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25 - Dyshemoglobinemias

from SECTION SIX - OTHER CLINICALLY IMPORTANT DISORDERS OF HEMOGLOBIN

Published online by Cambridge University Press:  03 May 2010

Martin H. Steinberg ,
Bernard G. Forget ,
Douglas R. Higgs  and
David J. Weatherall
By
Neeraj Agarwal ,
Ronald L. Nagel  and
Josef T. Prchal
Martin H. Steinberg
Affiliation:
Boston University
Bernard G. Forget
Affiliation:
Yale University, Connecticut
Douglas R. Higgs
Affiliation:
MRC Institute of Molecular Medicine, University of Oxford
David J. Weatherall
Affiliation:
Albert Einstein College of Medicine, New York
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Summary

Hemoglobin can bind gases other than oxygen (O2). These include carbon monoxide (CO) and nitric oxide (NO). Carboxyhemoglobin (COHb) precludes normal O2 transport and is toxic. Nitrosohemoglobin has critical physiological functions discussed in Chapter 10. Normal hemoglobin can be oxidized to methemoglobin and sulfhemoglobin by exogenous agents and these hemoglobin forms can also be found as a result of germline mutations. In aggregate, these modified hemoglobins, referred as dyshemoglobinemias, are the basis of a group of acquired and genetic disorders that are rare but can have serious clinical implications.

METHEMOGLOBINEMIA

Methemoglobin is formed when the iron of the heme group is oxidized or converted from the ferrous (Fe2+) to the ferric (Fe3+) state. The ferric hemes of methemoglobin are unable to reversibly bind O2. In addition, the presence of ferric heme increases the O2 affinity of the accompanying ferrous hemes in the hemoglobin tetramer. This leads to a left shift in the hemoglobin–O2 dissociation curve, which impairs tissue delivery of O2. Normally, methemoglobin is generated and then reduced physiologically to maintain a very low steady-state blood methemoglobin level of 1% or less of the total hemoglobin. The half-life of methemoglobin is approximately 1 hour if the reductase mechanism is normal. Methemoglobinemia occurs when there is imbalance between methemoglobin production and methemoglobin reduction. Methemoglobinemia can have both inherited and acquired causes; hemoglobin oxidation has been recently reviewed.

Pathophysiology of Methemoglobinemia

Production of Methemoglobin. O2 binds the ferrous form of iron present in hemoglobin to form oxyhemoglobin.

Type
Chapter
Information
Disorders of Hemoglobin
Genetics, Pathophysiology, and Clinical Management
 , pp. 607 - 622
Publisher: Cambridge University Press
Print publication year: 2009

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References

Darling, R, Roughton, F. The effect of methemoglobin on the equilibrium between oxygen and hemoglobin. Am J Physiol. 1942;137:56.Google Scholar
Olsen, M, McEvoy, GK. Methemoglobinemia induced by topical anesthetics. Am J Hosp Pharm. 1981;38:89–93.Google Scholar
Percy, MJ, McFerran, NV, Lappin, TR. Disorders of oxidised haemoglobin. Blood Rev. 2005;19:61–8.CrossRefGoogle ScholarPubMed
Misra, H, Fridorich, I. The generation of superoxide radical during the autoxidation of hemoglobin. J Biol Chem. 1972;247:6960.Google ScholarPubMed
Jaffe, E, Neumann, G. A comparison of the effect of mendione, methylene blue, and ascorbic acid on the reduction of methemoglobin in vivo. Nature. 1964;202:607.CrossRefGoogle Scholar
Jaffe, E, Hultquist, D. Cytochrome b5 reductase deficiency and enzymopenic hereditary methemoglobinemia. In: Scriver, C, Beaudet, A, Sly, W, Valle, D, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed., New York: McGraw Hill; 1995;2:3399.Google Scholar
Feelisch, M, Kubitzek, D, Werringloer, J.The oxyhemoglobin assay. In: Feelisch, M, Stamler, J, eds. Methods in Nitric Oxide Research; New York: John Wiley and Sons;1996:453.Google Scholar
Stuhlmeier, K, Kao, JJ, Wallbrandt, P, et al. Antioxidant protein 2 prevents methemoglobin formation in erythrocyte hemolysates. Eur J Biochem. 2003;270:334–41.CrossRefGoogle ScholarPubMed
Strittmatter, P. The reaction sequence in electron transfer in the reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase system. J Biol Chem. 1965;240:4481.Google ScholarPubMed
Iyanagi, T, Watanabe, S, Anan, KF. One-electron oxidation-reduction properties of hepatic NADH-cytochrome b5 reductase. Biochemistry. 1984;23:1418–25.CrossRefGoogle ScholarPubMed
Scott, EM, Mc, GJ. Purification and properties of diphosphopyridine nucleotide diaphorase of human erythrocytes. J Biol Chem. 1962;237:249–52.Google ScholarPubMed
Kuma, F, Ishizawa, S, Hirayama, K, et al. Studies on methemoglobin reductase. I. Comparative studies of diaphorases from normal and methemoglobinemic erythrocytes. J Biol Chem. 1972;247:550.Google ScholarPubMed
Passon, P, Hultquist, D. Soluble cytochrome b5 reductase from human erythrocytes. Biochim Biophys Acta. 1972;275:62.CrossRefGoogle ScholarPubMed
Hackett, C, Strittmatter, P. Covalent cross-linking of the active sites of vesicle-bound cytochrome b5 and NADH-cytochrome b5 reductase. J Biol Chem. 1984;259:3275.Google ScholarPubMed
Warburg, O, Kubowitz, F, Christian, W. Uber die katalytische wirkung von methlenblau in lebenden zellen. Biochem Z. 1930;227:245.Google Scholar
Kiese, M. Die reduktion des hamiglobins. 1944;316:264.
