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Acute Iron Poisoning: A Review

Acute Iron Poisoning: A Review Abstract The accidental ingestion of iron-containing preparations is relatively common in childhood, and intentional overdosage with iron is occasionally seen in adults. Though rarely fatal, the consequences of a substantial iron ingestion can result in profound mental retardation or death. The availability of deferoxamine mesylate, a specific and tenacious chelator of iron, and the necessity for its early administration demand that the physician be aware of a rational approach to the therapy for iron poisoning. Owing to our current understanding of the pathophysiology of iron poisoning, we believe that the simultaneous oral and continuous intravenous (IV) administration of deferoxamine offers the most rational specific therapy for this condition. In this review we shall outline the clinical description, pathophysiology, and therapeutic regimens for acute iron intoxication. We have used this information to derive an approach we believe to be reasonable. CLINICAL DESCRIPTION The oral lethal dose (LD) of elemental iron is generally References 1. Arena JM: Poisoning , ed 2. Springfield, Ill, Charles C Thomas Publisher, 1970, pp 349-353. 2. Westlin WF: Deferoxamine in the treatment of acute iron poisoning: Clinical experience with 172 children . Clin Pediatr 5:531-535, 1966.Crossref 3. Whitten CF, Gibson GW, Good MH, et al: Studies in acute iron poisoning: I. Deferoxamine in the treatment of acute iron poisoning: Clinical observations, experimental studies, and theoretical considerations . Pediatrics 36:322-335, 1965. 4. Fischer DS, Parkman R, Finch SC: Acute iron poisoning in children: The problem of appropriate therapy . JAMA 218:1179-1184, 1971.Crossref 5. Westlin WF: Deferoxamine as a chelating agent . Clin Toxicol 4:597-602, 1971.Crossref 6. McEnery JT, Greengard J: Treatment of acute iron ingestion with deferoxamine in 20 children . J Pediatr 68:773-779, 1966.Crossref 7. Whitten CF, Brough AJ: The pathophysiology of acute iron poisoning . Clin Toxicol 4:585-595, 1971.Crossref 8. Barker GA, Brown TCK, Hosking CS: Acute iron poisoning: Clinical features and management . Anaesth Intensive Care 4:345-350, 1974. 9. Covey TJ: Ferrous sulfate poisoning: A review, case summaries, and therapeutic regimen . J Pediatr 64:218-226, 1964.Crossref 10. James JA: Acute iron poisoning: Assessment of severity and prognosis . J Pediatr 77:117-119, 1970.Crossref 11. Wheby MS, Jones LG: Role of transferrin in iron absorption . J Clin Invest 42:1007-1016, 1963.Crossref 12. Reissmann KR, Coleman TJ, Budai BS, et al: Acute intestinal iron intoxication: I. Iron absorption, serum iron, and autopsy findings . Blood 10:35-45, 1955. 13. Barr DGD, Fraser DKB: Acute iron poisoning in children: Role of chelating agents . Br Med J 1:737-741, 1968.Crossref 14. McEnery JT: Hospital management of acute iron ingestion . Clin Toxicol 4:603-613, 1971.Crossref 15. Witzleben CL: The pathogenesis of iron hepatotoxicity . Ann NY Acad Sci 165:105-110, 1969.Crossref 16. Gandhi RK, Robarts FH: Hour-glass stricture of the stomach and pyloric stenosis due to ferrous sulfate poisoning . Br J Surg 49:613-617, 1962.Crossref 17. Murray MJ: Iron absorption . Clin Toxicol 4:545-558, 1971.Crossref 18. Fairbanks VF, Fahey JL, Beutler E: Clinical disorders of iron metabolism , in Clinical Disorders of Iron Metabolism , ed 2. New York, Grune & Stratton Inc, 1971, pp 42-127. 19. Whitten CF, Chen YC, Gibson GW: Studies in acute iron poisoning: II. Further observations on deferoxamine in the treatment of acute iron poisoning . Pediatrics 38:102-110, 1966. 