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In einer ersten klinischen Pilotstudie wurde die Wirksamkeit einer kontinuierlichen intravenosen Infusion des Xanthinderivates Pentoxifyllin zur Reduktion der Inzidenz des akuten Lungenversagens bei Hochrisiko-Patienten nach grosen herzchirurgischen Eingriffen untersucht. Unter 816 konsekutiv operierten Patienten wurden 40 Patienten mit einem hohen Risiko fur 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). Primare Studienendpunkte waren die Dauer der Beatmungspflichtigkeit, die Inzidenz eines akuten Nierenversagens (Dialyse-/Hamofiltrationspflichtigkeit) und die Verweildauer auf der Intensivstation. Die Ergebnisse von 37 der 40 Patienten konnten ausgewertet werden. Die Pentoxifyllin-Therapie (kontinuierliche intravenose Infusion von 1,5 mg/kg/h) wurde gut toleriert; es wurden keine anhaltenden signifikanten Nebenwirkungen beobachtet. Die Dauer der Beatmung war signifikant kurzer 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 haufiger 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 kurzer bei den Pentoxifyllin-behandelten Patienten (5,2±1,1 vs. 1,4±3,1 die; p

Der klinische Verlauf bei polytraumatisierten Patienten wird durch das haufige Auftreten schwerwiegender immunologischer Komplikationen beeintrachtigt. Die Immunantwort auf schweres Trauma kann durch die vermehrte Freisetzung proinflammatorischer Mediatoren uber das „systemic inflammatory response syndrome (SIRS)“ zum Mehrorganversagen [„multisystem organ failure (MOF)“] fuhren, welches mit einer Letalitat von bis zu 80 % behaftet ist. Charakteristisch fur 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 Uberblick uber 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 erortert. Trotz der vielen Fortschritte auf dem Gebiet der klinischen Immunologie und der vielfaltigen Informationen uber die Trauma-induzierten Immunfunktionsstorungen mussen jedoch noch viele offene Fragen gelost werden, bevor die immunologischen Veranderungen nach schwerem Trauma durch immunmodulatorische Therapieansatze nachhaltig positiv beeinflust werden konnen.

Health care is facing efficiency (quality) problems while costs are exploding. Quality management (QM) therefore becomes a major strategic challenge. Thus, the international QM system ISO9001:2000 was introduced and certified in the areas of translational medicine, clinical research and tissue banking, all promoting new and more efficient diagnostic and therapeutic strategies. Various measurement tools to ensure continuous quality improvement have been established, namely a trained QM advisory board, specific quality circles, internal audits, management reviews and an external quality assurance program. Initially the implementation of a comprehensive QM system is time consuming and expensive. However, the benefits obtained in organisation, documentation, process flows and resource management are obvious all resulting in the improvement of the research quality. Ongoing in the Plan-Do-Check-Act cycle will be an important approach in fund raising and patient acquisition

Nach einer langen Serie von enttauschenden Studien konnte jungst in einer grosen Multizenterstudie (PROWESS) eine signifikant hohere Uberlebensrate von Patienten mit schwerer Sepsis erzielt werden, wenn sie neben der Basistherapie mit Protein C behandelt wurden. Das erhohte Blutungsrisiko in der Behandlungsgruppe scheint jedoch den Einsatz von Protein C bei chirurgischen Patienten zu limitieren. Die Substitution von AT III (KYBERSEPT) fuhrte lediglich bei nicht heparinisierten Patienten zu einer Verbesserung des Uberlebens bei Sepsis. Hydrokortisonsubstitution reduziert die Therapiedauer mit vasopressiv wirkenden Katecholaminen. Die Ergebnisse von Hydrokortisonsubstitution auf das Uberleben septischer Patienten bleibt abzuwarten. Insgesamt stellt die fruhzeitige Fokussanierung und die Antibiotikatherapie nach Antibiogramm weiterhin die Basis der Sepsisthera — pie dar.