Yubisui, T, Takeshita, M, Yoneyama, Y. Reduction of methemoglobin through flavin at the physiological concentration by NADPH-flavin reductase of human erythrocytes. J Biochem (Tokyo). 1980;87:1715.CrossRefGoogle ScholarPubMed
Yubisui, T, Miyata, T, Iwanaga, S, et al. Complete amino acid sequence of NADH-cytochrome b5 reductase purified from human erythrocytes. J Biochem. 1986;99:407.CrossRefGoogle ScholarPubMed
Francois, . A case of congenital cyanosis without an apparent cause. Bull Acad Roy Med Belg. 1845;4:698.Google Scholar
Hitzenberger, K. Autotoxic cyanosis due to intraglobular methemoglobinemia. Wien Arch Med. 1932;23:85.Google Scholar
Gibson, Q. Historical note: methemoglobinemia-long ago and far away. Am J Hematol. 1993;42:3–6.CrossRefGoogle ScholarPubMed
Gibson, Q. Introduction: congenital methemoglobinemia revisited. Blood. 2002;100:3445.CrossRefGoogle ScholarPubMed
Percy, M, Gillespie, M, Savage, G, et al. Familial idiopathic mutations in NADH-cytochrome b5 reductase. Blood. 2002;100:3447.CrossRefGoogle ScholarPubMed
Bull, P, Shephard, E, Povey, S, et al. Cloning and chromosomal mapping of human cytochrome b5 reductase (DIA1). Ann Hum Genet. 1988;52:263.CrossRefGoogle Scholar
Tomatsu, S, Kobayashi, Y, Fukumaki, Y, et al. The organization and the complete nucleotide sequence of the human NADH-cytochrome b5 reductase gene. Gene. 1989;80:353–361.Google ScholarPubMed
Percy, MJ, Oren, H, Savage, G, Irken, G. Congenital methaemoglobinaemia Type I in a Turkish infant due to a novel mutation, Pro144Ser, in NADH-cytochrome b5 reductase. Hematol J. 2004;5(4):367–370.CrossRefGoogle Scholar
Percy, MJ, Crowley, LJ, Davis, CA, et al. Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase. Br J Haematol. 2005;129(6):847–853.CrossRefGoogle ScholarPubMed
Percy, MJ, Crowley, LJ, Boudreaux, J, et al. Expression of a novel P275L variant of NADH:cytochrome b5 reductase gives functional insight into the conserved motif important for pyridine nucleotide binding. Arch Biochem Biophys. 2006;447(1):59–67.CrossRefGoogle ScholarPubMed
Wang, Y, Wu, Y, Zheng, P, et al. A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia. Blood. 2000;95:3250.Google ScholarPubMed
Higasa, K, Manabe, J, Yubisui, T, et al. Molecular basis of hereditary methaemoglobinaemia, types I and II: two novel mutations in the NADH-cytochrome b5 reductase gene. Br J Haematol. 1998;103:922.CrossRefGoogle ScholarPubMed
Shotelersuk, V, Tosukhowong, P, Chotivitayatarakorn, P, et al. A Thai boy with hereditary enzymopenic methemoglobinemia type II. J Med Assoc Thai. 2000;83:1380.Google ScholarPubMed
Jenkins, M, Prchal, J. A novel mutation found in the 3′ domain of NADH-cytochrome b5 reductase in an African-American family with type I congenital methemoglobinemia. Blood. 1996;87:2993–2999.Google Scholar
Nussenzveig, R, Lingam, HB, Gaikwad, A, et al. A novel mutation of the cytochrome-b5 reductase gene in an Indian patient: the molecular basis of type I methemoglobinemia. Haematologica. 2006;91:1542–1545.Google Scholar
Jenkins, M, Prchal, J. A high frequency polymorphism of NADH-cytochrome b5 reductase in African-Americans. Hum Genet. 1997;99:248–250.CrossRefGoogle ScholarPubMed
Pietrini, G, Carrera, P, Borgese, N. Two transcripts encode rat cytochrome b5 reductase. Proc Natl Acad Sci USA. 1988;85:7246–7250.CrossRefGoogle ScholarPubMed
Pietrini, G, Aggujaro, D, Carrera, P, et al. A single mRNA, transcribed from an alternative erythroid-specific promoter, codes for two non-myristylated forms of NADH-cytochrome b5 reductase. J Cell Biol. 1992;117:975.CrossRefGoogle ScholarPubMed