20. Whitten CF, Chen YC, Gibson GW: Studies in acute iron poisoning: III. The hemodynamic alterations in acute experimental iron poisoning . Pediatr Res 2:479-485, 1978.Crossref 21. Witzleben CL, Chaffey NJ: Acute ferrous sulfate poisoning: A histochemical study of its effect on the liver . Arch Pathol Lab Med 82:454-461, 1966. 22. Witzleben CL: An electron microscopic study of ferrous sulfate-induced liver damage . Am J Pathol 49:1053-1068, 1966. 23. Ganote CE, Nahara G: Acute ferrous sulfate hepatotoxicity in rats: An electron microscopic and biochemical study . Lab Invest 28:426-436, 1973. 24. Hunter FE Jr, Gebicki JM, Hoffstein PE, et al: Swelling and lysis of rat liver mitochondria induced by ferrous ions . J Biol Chem 238:828-835, 1963. 25. Hoffstein PE, Hunter FE Jr, Gebicki JM, et al: Formation of "lipid peroxide" under conditions which lead to swelling and lysis of rat liver mitochondria . Biochem Biophys Res Commun 7:276-280, 1962.Crossref 26. Corwin LM, Lipsett MN: Studies on stability of rat liver mitochondria . J Biol Chem 234:2453-2458, 1959. 27. Lehninger AL: Water uptake and extrusion by mitochondria in relation to oxidative phosphorylation . Physiol Rev 42:467-517, 1962. 28. Hochstein P, Ernster L: Microsomal peroxidation of lipids and its possible role in cellular injury , in DeReuck AVS, Knight J (eds): Cellular Injury . Boston, Little Brown & Co, 1964, pp 123-135. 29. Gruger EH Jr, Tappel AL: Reactions of biological antioxidants: I. Fe(III)-catalyzed reactions of lipid hydroperoxides with alpha-tocopherol . Lipids 5:326-331, 1970.Crossref 30. McKnight RC, Hunter FE Jr: Mitochondrial membrane ghosts produced by lipid peroxidation induced by ferrous ion . J Biol Chem 241:2757-2765, 1966. 31. Wills ED: Lipid peroxide formation in microsomes: General considerations . Biochem J 113:315-324, 1969. 32. Barbar AA: Lipid peroxidation in rat tissue homogenates: Interaction of iron and ascorbic acid as the normal catalytic mechanism . Lipids 1:146-151, 1966.Crossref 33. Wills ED: Lipid peroxide formation in microsomes: The role of nonhaem iron . Biochem J 113:325-332, 1969. 34. McGray PB, Pfeifer PM, Stipe WH: Vitamin E protection of membrane lipids during electron transport functions . Ann NY Acad Sci 203:62-73, 1972.Crossref 35. Mustafa MG, Tierney DF: Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity . Am Rev Respir Dis 118:1061-1090, 1978. 36. Graeber JE, Williams ML, Oski FA: The use of intramuscular vitamin E in the premature infant . J Pediatr 90:282-284, 1977.Crossref 37. Roders MK, Glende EA, Recknagel RO: NADPH-dependent microsomal lipid peroxidation and the problem of pathological action at a distance . Biochem Pharmacol 27:437-443, 1978.Crossref 38. Yoshiokai T, Utsumi K, Sekibu K: Superoxide dismutase activity and lipid peroxidation of the rat liver during development . Biol Neonate 32:147-153, 1977.Crossref 39. Robotham JL, Troxler RF, Lietman PS: Iron poisoning: Another energy crisis . Lancet 2:664-665, 1974.Crossref 40. Barnes R, Connelly JL, Jones OTG: The utilization of iron and its complexes by mammalian mitochondria . Biochem J 128:1043-1055, 1972. 41. Trump BF, Valigrosky JM, Arstila AU, et al: The relationship of intracellular pathways of iron metabolism to cellular iron overload and the iron storage diseases . Am J Pathol 72:295-336, 1973. 42. Schubert J: The chemical basis of chelation , in Gross F (ed): Iron Metabolism: International Symposium on Iron Metabolism . Berlin, Springer-Verlag, 1964, pp 466-496. 