Objections to the Polyheme® trial are summarized in: The Polyheme® Trial Pt. 1
Links to submissions to FDA docket 1995s-0158 for the Polyheme® trial are available in: The Polyheme® Trial Pt. 2
Links to news stories and other publications on Polyheme® are available in: The Polyheme® Trial Pt. 3
A readable summary of clinical trials testing Polyheme®, including its confounding effect on medical lab tests, is: Swank K. Hemoglobin Based Oxygen Carriers in Trauma. Colorado Review of Anesthesia and Ski Holiday. CRASH 2004 Handout. Available from http://www.cucrash.com/Handouts04/HBOCsSwank.pdf
Medical Journal Publications: Northfield Laboratories Inc., Selected Bibliography. (1)
Moss GS, Gould SA, Sehgal LR, Sehgal HL, Rosen AL. Hemoglobin solution—from tetramer to polymer. Surgery. 1984;95(3):249-55. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6701780 (Discussion; formulation.)
Sehgal LR, Gould SA, Rosen AL, Sehgal HL, Moss GS. Polymerized pyridoxylated hemoglobin: a red cell substitute with normal oxygen capacity. Surgery. 1984;95(4):433-8. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6710339 (Animal study.)
Gould SA, Sehgal LR, Rosen AL, Sehgal HL, Moss GS. The development of polymerized pyridoxylated hemoglobin solution as a red cell substitute. Ann Emerg Med. 1986;15(12):1416-9. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3777613 (Discussion; formulation.)
Gould SA, Rosen AL, Sehgal LR, Sehgal HL, Moss GS. Polymerized pyridoxylated hemoglobin: efficacy as an O2 carrier. J Trauma. 1986;26(10):903-8. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=3772998 (Discussion; unspecified.)
Gould SA, Sehgal LR, Rosen AL, Sehgal HL, Moss GS. The efficacy of polymerized pyridoxylated hemoglobin solution as an O2 carrier. Ann Surg. 1990;211(4):394-8. Available from http://www.pubmedcentral.gov/picrender.fcgi?artid=1358023&blobtype=pdf (Animal study.)
Gould SA, Sehgal LR, Sehgal HL, Moss GS. The development of hemoglobin solutions as red cell substitutes: hemoglobin solutions. Transfus Sci. 1995;16(1):5-17. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10155705 (Review article.)
Gould SA, Moss GS. Clinical development of human polymerized hemoglobin as a blood substitute. World J Surg. 1996;20(9):1200-7. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8864082 (Review article.)
Gould SA, Moore EE, Moore FA, Haenel JB, Burch JM, Sehgal H, Sehgal L, DeWoskin R, Moss GS. Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery. J Trauma. 1997;43(2):325-31. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9291380 (Open label clinical trial; dose-ranging; N=39; trauma and urgent surgery.)
Johnson JL, Moore EE, Offner PJ, Haenel JB, Hides GA, Tamura DY. Resuscitation of the injured patient with polymerized stroma-free hemoglobin does not produce systemic or pulmonary hypertension. Am J Surg. 1998;176(6):612-7. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9926800 (Clinical trial; injured subjects NOS.)
Gould SA, Moore EE, Hoyt DB, Burch JM, Haenel JB, Garcia J, DeWoskin R, Moss GS. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. J Am Coll Surg. 1998;187(2):113-20. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9704955 (Controlled clinical trial; N=44; trauma and urgent surgery.)
Sauaia A, Moore FA, Moore EE, Norris JM, Lezotte DC, Hamman RF. Multiple organ failure can be predicted as early as 12 hours after injury. J Trauma. 1998;45(2):291-301. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9715186 (Retrospective study; no subjects receiving Polyheme® included.)
Chance JJ, Norris EJ, Kroll MH. Mechanism of interference of a polymerized hemoglobin blood substitute in an alkaline phosphatase method. Clin Chem. 2000;46(9):1331-7. Available from http://www.clinchem.org/cgi/reprint/46/9/1331 (Discussion; interference with medical lab tests.)
LaMuraglia GM, O'Hara PJ, Baker WH, Naslund TC, Norris EJ, Li J, Vandermeersch E. The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg. 2000;31(2):299-308. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10664499 (Controlled clinical trial; acute normovolemic hemodilution preparatory to surgery for repair of aortic aneurysm; N=72; did not evaluate Polyheme®; subjects randomized to receive either allogenic red blood cells or HBOC–201, the hemoglobin-based oxygen-carrying solution of bovine origin marketed by Biopure Incorporated.)