Mota Vieira, L, Kaplan, J-C, Kahn, A, et al. Heterogeneity of the rat NADH-cytochrome-b5-reductase transcripts resulting from multiple alternative first exons. FEBS. 1994;220:729.Google ScholarPubMed
Bulbarelli, A, Valentini, A, DeSilvestris, M, et al. An erythroid-specific transcript generates the soluble form of NADH-cytochrome b5 reductase in humans. Blood. 1998;92:310–319.Google ScholarPubMed
Borgese, N, Pietrini, G. Distribution of the integral membrane protein NADH-cytochrome b5 reductase in rat liver cells, studied with a quantitative radioimmunoblotting assay. Biochem J. 1986;239:393–403.CrossRefGoogle ScholarPubMed
Tamura, M, Yubisui, T, Takeshita, M, et al. Structural comparison of bovine erythrocyte, brain, and liver NADH-cytochrome b5 reductase by HPLC mapping. J Biochem (Tokyo). 1987;101:1147–1159.CrossRefGoogle ScholarPubMed
Ozols, J, Korza, G, Heinemann, FS, et al. Complete amino acid sequence of steer liver microsomal NADH-cytochrome b5 reductase. J Biol Chem. 1985;260:11953–11961.Google ScholarPubMed
Yubisui, T, Naitoh, Y, Zenno, S, et al. Molecular cloning of cDNAs of human liver and placenta NADH-cytochrome b5 reductase. Proc Natl Acad Sci USA. 1987;84:3609–3613.CrossRefGoogle ScholarPubMed
Zenno, S, Hattori, M, Misumi, Y, et al. Molecular cloning of a cDNA encoding rat NADH-cytochrome b5 reductase and the corresponding gene. J Biochem(Tokyo). 1990;107:810–816.CrossRefGoogle ScholarPubMed
Hultquist, D, Passon, P. Catalysis of methemoglobin reduction by erythrocyte cytochrome b5 and cytochrome b5 reductase. Nature. 1971;229:252.Google ScholarPubMed
Kitajima, S, Yasukochi, Y, Minakami, S. Purification and properties of human erythrocyte membrane NADH-cytochrome b5 reductase. Arch Biochem Biophys. 1981;210:330.CrossRefGoogle ScholarPubMed
Dekker, J, Eppink, M, Zwieten, R, et al. Seven new nucleotides in the nicotinamide adenine dinucleotide reduced-cytochrome b(5) reductase gene leading to methemoglobinemia type I. Blood. 2001;97:1106–1114.CrossRefGoogle ScholarPubMed
Gonzalez, R, Estrada, M, Wade, M, et al. Heterogeneity of hereditary methaemoglobinaemia: a study of 4 Cuban families with NADH-Methaemoglobin reductase deficiency including a new variant (Santiago de Cuba variant). Scand J Haematol. 1978;20(5):385–393.CrossRefGoogle Scholar
Board, P, Petcock, M. Methaemoglobinaemia resulting from heterozygosity for two NADH-methaemoglobin reductase variants: characterization as NADH-ferricyanide reductase. Br J Haematol. 1981;47:361–370.CrossRefGoogle ScholarPubMed
Jaffe, E. Hereditary methemoglobinemias associated with abnormalities in the metabolism of erythrocytes. Ann J Med. 1962;32:512.Google Scholar
Waller, H. Inherited methemoglobinemia (enzyme deficiencies). Humangenetik. 1970;9:217.CrossRefGoogle Scholar
Cohen, R, Sachs, J, Wicker, D, et al. Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. New Engl J Med. 1968;279:1127.CrossRefGoogle ScholarPubMed
Scott, E, Hoskins, D. Hereditary methemoglobinemia in Alaskan Eskimos and Indians. Blood. 1958;13:795.Google ScholarPubMed
Scott, E. The relation of diaphorase of human erythrocytes to inheritance of methemoglobinemia. J Clin Invest. 1960;39:1176.CrossRefGoogle ScholarPubMed
Balsamo, P, Hardy, W, Scott, E. Hereditary methemoglobinemia due to diaphorase deficiency in Navajo Indians. J Pediatr. 1964;65:928.CrossRefGoogle ScholarPubMed
Ilinskaia, I, Derviz, G, Lavrova, O, et al. Enzymatic methemoglobinemia. In: Papers of the Symposium: Biological Problems of the North State University, Yakutsk, and 1974:226.