In the sequelae of massive traumatic stress, substantial impairment of immunologic reactivity has been demonstrated to correlate clinically with increased susceptibility to serious infection. Posttraumatic immune abnormalities consist basically of two coexistent mechanisms: Hyperinflammation and depression of cell-mediated immune responses. It is our understanding that the endogenous ability of the organism to survive overwhelming trauma is insufficient and requires exogenous support to prevent the conversion from systemic inflammatory response syndrome to bacterial sepsis and septic shock. The objectives of immunomodulatory interventions, which should be started as early as possible after tissue destruction, include a) prevention of excessive macrophage stimulation via neutralization of circulating endotoxins and exotoxins with high doses of polyvalent immunoglobulin and soluble complement receptors, b) global short-term (72 hrs) down-regulation of inflammatory monocyte/macrophage and polymorphonuclear neutrophil activity, and c) restoration of cell-mediated immune performance to overcome posttraumatic functional paralysis. Among recent promising strategies, the use of granulocyte-macrophage colony-stimulating factor, pentoxifylline, and recombinant human interleukin-13 has been suggested, all of them predominantly down-regulating the Mphi (monocyte/macrophage) inflammatory potential. Cyclooxygenase inhibitors such as indomethacin and thymomimetic peptides can help normalize the immunoreactivity by restoring the forward-regulatory pathway of cell-mediated immunity responses. The efficacy of interferon to reduce infection and deaths in severely injured patients has been assessed in clinical trials. Still other compounds, i.e., CNI-1493, interleukin-11, tissue factor pathway inhibitors, and PGG-Glucan represent auspicious immunomodulatory approaches for control of posttraumatic or postoperative infections.

Seit der Einfuhrung der endovaskularen Stentgraftausschaltung von Aortenaneurysmen wurde uber eine bislang bei offenen Operationen nicht beschriebene inflammatorische Reaktion berichtet, welche auch als „Postimplantationssyndrom“ bezeichnet wird [1, 2]. Dieses Syndrom ist durch einen Anstieg der Leukozyten, des C-reaktiven Proteins und der Korpertemperatur charakterisiert und ist fur die Dauer von bis zu zwei Wochen nachzuweisen. In keiner der veroffentlichten Arbeiten konnte ein infektioser Herd dargestellt werden, ebenso war eine spezifische Therapie nicht von Noten. Die immunologische Grundlage dieser Reaktion ist bislang nicht bekannt und in ersten Ansatzen nur unzureichend beschrieben. Ziel dieser Studie war es, anhand des direkten Vergleiches von konventionell offen operierten und endovaskular mittels eines Stentgraftsystems versorgten Aortenaneurysmen das „Postimplantationssyndrom“ naher zu charakterisieren. Hierzu wurden neben den klinischen Daten, vor allem das Gerinnungssytem und die Akutphasereaktion untersucht.

To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma.Retrospective study.Teaching hospitals, USA and Germany.Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points.Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10).Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns.High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma.Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.

Major injury is a profound threat to the individual. Both the extent of injuries and the preinjury health of the patient greatly influence the outcome. In our experience with individuals having an injury severity score (ISS) of 30 points or higher who survive the immediate injury phase, only 50% begin convalescence without inflammatory or infectious complications (Faist et al. 1993). Thus in every second patient the metabolic and neuroendocrine stress reactions do not shut down and return to normal regulation and homeostasis. The causes of this phenomenon in multisystem injuries are extensive tissue necrosis, prolonged hemorrhagic shock, and perhaps immediate invasive endotoxemia by way of gut translocation.