Johnson JL, Moore EE, Offner PJ, Partrick DA, Tamura DY, Zallen G, Silliman CC. Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. J Trauma. 2001;50(3):449-55. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11265023 (Controlled clinical trial NOS.)
Lanzkron S, Moliterno AR, Norris EJ, Gould SA, Segal J, Nuermberger EL, Ness PM. Polymerized human Hb use in acute chest syndrome: a case report. Transfusion. 2002;42(11):1422-7. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12421214
Gould SA, Moore EE, Hoyt DB, Ness PM, Norris EJ, Carson JL, Hides GA, Freeman IH, DeWoskin R, Moss GS. The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. J Am Coll Surg. 2002;195(4):445-52 Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12375748 (Open label clinical trial; N=171; trauma and urgent surgery.)
Raff JP, Dobson CE, Tsai HM. Transfusion of polymerised human haemoglobin in a patient with severe sickle-cell anaemia. Lancet. 2002;360(9331):464-5. Available from http://www.thelancet.com/journals/lancet/article/PIIS014067360209640X/fulltext (Case report.)
Carson JL, Noveck H, Berlin JA, Gould SA. Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion. Transfusion. 2002;42(7):812-8. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12375651 (Retrospective study.)
Cothren C, Moore EE, Offner PJ, Haenel JB, Johnson JL. Blood substitute and erythropoietin therapy in a severely injured Jehovah's witness. N Engl J Med. 2002;346(14):1097-8. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11932486 (Case report.)
Norris EJ, Ness PM, Williams GM. Use of a human polymerized hemoglobin solution as an adjunct to acute normovolemic hemodilution during complex abdominal aortic reconstruction. J Clin Anesth. 2003;15(3):220-3. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12770661 (Case report.)
Ciesla DJ, Moore EE, Johnson JL, Burch JM, Cothren CC, Sauaia A. A 12-year prospective study of postinjury multiple organ failure: has anything changed? Arch Surg. 2005;140(5):432-8. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15897438&query_hl=13 (Cohort study; no data on Polyheme®.)
Thyes C, Spahn DR. Current Status of Artificial O(2) Carriers. Anesthesiol Clin North America. 2005;23(2):373-89. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15922907&query_hl=11 (Review article.)
Handrigan MT, Bentley TB, Oliver JD, Tabaku LS, Burge JR, Atkins JL. Choice of fluid influences outcome in prolonged hypotensive resuscitation after hemorrhage in awake rats. Shock. 2005;23(4):337-43. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15803057&query_hl=8
Sheppard FR, Moore EE, Johnson JL, Cheng AM, McLaughlin N, Silliman CC. Transfusion-induced leukocyte IL-8 gene expression is avoided by the use of human polymerized hemoglobin. J Trauma. 2004;57(4):720-4. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15514524&query_hl=6 (In vitro study.)
Silliman CC, Moore EE, Johnson JL, Gonzalez RJ, Biffl WL. Transfusion of the injured patient: proceed with caution. Shock. 2004;21(4):291-9. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15179127 (Review article.)
Cothren CC, Moore EE, Long JS, Haenel JB, Johnson JL, Ciesla DJ. Large volume polymerized haemoglobin solution in a Jehovah's Witness following abruptio placentae. Transfus Med. 2004;14(3):241-6. Available from http://www.blackwell-synergy.com/doi/abs/10.1111/j.0958-7578.2004.00502.x (Case report.)
Ciesla DJ, Moore EE, Johnson JL, Sauaia A, Cothren CC, Moore JB, Burch JM. Multiple organ dysfunction during resuscitation is not postinjury multiple organ failure. Arch Surg. 2004;139(6):590-4. Available from http://archsurg.ama-assn.org/cgi/content/full/139/6/590 (Retrospective study; no data on Polyheme®.)
Moore FA, McKinley BA, Moore EE. The next generation in shock resuscitation. Lancet. 2004;363(9425):1988-96. Available from http://www.thelancet.com/journals/lancet/article/PIIS0140673604164155/abstract (Review article.)
Johnson JL, Moore EE, Gonzalez RJ, Fedel N, Partrick DA, Silliman CC. Alteration of the postinjury hyperinflammatory response by means of resuscitation with a red cell substitute. J Trauma. 2003;54(1):133-9. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12544908 (Controlled clinical trial NOS.)