43. Goodwin JF, Whitten CF: Chelation of ferrous sulfate solution by deferoxamine B . Nature 205:281-283, 1965.Crossref 44. Keberle H: The biochemistry of deferoxamine and its relation to iron metabolism . Ann NY Acad Sci 119:758-768, 1964.Crossref 45. Moeschlin S, Schnider U: Treatment of primary and secondary hemochromatosis and acute iron poisoning with a new, potent, iron-eliminating agent (deferoxamine-B) . N Engl J Med 269:57-61, 1963.Crossref 46. Movassaghi N, Purugganan GG, Leikin S: Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning . J Pediatr 75:604-608, 1969.Crossref 47. Leikin S, Vossough P, Mochir-Fatemi F: Chelation therapy in acute iron poisoning . J Pediatr 71:425-430, 1967.Crossref 48. Lipschitz DA, Dugard J, Simon MO, et al: The site of action of deferoxamine . Br J Haematol 20:395-404, 1971.Crossref 49. Misra AL, Hunger A, Keberle H: The passage of drugs across the rat intestine in vitro . J Pharm Pharmacol 18:246-251, 1966.Crossref 50. Balcerzak SP, Jensen WN, Pollack S: Mechanism of action of deferoxamine on iron absorption . Scand J Haematol 3:205-212, 1966.Crossref 51. Bannerman RM, Malpas JS: Studies on deferoxamine in relation to absorption of iron . Br J Haematol 11:15-20, 1965.Crossref 52. Hwang YF, Brown EB: Effect of deferoxamine on iron absorption . Lancet 50:135-137, 1965.Crossref 53. Tripod J: A pharmacological comparison at the binding of iron and other metals , in Gross F (ed): Iron Metabolism: International Symposium on Iron Metabolism . Berlin, Springer-Verlag, 1964, pp 503-524. 54. Peters G, Keberle H, Schmid K, et al: Distribution and renal excretion of desferrioxamine and ferrioxamine in the dog and in the rat . Biochem Pharmacol 15:93-109, 1966.Crossref 55. Brown EB, Hwang YF, Allgood JW: Studies on the site of action of deferoxamine . J Lab Clin Med 69:382-404, 1967. 56. Meyer-Brunot HG, Keberle H: The metabolism of deferoxamine-B and ferrioxamine-B . Biochem Pharmacol 16:527-535, 1967.Crossref 57. Hosking CS: A pharmacologic investigation of acute iron poisoning and its treatment . Aust Paediatr J 6:92-96, 1970. 58. Diplock AT, Green J, Bunyan J, et al: Vitamin E and stress: Iron overloading and the metabolism of D-alpha-tocopherol in the rat . Br J Nutr 21:725-730, 1967.Crossref 59. Goldberg L, Smith JD: Vitamin A and E deficiencies in relation to iron overloading in the rat . J Pathol Bacteriol 80:173-180, 1960.Crossref 60. Cambridge GW, McDonald FF: The influence of diet on the acute toxicity of injectable iron preparations in the mouse . Br J Pharm Chemother 27:114-119, 1966.Crossref 61. King JT, Lee YCP, Visscher MB: Relationship between vitamin E and dietary minerals in mouse 'paralysis' . Proc Soc Exp Biol Med 88:406-409, 1955. 62. Tollerz G, Lanner N: Protection against iron toxicity in vitamin E deficient piglet and mice by vitamin E and synthetic antioxidants . Nature 201:846-847, 1964.Crossref 63. Green J: Vitamin E and the biological antioxidant theory . Ann NY Acad Sci 203:29-44, 1972.Crossref 64. Goldberg L, Smith JP: Changes associated with the accumulation of excessive amounts of iron in certain organs of the rat . Br J Exp Pathol 39:59-73, 1958. 65. Spencer IOB: Ferrous sulfate poisoning in children . Br Med J 2:1112-1117, 1951.Crossref 66. Matthew H, Lawson AAH: Treatment of Common Acute Poisonings . London, Churchill Livingstone, 1975, pp 93-95. 67. Helfer RE, Rodgerson DO: The effect of deferoxamine on the determination of serum iron and iron binding capacity . J Pediatr 68:804-806, 1966.Crossref 68. Gesvirtz NR, Wasserman LR: The measurement of iron and iron binding capacity in plasma containing deferoxamine . J Pediatr 68:802-804, 1966.Crossref 69. Propper RD, Shurin SB, Nathan DG: Reassessment of the use of deferoxamine B in iron overload . N Engl J Med 294:1421-1423, 1976.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

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American Medical Association
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Copyright © 1980 American Medical Association. All Rights Reserved.