Trauma and the subsequent stress response have been associated with widely varied changes in host defense. A large body of information has been accumulated characterizing the various types of immune dysfunction following injury and suggests that major accidental, burn, or operative trauma causes substantial immunosuppression [1–4]. The deficit of immunocompetence together with an overwhelming nondiscriminant whole body inflammatory response explains the high susceptibility of the injured individual for developing sepsis with consecutive multiple organ dysfunction syndrome (MODS). We and others have demonstrated that the alterations of cell-mediated immunity (CMI) following trauma is mainly due to the disruption of intact monocyte (Mo)/T cell interaction [5, 6]. Within this phenomenon we see a shift of the cell ratio in the compartment of peripheral blood mononuclear cells (PBMCs) with a considerable increase of prostaglandin E2 (PGE2)-synthesizing Mos and a simultaneous decrease of functionally competent CD3+ and CD4+ lymphocytes. T cell dysfunction in states of profound mechanical stress is characterized by impaired synthesis of two crucial cytokines — interleukin-2 (IL-2) and γ-interferon (γ-IFN) [7, 8]. The inability to produce adequate amounts of IL-2 results in incomplete proliferative T cell responses to antigenic stimuli, while a lack of γ-IFN results in inefficient Mo antigen presentation. It has been demonstrated that both defects are keystones of suppressed CMI function following trauma with subsequent development of sepsis. The information derived from the dissection of down-regulatory mechanisms responsible for the development of injury-related immunoincompetence also provided incentive for the development of therapeutic regimens designed to prevent a major collapse of CMI.

Lipopolysaccharide causes activation of monocytes/macrophages with excessive secretion of cytokines resulting in hypotension and shock in patients with sepsis. Lipopolysaccharide may induce these responses by interacting with lipopolysaccharide-binding protein and then binding to the cell surface protein CD14 or by acting directly with CD11-CD18 on monocytes/macrophages. The role of CD14 and CD11-CD18 in the activation of macrophages with enhanced cytokine transcription in patients with septic shock remains to be determined.To study this, heparinized blood was obtained from 16 patients with septic shock on days 0, 1, 3, 5, 7, and 10 and compared with 20 control patients. The expression of CD14 and CD11b on monocytes in whole blood was measured by direct immunofluorescence and flow cytometry. Moreover, whole blood was stimulated with lipopolysaccharide (1 microgram/ml) for 0, 1, 2, 4, 8, and 24 hours, and messenger RNA expression for tumor necrosis factor-alpha, interleukin-beta (IL-1 beta), and IL-6 was determined on isolated peripheral blood mononuclear cells with Northern blot analysis.Both CD14 expression and receptor density on monocytes from whole blood were markedly suppressed (-63% on day 3; p0.05) in the septic group compared with controls. Although CD11b expression was also decreased (-24% on day 1; p0.05), receptor density on monocytes was slightly increased in the septic group in comparison with the control group. Kinetics and intensity of messenger RNA expression for tumor necrosis factor-alpha, IL-1 beta, and IL-6 were similar in both groups.These data indicate that in patients with septic shock, lipopolysaccharide-mediated signaling and cytokine transcription are unchanged despite a significant reduction of CD14 expression and density on monocytes. Thus, lipopolysaccharide-induced activation of monocytes from patients with sepsis may occur through direct binding of lipopolysaccharide to the CD11-CD18 complex or other lipopolysaccharide receptors, whereas binding of the lipopolysaccharide-lipopolysaccharide-binding protein complex to the CD14 receptor may not play a pivotal role in sepsis.

