血液浄化とQOL

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Published in人工臓器 Vol. 29; no. 4; pp. 543 - 550
Main Authors 松田, 兼一, 志賀, 英敏, 平野, 剛, 北村, 伸哉, 織田, 成人, 平澤, 博之
Format Journal Article
LanguageJapanese
Published 一般社団法人 日本人工臓器学会 15.10.2000
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ISSN0300-0818
1883-6097
DOI10.11392/jsao1972.29.543

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Author 平澤, 博之
松田, 兼一
織田, 成人
平野, 剛
北村, 伸哉
志賀, 英敏
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  fullname: 志賀, 英敏
  organization: 千葉大学医学部救急部・集中治療部
– sequence: 1
  fullname: 平野, 剛
  organization: 千葉大学医学部救急部・集中治療部
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  fullname: 北村, 伸哉
  organization: 千葉大学医学部救急部・集中治療部
– sequence: 1
  fullname: 織田, 成人
  organization: 千葉大学医学部救急部・集中治療部
– sequence: 1
  fullname: 平澤, 博之
  organization: 千葉大学医学部救急部・集中治療部
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References 59) Majetschak M, Flohe S, Obertacke U, Schroeder J, Staubach K, Nast-Kolb D, Schade U, Stueber F: Relation of a TNF gene polymorphism to severe sepsis in trauma patients. Ann Surg 230: 207-214, 1999
56) Ishihara S, Ward JA, Tasaki O, Brinkley WW. Seraile LG, Pruitt BA Jr., Mozingo DW: Effects of long-term hemofiltration on circulating mediators and superoxide production during continuous endotoxin administration. J Trauma 46: 894-899, 1999
53) Gotloib L, Barzilay E, Shustak A, Lev A: Sequential hemofiltration in nonoliguric high capillary permeability pulmonary edema of severe sepsis: Preliminary report. Crit Care Med 12: 997-1000, 1984
41) De Vriese AS, Vanholder RC, Pascual M, Lameire NH, Colardyn FA: Can inflammatory cytokines be removed efficiency by continuous renal replacement therapies? Intensive Care Med 25: 903-910, 1999
47) Steczko J, Ash SR, Blake DE, Carr DJ, Bosley RH: Cytokines and endotoxin removal by sorbents and its application in push-pull sorbent-based pheresis: The BioLogic-DTPF system. Artif Organs 23: 310-318, 1999
65) 小川道雄, 広田昌彦, 早川哲夫, 松野正紀, 渡辺伸一郎, 跡見裕, 加嶋敬, 山本正博: 重症急性膵炎全国調査. 厚生省特定疾患消化器系調査研究班難治性膵疾患分科会平成10年度研究報告書: 23-35, 1999
61) Gross V, Leser HG, Heinisch A, Schoelmerich J: Inflammatory mediators and cytokines new aspects of the pathophysiology and assessment of severity of acute pancreatitis? Hepato-Gastroenterol 40: 522-530, 1993
3) Chang TMS, Malave N: The development and first clinical use of semipermeable microcapsules (artificial cells) as a compact artificial kidney. Trans Am Soc Artif Int Organs 16: 141-148, 1970
14) 日本人工臓器学会レジストリー委員会: 人工肝臓と血漿交換. 人工臓器27 (別冊): 95-100, 2000
22) Yoshiba M, Inoue K, Sekiyama K, Koh I: Favorable effect of new artificial liver support on survival of patients with fulminant hepatic failure. Artif Organs 20: 1169-1172, 1996
49) Reeves JH, Butt WW, Shann F, Layton JE, Stewart A, Waring PM, Presneill JJ, the plasmafiltration in sepsis study group: Continuous plasmafiltration in sepsis syndrome. Crit Care Med 27: 2096-2104, 1999
35) Sudan DL, Shaw BW Jr., Fox IJ, Langnas AN: Long-term follow-up of auxiliary orthotopic liver transplantation for the treatment of fulminant hepatic failure. Surgery 122: 771-778, 1997
16) Redeker AG, Yamahiro HS: Controlled trial of exchange-transfusion therapy in fulminant hepatitis. Lancet 2: 3-6, 1973
