Showing papers by "Eugen Faist published in 2000"

Coagulation inhibitor replacement during sepsis: useless?

Abstract: Objective: Because coagulatory activation in sepsis is triggered mainly by tissue factor release from endothelial cells and blood monocytes during their activation via proinflammatory cytokines, inhibition of coagulation by exogenous administration of coagulation inhibitors has been proposed. These strategies should allow us to prevent and treat excessive coagulatory activation, thereby potentially preventing sepsis-induced organ dysfunction. Potential therapies include the natural coagulation inhibitors antithrombin, activated protein C, and tissue factor pathway inhibitor, as well as direct thrombin inhibition by recombinant hirudin. Data Sources: A limited review of the published literature using all sources was undertaken. Study Selection: Selected clinical and experimental studies with coagulatory inhibitors were analyzed. Conclusions: The biological properties of coagulatory activation during sepsis (coagulation as a protective mechanism to control the septic focus, e.g., fibrin deposition during peritonitis) are not completely understood. Therefore, one has to be careful when administering coagulatory inhibitors, especially because patients with multiple organ dysfunction syndrome often do not show the widespread fibrin deposition in nutritive blood vessels that have been seen experimentally. How might these patients benefit from thrombin inhibition? Coagulatory activation per se seems unlikely to directly cause deterioration of organ function, although it is involved in generalized endothelial activation with consecutive mediator release and increased leukocyte-endothelial cell interaction. Antagonism of inflammatory mediators and, consecutively, endothelial cell activation might be a better target in adjunctive sepsis therapy, with improvement in septic microcirculatory disturbances. Administration of natural pleiotropic coagulation inhibitors that are documented positive effects on the microcirculation, (such as activated protein C, antithrombin) seems to be promising. (Crit Care Med 2000; 28[Suppl.]:S74 ‐S76)

Gender-Specific Immune Response Following Shock: Clinical and Experimental Data

Abstract: Several clinical and experimental studies demonstrate an increased susceptibility to and morbidity from shock, trauma, and sepsis in males compared to females. Moreover, cell-mediated immune responses have been found to be unchanged or enhanced in females whereas they are depressed in males following trauma hemorrhage. Sex hormones mediate this gender dimorphism of the immune response following shock. In this respect, male sex hormones have been shown to exhibit immunosuppressive properties following trauma-hemorrhage. In contrast, female sex steroids appear to be immunoprotective under those conditions. The precise underlying mechanisms for these immunomodulatory properties of sex steroids following shock, however, remain unknown. Both direct and indirect effects might act synergistically in mediating the immunomodulatory effects of sex hormones. Depletion of androgens prevented the depression of cardiovascular responses following trauma-hemorrhage which might contribute to maintained immune responses in testosterone-depleted animals. Furthermore, sex hormone receptors have been identified on various immune cells suggesting direct effects. In experimental animal models, administration of the testosterone receptor blocker flutamide or treatment with female sex steroids has been demonstrated to prevent immunodepression following trauma-hemorrhage and to decrease the mortality from subsequent sepsis. Thus, the immunomodulatory properties of sex hormones following trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

Immunosuppression with Injury and Operation and Increased Susceptibility to Infection

Abstract: In the United States, trauma is a leading cause of death during the first three decades of life and ranks as the fourth leading cause of overall mortality, with more than 100, 000 deaths each year1, 2 Much of the mortality observed during the first few hours after trauma is related to irreversible neurologic damage or exsanguination Assuming the patient survives the initial traumatic insult, he or she is still threatened by subsequent infections (sepsis) and multiple organ failure4–7 It has been reported that upward of 50% of trauma patients subsequently die owing to infections and multiple organ failure during the proceeding days to week(s) after trauma In view of this fact, most of the scientific and medical research has been directed toward measuring the progression and interrelations of events that follow trauma and major surgery These studies indicate that a causal relation exists between the traumatic injury or shock (or both) and the predisposition of these patients to develop septic/infectious complications and multiple organ failure8–10 The excessive inflammatory response together with a dramatic paralysis of cell-mediated immunity following trauma or major surgery8, 11 appears to be responsible for the increased susceptibility to subsequent sepsis

Pathophysiologic and Clinical Importance of Stress-Induced Th1/Th2 T Cell Shifts

Abstract: The fact that T cells can differentiate and become polarized to produce a certain limited spectrum of cytokines and mediate only a subset of potential T cell functions during cell-cell interactions continues to be an area of intense investigation. The mechanisms by which T-helper (Th) cels mobilize various effector reactions remained unclear until 1986 when Mosmann and Coffman started a conceptual revolution in immunology by dividing murine T cell clones, or Th cells, into the now familiar two subpopulations, Th1 and Th2 based on their restricted and stereotyped profile of cytokine secretion.1 These same two subsets can be generated from ex vivo populations when cultured under appropriate conditions;2 they can also be recovered from immunized animals3 and from patients suffering from a variety of diseases.4.

Summary and Overview: What does the Future Hold?

Abstract: This volume provides information that is on the leading edge of the care of critically ill patients. Each author is an expert in the field about which they write. They have written extensively on their subjects previously and now update the informatiation about where support and treatment are clinically feasible. Aldough basic concepts have been reviewed in many chapters, the thrust of this book is clinical patient care. The basic science underlying these therapies is important and is reviewed briefly but in depth; background information may be found in other books and journals.