Andreeva, A, Dmitrieva, M, Levina, A, et al. Molecular basis for disorders in the functional properties of hemoglobin in patients with enzymopenic methemoglobinemia. Papers of the 49th Scientific Session of the Central Scientific Research Institute of Hematology and Blood Transfusion. 1979;SSSR:73.Google Scholar
Prchal, J, Borgese, N, Moore, M, et al. Congenital methemoglobinemia due to methemoglobin reductase deficiency in two unrelated American black families. Am J Med. 1990;89:516.CrossRefGoogle ScholarPubMed
Katsube, T, Sakamoto, N, Kobayashi, Y, et al. Exonic point mutations in NADH-cytochrome B5 reductase genes of homozygotes for hereditary methemoglobinemia, types I and III: putative mechanisms of tissue-dependent enzyme deficiency. Am J Hum Genet. 1991;48(4):799–808.Google ScholarPubMed
Shirabe, K, Yubisui, T, Borgese, N, et al. Enzymatic instability of NADH-cytochrome b5 reductase as a cause of hereditary methemoglobinemia type I (red cell type). J Biol Chem. 1992;267:20416–20421.Google Scholar
Leroux, A, Junien, C, Kaplan, J-C, et al. Generalised deficiency of cytochrome b5 reductase in congenital methaemoglobinaemia with mental retardation. Nature. 1975;258:619.CrossRefGoogle ScholarPubMed
Takeshita, M, Tamura, M, Kugi, M, et al. Decrease of palmitoyl-CoA elongation in platelets and leukocytes in the patient of hereditary methemoglobinemia associated with mental retardation. Biochem Biophys Res Commun. 1987;148:384–391.CrossRefGoogle ScholarPubMed
Kobayashi, Y, Fukumaki, Y, Yubisui, T, et al. Serine-proline replacement at residue 127 of NADH-cytochrome b5 reductase causes hereditary methemoglobinemia, generalized type. Blood. 1990;75:1408–1413.Google Scholar
Shirabe, K, Fujimoto, Y, Yubisui, T, et al. An in-frame deletion of codon 298 of the NADH-cytochrome b5 reductase gene results in hereditary methemoglobinemia type II (generalized type). A functional implication for the role of the COOH-terminal region of the enzyme. J Biol Chem. 1994;269:5952–5957.Google ScholarPubMed
Jenkins, M, Prchal, J. A novel mutation found in the NADH-cytochrome b5 reductase gene in African-American family with type I congenital methemoglobinemia. Blood. 1995;86:649.Google Scholar
Shirabe, K, Landi, M, Takeshita, M, et al. A novel point mutation in a 3′ splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia. Am J Hum Genet. 1995;57:302–310.Google Scholar
Vieira, L, Kaplan, JC, Kahn, A, et al. Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II. Blood. 1995;85:2254–2262.Google ScholarPubMed
Manabe, J, Arya, R, Sumimoto, H, et al. Two novel mutations in the reduced nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase gene of a patient with generalized type, hereditary methemoglobinemia. Blood. 1996;88:3208–3215.Google ScholarPubMed
Owen, E, Berens, J, Marinaki, AM, et al. Recessive congenital methaemoglobinaemia type II a new mutation which causes incorrect splicing in the NADH-cytochrome b5 reductase gene. J Inherit Metab Dis. 1997;20:610.CrossRefGoogle Scholar
Hegesh, E, Hegesh, J, Kaftory, A. Congenital methemoglobinemia with a deficiency of cytochrome b5. N Engl J Med. 1986;314:757.CrossRefGoogle ScholarPubMed
Giordano, S, Kaftory, A, Steggles, A. A splicing mutation in the cytochrome b5 gene from a patient with congenital methemoglobinemia and pseudohermaphrodism. Hum Genet. 1994;93:568.CrossRefGoogle ScholarPubMed
Townes, P, Morrison, M. Investigation of the defect in a variant of hereditary methemoglobinemia. Blood. 1962;19:60.Google Scholar
Mansouri, A, Lurie, AA. Concise review: methemoglobinemia. Am J Hematol. 1993;42:7–12.CrossRefGoogle ScholarPubMed
Coleman, M, Coleman, NA. Drug-induced methaemoglobinaemia. Treatment issues. Drug Saf. 1996;14:394–405.CrossRefGoogle ScholarPubMed
Hadjiliadis, D, Govert, J. Methemoglobinemia after infusion of ifosfamide chemotherapy: first report of a potentially serious adverse reaction related to ifosfamide. Chest. 2000;118:1208.CrossRefGoogle ScholarPubMed
Kizer, N, Martinez, E, Powell, M. Report of two cases of rasburicase-induced methemoglobinemia. Leuk Lymphoma. 2006;47:2648–2650.CrossRefGoogle ScholarPubMed