27) Ash SR, Blake DE, Carr DJ, Carter C, Howard T, Makowka L: Clinical effects of a sorbent suspension dialysis system in treatment of hepatic toma (the BioLogic-DT). Int J Artif Organs 15: 151-161, 1992
54) Hirasawa H, Osaka M, Kobayashi H, Soda K, Kobayashi S, Mauritania N, Ito Y, Isogo K: Hemopurification in the treatment of patients with multiple organ failure. Progress in Artificial Organs-1985, eds by Nose Y, Kjellstrand C, Ivanovich P ISAO Press, Cleveland, 1986, 730-734
6) Hirasawa H, Sugai T, Ohtake Y, Oda S, Matsuda K, Kitamura N. Blood purification for prevention and treatment of multiple organ failure. World J Surg 20: 482-486, 1996
36) American College of Chest Physicians/ Society of Critical Care Medicine Consensus conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864-874, 1992
10) Abouna GM, Serrou B, Boehmig HG, Amemiya H: Long-term hepatic support by intermittent multispecies liver perfusions. Lancet 2: 391-396, 1970
5) Hirasawa H, Sugai T, Oda S, Shiga H, Matsuda K, Ueno H, Sadahiro T: Efficacy and limitation of apheresis therapy in critical care. Ther Apher 1: 228-232, 1997
64) 北村伸哉, 平澤博之, 貞広智仁, 中田孝明: 重症急性膵炎に対する血液浄化法罪適応.救急医23: 1603-1607, 1999
4) Henderson LW, Besarab A, Michaels A, Bluemle LW Jr.: Blood purification by ultrafiltration and fluid replacement (diafiltration). Trans Am Soc Artif Int Organs 13: 216-226, 1967
55) Rogiers P, Zhang H, Smail N, Pauwels D, Vincent JL: Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-α attenuation during endotoxic shock. Crit Care Med 27: 1848-1855, 1999
12) Gazzard BG, Portmann B, Weston MJ, Langley PG, Murray-Lyon IM, Dunlop EH, Flax H, Mellon PJ, Record CO, Ward MB: Charcoal haemoperfusion in the treatment of fulminant hepatic failure. Lancet 1: 1301-1307, 1974
19) Stieber AC, Iwatsuki S, Starzl TE: Orthotopic liver transplantation for fulminant and subacute hepatic failure. ASAIO Trans 34: 959-964, 1988
51) Tetta C, Gianotti L, Cavaillon JM, Wratten ML, Fini M, Braga M, Bisagni P, Giavaresi G, Bolzani R, Giardino R: Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock. Crit Care Med 28: 1526-1533, 2000
57) Bouman CSC, van Olden RW, Stoutenbeek CP: Cytokine filtration and adsorption during pre- and postdilution hemofiltration in four different membranes. Blood Purif 16: 261-268, 1998
42) Kellum JA: Immunomodulation in sepsis: the role of hemofiltration. Minerva Anestesiol 65: 410-418, 1999
29) 松田兼一, 平澤博之, 菅井桂雄, 大竹喜雄, 織田成人, 中西加寿也, 河邊統一, 北村伸哉, 上野博一, 疋田聡: BioLogic DTの使用経験. 集中治療7: S113-S114, 1995
48) Awad SS, Sawada S, Soldes OS, Rich PB, Klein R, Alarcon WH, Wang SC, Bartlett RH: Can the clearance of tumor necrosis factor alpha and interleukin 6 be enhanced using an albumin dialysate hemodiafiltration system? ASAIO J 45: 47-49, 1999
62) Denham W, Yang J, Fink G, Zervos EE, Carter G, Norman J: Pancreatic ascites as a powerful inducer of inflammatory cytokines. Ann Surg 132: 1231-1236, 1997
11) Trey C, Burns DG, Saunders SJ: Treatment of hepatic coma by exchange blood transfusion. N Engl J Med 274: 473-481, 1966
2) Kolff WJ: First clinical experience with the artificial kidney. Ann Intern Med 62: 608-619, 1965
46) Levy H, Ash SR, Knab W, Steczko J, Carr DJ, Blake DE: Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: The BioLogic-Detoxification plasma filtration system. ASAIO J 44: M659-M665, 1998
43) De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, De Sutter JH, Lameire NH: Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 10: 846-853, 1999
