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Hans-Christoph Pape

Publications and source records attributed to Hans-Christoph Pape.

At least 19 recordsLinked to original sources
PubMed2007

Effects of 17beta-estradiol and flutamide on splenic macrophages and splenocytes after trauma-hemorrhage.

Since splenic immune functions are depressed in metestrus females following trauma-hemorrhage, we hypothesized that administration of the androgen receptor antagonist flutamide at the onset of resuscitation will maintain the immune function of the spleen following trauma-hemorrhage. Female C57BL6/J mice (metestrus state, 8-12 weeks old), underwent laparotomy and hemorrhagic shock (35.0+/-5.0 mm Hg for 90 min) and received 17beta-estradiol (50 microg/25 g), flutamide (625 microg/25 g) or 17beta-estradiol+flutamide. Four hours after resuscitation, the in vitro productive capacity of different cytokines (TNF-alpha, IL-6, IL-10, and IFN-gamma) by splenic MPhi and splenocytes were determined by flow cytometry. A significantly decreased cytokine production by both splenocytes and splenic MPhi was observed following trauma-hemorrhage compared to shams. Administration of 17beta-estradiol, flutamide and 17beta-estradiol+flutamide following trauma-hemorrhage resulted in a significant increase in the in vitro IL-6 release by splenic MPhi. The TNF-alpha productive capacity, however, was only restored by 17beta-estradiol and 17beta-estradiol+flutamide administration following trauma-hemorrhage. No significant effect of either treatment was observed with regard to the suppressed splenic MPhi IL-10 release. Anti-CD3 stimulation, administration of 17beta-estradiol and 17beta-estradiol+flutamide, but not the administration of flutamide alone resulted in a significant increased release of TNF-alpha, IL-6 and IFN-gamma compared to vehicle-treated animals. No significant effect of either treatment was found on IL-10 productive capacity. These results collectively suggest that flutamide administration following trauma-hemorrhage in females has beneficial effects on splenic immune function. However, flutamide administration in combination with estrogen does not provide any significant, additional effects over 17beta-estradiol administration alone.

Animals↗
PubMed2007

Influence of sex and age on mods and cytokines after multiple injuries.

Although salutary effects of female sex steroids have been demonstrated not only in proestrus females but also in male animals treated with estradiol in different models of trauma, it remains unknown whether sex hormones influence post-traumatic immune response in humans. We therefore investigated the effect of sex and age on organ dysfunction and clinical course in patients with multiple injuries. Polytraumatized patients (injury severity score>16) between 16 and 65 years old admitted to the Hannover Medical School Level 1 trauma center between January 1997 and December 2001 were included. Marshall Score for multiple organ dysfunction syndrome (MODS) was calculated for at least 14 days. The length of stay in intensive care unit and the ventilator days were recorded in addition to the number of transfusions the patient received. A total of 106 males and 37 females were included in the study. Patients with MODS had increased plasma levels of IL-6, IL-8, and IL-10. Furthermore, patients with organ dysfunction had more frequent sepsis and higher mortality rates. In addition, MODS was associated with extended length of stay in the intensive care unit and increased ventilator days. Females not older than 50 years with an injury severity score greater than 25 suffered significantly less MODS and sepsis compared with age-matched males. Moreover, they had significantly lower plasma cytokines. Thus, in this prospective study, sex difference was confirmed in MODS and sepsis, with a benefit observed in females. Although the levels of sex steroids were not measured, it seems that the protective effects may be due to estrogen effects on plasma cytokines. This suggestion is based on the fact that such salutary effects were apparent predominantly in premenopausal females.

Adolescent↗
PubMed2006

Effects of 17beta-estradiol and flutamide on inflammatory response and distant organ damage following trauma-hemorrhage in metestrus females.

