OSCEs werden immer häufiger in der Ausbildung von Studierenden eingesetzt. Die Einführung eines OSCEs im fach Chirurgie ist in Planung. Durch die große Anzahl von Studierenden pro Semester oder Studienjahr (400 Studierende in Frankfurt) ist die Durchführung einer OSCE Prüfung mit großem personellen Aufwand verbunden. Vor allem während der Prüfung müssen eine Vielzahl von Chirurgen simultan zu Prüfungszwecken zur Verfügung stehen. Ziel der Studie war es, zu überprüfen, ob eine video-basierte Bewertung einer „Nahtstation“ zu einem späteren Zeitpunkt zu gleichen Ergebnissen in der Bewertung der Leistung der Studierenden führt. Methode: 33 Studierende führten unter standardisierten Bedingungen eine Hautnaht an einem Modell durchzuführen. Die Studierenden wurden während der Prozedur von zwei prüfenden Chirurgen und zwei Studierenden im PJ (praktischen Jahr) beobachtet und anhand einer objektiv strukturierten Checkliste bewertet (Prozessevaluation). Die Prozedur wurde gleichzeitig auf Video aufgezeichnet und zu einem späteren Zeitpunkt zwei weiteren Chirurgen und zwei weiteren Studierenden im PJ zur Bewertung gezeigt. Ergebnisse: Der Vergleich zwischen "live“-prüfenden und "video“-prüfenden Chirurgen zeigt eine signifikant hohe Korrelation (r=0,87; p<0,01) und eine hohe Übereinstimmung (88,2%) in der Bewertung. Ebenso zeigen die prüfenden PJler eine signifikant hohe Korrelation (r=0,84; p<0,01). Die Übereinstimmung ist bei den PJlern mit (82.4%) etwas niedriger als bei den beteiligten Chirurgen. Zusammenfassung: Mit dieser Studie konnte zeigt werden, daß es bei der Beurteilung der Performance von Studierenden bei einer Hautnaht am Modell unter Anwendung von objektiv strukturierten Checklisten möglich ist, eine direkte Beobachtung der Studierenden durch eine video-basierte Beobachtung zu ersetzen. Eine "Nahtstation“ in einem OSCE kann somit während der Prüfungszeit ohne Prüfer auskommen und im Anschluß bewertet werden.
- Comparative analysis of the regulatory T cells dynamics in peripheral blood in human and porcine polytrauma (2018)
- Background: Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma. Methods: Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127−, and CD4+CD25+CD127−FoxP3+ were characterized by flow cytometry. Results: Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127−), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain. Conclusion: Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127− was characterized in porcine samples.
- Myeloid knockout of HIF-1α does not markedly affect hemorrhage/resuscitation-induced inflammation and hepatic injury (2014)
- Background: Hypoxia-inducible factor-1α (HIF-1α) and NF-κB play important roles in the inflammatory response after hemorrhagic shock and resuscitation (H/R). Here, the role of myeloid HIF-1α in liver hypoxia, injury, and inflammation after H/R with special regard to NF-κB activation was studied. Methods: Mice with a conditional HIF-1α knockout (KO) in myeloid cell-line and wild-type (WT) controls were hemorrhaged for 90 min ( mm Hg) and resuscitated. Controls underwent only surgical procedures. Results: After six hours, H/R enhanced the expression of HIF-1α-induced genes vascular endothelial growth factor (VEGF) and adrenomedullin (ADM). In KO mice, this was not observed. H/R-induced liver injury in HIF-1α KO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1α KO. Local hepatic hypoxia was not significantly reduced in HIF-1α KO compared to controls after H/R. H/R-induced NF-κB phosphorylation in liver did not significantly differ between WT and KO. Conclusions: Here, deleting HIF-1α in myeloid cells and thereby in Kupffer cells was not protective after H/R. This data indicates that other factors, such as NF-κB, due to its upregulated phosphorylation in WT and KO mice, contrary to HIF-1α, are rather key modulators of inflammation after H/R in our model.
- Minocycline decreases liver injury after hemorrhagic shock and resuscitation in mice (2012)
- Patients that survive hemorrhage and resuscitation (H/R) may develop a systemic inflammatory response syndrome (SIRS) that leads to dysfunction of vital organs (multiple organ dysfunction syndrome, MODS). SIRS and MODS may involve mitochondrial dysfunction. Under pentobarbital anesthesia, C57BL6 mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer’s solution containing minocycline, tetracycline (both 10 mg/kg body weight) or vehicle. Serum alanine aminotransferase (ALT), necrosis, apoptosis and oxidative stress were assessed 6 h after resuscitation. Mitochondrial polarization was assessed by intravital microscopy. After H/R with vehicle or tetracycline, ALT increased to 4538 U/L and 3999 U/L, respectively, which minocycline decreased to 1763 U/L (P<0.01). Necrosis and TUNEL also decreased from 24.5% and 17.7 cells/field, respectively, after vehicle to 8.3% and 8.7 cells/field after minocycline. Tetracycline failed to decrease necrosis (23.3%) but decreased apoptosis to 9 cells/field (P<0.05). Minocycline and tetracycline also decreased caspase-3 activity in liver homogenates. Minocycline but not tetracycline decreased lipid peroxidation after resuscitation by 70% (P<0.05). Intravital microscopy showed that minocycline preserved mitochondrial polarization after H/R (P<0.05). In conclusion, minocycline decreases liver injury and oxidative stress after H/R by preventing mitochondrial dysfunction.