Moore EE. Blood substitutes: the future is now. J Am Coll Surg. 2003;196(1):1-17. Available from http://dx.doi.org/10.1016/S1072-7515(02)01704-0 (Talk; Scudder Oration in Trauma; select the link for Article via Science Direct.
)
PubMed Search: Gould SA.
(2)
Gould SA, Rosen AL, Sehgal L, Sehgal H, Rice CL, Moss GS. Hemoglobin solutions as red cell substitutes. Trans Am Soc Artif Intern Organs. 1980;26:350-3. Available from http://tinyurl.com/pl7kj
Gould SA, Rosen A, Sehgal L, Noud G, Sehgal H, DeWoskin R, Levine H, Kerstein M, Rice C, Moss GS. The effect of altered hemoglobin-oxygen affinity on oxygen transport by hemoglobin solution. J Surg Res. 1980;28(3):246-51. Available from http://tinyurl.com/q4l8y (Animal study; comparative formulations.)
Sehgal LR, Rosen AL, Noud G, Sehgal HL, Gould SA, DeWoskin R, Rice CL, Moss GS. Large-volume preparation of pyridoxylated hemoglobin with high P50. J Surg Res. 1981;30(1):14-20. Available from http://tinyurl.com/q89ju (Discussion; formulation.)
Sehgal LR, Sehgal HL, Rosen AL, Gould SA, Rice CL, Moss GS. Control of methemoglobin formation in stroma-free hemoglobin solutions. J Surg Res. 1981;31(1):13-7. Available from http://tinyurl.com/kqlst (Discussion; formulation.)
Rosen AL, Gould SA, Sehgal LR, Sehgal HL, Rice CL, Rushing D, Moss GS. Hemoglobin solutions as red cell substitutes. Crit Care Med. 1982;10(4):275-8. Available from http://tinyurl.com/ky4bo (Discussion; formulation.)
Gould SA, Sehgal LR, Rosen AL, Sehgal HL, Levine HD, Rice CL, Moss GS. Hemoglobin solution: is a normal [Hb] or P50 more important? J Surg Res. 1982;33(3):189-93. Available from http://tinyurl.com/gt636 (Discussion; formulation.)
Gould SA, Rosen AL, Sehgal LR, Sehgal HL, Rice CL, Moss GS. Red cell substitutes: hemoglobin solution or fluorocarbon? J Trauma. 1982;22(9):736-40. Available from http://tinyurl.com/ept8g (Discussion; formulation.)
Sehgal LR, Rosen AL, Gould SA, Sehgal HL, Moss GS. An appraisal of polymerized pyridoxylated hemoglobin as an acellular oxygen carrier. Prog Clin Biol Res. 1983;122:19-28. Available from http://tinyurl.com/gcae8 (Discussion; previous animal and in vitro studies.)
Rosen AL, Gould SA, Sehgal LR, Sehgal HL, Moss GS. Evaluation of efficacy of stroma free hemoglobin solutions. Prog Clin Biol Res. 1983;122:79-88. Available from http://tinyurl.com/z7df7 (Discussion NOS.)
Sehgal LR, Rosen AL, Gould SA, Sehgal HL, Moss GS. Preparation and in vitro characteristics of polymerized pyridoxylated hemoglobin. Transfusion. 1983;23(2):158-62. Available from http://tinyurl.com/gpwpq (Discussion; formulation.)
Langdale LA, Gould SA, Sehgal LR, Rosen AL, Krause LM, Sehgal HL, Moss GS. Stroma-free hemoglobin: effective in resuscitation? Curr Surg. 1983;40(6):446-8. Available from http://tinyurl.com/hqgje (Discussion NOS.)
Moss GS, Gould SA, Sehgal LR, Sehgal HL, Rosen AL. Hemoglobin solution—from tetramer to polymer. Prog Clin Biol Res. 1984;165:191-210. Available from http://tinyurl.com/g2wxa (Clinical trial NOS; cf Moss GS, Gould SA, Sehgal LR, Sehgal HL, Rosen AL. Hemoglobin solution—from tetramer to polymer. Surgery. 1984;95(3):249-55. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6701780)
Gould SA, Rice CL, Moss GS. The physiologic basis of the use of blood and blood products. Surg Annu. 1984;16:13-38. Available from http://tinyurl.com/gdqar (Review article.)
