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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 20 (1996), S. 454-459 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Major trauma results in massive impairment of immunologic reactivity, the clinical consequence of which consists in the high susceptibility of the traumatized individual toward serious infection. Whereas parts of the immune system are stimulated within a systemic, nondiscriminant, excessive whole-body inflammation, other functions within the complex of cell-mediated immunity (CMI) are dramatically paralyzed. Immune abnormalities in the aftermath of trauma occur in a sequence of states of cellular activation and within a complex order of events that is not yet well understood. Traumatic stress is causing disintegration of the intact monocyte (Mφ)–T cell interaction, which is associated with profound changes in Mφ forward-regulatory capacities and substantial depression of T cell function. Extensive tissue destruction results in the generation of numerous stimuli, such as phagocytosis, immune complexes, complement split products, and endo- and exotoxins, all of which contribute to excessive Mφ activation. Mφ then rapidly produce and release prostaglandin E2 (PGE2), a powerful endogenous immune suppressant. PGE2 is an inhibitor of T cell mitogenesis, interleukin 2 (IL-2) production, and IL-2 receptor expression; and it has a massive impact on the quality of B cell antibody synthesis. Most importantly, PGE2 represents an important cofactor for the induction of T-helper lymphocyte (TH) activity toward the TH2 direction. TH2 cells are associated with the synthesis of immunosuppressive cytokines, such as IL-4 and IL-10. Although immunosuppressive substrates are inhibitory for TH1 cells—the functional carriers of CMI—they support TH2 activity, which predisposes the host to develop infection. The endogenous ability of the organism to survive overwhelming trauma is insufficient and requires major exogenous support. Immune modulatory interventions, depending on the immune abnormalities seen in the traumatized host, should be started as early as possible after trauma in a preventive fashion to protect against organ tissue destruction. Ideally, it should protect all cellular host defense compartments from hyperactivation as well as from exhaustion. We do believe that only a combination of drugs can effectively control the posttraumatic dyshomeostasis of the various cell systems.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Der Chirurg 68 (1997), S. 1066-1070 
    ISSN: 1433-0385
    Keywords: Key words: Traum ; Immunology ; Cytokines ; SIRS ; MOF. ; Schlüsselwörter: Trauma ; Immunologie ; Cyokine ; SIRS ; MOF.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung. Der klinische Verlauf bei polytraumatisierten Patienten wird durch das häufige Auftreten schwerwiegender immunologischer Komplikationen beeinträchtigt. Die Immunantwort auf schweres Trauma kann durch die vermehrte Freisetzung proinflammatorischer Mediatoren über das „systemic inflammatory response syndrome (SIRS)“ zum Mehrorganversagen [„multisystem organ failure (MOF)“] führen, welches mit einer Letalität von bis zu 80 % behaftet ist. Charakteristisch für die Entwicklung des Multiorganversagens ist das Auftreten des „remote organ failure (ROF)“, eine Fehlfunktion von Organen, die durch das eigentliche Trauma keinen direkten Schaden erlitten haben. Diese Arbeit gibt einen kurzen Überblick über die neueren Entwicklungen auf dem Gebiet der tierexperimentell-immunologischen Traumaforschung und geht eingehend auf den aktuellen Stand der klinisch-immunologischen Traumaforschung ein. Insbesondere wird die Bedeutung der sog. pro- und antiinflammatorischen Cytokine bei der Entstehung von SIRS, MOF und ROF erörtert. Trotz der vielen Fortschritte auf dem Gebiet der klinischen Immunologie und der vielfältigen Informationen über die Trauma-induzierten Immunfunktionsstörungen müssen jedoch noch viele offene Fragen gelöst werden, bevor die immunologischen Veränderungen nach schwerem Trauma durch immunmodulatorische Therapieansätze nachhaltig positiv beeinflußt werden können.