We hypothesized that administration of androgen receptors antagonist flutamide following trauma-hemorrhage (T-H) in metestrus females will maintain immune function and reduce remote organ damage under those conditions. Female B57BL/J6 mice (metestrus state, 8-12 weeks old) underwent laparotomy and hemorrhagic shock (35.0+/-5.0 mmHg for 90 min) and then received 17beta-estradiol (E2; 50 microg/25 g), flutamide (625 microg/25 g), or E2 + flutamide. Four hours after resuscitation, plasma cytokine and chemokine (TNF-alpha, IL-6, IL-10, IFN-gamma, and MCP-1) concentrations and their release in vitro by hepatic and pulmonary tissue macrophages (M Phi) were determined by flow cytometry. Organ damage was assessed by edema formation (wet-to-dry weight ratio) and neutrophil infiltration [myeloperoxidase (MPO) activity]. Administration of E2, flutamide, or E2 + flutamide following T-H resulted in a significant decrease in systemic TNF-alpha, IL-6, and MCP-1 concentrations under those conditions. This was accompanied by significantly decreased in vitro TNF-alpha release by Kupffer cells after administration of E2, flutamide, or E2 + flutamide. The in vitro release of proinflammatory cytokines by alveolar M Phi, however, was reduced significantly only by the addition of E2 or E2 + flutamide but not by the addition of flutamide. A significant decrease in pulmonary and hepatic edema formation as well as neutrophil infiltration in the lung was observed after E2, flutamide and E2 + flutamide administration. In contrast, hepatic neutrophil infiltration was only significantly reduced following E2 and E2 + flutamide administration. Thus, although flutamide does not produce synergistic, salutary effects with E2, its administration in females following T-H also produces salutary effects on the immune and organ function, similar to E2 administration under those conditions.

Animals↗
PubMed2006

Are the protective effects of 17beta-estradiol on splenic macrophages and splenocytes after trauma-hemorrhage mediated via estrogen-receptor (ER)-alpha or ER-beta?

The depression in cell-mediated immune function following trauma-hemorrhage is shown to be restored by 17beta-estradiol (E2) administration. However, it remains unknown which of the two estrogen-receptors, (ER)-alpha or ER-beta, plays the predominant role in mediating the beneficial effects of E2. Female B57BL/J6 ER-beta(-/-) transgenic mice [knockout (KO)] and corresponding ovariectomized wild-type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0+/-5.0 mmHg for 90 min) and treated with E2 (50 microg/25 g) or ER-alpha agonist propyl pyrazole triol (PPT; 50 microg/25 g) following trauma-hemorrhage. Four hours after resuscitation, systemic cytokine concentrations and cytokine release by splenocytes and splenic macrophages were determined by cytometric bead array. Trauma-hemorrhage resulted in a significant increase in plasma tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-10. In contrast, the release of these cytokines by splenic macrophages was decreased significantly in WT and KO animals. Administration of E2 or PPT following trauma-hemorrhage produced a significant reduction in systemic TNF-alpha and IL-6 concentrations in WT and KO mice. Although the suppression in the productive capacity of these cytokines following trauma-hemorrhage by macrophages and splenocyte was also prevented in E2- and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2- and PPT-treated KO mice was not restored to the levels observed in sham animals. These findings collectively suggest that both receptors appear to play a significant role in mediating the immunoprotective effects of E2 in different tissue compartments following trauma-hemorrhage.

Animals↗
PubMed2006

Staged management and outcome of combined pelvic and liver trauma. An international experience of the deadly duo.

Pelvic fracture associated with liver trauma is not an uncommon injury combination in multiple trauma and is associated with high morbidity and mortality. The aim of this study was to examine the characteristics of this specific patient group, to describe the diagnostic and treatment protocols and finally to analyse risk factors associated with mortality. Data were collected over a 6-year period, ending in 2001. The pelvic injury was graded according to the Tile classification system and the hepatic injury was scored using the organ injury scale (OIS). Treatment protocol, associated injuries, complications, length of ICU/Hospital stay and mortality were recorded and analysed. A total of 140 patients (40% female) with a mean age of 35.1+/-15.9 years and a median ISS of 41 were included in this study. The overall mortality rate was 40.7%. Binomial logistic regression analysis revealed age, initial blood pressure, transfusion requirement as well as the severity of head, chest, spleen and liver injury as independent parameters predicting reduced survival rates. This deadly duo of injuries presents a challenge to the trauma surgeon. Rapid assessment and treatment is required to prevent death by haemorrhage. The presence of concomitant injuries renders the patient very sensitive to ongoing or additional physiological disturbance. The principles of 'damage control surgery' must be applied to avoid complications such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).