18) Chang TMS: Experimental artificial liver support with emphasis on fulminant hepatic failure: Concepts and review. Semin Liver Dis 6: 148-158, 1986
52) Opal SM: Hemofiltration-absorption systems for the treatment of experimental sepsis: Is it possible to remove the “evil humors” responsible for septic shock? Crit Care Med 28: 1681-1682, 2000
63) Yekebas EF, Treede H, Knoefel WT, Bloechle C, Fink E, Izbicki JR: Influence of zero-balanced hemofiltration on the course of severe experimental pancreatitis in pigs. Ann Surg 229: 514-522, 1999
8) Burnell JM, Dawborn JK, Epstein RB, Gutman RA, Leinbach GE, Thomas ED: Acute hepatic coma treated by cross-circulation or exchange transfusion. N Engl J Med 276: 935-943, 1967
9) Eiseman B, Liem DS, Raffucci F: Heterologous liver perfusion in treatment of hepatic failure. Ann Surg 162: 329-345, 1965
13) Silk DBA, Hanid MA, Trewby PN, Davis M, Chase RA, Langley PG, Mellon PJ, Wheeler PG: Treatment of fulminant hepatic failure by polyacrylonitrile-membrane haemodialysis. Lancet 2: 1-3, 1977
40) Partrick DA, Moore EE, Moore FA, Biffl WL, Barnett CC Jr.: Release of anti-inflammatory mediators after major torso trauma correlates with the development of postinjury multiple organ failure. Am J Surg 178: 564-569, 1999
30) Ash SR, Blake DE, Carr DJ, Harker KD: Push-pull sorbent based pheresis for treatment of acute hepatic failure. ASAIO J 44: 129-139, 1998
17) O'Grady JG, Gimson AES, O'Brien CJ, Pucknell A, Hughes RD, Williams R: Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 94: 1186-1192, 1988
34) Miwa S, Hashikura Y, Mita A, Kubota T, Chisuwa H, Nakazawa Y, Ikegami T, Terada M, Miyagawa S, Kawasaki S: Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure. Hepatology 30: 1521-1526, 1999
37) Lin E, Calvano SE, Lowry SF: Inflammatory cytokines and cell response in surgery. Surgery 127: 117-126, 2000
33) 田中紘一: わが国における肝移植外科の現況. 外科治療82: 131-135, 2000
38) Balk RA: Pathogenesis and management of multiple organ dysfunction or failure in severe sepsis and septic shock. Crit Care Clin 16: 337-352, 2000
7) Burnell JM, Thomas ED, Ansell JS, Cross HE, Dillard DH, Epstein RB, Eschbach JW, Hogan R: Observations on cross circulation in man. Am J Med 38: 832-841, 1965
28) Ash S, Wilkinson A, Hughes R, Williams R: BioLogic-DT system in treatment of acute hepatic coma; Results of randomized, controlled trials. ASAIO J 42: 11, 1996
1) Abel JJ, Rowntree LG, Turner BB: On the removal of diffusible substances from the circulating blood of living animals by dialysis. J Pharmacol Exp Ther 5: 275-317, 1914
20) O'Grady JG, Alexander GJ, Thick M, Potter D, Calne RY, Williams R: Outcome of orthotopic liver transplantation in the aetiological and clinical variants of acute liver failure. Q J Med 68: 817-824, 1988
45) 松田兼一, 平澤博之, 志賀英敏, 仲村将高: CHDFの理論と実際-CHDFによるhumoral mediatorの除去. 集中治療10: 1341-1356, 1998
15) Lepore MJ, Martel AJ: Plasmapheresis in hepatic coma. Lancet 2: 771-772, 1967
58) Kellum JA, Johnson JP, Kramer D, Palevsky P, Brady JJ, Pinsky MR: Diffusive vs. convective therapy: Effects on mediators of inflammation in patients with severe systemic inflammatory response syndrome. Crit Care Med 26: 1995-2000, 1998
39) Talmor M, Hydo L, Barie PS: Relationship of systemic inflammatory response syndrome to organ dysfunction, length of stay, and mortality in clinical surgical illness. Arch Surg 134: 81-87, 1999