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10.1001/archpedi.1980.02130210059016
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Abstract

Abstract The accidental ingestion of iron-containing preparations is relatively common in childhood, and intentional overdosage with iron is occasionally seen in adults. Though rarely fatal, the consequences of a substantial iron ingestion can result in profound mental retardation or death. The availability of deferoxamine mesylate, a specific and tenacious chelator of iron, and the necessity for its early administration demand that the physician be aware of a rational approach to the therapy for iron poisoning. Owing to our current understanding of the pathophysiology of iron poisoning, we believe that the simultaneous oral and continuous intravenous (IV) administration of deferoxamine offers the most rational specific therapy for this condition. In this review we shall outline the clinical description, pathophysiology, and therapeutic regimens for acute iron intoxication. We have used this information to derive an approach we believe to be reasonable. CLINICAL DESCRIPTION The oral lethal dose (LD) of elemental iron is generally References 1. Arena JM: Poisoning , ed 2. Springfield, Ill, Charles C Thomas Publisher, 1970, pp 349-353. 2. Westlin WF: Deferoxamine in the treatment of acute iron poisoning: Clinical experience with 172 children . Clin Pediatr 5:531-535, 1966.Crossref 3. Whitten CF, Gibson GW, Good MH, et al: Studies in acute iron poisoning: I. Deferoxamine in the treatment of acute iron poisoning: Clinical observations, experimental studies, and theoretical considerations . Pediatrics 36:322-335, 1965. 4. Fischer DS, Parkman R, Finch SC: Acute iron poisoning in children: The problem of appropriate therapy . JAMA 218:1179-1184, 1971.Crossref 5. Westlin WF: Deferoxamine as a chelating agent . Clin Toxicol 4:597-602, 1971.Crossref 6. McEnery JT, Greengard J: Treatment of acute iron ingestion with deferoxamine in 20 children . J Pediatr 68:773-779, 1966.Crossref 7. Whitten CF, Brough AJ: The pathophysiology of acute iron poisoning . Clin Toxicol 4:585-595, 1971.Crossref 8. Barker GA, Brown TCK, Hosking CS: Acute iron poisoning: Clinical features and management . Anaesth Intensive Care 4:345-350, 1974. 9. Covey TJ: Ferrous sulfate poisoning: A review, case summaries, and therapeutic regimen . J Pediatr 64:218-226, 1964.Crossref 10. James JA: Acute iron poisoning: Assessment of severity and prognosis . J Pediatr 77:117-119, 1970.Crossref 11. Wheby MS, Jones LG: Role of transferrin in iron absorption . J Clin Invest 42:1007-1016, 1963.Crossref 12. Reissmann KR, Coleman TJ, Budai BS, et al: Acute intestinal iron intoxication: I. Iron absorption, serum iron, and autopsy findings . Blood 10:35-45, 1955. 13. Barr DGD, Fraser DKB: Acute iron poisoning in children: Role of chelating agents . Br Med J 1:737-741, 1968.Crossref 14. McEnery JT: Hospital management of acute iron ingestion . Clin Toxicol 4:603-613, 1971.Crossref 15. Witzleben CL: The pathogenesis of iron hepatotoxicity . Ann NY Acad Sci 165:105-110, 1969.Crossref 16. Gandhi RK, Robarts FH: Hour-glass stricture of the stomach and pyloric stenosis due to ferrous sulfate poisoning . Br J Surg 49:613-617, 1962.Crossref 17. Murray MJ: Iron absorption . Clin Toxicol 4:545-558, 1971.Crossref 18. Fairbanks VF, Fahey JL, Beutler E: Clinical disorders of iron metabolism , in Clinical Disorders of Iron Metabolism , ed 2. New York, Grune & Stratton Inc, 1971, pp 42-127. 19. Whitten CF, Chen YC, Gibson GW: Studies in acute iron poisoning: II. Further observations on deferoxamine in the treatment of acute iron poisoning . Pediatrics 38:102-110, 1966. 20. Whitten CF, Chen YC, Gibson GW: Studies in acute iron poisoning: III. The hemodynamic alterations in acute experimental iron poisoning . Pediatr Res 2:479-485, 1978.Crossref 21. Witzleben CL, Chaffey NJ: Acute ferrous sulfate poisoning: A histochemical study of its effect on the liver . Arch Pathol Lab Med 82:454-461, 1966. 