Adolescent↗
PubMed2006

Fat embolism: special situations bilateral femoral fractures and pathologic femoral fractures.

Few data are available in the literature regarding fat embolism in cases of bilateral femoral and pathological femoral fractures. The incidence of bilateral femoral fractures ranges from 2-9.5% of the total number of patients with femoral fractures, and they usually occur in high energy trauma and multi-trauma patients. Although injury severity scores tend to underestimate the severity of these injuries, fat embolism seems to occur in increased frequency ranging from 4.8-7.5%. Intramedullary nailing, which is the preferred surgical treatment, triggers a systemic inflammatory response that poses an additional burden to pulmonary function. In addition, the femur is a common site of metastatic bone disease. The treatment of impending and actual pathological fractures is complicated by increased rates of lung damage due to various factors. Fat embolism during treatment--mainly with intramedullary nails--generally seems to range from 0-10%.

Embolism, Fat↗
PubMed2006

Experimental background--review of animal studies.

UNLABELLED: Most of the research on the physiological effects of intramedullary nailing is technically difficult or ethically impossible to perform in humans. A substantial range of factors apply in clinical cases, which means that the data obtained from this source may lack the control needed to reveal the basic mechanisms of pathophysiology associated with this surgical procedure. Consequently, animal studies have been relied upon to provide answers that would otherwise be unavailable. This review manuscript summarizes the available literature on animal studies dealing with the local and systemic effects of intramedullary nailing. It focuses on whether these studies have contributed to our clinical knowledge of the procedure's impact on perfusion and fracture healing, as well as the medical relevance of coincident systemic effects. DATA SOURCES: Medline, personal library of the first author and of the Department of Trauma Surgery, University of Pittsburgh Medical Center. STUDY SELECTION: All animal studies on intramedullary stabilization published in English, German, and French. CONCLUSIONS: The relevance of animal studies investigating the impact of a surgical procedure and its influence on concomitant injuries depends on the design and the type of the animal model. If this fact is considered, and if a model is selected that simulates a systemic impact comparable with the clinical situation, then animal studies may provide a valuable source of otherwise unobtainable information. Such an example is the study of fat embolization associated with intramedullary nailing. Animal subjects enable assessment of the intervention's additive surgical impact, measurement of side effects that may have adverse results, and influence of cofactors (eg, thoracic trauma, severe shock, polytrauma) that predispose the individual to postoperative complications.

Animals↗
PubMed2006

Fat embolism: the reaming controversy.

Intramedullary nailing is the preferred treatment method for stabilizing femoral diaphyseal fractures. Despite its superior biomechanical advantages over other implants, its use, particularly in selected groups of patients, has been questioned because of the possible harmful systemic effects of intramedullary reaming. The increase in intramedullary canal pressure during intramedullary nailing can result in intravasation of bone marrow and fat into the venous blood system. The subsequent consequences can be fat embolism syndrome (FES), adult respiratory distress syndrome (ARDS), and multiple organ failure. The lung seems to be the primary target for fat embolization and for the mediated effects primed by inflammatory reactions. In laboratory studies, both reamed and unreamed intramedullary nailing has been shown to alter selected pulmonary variables. Although transient, this effect appears to be more prominent with reamed than unreamed techniques. Additional studies are required to determine whether a subgroup of trauma patients is adversely affected by intramedullary reaming, thus necessitating other fixation techniques.

Bone and Bones↗
PubMed2006

The risk of local infective complications after damage control procedures for femoral shaft fracture.