    Notes: Summary. Immunologial complications frequently occur during the clinical course in patients with multiple injuries. The increased release of pro-inflammatory mediators during the immunological response to trauma may lead to the systemic inflammatory response syndrome (SIRS) and furthermore, to multisystem organ failure (MOF), which is associated with a mortality of up to 80%. The development of multiple organ failure following major trauma is associated with remote organ failure, the dysfunction of organs which were not initially affected by the traum. This manuscript reviews recent data in experimental trauma research and offers a more detailed evaluation of the immunological findings in trauma patients. In particular, the role of pro- and anti-inflammatory cytokines in the development or SIRS, MOF and ROF is discussed. Despite the enormous progress in clinical immunology and the available data on trauma-induced immune dysfunction, a large number of questions still remain to be answered before the immunological alterations following severe trauma can be beneficially influenced by immunomodulatory therapeutic efforts.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1420-908X
    Keywords: Key words: Anticoagulants — Interleukins — Tumor necrosis factor assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective and Design: Unfractionated heparin is frequently used as an anticoagulant during blood sampling and in cell culture experiments. In the present study we investigated whether heparin and other anticoagulants (citrate and EDTA) interfered with measurements of plasma tumor necrosis factor alpha (TNFα) concentrations or with TNFα release from endotoxin-stimulated monocytes.¶Material and Methods: TNFα was measured by a WEHI 164 bioassay in the plasma of 16 septic patients anticoagulated with heparin, citrate, or EDTA. Anticoagulants were incubated with the bioassay cell line and cell lysis was monitored. To exclude falsely low TNFα concentrations, anticoagulants were incubated in increasing amounts with human recombinant TNFα/saline solution, and rTNFα recovery was measured either with the WEHI 164 bioassay or an ELISA test. Further, anticoagulants were incubated with monocytes isolated from healthy volunteers and stimulated with endotoxin. Supernatants were analyzed for TNFα with both test systems.¶Results: No biologically active TNFα was detected in the plasma with heparin anticoagulation, whereas with citrate, reproducible, TNFα-induced cytotoxicity was detectable in blood samples of 13 of the 16 patients. Anticoagulation with EDTA resulted in fairly high, variable and poorly reproducible TNFα values. Only EDTA produced falsely high values by unspecific lysis of WEHI cells. Only heparin at a concentration of 20 I.U./ml or more was found to produce falsely low values by interaction with the TNFα bioassay, but also with the ELISA test. In monocyte culture experiments, heparin significantly attenuated the stimulatory effect of endotoxin on TNFα release already at the lowest concentration tested (25 I.U./ml).¶Conclusions: Heparin and EDTA may have significant adverse effects on TNFα measurement when used for blood sampling. Citrate does not interfere with the TNFα bioassay or ELISA, and seems, therefore, to be the anticoagulant of choice. Due to intrinsic interactions with various cell systems (including the WEHI cell and monocytes), one should be careful in using heparin in cell culture studies in which effects of TNFα or of endotoxin are being studied.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0930-9225
    Keywords: Schlüsselwörter Herzchirurgie – multiples Organversagen (MOF) – akutes Atemnotsyndrom des Erwachsenen (ARDS) – Systemic inflammatory response syndrome (SIRS) – Xanthinderivate ; Key words Cardiac surgery – multiple organ failure (MOF) – adult respiratory distress syndrom (ARDS) – systemic inflammatory response syndrome (SIRS) – xanthine derivatives
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The potential therapeutic effect of intravenous 3,7-dimethyl-1-(5-oxohexyl)xanthine (Pentoxifylline) in patients at risk for developing multiple organ failure following major cardio-thoracic surgery was assessed. Forty petients having APACHE II score values ≥19 at the first postoperative day after major cardio-thoracic surgery were randomized into two groups to receive either placebo (Control; n=25) or intravenous pentoxifylline (1.5 mg/kg/h) treatment (Pentoxifylline; n=15) as an adjunct to standard supportive therapy. The control group patients as compared to pentoxifylline treated patients required a longer period of time of ventilator support (8.3±3.1 days vs. 3.1±0.9 days; p〈0.05), experienced a higher incidence of renal failure (days on dialysis/hemofiltration: 6.8±3.3 vs 1.2±0.8; p〈0.05) and a longer ICU stay (11.4±3.1 vs. 5.2±1.1 days; p〈0.05). Overall mortality was not different between treatment groups. The results of this first clinical pilot study suggest that supplemental intravenous pentoxifylline treatment may decrease the incidence of acute lung injury and renal failure in patients after cardiac surgery.