The monokine Interleukin-1 (IL-1) and the lymphokine IL-2 are playing a crucial role within the course of an intact cell mediated immune response (CMI). It was the objective of this study to further elucidate the cytokine associate mechanisms of dysfunctional T-cell activation following major burn and mechanical trauma. Via comparative analysis of mRNA expression and protein release the major regulatory levels of IL-1 and IL-2 release under stressful conditions were to be determined in mitogen respectively LPS stimulated PBMC (peripheral blood mononuclear cells) cultures on consecutive days (D) 1, 3, 5, 7 and 10 post injury. Further, we wanted to scrutinize if inadequate IL-2 production post-trauma is possible due to a defective transduction of extracellular signals to the T-cell nucleus. In order to answer this question IL-2 mRNA expression and IL-2 protein releases were determined in PBMC cultures using the phosphokinase C (PKC) activator phorbol ester (PMA) as a costimulus together with PHA. When analyzing the cumulative data for IL-1 beta we saw until D 5 post-trauma a considerable impairment of the protein release in LPS stimulated PBMC cultures and recovery thereafter. In only a few individual PBMC cultures we saw a concurrence between the IL-1 beta mRNA signal intensity and the protein production. In the majority of the autoradiographies analyzed, the mRNA expression for IL-1 beta was considerably more distinct compared to controls while the corresponding protein release values were on control level or below. These results implicate that the suppression of IL-1 beta post-trauma is regulated mainly on a posttranscriptional level. Since Prostaglandin E2 (PGE2) has been found to have a vigorous impact on the IL-1 beta synthesis on the translational level, we assume that the high PGE2 levels post-trauma inhibit--via cAMP--sufficient IL-1 beta synthesis on the posttranscriptional level. IL-2 protein synthesis as well as mRNA expression in mitogen (PHA) stimulated PBMC cultures following trauma, was persistently and significantly depressed compared to controls during the time of observation. The addition of PMA as a costimulus to PHA, could induce very distinct mRNA signals for IL-2 with a signal intensity which was comparable to that found in the cells of healthy controls. Also the quantity of IL-2 protein release in the vast majority of all patients PBMC cultures following PHA/PMA induction was within the control range.(ABSTRACT TRUNCATED AT 400 WORDS)

Die traumainduzierte Suppression des T-Zellwachstumsfaktors IL-2 ist eine der folgenschwersten Funktionsstorungen der spezifischen Immunantwort, da aufgrund der daraus resultierenden mangelnden klonalen T-Zellexpansion die Entstehung opportunistischer Infektionen bei Schwerverletzten begunstigt, respektive die anerge Reaktionslage des kritisch kranken Patienten nicht durchbrochen werden kann.

This study was designed to further differentiate monocyte behavior in critically ill patients with operative or accidental trauma. The patient population studied consisted of 39 patients (17 patients undergoing elective surgery [ES], seven patients with major multiple injuries [MI], and 15 patients in an acute septic state [S]). Immunologic parameters assessed included monocyte phenotyping with the monoclonal antibody LeuM3, measurement of the cytokines interleukin (IL)-1, IL-6, and IL-8 in lipopolysaccharide-stimulated in vitro cultures of mononuclear leukocytes (PBMCs), and determination of neopterin in gamma-interferon-stimulated in vitro cultures and corresponding serum samples. Serum neopterin levels were very high in S patients (89.0 nmol/L; p less than 0.05) compared with control values (4.6 nmol/L), with a rise to 16.4 nmol/L in ES patients on day 7 and 13.4 nmol/L in MI patients on day 7. The concentrations of gamma-interferon-induced neopterin in the supernatants of the PBMC cultures were elevated in all patient groups. Severe impairment of IL-1 synthesis was seen in MI and S patients. IL-8 synthesis (818 +/- 150 units/ml, control value) was also suppressed (p less than 0.05) in MI patients; the values were 135 +/- 65 units/ml on day 1,231 +/- 110 units/ml on day 3,347 +/- 131 units/ml on day 7, and 355 +/- 107 units/ml in S patients. The kinetic patterns of synthesis were comparable for IL-1 and IL-8 in all patient groups. Lipopolysaccharide-induced IL-6 synthesis (9.4 +/- 1.5 x 10(3) units/ml, control value) was significantly elevated in the PBMC cultures of all patient groups, with the exception of the early phase after accidental trauma. Maximum amounts of IL-6 synthesis after surgery were 19.6 +/- 7 x 10(3) units/ml in S patients and 19.0 +/- 2.2 x 10(3) units/ml in ES patients. These results demonstrate (1) the impairment of the functional capacity of circulating monocytes and (2) that the degree of functional impairment is proportional to the severity of the injury.