21) 平野剛, 平澤博之, 織田成人, 志賀英敏, 松田兼一, 上野博一, 森口武史: 劇症肝炎 (FH) に対する肝移植の適応とbridge useとしての人工肝補助療法. 集中治療12: 865-872, 2000
50) Holmes CL, Russell JA: Plasmafiltration in sepsis: Removing the evil humors. Crit Care Med 27: 2287-2289, 1999
24) Sussman NL, Kelly JH: Improved liver function following treatment with an extracorporeal liver assist device. Artif Organs 17: 27-30, 1993
60) Rogiers P: Hemofiltration treatment for sepsis: Is it time for controlled trials? Kidney Int 72 (Suppl.): S99-S103, 1999
31) Stange J, Mitzner 5, Ramlow W, Gliesche T, Hi
References_xml – reference: 29) 松田兼一, 平澤博之, 菅井桂雄, 大竹喜雄, 織田成人, 中西加寿也, 河邊統一, 北村伸哉, 上野博一, 疋田聡: BioLogic DTの使用経験. 集中治療7: S113-S114, 1995
– reference: 34) Miwa S, Hashikura Y, Mita A, Kubota T, Chisuwa H, Nakazawa Y, Ikegami T, Terada M, Miyagawa S, Kawasaki S: Living-related liver transplantation for patients with fulminant and subfulminant hepatic failure. Hepatology 30: 1521-1526, 1999
– reference: 33) 田中紘一: わが国における肝移植外科の現況. 外科治療82: 131-135, 2000
– reference: 56) Ishihara S, Ward JA, Tasaki O, Brinkley WW. Seraile LG, Pruitt BA Jr., Mozingo DW: Effects of long-term hemofiltration on circulating mediators and superoxide production during continuous endotoxin administration. J Trauma 46: 894-899, 1999
– reference: 7) Burnell JM, Thomas ED, Ansell JS, Cross HE, Dillard DH, Epstein RB, Eschbach JW, Hogan R: Observations on cross circulation in man. Am J Med 38: 832-841, 1965
– reference: 31) Stange J, Mitzner 5, Ramlow W, Gliesche T, Hickstein H, Schmidt R: A new procedure for the removal of protein bound drugs and toxins. ASAIO J 39: M621-M625, 1993
– reference: 19) Stieber AC, Iwatsuki S, Starzl TE: Orthotopic liver transplantation for fulminant and subacute hepatic failure. ASAIO Trans 34: 959-964, 1988
– reference: 32) Stange J, Mitzner SR, Risler T, Erley CM, Lauchart W, Goehl H, Klammt S, Peszynski P, Freytag J, Hickstein H, Loehr M, Liebe S, Schareck W, Hopt UT, Schmidt R: Molecular adsorbent recycling system (MARS): Clinical results of a new membranebased blood purification system for bioartificial liver support. Artif Organs 23: 319-330, 1999
– reference: 54) Hirasawa H, Osaka M, Kobayashi H, Soda K, Kobayashi S, Mauritania N, Ito Y, Isogo K: Hemopurification in the treatment of patients with multiple organ failure. Progress in Artificial Organs-1985, eds by Nose Y, Kjellstrand C, Ivanovich P ISAO Press, Cleveland, 1986, 730-734
– reference: 24) Sussman NL, Kelly JH: Improved liver function following treatment with an extracorporeal liver assist device. Artif Organs 17: 27-30, 1993
– reference: 48) Awad SS, Sawada S, Soldes OS, Rich PB, Klein R, Alarcon WH, Wang SC, Bartlett RH: Can the clearance of tumor necrosis factor alpha and interleukin 6 be enhanced using an albumin dialysate hemodiafiltration system? ASAIO J 45: 47-49, 1999
– reference: 39) Talmor M, Hydo L, Barie PS: Relationship of systemic inflammatory response syndrome to organ dysfunction, length of stay, and mortality in clinical surgical illness. Arch Surg 134: 81-87, 1999
– reference: 57) Bouman CSC, van Olden RW, Stoutenbeek CP: Cytokine filtration and adsorption during pre- and postdilution hemofiltration in four different membranes. Blood Purif 16: 261-268, 1998