Sehgal LR, Gould SA, Rosen AL, Sehgal HL, Moss GS. Polymerized pyridoxylated hemoglobin: a red cell substitute with normal oxygen capacity. Surgery. 1984;95(4):433-8. Available from http://tinyurl.com/g25mf (Animal study.)
Gould SA, Sehgal LR, Rosen AL, Sehgal HL, Moss GS. Red cell substitutes: an update. Ann Emerg Med. 1985;14(8):798-803. Available from http://tinyurl.com/gdlkm (Review article.)
Gould SA, Rosen AL, Sehgal LR, Sehgal HL, Langdale LA, Krause LM, Rice CL, Chamberlin WH, Moss GS. Fluosol-DA as a red-cell substitute in acute anemia. N Engl J Med. 1986;314(26):1653-6. Available from http://tinyurl.com/zcdxh (Open label clinical trial; Fluosol-DA.)
Moss GS, Gould SA, Sehgal LR, Rosen AL, Sehgal HL. Polyhemoglobin and fluorocarbon as blood substitutes. Biomater Artif Cells Artif Organs. 1987;15(2):333-6. Available from http://tinyurl.com/fzcrk (Discussion NOS.)
Sehgal LR, Sehgal HL, Gould SA, Rosen AL, DeWoskin R, Moss GS. Red cell substitutes: present status. Indian J Pediatr. 1987;54(3):403-8. Available from http://tinyurl.com/gaubp (Review article; cf Gould SA, Sehgal LR, Rosen AL, Sehgal HL, Moss GS. Red cell substitutes: an update. Ann Emerg Med. 1985;14(8):798-803. Available from http://tinyurl.com/gdlkm.)
Sehgal LR, Sehgal HL, Rosen AL, Gould SA, DeWoskin R, Moss GS. Characteristics of polymerized pyridoxylated hemoglobin. Biomater Artif Cells Artif Organs. 1988;16(1-3):173-83. Available from http://tinyurl.com/hzgbu (Discussion.)
Rosen AL, Gould SA, Sehgal LR, Sehgal HL, Levine HD, DeWoskin RD, Moss GS. Effect of hemoglobin solution on compensation to anemia in the erythrocyte-free primate. J Appl Physiol. 1990;68(3):938-43. Available from http://tinyurl.com/ejn6u (Animal study.)
Gould SA, Sehgal LR, Sehgal HL, Moss GS. Artificial blood: current status of hemoglobin solutions. Crit Care Clin. 1992;8(2):293-309. Available from http://tinyurl.com/gwzwq (Review article.)
Gould SA, Forbes JM. Controversies in transfusion medicine: indications for autologous and allogeneic transfusion should be the same: pro. Transfusion. 1995;35(5):446-9. Available from http://tinyurl.com/kypwe (Discussion.)
PubMed Search: Polyheme.
Spahn DR, Kocian R. Artificial O2 carriers: status in 2005. Curr Pharm Des. 2005;11(31):4099-114. Available from http://tinyurl.com/z49vu (Review article.)
Greenburg AG, Kim HW. Hemoglobin-based oxygen carriers. Crit Care. 2004;8 Suppl 2:S61-4. Epub 2004 Jun 14. Available from http://ccforum.com/content/pdf/cc2455.pdf (Review article.)
Anon. Human haemoglobin — Northfield. BioDrugs. 2003;17(4):296-8. Available from http://tinyurl.com/ee3tw (Review article.)
Masuno T, Moore EE, Cheng AM, Moore PK, Grant AR, Johnson JL. Prehospital hemoglobin-based oxygen carrier resuscitation attenuates postinjury acute lung injury. Surgery. 2005;138(2):335-41. Available from http://tinyurl.com/z7y7r (Animal study.)
Klein HG. Blood substitutes: how close to a solution? Dev Biol (Basel). 2005;120:45-52. Available from http://tinyurl.com/es8ax (Review article.)
Notes
1. Northfield Laboratories Inc. Selected Bibliography. 2005. Available from http://www.northfieldlabs.com/bibliography.html. Accessibility verified 2006-04-15.
2. National Library of Medicine. PubMed Search. 2006-04-15. Available from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed. Links to PubMed abstracts courtesy of TinyURL.com.
Last Updated: 2006-04-17
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