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284 Haematologica (ed. esp.), volumen 85, supl. 2, octubre 2000 24. Fong Y, Tracey KJ, Moldawer LL et al. Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia. J Exp Med 1989; 170: 1627-1633. 25. Endo S, Inada K, Inoue Y et al. Two types of septic shock classified by the plasma levels of cytokines and endotoxin. Circ Shock 1992; 38: 264-274. 26. ten Cate JW, van der Poll T, Levi M, ten Cate H, van Deventer SJ. Cytokines: triggers of clinical thrombotic disease. Thromb Haemost 1997; 78: 415-419. 27. Boermeester MA, van Leeuwen PA, Coyle SM, Wolbink GJ, Hack CE, Lowry SF. Interleukin-1 blockade attenuates mediator release and dysregulation of the hemostatic mechanism during human sepsis. Arch Surg 1995; 130: 739-748. 28. Fischer E, Marano MA, Van Zee KJ et al. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock, but fails to alter host responses to sublethal endotoxemia. J Clin Invest 1992; 89: 1551-1557. 29. Jansen PM, Boermeester MA, Fischer E et al. Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates after interleukin-1 alpha administration and during lethal bacteremia. Blood 1995; 86: 1027-1034. 30. Shalaby MR, Waage A, Aarden L, Espevik T. Endotoxin, tumor necrosis factor-alpha and interleukin 1 induce interleukin 6 production in vivo. Clin Immunol Immunopathol 1989; 53: 488-498. 31. Van der Poll T, Levi M, Hack CE et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 1994; 179: 1253-1259. 32. Creasey AA, Chang AC, Feigen L, Wun TC, Taylor FB Jr, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91: 2850-2856. 33. Hack CE, De Groot ER, Felt-Bersma RJ et al. Increased plasma levels of interleukin-6 in sepsis. Blood 1989; 74: 1704-1710. 34. Taylor FB Jr, Chang AC, Peer GT et al. DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage. Blood 1991; 78: 364-368. 35. Muñoz MC, Montes R, Hermida J, Orbe J, Páramo JA, Rocha E. Effect of the administration of recombinant hirudin and/or tissue-plasminogen activator (t-PA) on endotoxin-induced disseminated intravascular coagulation model in rabbits. Br J Haematol 1999; 105: 117-121. 36. Taylor FB Jr, Chang A, Ruf W et al. Lethal E. coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-134. 37. Lauw FN, Dekkers PE, te Velde AA et al. Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. J Infect Dis 1999; 179: 646-652. 38. Kuipers B, van der Poll T, Levi M et al. Platelet-activating factor antagonist TCV-309 attenuates the induction of the cytokine network in experimental endotoxemia in chimpanzees. J Immunol 1994; 152: 2438-2446. 39. Held TK, Weihua X, Yuan L, Kalvakolanu DV, Cross AS. Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms, at the signal transduction level and via an autocrine mechanism involving tumor necrosis factor alpha and interleukin-1. Infect Immun 1999; 67: 206-212. 40. Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10. Annu Rev Immunol 1993; 11: 165-190. 41. Howard M, Muchamuel T, Andrade S, Menon S. Interleukin 10 protects mice from lethal endotoxemia. J Exp Med 1993; 177: 1205-1208. 42. Marchant A, Bruyns C, Vandenabeele P et al. Interleukin-10 controls interferon-gamma and tumor necrosis factor production during experimental endotoxemia. Eur J Immunol 1994; 24: 1167-1171. 43. Pradier O, Gerard C, Delvaux A et al. Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide. Eur J Immunol 1993; 23: 2700-2703. 44. Van der Poll T, Jansen PM, Montegut WJ et al. Effects of IL-10 on systemic inflammatory responses during sublethal primate endotoxemia. J Immunol 1997; 158: 1971-1975. 45. Pajkrt D, van der Poll T, Levi M et al. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood 1997; 89: 2701-2705. 46. Kremer JP, Jarrar D, Steckholzer U, Ertel W. Interleukin-1, -6 and tumor necrosis factor-alpha release is down-regulated in whole blood from septic patients. Acta Haematol 1996; 95: 268-273. 47. Collen D, Lijnen HR. Molecular basis of fibrinolysis, as relevant for thrombolytic therapy. Thromb Haemost 1995; 74: 167-171. 48. Bajzar L, Morser J, Nesheim M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex. J Biol Chem 1996; 271: 16603-16608. 49. Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood 1996; 88: 2093-2100. 50. Klement P, Liao P, Bajzar L. A novel approach to arterial thrombolysis. Blood 1999; 94: 2735-2743. 51. Van Tilburg NH, Rosendaal FR, Bertina RM. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis. Blood 2000; 95: 2855-2859. 52. Colucci M, Páramo JA, Collen D. Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 1985; 75: 818-824. 53. Páramo JA, Pérez JL, Serrano M, Rocha E. Types 1 and 2 plasminogen activator inhibitor and tumor necrosis factor alpha in patients with sepsis. Thromb Haemost 1990; 64: 3-6. 54. Gómez C, Páramo JA, Colucci M, Rocha E. Effect of heparin and/or antithrombin III on the generation of endotoxin-induced plasminogen activator inhibitor. Thromb Haemost 1989; 62: 694-698. 55. Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest 1996; 97: 2440-2451. 56. Hermida J, Montes R, Muñoz MC, Orbe J, Páramo JA, Rocha E. Effects of low molecular weight heparin, alone or combined with antithrombin III, on mortality, fibrin deposits and hemostatic parameters in endotoxin-induced disseminated intravascular coagulation in rabbits. Am J Hematol 1999; 60: 6-11. 57. Van Hinsberg VW, Sprengers ED, Kooistra T. Effect of thrombin on the production of plasminogen activators and PA inhibitor-1 by human foreskin microvascular endothelial cells. Thromb Haemost 1987; 57: 148-153. 58. Chordá C, Páramo JA, Rocha E. Comparison of the effects of unfractionated heparin, low molecular weight heparin and hirudin (Revasc TM ) on the fibrinolytic potential of cultured human umbilical vein endothelial cells. Fibrinolysis 1996; 10: 43-48. 59. Paloma MJ, Páramo JA, Rocha E. Effect of DDAVP on endotoxin-induced intravascular coagulation in rabbits. Thromb Haemost 1992; 68: 306-309. 60. Paloma MJ, Páramo JA, Rocha E. Endotoxin-induced intravascular coagulation in rabbits: effect of tissue plasminogen activator vs urokinase of PAI generation, fibrin deposits and mortality. Thromb Haemost 1995; 74: 1578-1582. 61. Gurewich V, Pannell R, Louie S, Kelley P, Suddith RL, Greenlee R. Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase). A study in vitro and in two animal species. J Clin Invest 1984; 73: 1731-1739. 62. Esmon CT. Introduction: are natural anticoagulants candidates for modulating the inflammatory response to endotoxin Blood 2000; 95: 1113-1116. 63. Montes R, Declerck PJ, Calvo A et al. Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition of PAI-1. Thromb Haemost 2000 (en prensa). 64. Abrahamsson T, Nerme V, Stromqvist M et al. Anti-thrombotic effect of a PAI-1 inhibitor in rats given endotoxin. Thromb Haemost 1996; 75: 118-126. 65. Suffredini AF. Current prospects for the treatment of clinical sepsis. Crit Care Med 1994; 22: S12-18. 66. Cohen J, Heumann D, Glauser MP. Do monoclonal antibodies and anticytokines still have a future in infectious diseases Am J Med 1995; 99: 45S-52S; discussion 52S-53S. 67. Sasayama S, Matsumori A. Vesnarinone: a potential cytokine inhibitor. J Card Fail 1996; 2: 251-258. 68. Gullo A, Berlot G. Ingredients of organ dysfunction or failure. World J Surg 1996; 20: 430-436. 69. Baue AE, Durham R, Faist E. Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle Shock 1998; 10: 79-89. 70. Cross A. Novel approaches to the treatment of sepsis: lessons learned and future directions. Shock 1996; 6: S71-74. 71. Abraham E. Why immunomodulatory therapies have not worked in sepsis. Intensive Care Med 1999; 25: 556-566. 72. Pittet D, Harbarth S, Suter PM et al. Impact of immunomodulating therapy on morbidity in patients with severe sepsis. Am J Respir Crit Care Med 1999; 160: 852-857. 73. Abraham E. Cytokine modifiers: pipe dream or reality Chest 1998; 113: 224S-227S. 74. Bozza M, Satoskar AR, Lin G et al. Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med 1999; 189: 341-346. 75. Wang H, Bloom O, Zhang M et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285: 248-251. 76. Christman JW, Lancaster LH, Blackwell TS. Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med 1998; 24: 1131-1138.