- Rapid development of intestinal cell damage following severe trauma : a prospective observational cohort study (2009)
- Introduction Loss of intestinal integrity has been implicated as an important contributor to the development of excessive inflammation following severe trauma. Thus far, clinical data concerning the occurrence and significance of intestinal damage after trauma remain scarce. This study investigates whether early intestinal epithelial cell damage occurs in trauma patients and, if present, whether such cell injury is related to shock, injury severity and the subsequent inflammatory response. Methods Prospective observational cohort study in 96 adult trauma patients. Upon arrival at the emergency room (ER) plasma levels of intestinal fatty acid binding protein (i-FABP), a specific marker for damage of differentiated enterocytes, were measured. Factors that potentially influence the development of intestinal cell damage after trauma were determined, including the presence of shock and the extent of abdominal trauma and general injury severity. Furthermore, early plasma levels of i-FABP were related to inflammatory markers interleukin-6 (IL-6), procalcitonin (PCT) and C-reactive protein (CRP). Results Upon arrival at the ER, plasma i-FABP levels were increased compared with healthy volunteers, especially in the presence of shock (P < 0.01). The elevation of i-FABP was related to the extent of abdominal trauma as well as general injury severity (P < 0.05). Circulatory i-FABP concentrations at ER correlated positively with IL-6 and PCT levels at the first day (r2 = 0.19; P < 0.01 and r2 = 0.36; P < 0.001 respectively) and CRP concentrations at the second day after trauma (r2 = 0.25; P < 0.01). Conclusions This study reveals early presence of intestinal epithelial cell damage in trauma patients. The extent of intestinal damage is associated with the presence of shock and injury severity. Early intestinal damage precedes and is related to the subsequent developing inflammatory response.
- Funktionelle Ergebnisse und Outcome operativ stabilisierter distaler Radiusfrakturen : die besondere Relevanz der Begleitverletzung (2003)
- Meeting Abstract (DGU 2003) 67. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie 89. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie 44. Tagung des Berufsverbandes der Fachärzte für Orthopädie Fragestellung Ziel dieser prospektiven Untersuchung ist die Analyse der Funktion und des Outcomes nach distaler Radiusfraktur in Abhängigkeit von Frakturtyp, Therapieform und Begeleitverletzungen. Berücksichtigt wurden diesbezüglich insbesondere auch neuere Implantate wie die volaren winkelstabilen Titanplatten und dorsale low profile Implantate. Methodik Innerhalb von 2 Jahren (01/01 bis 12/02) wurden insgesamt 150 Radiusfrakturen bei 145 Patienten (82 Frauen; 63 Männer) mit einem Durchschnittsalter von 51,8 (17-93) Jahren operativ versorgt. Die operative Versorgung erfolgte in 56,7 % der Fälle mittels volarer Plattenosteosynthese, davon wurde bei 60 % eine winkelstabile Platte eingesetzt. Die übrigen Frakturen wurden durch eine dorsale Platte (8%) bzw. durch Materialkombination Spickdraht/Schrauben und/oder Fixateur externe stabilisiert. Die radiologische und klinische Nachuntersuchung erfolgt frühestens 1 Jahr nach operativer Versorgung. Zusätzlich wird anhand eines Fragebogens der DASH - Score bestimmt. Ergebnisse Nach der AO-Klassifikation fanden sich in 47,7 % Typ A-, 8,6% Typ B- und 55,6% Typ C-Frakturen. Dabei fand sich bei 53,1 % eine relevante Begleitverletzung (Bandverletzungen 14,3 %; Handwurzelfrakturen 3,9 %; distale Ulnafrakturen 10,4%; TFC/Proc. styloideus ulnae 70,1%). Von den 25 bisher untersuchten Patienten (15 Frauen, 10 Männer; Durchschnittsalter: 55,3 Jahre; NU nach: 14 Monaten) waren 32% Typ A-, 20% Typ B- u. 48% Typ C-Frakturen. Die Greifkraft betrug 87,7 % und das Bewegungsausmaß 83,6 % im Vergleich zur Gegenseite. Der durchschnittliche standardisierte DASH-Score betrug 22,6 Punkte (0: optimale Funktion). Bei den mit volarer Platte stabilisierten C-Frakturen (9 der nachuntersuchten Patienten) fand sich ein DASH-Score von 41 Punkten. Die Greifkraft betrug 67,5% und das Bewegungsausmaß 79,6% im Vergleich zur Gegenseite. Bisher konnte weder bei der konventionellen, noch der winkelstabilen Plattenosteosynthese ein radiologischer Korrekturverlust nachgewiesen werden. Bei den Frakturen ohne lokale Begleitverletzungen waren Greifkraft (91% vs. 79,8%), Bewegungsausmaß (89,5% vs. 83,4%) und DASH-Score (16,8 vs. 26,1) besser als bei den Frakturen mit Begleitverletzungen. Schlussfolgerung Bei korrekter Reposition und Stabilisierung, wird der Outcome nach distaler Radiusfraktur neben dem Frakturtyp wesentlich durch die Begleitverletzung mitbestimmt. Daraus resultiert dass eine Verbesserung nur durch eine Optimierung der Therapie der Begleitverletzungen erreichbar ist.