Daly, J, Hultquist, D, Rucknagel, D. Phenazopyridine induced methaemoglobinaemia associated with decreased activity of erythrocyte cytochrome-b5 reductase. J Med Genet. 1983;20:307.CrossRefGoogle ScholarPubMed
Linden, C, Burns, MJ. Poisoning and drug overdosage. In: Braunwald, E FA, Kasper, D, Hauser, S, Longo, D, Jameson, J, et al., eds. Harrison's Principles of Internal Medicine 15th ed: New York: McGraw-Hill; 2001:2612.Google Scholar
Ash-Bernal, R, Wise, R, Wright, SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore). 2004;83:265.CrossRefGoogle Scholar
Moore, T, Walsh, CS, Cohen, MR. Reported adverse event cases of methemoglobinemia associated with benzocaine products. Arch Intern Med. 2004;164:1192–1196.CrossRefGoogle ScholarPubMed
Novaro, G, Aronow, H, Militello, M, et al. Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory. J Am Soc Echocardiogr. 2003;16:170.CrossRefGoogle ScholarPubMed
Ross, J. Deficient activity of DPNH-dependent methemoglobin diaphorase in cord blood erythrocytes. Blood. 1963;21:51.Google ScholarPubMed
Bartos, H, Desforges, J. Erythrocyte DPNH-dependent diaphorase levels in infants. Pediatrics. 1966;37:991.Google ScholarPubMed
Eng, L, Loo, M, Fah, FK. Diaphroase activity and variants in normal adults and newborns. Br J Haematol. 1972;23:419.CrossRefGoogle ScholarPubMed
Comly, H. Cyanosis in infants caused by nitrates in well water. JAMA. 1945;129:112.CrossRefGoogle Scholar
Kross, B, Ayebo, A, Fuortes, L. Methemoglobinemia: nitrate toxicity in rural America. Am Fam Physician. 1992;46:183.Google ScholarPubMed
Greer, F, Shannon, M. Infant methemoglobinemia: the role of dietary nitrate in food and water. Pediatrics. 2005;116:784–786.CrossRefGoogle ScholarPubMed
Heyman, I. Methemoglobinemia in infants. Harefuah. 1954;46:144.Google ScholarPubMed
Yano, S, Danish, E, Hsia, Y. Transient methemoglobinemia with acidosis in infants. J Pediatr. 1982;100:415.CrossRefGoogle ScholarPubMed
Hegesh, E, Shiloah, J. Blood nitrates and infantile methemoglobinemia. Clin Chim Acta. 1982;125:107.CrossRefGoogle ScholarPubMed
Pollack, E, Pollack, CJ. Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med. 1994;24:652.CrossRefGoogle ScholarPubMed
Hanakoglu, A, Danon, P. Endogenous methemoglobinemia associated with diarrheal disease in infancy. J Pediatr Gastroenterol and Nutr. 1996;23:1.CrossRefGoogle Scholar
Carlson, G, Negri, E, McGrew, A, et al. Two cases of methemoglobinemia from the use of topical anesthetics. J Emerg Nurs. 2003;29:106–108.CrossRefGoogle ScholarPubMed
Kilbourn, R, Belloni, P. Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst. 1990;82:772–776.CrossRefGoogle ScholarPubMed
Moncada, S, Palmer, RMJ, Higgs, EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991;43:109–142.Google ScholarPubMed
Szabo, C, Thiemermann, C. Role of nitric oxide in haemorrhagic, traumatic and anaphylactic shock and in thermal injury. Shock. 1994;2:145–155.CrossRefGoogle Scholar
Sharma, V, Isaacson, RA, John, ME, et al. Reaction of nitric oxide with heme proteins: Studies on metmyoglobin, opossum methemoglobin and microperoxidase. Biochemistry. 1983;22:3897–3902.CrossRefGoogle ScholarPubMed
Wennmalm, A, Benthin, G, Patersson, AS. Dependence of the metabolism of nitric oxide in healthy human whole blood on the oxygenation of its red cell hemoglobin. Br J Pharmacol. 1992;106:507–508.CrossRefGoogle Scholar
Chou, T, Gibran, NS, Urdahl, K, et al. Methemoglobinemia secondary to topical silver nitrate therapy-a case report. Burns. 1999;25:549–552.CrossRefGoogle ScholarPubMed
Bhattacharya, J, Swarup-Mitra, S. Role of Plasmodium vivax in oxidation of haemoglobin in red cells of the host. Indian J Med Res. 1986;83:111–113.Google Scholar
Baird, J, Lacy, MD, Basri, H, et al. Randomized, parallel placebo-controlled trial of primaquine for malaria prophylaxis in Papua, Indonesia. Clin Infect Dis. 2001;33:1990–1997.CrossRefGoogle ScholarPubMed