OBJECTIVES: To determine infection rates after damage control orthopaedics (DCO) and primary intramedullary nailing (1' IMN) in multiply injured patients with femoral shaft fracture. DESIGN: Retrospective case analysis. SETTING: Level I trauma center. PATIENTS: All patients with New Injury Severity Score (NISS) >20 and femoral shaft fracture (AO 32-) treated in our unit between 1996 and 2002. INTERVENTION: Damage control orthopaedics, defined as primary external fixation of the femoral shaft fracture and subsequent conversion to an intramedullary nail, or primary IMN. MAIN OUTCOME MEASUREMENTS: Rates of infection classified as contamination (positive swabs with no clinical change), superficial, deep (requiring surgery), and removal of hardware (those requiring removal of femoral instrumentation or amputation). RESULTS: A total of 173 patients with 192 fractures were included; 111 fractures were treated by DCO and 81 by primary IMN. Mean follow-up was 19.1 months [median, 16.7, range, 1 (patient died)-67 months]. DCO patients had a significantly higher NISS and more grade III open fractures (P<0.001). IMN procedures took a median of 150 minutes compared with 85 minutes for DCO (P<0.0001). Although wound contamination (including contaminated pin sites) was more common in the DCO group (P<0.05), the risk of infectious complications was equivalent (P=0.86). Contamination was significantly more likely when conversion to IMN occurred after more than 14 days (P<0.05); however, this did not lead to more clinically relevant infections. Logistic regression analysis showed that although a DCO approach was not associated with infection, delay before conversion in the DCO group might be [P=0.002 for contamination and removal of hardware, P=0.065 for serious infection (deep or worse), not significant for other infection outcomes]. Grade III open injury also was significantly associated with serious infection in all patients (P<0.05). CONCLUSIONS: Infection rates after DCO for femoral fractures are comparable to those after primary IMN. We see no contraindication to the implementation of a damage control approach for severely injured patients with femoral shaft fracture where appropriate. Pin-site contamination was more common where the fixator was in place for more than 2 weeks. For patients treated by using a DCO approach, conversion to definitive fixation should be performed in a timely fashion.

Adult↗
PubMed2006

Leukocyte-endothelial interactions via ICAM-1 are detrimental in polymicrobial sepsis.

Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the transmigration of polymorphonuclear neutrophils (PMN) in sepsis. Moreover, the transmigration rate of leukocytes from the blood via endothelial adhesion molecules into tissues correlates with the severity of multi organ failure. We examined the effect of the deletion of the ICAM-1 gene in polymicrobial sepsis using a cecal ligation and puncture (CLP) sepsis model in mice. Twenty male ICAM-1 knockout (KO) mice and 20 wild-type (WT) male C57BL/6 mice were studied. CLP was performed. At several time points during a 96-hour postoperative observation period, we measured mortality, body weight, and temperature. The delayed type of hypersensitivity (DTH) reaction was determined by pinna swelling after sensitization with 50 microL of dinitrofluorobenzene (DNFB) 1%. Lymphocyte subpopulations (CD4, CD8, and CD56) and cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-10 (IL-10)] were measured using flow cytometry and ELISA testing, respectively. Also, a histologic examination of the liver and lung was performed. CLP-induced mortality was lower in the ICAM-1 group compared to normal mice (5% vs 45.0%). So were the ratios of lymphocyte subpopulations in the KO versus the WT group [CD4: 16.4 +/- 1.6% vs 25.7 +/- 4.7%; CD8: 18.3 +/- 1.4% vs 34.9 +/- 2.9%; natural killer (NK) cells: 5.6 +/- 0.3% vs 49.5 +/- 0.7%; P < 0.01]. And also the cytokine blood levels of the KO mice were significantly lower versus the WT mice (TNF-alpha: 67.2 +/- 42.2 vs 823.9 +/- 170.5 pg/mL; IL-1beta: 5.9 +/- 0.9 vs 296.2 +/- 66.2 pg/mL; IL-6: 223.1 +/- 48.8 vs 3062.5 +/- 1222.8 pg/mL; IL-10: 34.6 +/- 5.8 vs 1565.6 +/- 448.8 pg/mL; P < 0.01). With respect to the histology, significantly less leukocyte invasion and organ damage (eg, hydropic degeneration) were present in the ICAM-1-/- group compared to controls in liver and lung tissues. The DTH reaction was significantly decreased in ICAM-1-/- mice versus WT mice (0.34 vs 0.41 mm; P < 0.05). Our results demonstrate a significant reduction of mortality after septic challenge in ICAM-1-/- mice compared to normal mice. This is associated with a decrease in lymphocyte subpopulations, cytokine levels, and DTH type 4 reaction, possibly reflecting an overall attenuation of the immune system.