– reference: 15) Lepore MJ, Martel AJ: Plasmapheresis in hepatic coma. Lancet 2: 771-772, 1967
– reference: 3) Chang TMS, Malave N: The development and first clinical use of semipermeable microcapsules (artificial cells) as a compact artificial kidney. Trans Am Soc Artif Int Organs 16: 141-148, 1970
– reference: 12) Gazzard BG, Portmann B, Weston MJ, Langley PG, Murray-Lyon IM, Dunlop EH, Flax H, Mellon PJ, Record CO, Ward MB: Charcoal haemoperfusion in the treatment of fulminant hepatic failure. Lancet 1: 1301-1307, 1974
– reference: 10) Abouna GM, Serrou B, Boehmig HG, Amemiya H: Long-term hepatic support by intermittent multispecies liver perfusions. Lancet 2: 391-396, 1970
– reference: 45) 松田兼一, 平澤博之, 志賀英敏, 仲村将高: CHDFの理論と実際-CHDFによるhumoral mediatorの除去. 集中治療10: 1341-1356, 1998
– reference: 61) Gross V, Leser HG, Heinisch A, Schoelmerich J: Inflammatory mediators and cytokines new aspects of the pathophysiology and assessment of severity of acute pancreatitis? Hepato-Gastroenterol 40: 522-530, 1993
– reference: 63) Yekebas EF, Treede H, Knoefel WT, Bloechle C, Fink E, Izbicki JR: Influence of zero-balanced hemofiltration on the course of severe experimental pancreatitis in pigs. Ann Surg 229: 514-522, 1999
– reference: 38) Balk RA: Pathogenesis and management of multiple organ dysfunction or failure in severe sepsis and septic shock. Crit Care Clin 16: 337-352, 2000
– reference: 9) Eiseman B, Liem DS, Raffucci F: Heterologous liver perfusion in treatment of hepatic failure. Ann Surg 162: 329-345, 1965
– reference: 40) Partrick DA, Moore EE, Moore FA, Biffl WL, Barnett CC Jr.: Release of anti-inflammatory mediators after major torso trauma correlates with the development of postinjury multiple organ failure. Am J Surg 178: 564-569, 1999
– reference: 16) Redeker AG, Yamahiro HS: Controlled trial of exchange-transfusion therapy in fulminant hepatitis. Lancet 2: 3-6, 1973
– reference: 36) American College of Chest Physicians/ Society of Critical Care Medicine Consensus conference: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 20: 864-874, 1992
– reference: 37) Lin E, Calvano SE, Lowry SF: Inflammatory cytokines and cell response in surgery. Surgery 127: 117-126, 2000
– reference: 20) O'Grady JG, Alexander GJ, Thick M, Potter D, Calne RY, Williams R: Outcome of orthotopic liver transplantation in the aetiological and clinical variants of acute liver failure. Q J Med 68: 817-824, 1988
– reference: 43) De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, De Sutter JH, Lameire NH: Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 10: 846-853, 1999
– reference: 30) Ash SR, Blake DE, Carr DJ, Harker KD: Push-pull sorbent based pheresis for treatment of acute hepatic failure. ASAIO J 44: 129-139, 1998
– reference: 1) Abel JJ, Rowntree LG, Turner BB: On the removal of diffusible substances from the circulating blood of living animals by dialysis. J Pharmacol Exp Ther 5: 275-317, 1914
– reference: 22) Yoshiba M, Inoue K, Sekiyama K, Koh I: Favorable effect of new artificial liver support on survival of patients with fulminant hepatic failure. Artif Organs 20: 1169-1172, 1996
– reference: 6) Hirasawa H, Sugai T, Ohtake Y, Oda S, Matsuda K, Kitamura N. Blood purification for prevention and treatment of multiple organ failure. World J Surg 20: 482-486, 1996