Maran, J, Guan, Y, Ou, CN, et al. Heterogeneity of the molecular biology of methemoglobinemia: a study of eight consecutive patients. Haematologica. 2005;90:687.Google ScholarPubMed
Barker, S, Tremper, K, Hyatt, J. Effects of methemoglobinemia on pulse oximetry and mixed venous oximetry. Anesthesiology. 1989;70:112.CrossRefGoogle ScholarPubMed
Kelner, M, Bailey, D. Mismeasurement of methemoglobin (“methemoglobin revisited”). Clin Chem. 1985;31:168.Google Scholar
Molthrop, D, Wheeler, R, Hall, K, et al. Evaluation of the methemoglobinemia associated with sulofenur. Invest New Drugs. 1994;12:99.CrossRefGoogle ScholarPubMed
Evelyn, K, Malloy, H. Microdetermination of oxyhemoglobin, methemoglobin, and sulfhemoglobin in a single sample of blood. J Biol Chem. 1938;126:655.Google Scholar
Barker, S, Curry, J, Redford, D, et al. Measurement of carboxyhemoglobin and methemoglobin by pulse oximetry: a human volunteer study. Anesthesiology. 2006;105:892–897.CrossRefGoogle ScholarPubMed
Beutler, E, Baluda, M. Methemoglobin reduction: Studies of the interaction between cell populations and of the role of methylene blue. Blood. 1963;22:323.Google ScholarPubMed
Jaffe, E. Hereditary methemoglobinemias associated with abnormalities in the metabolism of erythrocytes. Am J Med. 1966;41:786.CrossRefGoogle Scholar
Jaffe, E, Hsieh, H. DPNH-methemoglobin reductase deficiency and hereditary methemoglobinemia. Semin Hemat. 1971;8:417.Google ScholarPubMed
Hegesh, E, Calmanovici, N, Avron, M. New method for determining ferrihemoglobin reductase (NADH-methemoglobin reductase) in erythrocytes. J Lab Clin Med. 1968;72:339.Google Scholar
Board, P. NADH-ferricyanide reductase, a convenient approach to the evaluation of NADH-methaemoglobin reductase in human erythrocytes. Clin Chim Acta. 1981;109:233.CrossRefGoogle ScholarPubMed
Kaftory, A, Freundlich, E, Manaster, J, et al. Prenatal diagnosis of congenital methemoglobinemia with mental retardation. Isr J Med Sci. 1986;22:837.Google ScholarPubMed
Leroux, A, Leturcq, F, Deburgrave, N, Szajnert, MF. Prenatal diagnosis of recessive congenital methaemoglobinaemia type II: novel mutation in the NADH-cytochrome b5 reductase gene leading to stop codon read-through. Eur J Haematol. 2005;74:389–395.CrossRefGoogle ScholarPubMed
Arnold, H, Botcher, H, Hufnagel, D, et al. Hereditary methemoglobinemia due to methemoglobin reductase deficiency in erythrocytes and leukocytes without neurological symptoms (abstract). In: XVII Congress of the International Society of Hematology. Paris; 1978:752.Google Scholar
Tanishima, K, Tanimoto, K, Tomoda, A, et al. Hereditary methemoglobinemia due to cytochrome b5 reductase deficiency in blood cells without associated neurologic and mental disorders. Blood. 1985;66:1288.Google ScholarPubMed
Nagai, T, Shirabe, K, Yubisui, T, et al. Analysis of mutant NADH-cytochrome b5 reductase: apparent “type III” methemoglobinemia can be explained as type I with an unstable reductase. Blood. 1993;81:808.Google ScholarPubMed
Beutler, E. Methemoglobinemia and other causes of cyanosis. In: Beutler, E, Lichtman, MA, Coller, B, Kipps, TJ, eds. Williams' Hematology. 5th ed. New York: McGraw-Hill; 1995:654.Google Scholar
Kaplan, J, Chirouze, M. Therapy of recessive congenital methaemoglobinemia by oral riboflavin. Lancet. 1978;2:1043.CrossRefGoogle Scholar
Goluboff, N, Wheaton, R. Methylene blue induced cyanosis and acute hemolytic anemia complicating the treatment of methemoglobinemia. J Pediatr. 1961;58:86.CrossRefGoogle ScholarPubMed
Harvey, J, Keitt, A. Studies of the efficacy and potential hazards of methylene blue therapy in aniline-induced methemoglobinemia. Br J Haematol. 1983;54:29.CrossRefGoogle Scholar
Rosen, P, Johnson, C, McGehee, WG, et al. Failure of methylene blue treatment in toxic methemoglobinemia: associations with glucose-6-phosphate dehydrogenase deficiency. Ann Intern Med. 1971;75:83.CrossRefGoogle ScholarPubMed
Goldstein, G, Doull, J. Treatment of nitrite-induce methemoglobinemia with hyperbaric oxygen. Proc Soc Experimental Biology and Medicine. 1971;138:134.CrossRefGoogle ScholarPubMed