CASOS CLÍNICO-CITOLÓGICOS CLUB ESPAÑOL DE CITOLOGÍA HEMATOLÓGICA COORDINADORAS: T. VALLESPÍ. Barcelona L. FLORENSA. Barcelona Caso 1 VARÓN DE 41 AÑOS CON INFECCIÓN POR EL VIH ASINTOMÁTICO AFECTADO DE LEUCEMIA LINFOIDE AGUDA G. RAMÍREZ, A. CAMPOS, S. DEL CASTILLO, G.G.ª BREDEMBERG, M.J. MORENO, M. NARBONA, I. PEREZ, M.P. QUEIPO, S. DE LA TORRE. Servicio de Hematología. Hospital Clínico “Virgen de la Victoria”. Málaga. Historia clínica: Varón de 41 años de edad, con infección por el VIH conocida desde 1990, sin precisar tratamiento antiretroviral por mantener cifras normales de linfocitos CD4. Ex adicto a drogas por vía parenteral (ADVP) y en programa de metadona. Infección por VHC desde 1993 con diagnóstico histológico de hepatitis crónica viral agresiva. Ulcus de cuerpo gástrico con vaso visible esclerosado, sin detección de H. pylori en 1993. Consulta por un cuadro de 10 días de evolución consistente en fiebre termometrada de 38,5 °C y escalofríos al que se le añade dolor en región escapular izquierda y en plano anterior del hemitórax izquierdo. Exploración física: Paciente consciente y orientado, eupneico y bien perfundido. Lesiones equimóticas en labios. Microadenopatias laterocervicales izquierdas. Tórax doloroso a la presión en hemitórax izquierdo. Auscultación pulmonar normal; corazón rítmico a 78 latidos/min. Abdomen y extremidades normales. Pruebas complementarias: Hb 68 g/L, leucocitos 1,3 × 10 9 /L (células blásticas 70 %). Plaquetas 41 × 10 9 /L. Estudio de coagulación normal. Bioquímica general normal. Amplio panel de serología con resultados negativos (incluido CMV), salvo VEB IgG. CD4: 661 × 10 6 /l, CD8 385 × 10 6 /l; cociente 1,72. TC toracoabdominal: lesión sólida en el mediastino anterior de 3,5 × 2,5 × 2 cm de localización preaórtica y otra de 2 × 2 cm carotraqueal compatibles con conglomerado adenopático. Resto del estudio sin interés significativo. Carga viral HIV 1.800 copias/ml. (Incremento con respecto a cargas previas). Carga viral VHC 1.254.000 copias/ml. Realizadas por PCR cuantificada. Estudio de medula ósea: Producto suficiente con dificultad de obtención. Infiltración de 76 % de blastos de mediano tamaño (7-15 m) con escasa relación núcleo/citoplasma, algunos de núcleo hendido, cromatina de mediana densidad con 1 o 2 nucléolos. Basofilia citoplasmática y excepcionalmente se observa algún blasto vacuolado. Citoquímicamente son peroxidasa negativos, ANAE + en 78 % y fosfatasa ácida + en 52 % de los blastos. Positividad de tipo centrosómico. Figura 1. Imagen de TAC que muestra las adenopatías mediastínicas. Figura 2. Frotis de medula ósea donde se observa la morfología de las células blásticas.