– reference: 5) Hirasawa H, Sugai T, Oda S, Shiga H, Matsuda K, Ueno H, Sadahiro T: Efficacy and limitation of apheresis therapy in critical care. Ther Apher 1: 228-232, 1997
– reference: 59) Majetschak M, Flohe S, Obertacke U, Schroeder J, Staubach K, Nast-Kolb D, Schade U, Stueber F: Relation of a TNF gene polymorphism to severe sepsis in trauma patients. Ann Surg 230: 207-214, 1999
– reference: 17) O'Grady JG, Gimson AES, O'Brien CJ, Pucknell A, Hughes RD, Williams R: Controlled trials of charcoal hemoperfusion and prognostic factors in fulminant hepatic failure. Gastroenterology 94: 1186-1192, 1988
– reference: 2) Kolff WJ: First clinical experience with the artificial kidney. Ann Intern Med 62: 608-619, 1965
– reference: 13) Silk DBA, Hanid MA, Trewby PN, Davis M, Chase RA, Langley PG, Mellon PJ, Wheeler PG: Treatment of fulminant hepatic failure by polyacrylonitrile-membrane haemodialysis. Lancet 2: 1-3, 1977
– reference: 14) 日本人工臓器学会レジストリー委員会: 人工肝臓と血漿交換. 人工臓器27 (別冊): 95-100, 2000
– reference: 41) De Vriese AS, Vanholder RC, Pascual M, Lameire NH, Colardyn FA: Can inflammatory cytokines be removed efficiency by continuous renal replacement therapies? Intensive Care Med 25: 903-910, 1999
– reference: 60) Rogiers P: Hemofiltration treatment for sepsis: Is it time for controlled trials? Kidney Int 72 (Suppl.): S99-S103, 1999
– reference: 46) Levy H, Ash SR, Knab W, Steczko J, Carr DJ, Blake DE: Systemic inflammatory response syndrome treatment by powdered sorbent pheresis: The BioLogic-Detoxification plasma filtration system. ASAIO J 44: M659-M665, 1998
– reference: 28) Ash S, Wilkinson A, Hughes R, Williams R: BioLogic-DT system in treatment of acute hepatic coma; Results of randomized, controlled trials. ASAIO J 42: 11, 1996
– reference: 47) Steczko J, Ash SR, Blake DE, Carr DJ, Bosley RH: Cytokines and endotoxin removal by sorbents and its application in push-pull sorbent-based pheresis: The BioLogic-DTPF system. Artif Organs 23: 310-318, 1999
– reference: 4) Henderson LW, Besarab A, Michaels A, Bluemle LW Jr.: Blood purification by ultrafiltration and fluid replacement (diafiltration). Trans Am Soc Artif Int Organs 13: 216-226, 1967
– reference: 44) Lonnemann G, Bechstein M. Linnenweber S, Burg M, Koch KM: Tumor necrosis factor-alpha during continuous high-flux hemodialysis in sepsis with acute renal failure. Kidney Int 72 (Suppl.): S84-S87, 1999
– reference: 21) 平野剛, 平澤博之, 織田成人, 志賀英敏, 松田兼一, 上野博一, 森口武史: 劇症肝炎 (FH) に対する肝移植の適応とbridge useとしての人工肝補助療法. 集中治療12: 865-872, 2000
– reference: 23) 田中紘一, 猪俣裕紀洋, 阿曽沼克宏, 上本伸二, 武市卒之: 移植, 劇症肝炎, 難治性肝疾患: 診断と治療の進歩. 日内会誌88: 653-658, 1999
– reference: 18) Chang TMS: Experimental artificial liver support with emphasis on fulminant hepatic failure: Concepts and review. Semin Liver Dis 6: 148-158, 1986
– reference: 51) Tetta C, Gianotti L, Cavaillon JM, Wratten ML, Fini M, Braga M, Bisagni P, Giavaresi G, Bolzani R, Giardino R: Coupled plasma filtration-adsorption in a rabbit model of endotoxic shock. Crit Care Med 28: 1526-1533, 2000
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– reference: 27) Ash SR, Blake DE, Carr DJ, Carter C, Howard T, Makowka L: Clinical effects of a sorbent suspension dialysis system in treatment of hepatic toma (the BioLogic-DT). Int J Artif Organs 15: 151-161, 1992
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Title 血液浄化とQOL
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