Coleman, M, Rhodes, , Scott, AK, et al. The use of cimetidine to reduce dapsone-dependent methaemoglobinaemia in dermatitis herpetiformis patients. Br J Clin Pharmacol. 1992;34:244.CrossRefGoogle ScholarPubMed
Vreman, H, Mahoney, JJ, Stevenson, DK. Carbon monoxide and carboxyhemoglobin. Adv Pediatr. 1995;42:303–325.Google ScholarPubMed
Hampson, N. Trends in the incidence of carbon monoxide poisoning in the United States. Am J Emerg Med. 2005;23:838–841.CrossRefGoogle ScholarPubMed
Hampson, N. Emergency department visits for carbon monoxide poisoning in the Pacific northwest. J Emerg Med. 1998;16:695–698.CrossRefGoogle ScholarPubMed
Weaver, L. Carbon monoxide poisoning. Crit Care Clin. 1999;15:297–317.CrossRefGoogle ScholarPubMed
Ernst, A, Zibrak, JD. Carbon monoxide poisoning. N Engl J Med. 1998;339:1603–1608.CrossRefGoogle ScholarPubMed
,Centres for Disease Control and Prevention C. Carbon monoxide poisoning from hurricane-associated use of portable generators – Florida 2004. MMWR. 2005;54:697–700.Google Scholar
,Centers for Disease Control and Prevention C. Unintentional non-fire-related carbon monoxide exposures–United States, 2001–2003. MMWR. 2005;54:36–39.Google Scholar
Mott, J, Wolfe, MI, Alverson, CJ, et al. National vehicle emissions policies and practices and declining US carbon monoxide-related mortality. JAMA. 2002;288:988–995.CrossRefGoogle ScholarPubMed
Harper, A, Croft-Baker, J. Carbon monoxide poisoning: undetected by both patients and their doctors. Age Ageing. 2004;33:105–109.CrossRefGoogle ScholarPubMed
,US Environmental Protection AgencyEmission facts: Idling vehicle emissions. US Environmental Protection Agency, Washington, DC; 1998 Publication EPA420-F-98-014 1998.Google Scholar
,Centers for Disease Control and PreventionCarbon monoxide poisoning from hurricane-associated use of portable generators – Florida 2004. MMWR. 2005;54:697–700.Google Scholar
Stewart, R, Fisher, TN, Hosko, MJ, et al. Carboxyhemoglobin elevation after exposure to dichloromethane. Science. 1972;176:295–296.CrossRefGoogle ScholarPubMed
Antonini, E, Brunori, M. Hemoglobin and myoglobin in their reactions with ligands. In: Neuberger, A, Tatum, EL, eds. Frontiers of Biology. Amsterdam, London: North-Holland Publishing Company; 1971.Google Scholar
Bunn, H, Forget, BG. Hemoglobin: Molecular, Genetic and Clinical Aspects. New York: Saunders; 1986.Google Scholar
Cheng, X, Schoenborn, BP. Neutron diffraction study of carbon- monoxymyoglobin. J Mol Biol. 1991;220:381–399.CrossRefGoogle Scholar
Kachalova, G, Popov, AN, Bartunik, HD. A steric mechanism for inhibition of CO binding of heme proteins. Science. 1999;284:473–476.CrossRefGoogle ScholarPubMed
Sjostrand, T. Endogenous formation of carbon monoxide in man. Nature. 1949;164:580–581.CrossRefGoogle ScholarPubMed
Coburn, R, Danielson, GK, Blakemore, WS, et al. Carbon monoxide in blood: Analytical method and sources of error. J Appl Physiol. 1964;19:510–515.CrossRefGoogle ScholarPubMed
Coburn, R, Williams, WJ, Kahn, SB. Endogenous carbon dioxide production in patients with hemolytic anemia. J Clin Invest. 1966;44:460–468.CrossRefGoogle Scholar
,EPA. 600/8–90/045F: Air Quality Criteria for Carbon Monoxide. Research Triangle Park, NC, Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, 1991:1–1 to 12–23.
Marks, G, Brien, JF, Nakatsu, K, et al. Does carbon monoxide have a biological function?Trends Pharmacol Sci. 1991;12:185–188.CrossRefGoogle Scholar
McGrath, J. Effects of altitude on endogenous carboxyhemoglobin levels. J Toxicol Environ Health. 1992;35:127–33.CrossRefGoogle ScholarPubMed
Giacometti, G, Brunori, M, Antonini, E, et al. The reaction of hemoglobin Zurich with oxygen and carbon monoxide. J Biol Chem. 1980;255:6160–6165.Google ScholarPubMed
Balster, R, Ekelund, LG, Grover, RF. Evaluation of subpopulations potentially at risk to carbon monoxide exposure, in EPA 600/8–90/045F: Air quality criteria for carbon monoxide. Research Triangle Park, NC, Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, US Environmental Protection Agency 1991:12–1 to 12–23.