Animals↗
PubMed2006

Which AIS based scoring system is the best predictor of outcome in orthopaedic blunt trauma patients?

BACKGROUND: Abbreviated Injury Scale (AIS)-based systems-the Injury Severity Score (ISS), New Injury Severity Score (NISS), and AISmax-are used to assess trauma patients. The merits of each in predicting outcome are controversial. METHODS: A large prospective database was used to assess their predictive capacity using receiver operator characteristic curves. RESULTS: In all, 10,062 adult, blunt-trauma patients met the inclusion criteria. All systems were significant outcome predictors for sepsis, multiple organ failure (MOF), length of hospital stay, length of intensive care unit (ICU) admission and mortality (p < 0.0001). NISS was a significantly better predictor than the ISS for mortality (p < 0.0001). NISS was equivalent to the AISmax for mortality prediction and superior in patients with orthopaedic injuries. NISS was significantly better for sepsis, MOF, ICU stay, and total hospital stay (p < 0.0001). CONCLUSIONS: NISS is superior or equivalent to the ISS and AISmax for prediction of all investigated outcomes in a population of blunt trauma patients. As NISS is easier to calculate, its use is recommended to stratify patients for clinical and research purposes.

Abbreviated Injury Scale↗
PubMed2006

Kupffer cells and their mediators: the culprits in producing distant organ damage after trauma-hemorrhage.

Posttraumatic activation of macrophages enhances development of systemic inflammation/immunosuppression and organ dysfunction. We hypothesized that Kupffer cells are the main source of monocyte chemoattractant protein-1 (MCP-1) production after trauma-hemorrhage, that administration of 17beta-estradiol (E2) after trauma-hemorrhage modulates MCP-1 release and reduces remote organ damage, and that salutary effects of E2 are mediated via estrogen receptor (ER)-alpha. To test these hypotheses, female B57BL/J6 mice received E2 (50 microg/25 g) or vehicle after trauma-hemorrhage and female 129 Sve ER-beta-/- transgenic mice and ovariectomized wild-type mice received E2 or ER-alpha agonist propyl pyrazole triol (50 microg/25 g) after trauma-hemorrhage. Systemic MCP-1 and interleukin-6 and their release by liver, spleen, and lung macrophages were determined by flow cytometry 4 hours after trauma-hemorrhage. Prior Kupffer cell depletion with gadolinium chloride significantly decreased systemic MCP-1 and interleukin-6 after trauma-hemorrhage and was associated with decreased edema/neutrophil infiltration in lung and liver. Kupffer cells were the only macrophages showing significant MCP-1 release, which was markedly reduced by E2 or propyl pyrazole triol in wild-type and in ER-beta-/- mice. Pretreatment of mice with anti-MCP-1 antiserum prevented an increase in myeloperoxidase and edema in lung and liver. These findings suggest that Kupffer cell-derived MCP-1 plays a major role in remote organ dysfunction after trauma-hemorrhage.

Animals↗
PubMed2005

Effects of hypothermia and re-warming on the inflammatory response in a murine multiple hit model of trauma.