284 <strong>Haematologica</strong> (ed. esp.), volumen 85, supl. 2, octubre 2000<br />

24. Fong Y, Tracey KJ, Moldawer LL et al. Antibodies to cachectin/tumor<br />

necrosis factor reduce interleukin 1 beta and interleukin 6 appearance<br />

during lethal bacteremia. J Exp Med 1989; 170: 1627-1633.<br />

25. Endo S, Inada K, Inoue Y et al. Two types of septic shock classified by the<br />

plasma levels of cytokines and endotoxin. Circ Shock 1992; 38: 264-274.<br />

26. ten Cate JW, van der Poll T, Levi M, ten Cate H, van Deventer SJ. Cytokines:<br />

triggers of clinical thrombotic disease. Thromb Haemost 1997;<br />

78: 415-419.<br />

27. Boermeester MA, van Leeuwen PA, Coyle SM, Wolbink GJ, Hack CE,<br />

Lowry SF. Interleukin-1 blockade attenuates mediator release and dysregulation<br />

of the hemostatic mechanism during human sepsis. Arch<br />

Surg 1995; 130: 739-748.<br />

28. Fischer E, Marano MA, Van Zee KJ et al. Interleukin-1 receptor blockade<br />

improves survival and hemodynamic performance in Escherichia coli<br />

septic shock, but fails to alter host responses to sublethal endotoxemia.<br />

J Clin Invest 1992; 89: 1551-1557.<br />

29. Jansen PM, Boermeester MA, Fischer E et al. Contribution of interleukin-1<br />

to activation of coagulation and fibrinolysis, neutrophil degranulation,<br />

and the release of secretory-type phospholipase A2 in sepsis:<br />

studies in nonhuman primates after interleukin-1 alpha administration<br />

and during lethal bacteremia. Blood 1995; 86: 1027-1034.<br />

30. Shalaby MR, Waage A, Aarden L, Espevik T. Endotoxin, tumor necrosis<br />

factor-alpha and interleukin 1 induce interleukin 6 production in<br />

vivo. Clin Immunol Immunopathol 1989; 53: 488-498.<br />

31. Van der Poll T, Levi M, Hack CE et al. Elimination of interleukin 6 attenuates<br />

coagulation activation in experimental endotoxemia in chimpanzees.<br />

J Exp Med 1994; 179: 1253-1259.<br />

32. Creasey AA, Chang AC, Feigen L, Wun TC, Taylor FB Jr, Hinshaw LB.<br />

Tissue factor pathway inhibitor reduces mortality from Escherichia coli<br />

septic shock. J Clin Invest 1993; 91: 2850-2856.<br />

33. Hack CE, De Groot ER, Felt-Bersma RJ et al. Increased plasma levels of<br />

interleukin-6 in sepsis. Blood 1989; 74: 1704-1710.<br />

34. Taylor FB Jr, Chang AC, Peer GT et al. DEGR-factor Xa blocks disseminated<br />

intravascular coagulation initiated by Escherichia coli without<br />

preventing shock or organ damage. Blood 1991; 78: 364-368.<br />

35. Muñoz MC, Montes R, Hermida J, Orbe J, Páramo JA, Rocha E. Effect<br />

of the administration of recombinant hirudin and/or tissue-plasminogen<br />

activator (t-PA) on endotoxin-induced disseminated intravascular<br />

coagulation model in rabbits. Br J Haematol 1999; 105: 117-121.<br />

36. Taylor FB Jr, Chang A, Ruf W et al. Lethal E. coli septic shock is prevented<br />

by blocking tissue factor with monoclonal antibody. Circ Shock<br />

1991; 33: 127-134.<br />

37. Lauw FN, Dekkers PE, te Velde AA et al. Interleukin-12 induces sustained<br />