    Notes: Zusammenfassung In einer ersten klinischen Pilotstudie wurde die Wirksamkeit einer kontinuierlichen intravenösen Infusion des Xanthinderivates Pentoxifyllin zur Reduktion der Inzidenz des akuten Lungenversagens bei Hochrisiko-Patienten nach großen herzchirurgischen Eingriffen untersucht. Unter 816 konsekutiv operierten Patienten wurden 40 Patienten mit einem hohen Risiko für die Entwicklung eines Multiorganversagens anhand des APACHE II Scores (≥19) am ersten postoperativen Tag identifiziert. Die Patienten wurden in zwei Gruppen randomisiert: Standard-Behandlung (Kontrolle n=25) oder Standard-Behandlung+Pentoxifyllin-Therapie (Pentoxifyllin n=15). Primäre Studienendpunkte waren die Dauer der Beatmungspflichtigkeit, die Inzidenz eines akuten Nierenversagens (Dialyse-/Hämofiltrationspflichtigkeit) und die Verweildauer auf der Intensivstation. Die Ergebnisse von 37 der 40 Patienten konnten ausgewertet werden. Die Pentoxifyllin-Therapie (kontinuierliche intravenöse Infusion von 1,5 mg/kg/h) wurde gut toleriert; es wurden keine anhaltenden signifikanten Nebenwirkungen beobachtet. Die Dauer der Beatmung war signifikant kürzer in der Pentoxifyllin-Gruppe (3,1±0,9 die) als in der Kontrollgruppe (8,3+3,1 die, p=0,037) Im Vergleich zu den mit Pentoxifyllin behandelten Patienten trat bei den Kontroll-Patienten häufiger ein therapiepflichtiges Nierenversagen auf (Dialysetage 6,8±3,3 vs. Pentoxifyllin-Gruppe: 1,2+0,8 die, p=0,048). Die Verweildauer auf der Intensivstation war signifikant kürzer bei den Pentoxifyllin-behandelten Patienten (5,2±1,1 vs. 1,4±3,1 die; p〈0,05). Die Gesamtletalität betrug 36% in der Kontrollgruppe und 33% in der Pentoxifyllin-Gruppe und war nicht signifikant unterschiedlich. Zusammengefaßt konnten wir in dieser ersten klinischen Pilotstudie zeigen, daß eine kontinuierliche Infusion von Pentoxifyllin bei Hochrisiko-Patienten nach großen herzchirurgischen Eingriffen die Inzidenz des akuten Lungen-, und Nierenversagens reduzieren kann.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1238
    Keywords: Key words Hemofiltration ; Cytokines ; Anaphylatoxins ; Hemodynamics ; Sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. Design: Prospective observation study. Setting: Surgical intensive care unit of a university hospital. Patients: 16 patients with severe sepsis. Interventions: Continuous zero-balanced HF without dialysis (ultrafiltrate rate 2 l/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. Measurements and main results: Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1β, IL-6, IL-8, and tumor necrosis factor α) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0=676.9±99.7 ng/ml vs t12=467.8±71, p〈0.01; C5adesArg: 26.6±4.7 ng/ml vs 17.6±6.2, p〈0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669±85 dyne·s/cm5 vs SVR at t12: 864±75, p〈0.01; MAP at t0: 69.9±3.5 mmHg vs MAP at t12: 82.2±3.7, p〈0.01). Conclusions: HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1238
    Keywords: Hemofiltration ; Cytokines ; Anaphylatoxins ; hemodynamics ; Sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To determine whether hemofiltration (HF) can eliminate cytokines and complement components and alter systemic hemodynamics in patients with severe sepsis. Design Prospective observation study. Setting Surgical intensive care unit of a university hospital. Patients 16 patients with severe sepsis. Interventions Continuous zero-balanced HF without dialysis (ultrafiltrate rate 21/h) was performed in addition to pulmonary artery catheterization, arterial cannulation, and standard intensive care treatment. Measurements and main results Plasma and ultrafiltrate concentrations of cytokines (the interleukins IL-1β, IL-6, IL-8, and tumor necrosis factor α) and of complement components (C3adesArg, C5adesArg) were measured after starting HF (t0) and 4 h (t4) and 12 h later (t12). Hemodynamic variables including mean arterial pressure (MAP), mean central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were serially determined. During HF, cytokine plasma concentrations remained constant. However, C3adesArg and C5adesArg plasma concentrations showed a significant decline during 12-h HF (C3adesArg: t0=676.9±99.7 ng/ml vs t12=467.8±71,p〈0.01; C5adesArg: 26.6±4.7 ng/ml vs 17.6±6.2,p〈0.01). HF resulted in a significant increase over time in systemic vascular resistance (SVR) and MAP (SVR at t0: 669±85 dyne·s/cm5 vs SVR at t12: 864±75,p〈0.01; MAP at t0: 69.9±3.5 mmHg vs MAP at t12: 82.2±3.7,p〈0.01). Conclusions HF effectively eliminated the anaphylatoxins C3adesArg and C5adesArg during sepsis. There was also a significant rise in SVR and MAP during high volume HF. Therefore, HF may represent a new modality for removal of anaphylatoxins and may, thereby, deserve clinical testing in patients with severe sepsis.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 358 (1982), S. 578-578 
    ISSN: 1435-2451
    Keywords: Polytrauma ; Multiple organ failure ; Sepsis ; Traumatic shock ; Polytrauma ; Vielfach-Organversagen ; traumatischer Schock ; Sepsis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine Analyse von 375 Polytraumatisierten aus 4 Jahren ergab in 8 % ein isoliertes, in 6,7 ein multiples Organversagen. Das IOV betraf überwiegend die Lunge (27/30), beim MOV war grundsätzlich die Lunge der Ausgangsort. Die Letalität stieg mit der Zahl der befallenen Organe: Lunge allein: 37 %, Lunge und Leber 70 %. Ein Vierfach-Organversagen überlebten 2 von 6. Schock und Sepsis waren die prädisponierenden Faktoren. Bei ihrer Verhütung sowie ausreichender frühzeitiger Beatmung muß auch die Prophylaxe ansetzen.
    Notes: Summary The analysis of 375 polytraumatized patients during 4-year period showed in 8 % a single (SOF) and in 6.7 % a consecutive multiple organ failure (MOF). The SOF concerned the lung in 27 of 30 cases; in MOF the lung was the first organ concerned in all cases, followed by the liver. Mortality rose with the number of organs involved: lung alone 37 %, lung and liver 70 %. A quadruple failure was only survived by 2 of 6. Traumatic shock and sepsis were predisposing factors; their prevention was the main prophylaxis of MOF, together with sufficient and early respirator treatment.
    Type of Medium: Electronic Resource
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