INTRODUCTION: Although, hypothermia is a frequent event after trauma, it is unclear whether its beneficial or detrimental effects are more important. This study aims to quantify the effects of hypothermia and re-warming on the inflammatory response after fracture/hemorrhage and subsequent fracture stabilization with resuscitation. MATERIALS AND METHODS: Eighty-one male C57Bl/6 mice (aged 8-10 weeks, weighing 22.0+/-3.0 g) underwent femoral fracture and hemorrhage followed by resuscitation and splint fixation of the fracture. Animals were sacrificed 3h after induction of hemorrhage and fracture. Besides a sham group (n=6), four experimental groups were created: A: normothermia (n=12), B: hypothermia after trauma (n=21), C: re-warming after resuscitation and before stabilization (n=21), and D: hypothermia before trauma (n=21). Groups B-D were further subdivided into three subgroups according to the degree of hypothermia (subgroup 1: 35-33 degrees C, subgroup 2: 32.9-30.0 degrees C, and subgroup 3: 29.9-27.0 degrees C). Plasma cytokine (TNF-alpha, IL-6, and IL-10) and chemokine (MCP-1) concentrations were determined by ELISA, pulmonary permeability changes were quantified, and histological analysis of lung and liver tissues was performed. RESULTS: Normothermia resulted in a significantly increased early mortality rate. A significantly increased pro-inflammatory and decreased anti-inflammatory responses were also observed in normothermia as compared to hypothermia. The extent of these changes was most pronounced in the severe hypothermic group. Re-warming after mild hypothermia resulted in a pro-inflammatory response comparable to normothermia. CONCLUSION: Hypothermia has a beneficial effect on early survival after trauma, which appears to be independent of the level of hypothermia and re-warming. Re-warming, however, enhanced the pro-inflammatory response. Further studies with a longer posttraumatic observation period are required to investigate the long term effects of the hypothermia and re-warming-induced changes on the pro- and anti-inflammatory responses.

Animals↗
PubMed2005

Implant retention and removal after internal fixation of the symphysis pubis.

Although internal fixation of diastasis of the symphysis pubis is commonly performed, there are no clear guidelines regarding the indications for removal of these implants. The long-term physiologic effects of retaining these internal fixation devices are not well described. We surveyed the literature to assess the current thinking and recommendations regarding implant retention and removal. Twenty-four case series and two case reports were found, for a total of 482 cases. Complications arose as a result of implant retention in 7.5% of patients, with infection the most common complication. There is no consensus in the literature regarding implant retention and removal after internal fixation of diastasis of the symphysis pubis.

Device Removal↗
PubMed2005

Secondary effects of femoral instrumentation on pulmonary physiology in a standardised sheep model: what is the effect of lung contusion and reaming?

Intramedullary nailing is the treatment of choice for patients with femoral shaft fractures. However, there is an ongoing debate in multiple trauma patients with associated lung contusion when primary or secondary definitive stabilisation of the long bone fracture should be performed, as nailing is thought to play an important role in the pathogenesis of adult respiratory distress syndrome (ARDS). In a standardised sheep model, this study aimed to quantify the development of acute pulmonary endothelial changes, to assess the activation of polymorphonuclear leucocytes (PMNL) and to observe the effects on the coagulation system associated with the reamed nailing procedure. Furthermore, the effect of coexisting lung contusion in an experimental model was evaluated. The animals were randomly assigned to one of four different groups (6 animals/group). In control groups, only a sham operation (thoracotomy) was performed, whereas in study groups, lung contusion was induced prior to femoral stabilisation either by external fixation or reamed femoral nailing. Using bronchoalveolar lavage (BAL) pulmonary permeability changes were quantified and PMNL activation was assessed by chemiluminescence. Additionally PMNL diapedesis and interstitial lung oedema were determined by histological analysis. All animals were sacrificed 4 h after the start of the femoral instrumentation. Without an associated lung injury, instrumentation of the femoral canal with the reamed nailing technique induced a transient increase in pulmonary permeability. In the face of an induced lung contusion, reamed femoral nailing resulted in significant increases in PMNL activation, pulmonary permeability and interstitial lung oedema, compared with external fixation. Without pulmonary contusion, reaming of the femoral canal was associated with a transient increase in pulmonary permeability. This was exacerbated in the presence of lung contusion along with increased PMNL activation. External fixation did not provoke similar changes. The findings of this study support the view that reaming of the femoral canal should be avoided in polytrauma patients with severe chest trauma as it could act as an additional stimulus for adverse outcome. Temporary external fixation appears to be a safe method for fracture stabilisation until inflammatory and coagulatory disturbances after trauma have been normalized.

Animals↗