Hampson, N, Dunford, RG, Kramer, CC, et al. Selection criteria utilized for hyperbaric oxygen treatment of carbon monoxide poisoning. J Emerg Med. 1995;13:227–231.CrossRefGoogle ScholarPubMed
Benesch, R, Maeda, N, Benesch, R. 2,3-Diphosphoglycerate and the relative affinity of adult and fetal hemoglobin for oxygen and carbon dioxide. Biochim Biophys Acta. 1972;257:178–182.CrossRefGoogle Scholar
Engel, R, Rodkey, FL, O'Neal, JD, et al. Relative affinity of human fetal hemoglobin for CO and O2. Blood. 1969;33:37–45.Google Scholar
Gemelli, F, Cattani, R. Carbon monoxide poisoning in childhood. Br Med J. 1985;291:1197.CrossRefGoogle ScholarPubMed
Lacey, D. Neurologic sequellae of acute carbon monoxide intoxication. Am J Dis Child. 1981;135:145–147.Google Scholar
Kao, L, Nanagas, KA. Carbon monoxide poisoning. Emerg Med Clin North Am. 2004;22:985–1018.CrossRefGoogle ScholarPubMed
Elkharrat, D, Raphael, JC, Korach, JM, et al. Acute carbon monoxide intoxication and hyperbaric oxygen in pregnancy. Intensive Care Med. 1991;17:289–292.CrossRefGoogle ScholarPubMed
Koren, G, Sharav, T, Pastuszak, A, et al. A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy. Reprod Toxicol. 1991;5:397–403.CrossRefGoogle ScholarPubMed
Evans, A, Enzer, N, Eder, HA, et al. Hemolytic anemia with paroxymal methemoglobnemia and sulfhemoglobinemia. Arch Intern Med. 1950;86:22.CrossRefGoogle Scholar
Bradenburg, R, Smith, HL. Sulfhemoglobinemia: a study of 62 clinical cases. Am Heart J. 1951;42:582.CrossRefGoogle Scholar
Reynolds, T, Ware, AG. Sulfhemoglobinemia following habitual use of acetanilid. JAMA. 1952;149:538–542.CrossRefGoogle Scholar
Cumming, R, Pollock, A. Drug induced sulphaemoglobinemia and Heinz body anemia in pregnancy with involvement of the foetus. Scott Med J. 1967;12:320–322.CrossRefGoogle ScholarPubMed
Kneezel, LD, Kitchens, CS. Phenacetin-induced sulfhemoglobinemia: Report of a case and review of the literature. Johns Hopkins Med J. 1967;139:175–180.Google Scholar
Lambert, M, Sonnet, J, Mahien, P, et al. Delayed sulfhemoglobinemia after acute dapsone intoxication. Clin Toxicol. 1982;19:45–49.Google ScholarPubMed
Ford, R, Shkov, J, Akman, WV, et al. Deaths from asphyxia among fisherman. PFR: MMWR. 1978;27:309.Google Scholar
Madeiros, M, Bechara, EJ, Naoum, PC, et al. Oxygen toxicity and hemoglobinemia in subjects from a highly polluted town. Arch Environ Health. 1983;38:11–15.CrossRefGoogle Scholar
Carrico, R, Blumberg, WE, Peisach, J J. The reversible binding of oxygen to sulfhemoglobin. J Biol Chem. 1978;253:7212–7215.Google ScholarPubMed
Park, C, Nagel, RL. Sulfhemoglobinemia. Clinical and molecular aspects. N Engl J Med. 1984;310:1579–1584.CrossRefGoogle ScholarPubMed
Park, C, Nagel, RL, Blumberg, WE. Sulfhemoglobin. Properties of partially sulfurated tetramers. J Bio Chem. 1986;261:8805–8810.Google ScholarPubMed
Berzofsky, J, Peisach, J, Blumberg, WE. Sulfheme proteins. II. The reversible oxygenation of ferrous sulfmyoglobin. J Biol Chem. 1971;246:7366–7372.Google ScholarPubMed
Nichol, A, Hendry, I, Movell, DB, et al. Mechanism of formation of sulfhemoglobin. Biochim Biophys Acta. 1968;156:97–103.CrossRefGoogle Scholar
Kiese, M. The biochemical production of ferrihemoglobin-forming derivatives from aromatic amines and mechanisms of ferrihemoglobin formation. Pharmacol Rev. 1966;18:1091–1161.Google ScholarPubMed
McCutcheon, A. Sulphaemoglobinaemia and glutathione. Lancet. 1960;2:290.Google Scholar
Gibson, Q, Roughton, FJW. The kinetics and equilibria of the reactions of nitric oxide with sheep haemoglobin. J Physiol. 1957;136:507–526.CrossRefGoogle ScholarPubMed
Suzuki, T, Hayshi, A, Shimizu, A, et al. The oxygen equilibrium of hemoglobin M Saskatoon. Biochim. Biophys Acta. 1966;127:280–282.CrossRefGoogle Scholar
Basch, F. On hydrogen sulfide poisoning from external application of elementary sulfur as an ointment. Arch Exp Pathol Pharmacol. 1926;111:126.CrossRefGoogle Scholar
Glud, T. A case of enterogenic cyanosis? Complete recovery from acquired met- and sulfhemoglobinemia following treatment with neomycin and bacitracin. Ugeskr Laeg. 1979;141:1410–1411.Google Scholar
Burnett, E, King, EG, Grace, M, et al. Hydrogen sulfide poisoning: review of 5 years' experience. Can Med Assoc. 1977;117:1277–1280.Google ScholarPubMed
Afane Ze, E, Roche, N, Atchou, G, et al. Respiratory symptoms and peak expiratory flow in survivors of the Nyos disaster. Chest. 1996;110:1278–1281.CrossRefGoogle ScholarPubMed
Ensabella, F, Spirito, A, Dupre, S, et al. Measurement of sulfhemoglobin (S-Hb) blood levels to determine individual hydrogen sulfide exposure in thermal baths in Italy. Italian. Ig Sanita Pubbl. 2004;60:201–217.Google Scholar

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