Monocyten/Makrophagen (M0) spielen eine entscheidende Rolle innerhalb der Immunantwort, indem sie durch Antigenprasentation und Freisetzung wichtiger Monokine regulativ in die durch Lymphocyten getragenen Ablaufe der zellvermittelten Immunitat eingreifen. Funktionsveranderungen zirkulierender Mo sind in den letzten Jahren gut untersucht worden und fur viele der immunologischen Alterationen nach Trauma und in der Sepsis wesentlich mitverantwortlich. Zu den wichtigsten Defekten zahlt, bedingt durch Endotoxin und andere aus der Endotoxinamie resultierenden Mediatoren, die verminderte Freisetzung vorwartsregulatorischer Monokine zugunsten immunsuppressiver Substanzen [1]. Ein wesentliches Cytokin innerhalb des komplexen Netzwerkes von Signalstoffen des Immunsystems ist Interleukin-6 (IL-6), welches im wesentlichen von Makrophagen, zu einem geringen Anteil auch von Lymphocyten, synthetisiert und freigesetzt wird. IL-6 ist ein pleiotropes Cytokin mit Wirkungen auf das T- und B-Zellsystem, mit antiviralen Eigenschaften (identisch mit Interferon beta 2) und der wesentlichen Wirkung der Akut-Phase-Induktion in Hepatocyten [2]. Ziel der vorliegenden Studie war die weitergehende Analyse, ob innerhalb des Mo-Systems eine phanotypisch unterscheidbare Untergruppe (durch den Fc-Receptor) ein anderes Syntheseprofil fur IL-6 zeigt.

Endotoxin mediates the pathophysiological changes associated with sepsis and multisystem organ failure (MSOF).

Die supprimierte zellvermittelte Immunitat (CMI) nach ausgedehntem operativen Trauma ist ein zentraler atiologischer Faktor fur die Entwicklung postoperativer opportunistischer Infektionen. Patienten mit fehlender Hauttestreaktion vom verzogerten Typ (DTH-response) als Mas fur deren Immunitat weisen eine hohere Incidenz von postoperativ septischen Komplikationen auf (1), welche sich in der Literatur zwischen 14% (2) bis 53% (3) bewegt. Ursache fur die cutane Anergie ist eine in-vivo Blokkierung immunkompetenter Zellen, da isolierte in-vitro aktivierte Lymphocyten nach intradermaler Reinjektion eine Hautreaktion hervorrufen konnen (4). In eigenen Untersuchungen zur Genese der traumainduzierten Suppression der CMI wurden als wesentliche atiologische Faktoren das Uberwiegen von suppressorisch aktiven Makrophagen mit hoher PGE2-Produktion sowie eine durch konsekutiven Mangel an Interleukin-1 bedingte Unterreprasentation funktionell intakter T-Lymphocyten (CD4+) herausgestellt (5, 6).

The term immunomodulation has started to come into use through an increasing number of experiments showing that substances of various origin can stimulate as well as inhibit immune responses induced by a primary stimulus. At the beginning of this decade, it had been generally accepted that the effect of such substances (named as immunomodulators, immune regulators, biological response modifiers, etc.) depends on the dose, route of administration, and treatment regimen as well as on the actual immune status of the subject treated [1–3]. The influence of the dose is easy to understand and even the importance of the actual immune status of the subject treated cannot be declared as surprising. Considering that any immune response is the net result of a series of interactions between different cell populations, the response will necessarily be modified by any change in the proportion or function of the various cells involved. In fact, investigations into the mechanism of action of thymopentin — a pentapeptide segment 32–36 of the thymic hormone thymopoietin [4–6] — showed that the actual immune status is not only one but the most important factor in determining the outcome of the immunomodulation [7]. As to the other factors mentioned, only the dose of the immunomodulator has been shown as being of primary importance; the influence of timing and frequency of drug administration reflect only the importance of the actual immune status [7], while that of the route of administration can be explained by the bioavailability of the pentapeptide [7, 8].