activation of multiple host inflammatory mediator systems in chimpanzees.<br />

J Infect Dis 1999; 179: 646-652.<br />

38. Kuipers B, van der Poll T, Levi M et al. Platelet-activating factor antagonist<br />

TCV-309 attenuates the induction of the cytokine network in experimental<br />

endotoxemia in chimpanzees. J Immunol 1994; 152: 2438-2446.<br />

39. Held TK, Weihua X, Yuan L, Kalvakolanu DV, Cross AS. Gamma interferon<br />

augments macrophage activation by lipopolysaccharide by two<br />

distinct mechanisms, at the signal transduction level and via an autocrine<br />

mechanism involving tumor necrosis factor alpha and interleukin-1.<br />

Infect Immun 1999; 67: 206-212.<br />

40. Moore KW, O’Garra A, de Waal Malefyt R, Vieira P, Mosmann TR. Interleukin-10.<br />

Annu Rev Immunol 1993; 11: 165-190.<br />

41. Howard M, Muchamuel T, Andrade S, Menon S. Interleukin 10 protects<br />

mice from lethal endotoxemia. J Exp Med 1993; 177: 1205-1208.<br />

42. Marchant A, Bruyns C, Vandenabeele P et al. Interleukin-10 controls interferon-gamma<br />

and tumor necrosis factor production during experimental<br />

endotoxemia. Eur J Immunol 1994; 24: 1167-1171.<br />

43. Pradier O, Gerard C, Delvaux A et al. Interleukin-10 inhibits the induction<br />

of monocyte procoagulant activity by bacterial lipopolysaccharide.<br />

Eur J Immunol 1993; 23: 2700-2703.<br />

44. Van der Poll T, Jansen PM, Montegut WJ et al. Effects of IL-10 on systemic<br />

inflammatory responses during sublethal primate endotoxemia.<br />

J Immunol 1997; 158: 1971-1975.<br />

45. Pajkrt D, van der Poll T, Levi M et al. Interleukin-10 inhibits activation of<br />

coagulation and fibrinolysis during human endotoxemia. Blood 1997;<br />

89: 2701-2705.<br />

46. Kremer JP, Jarrar D, Steckholzer U, Ertel W. Interleukin-1, -6 and tumor<br />

necrosis factor-alpha release is down-regulated in whole blood from<br />

septic patients. Acta Haematol 1996; 95: 268-273.<br />

47. Collen D, Lijnen HR. Molecular basis of fibrinolysis, as relevant for thrombolytic<br />

therapy. Thromb Haemost 1995; 74: 167-171.<br />

48. Bajzar L, Morser J, Nesheim M. TAFI, or plasma procarboxypeptidase B,<br />

couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin<br />

complex. J Biol Chem 1996; 271: 16603-16608.<br />

49. Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated<br />

protein C in clots formed from plasma is TAFI-dependent. Blood 1996;<br />

88: 2093-2100.<br />

50. Klement P, Liao P, Bajzar L. A novel approach to arterial thrombolysis.<br />

Blood 1999; 94: 2735-2743.<br />

51. Van Tilburg NH, Rosendaal FR, Bertina RM. Thrombin activatable fibrinolysis<br />

inhibitor and the risk for deep vein thrombosis. Blood 2000;<br />

95: 2855-2859.<br />

52. Colucci M, Páramo JA, Collen D. Generation in plasma of a fast-acting<br />

inhibitor of plasminogen activator in response to endotoxin stimulation.<br />

J Clin Invest 1985; 75: 818-824.<br />

53. Páramo JA, Pérez JL, Serrano M, Rocha E. Types 1 and 2 plasminogen<br />

activator inhibitor and tumor necrosis factor alpha in patients with sepsis.<br />