Nachblutungen, biliare Fisteln und Parchymnekrosen sowie die sekundare Entwicklung subphrenischer Abscesse oder einer galligen Peritonitis komplizieren den postoperativen Verlauf nach Leberresektionen vor allem bei ausschlieslich konventioneller chirurgischer Technik (1, 4, 5). Zwei in den letzten Jahren entwickelte dominierende Verfahren versprechen die sorgfaltige chirurgische Blutstillung bei Leberparenchymdefekten zu verbessern: Die Infrarotsaphir-Coagulation (ISK) und der biologische 2-KomponentenFibrinkleber (FK) (2, 3, 4).

While many investigators agree that the trauma-induced breakdown of the lymphokine cascade (interleukins 1 and 2; IL-1, IL-2) is responsible for the lack of T-lymphocyte activation and proliferation following injury [7–9], its potential effect on B-cell responses has not been investigated extensively so far. While there have been some studies on specific and unspecific humoral immune responses in burned individuals [25, 30], there have been only a very limited number of observations made of humoral immune responses following major trauma. It is known that in patients who develop severe sepsis, the antibody-forming cell responses are profoundly depressed compared to those of patients who did not develop sepsis and who had normal amounts of antibody-forming cells [4]. Nohr et al. [20, 21] studied humoral immunity in surgical patients in vivo and in vitro. They found a deficiency of in vitro B-cell responses to tetanus toxoid compared to those of controls, who showed a population of B-cells that spontaneously secreted tetanus toxoid in vitro following immunization. In vitro antibody production in their study reflected the in vivo antibody responses. Nohr et al. concluded from their results that the failure of specific antibody production might be caused by a failure of the antigen recognition and/or lymphocyte activation in unresponsive surgical patients.

Sepsis is responsible for 75% of late deaths after major thermal or traumatic injury. In the clinical setting, efforts to prevent or control sepsis, or both, should include an understanding of normal host resistance, proper resuscitation techniques, and nutritional support. Previous studies have identified T suppressor cell abnormalities following thermal injury and have suggested macrophage defects after traumatic injury. Although major thermal injury is easier to quantify than mechanical trauma, both insults can stress patients' host resistance to a maximal degree, leading to profound and often fatal immunosuppression. Recent studies summarized in this paper have suggested that the macrophage and the interleukin system may play a major role in initiating some of these immune abnormalities following injury.

The effect of a single dose (50 mg) of thymopentin, administered subcutaneously, on antigen-induced proliferation of peripheral blood mononuclear cells (PBMCs) was investigated in 25 volunteers (all over 50 years of age) and in nine patients undergoing major surgery. Blood samples from another nine patients having the same type of surgery were used as control in the second trial. A statistically significant increase in the proliferative response was observed in the group of volunteers two hours after thymopentin administration. This increment was not demonstrable as significant 24 h later. In contrast to this observation, the surgical procedure-induced significant decrement in the proliferation of PBMCs observed on the first and third postoperative days did not occur in the thymopentin-treated patients on the first postoperative day. This preventive effect of the single dose of thymopentin administered two hours before surgery was no longer demonstrable on the third postoperative day. Further studies are ongoing in order to establish a treatment regimen with thymopentin for the therapy of trauma-induced immune deficiencies.

Eine Analyse von 375 Polytraumatisierten aus 4 Jahren ergab in 8 % ein isoliertes, in 6,7 ein multiples Organversagen. Das IOV betraf uberwiegend die Lunge (27/30), beim MOV war grundsatzlich die Lunge der Ausgangsort. Die Letalitat stieg mit der Zahl der befallenen Organe: Lunge allein: 37 %, Lunge und Leber 70 %. Ein Vierfach-Organversagen uberlebten 2 von 6. Schock und Sepsis waren die pradisponierenden Faktoren. Bei ihrer Verhutung sowie ausreichender fruhzeitiger Beatmung mus auch die Prophylaxe ansetzen.