Thromb Haemost 1990; 64: 3-6.<br />

54. Gómez C, Páramo JA, Colucci M, Rocha E. Effect of heparin and/or antithrombin<br />

III on the generation of endotoxin-induced plasminogen<br />

activator inhibitor. Thromb Haemost 1989; 62: 694-698.<br />

55. Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated<br />

mice correlates with decreases in the expression of urokinase-type<br />

but not tissue-type plasminogen activator. J Clin Invest 1996;<br />

97: 2440-2451.<br />

56. Hermida J, Montes R, Muñoz MC, Orbe J, Páramo JA, Rocha E. Effects<br />

of low molecular weight heparin, alone or combined with antithrombin<br />

III, on mortality, fibrin deposits and hemostatic parameters in<br />

endotoxin-induced disseminated intravascular coagulation in rabbits.<br />

Am J Hematol 1999; 60: 6-11.<br />

57. Van Hinsberg VW, Sprengers ED, Kooistra T. Effect of thrombin on the<br />

production of plasminogen activators and PA inhibitor-1 by human<br />

foreskin microvascular endothelial cells. Thromb Haemost 1987; 57:<br />

148-153.<br />

58. Chordá C, Páramo JA, Rocha E. Comparison of the effects of unfractionated<br />

heparin, low molecular weight heparin and hirudin (Revasc TM )<br />

on the fibrinolytic potential of cultured human umbilical vein endothelial<br />

cells. Fibrinolysis 1996; 10: 43-48.<br />

59. Paloma MJ, Páramo JA, Rocha E. Effect of DDAVP on endotoxin-induced<br />

intravascular coagulation in rabbits. Thromb Haemost 1992; 68:<br />

306-309.<br />

60. Paloma MJ, Páramo JA, Rocha E. Endotoxin-induced intravascular coagulation<br />

in rabbits: effect of tissue plasminogen activator vs urokinase<br />

of PAI generation, fibrin deposits and mortality. Thromb Haemost<br />

1995; 74: 1578-1582.<br />

61. Gurewich V, Pannell R, Louie S, Kelley P, Suddith RL, Greenlee R. Effective<br />

and fibrin-specific clot lysis by a zymogen precursor form of urokinase<br />

(pro-urokinase). A study in vitro and in two animal species. J Clin<br />

Invest 1984; 73: 1731-1739.<br />

62. Esmon CT. Introduction: are natural anticoagulants candidates for modulating<br />

the inflammatory response to endotoxin Blood 2000; 95:<br />

1113-1116.<br />

63. Montes R, Declerck PJ, Calvo A et al. Prevention of renal fibrin deposition<br />

in endotoxin-induced DIC through inhibition of PAI-1. Thromb<br />

Haemost 2000 (en prensa).<br />

64. Abrahamsson T, Nerme V, Stromqvist M et al. Anti-thrombotic effect of<br />

a PAI-1 inhibitor in rats given endotoxin. Thromb Haemost 1996; 75:<br />

118-126.<br />

65. Suffredini AF. Current prospects for the treatment of clinical sepsis. Crit<br />

Care Med 1994; 22: S12-18.<br />

66. Cohen J, Heumann D, Glauser MP. Do monoclonal antibodies and anticytokines<br />

still have a future in infectious diseases Am J Med 1995; 99:<br />

45S-52S; discussion 52S-53S.<br />

67. Sasayama S, Matsumori A. Vesnarinone: a potential cytokine inhibitor.<br />

J Card Fail 1996; 2: 251-258.<br />

68. Gullo A, Berlot G. Ingredients of organ dysfunction or failure. World J<br />

Surg 1996; 20: 430-436.<br />

69. Baue AE, Durham R, Faist E. Systemic inflammatory response syndrome<br />

(SIRS), multiple organ dysfunction syndrome (MODS), multiple organ<br />

failure (MOF): are we winning the battle Shock 1998; 10: 79-89.<br />

70. Cross A. Novel approaches to the treatment of sepsis: lessons learned<br />

and future directions. Shock 1996; 6: S71-74.<br />

71. Abraham E. Why immunomodulatory therapies have not worked in<br />

sepsis. Intensive Care Med 1999; 25: 556-566.<br />

72. Pittet D, Harbarth S, Suter PM et al. Impact of immunomodulating therapy<br />

on morbidity in patients with severe sepsis. Am J Respir Crit Care<br />

Med 1999; 160: 852-857.<br />

73. Abraham E. Cytokine modifiers: pipe dream or reality Chest 1998;<br />

113: 224S-227S.<br />

74. Bozza M, Satoskar AR, Lin G et al. Targeted disruption of migration inhibitory<br />

factor gene reveals its critical role in sepsis. J Exp Med 1999;<br />

189: 341-346.<br />

75. Wang H, Bloom O, Zhang M et al. HMG-1 as a late mediator of endotoxin<br />

lethality in mice. Science 1999; 285: 248-251.<br />

76. Christman JW, Lancaster LH, Blackwell TS. Nuclear factor kappa B:<br />

a pivotal role in the systemic inflammatory response syndrome and new<br />

target for therapy. Intensive Care Med 1998; 24: 1131-1138.

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