22. Witzleben CL: An electron microscopic study of ferrous sulfate-induced liver damage . Am J Pathol 49:1053-1068, 1966. 23. Ganote CE, Nahara G: Acute ferrous sulfate hepatotoxicity in rats: An electron microscopic and biochemical study . Lab Invest 28:426-436, 1973. 24. Hunter FE Jr, Gebicki JM, Hoffstein PE, et al: Swelling and lysis of rat liver mitochondria induced by ferrous ions . J Biol Chem 238:828-835, 1963. 25. Hoffstein PE, Hunter FE Jr, Gebicki JM, et al: Formation of "lipid peroxide" under conditions which lead to swelling and lysis of rat liver mitochondria . Biochem Biophys Res Commun 7:276-280, 1962.Crossref 26. Corwin LM, Lipsett MN: Studies on stability of rat liver mitochondria . J Biol Chem 234:2453-2458, 1959. 27. Lehninger AL: Water uptake and extrusion by mitochondria in relation to oxidative phosphorylation . Physiol Rev 42:467-517, 1962. 28. Hochstein P, Ernster L: Microsomal peroxidation of lipids and its possible role in cellular injury , in DeReuck AVS, Knight J (eds): Cellular Injury . Boston, Little Brown & Co, 1964, pp 123-135. 29. Gruger EH Jr, Tappel AL: Reactions of biological antioxidants: I. Fe(III)-catalyzed reactions of lipid hydroperoxides with alpha-tocopherol . Lipids 5:326-331, 1970.Crossref 30. McKnight RC, Hunter FE Jr: Mitochondrial membrane ghosts produced by lipid peroxidation induced by ferrous ion . J Biol Chem 241:2757-2765, 1966. 31. Wills ED: Lipid peroxide formation in microsomes: General considerations . Biochem J 113:315-324, 1969. 32. Barbar AA: Lipid peroxidation in rat tissue homogenates: Interaction of iron and ascorbic acid as the normal catalytic mechanism . Lipids 1:146-151, 1966.Crossref 33. Wills ED: Lipid peroxide formation in microsomes: The role of nonhaem iron . Biochem J 113:325-332, 1969. 34. McGray PB, Pfeifer PM, Stipe WH: Vitamin E protection of membrane lipids during electron transport functions . Ann NY Acad Sci 203:62-73, 1972.Crossref 35. Mustafa MG, Tierney DF: Biochemical and metabolic changes in the lung with oxygen, ozone, and nitrogen dioxide toxicity . Am Rev Respir Dis 118:1061-1090, 1978. 36. Graeber JE, Williams ML, Oski FA: The use of intramuscular vitamin E in the premature infant . J Pediatr 90:282-284, 1977.Crossref 37. Roders MK, Glende EA, Recknagel RO: NADPH-dependent microsomal lipid peroxidation and the problem of pathological action at a distance . Biochem Pharmacol 27:437-443, 1978.Crossref 38. Yoshiokai T, Utsumi K, Sekibu K: Superoxide dismutase activity and lipid peroxidation of the rat liver during development . Biol Neonate 32:147-153, 1977.Crossref 39. Robotham JL, Troxler RF, Lietman PS: Iron poisoning: Another energy crisis . Lancet 2:664-665, 1974.Crossref 40. Barnes R, Connelly JL, Jones OTG: The utilization of iron and its complexes by mammalian mitochondria . Biochem J 128:1043-1055, 1972. 41. Trump BF, Valigrosky JM, Arstila AU, et al: The relationship of intracellular pathways of iron metabolism to cellular iron overload and the iron storage diseases . Am J Pathol 72:295-336, 1973. 42. Schubert J: The chemical basis of chelation , in Gross F (ed): Iron Metabolism: International Symposium on Iron Metabolism . Berlin, Springer-Verlag, 1964, pp 466-496. 43. Goodwin JF, Whitten CF: Chelation of ferrous sulfate solution by deferoxamine B . Nature 205:281-283, 1965.Crossref 44. Keberle H: The biochemistry of deferoxamine and its relation to iron metabolism . Ann NY Acad Sci 119:758-768, 1964.Crossref 45. Moeschlin S, Schnider U: Treatment of primary and secondary hemochromatosis and acute iron poisoning with a new, potent, iron-eliminating agent (deferoxamine-B) . N Engl J Med 269:57-61, 1963.Crossref 46. Movassaghi N, Purugganan GG, Leikin S: Comparison of exchange transfusion and deferoxamine in the treatment of acute iron poisoning . J Pediatr 75:604-608, 1969.Crossref 47. Leikin S, Vossough P, Mochir-Fatemi F: Chelation therapy in acute iron poisoning . J Pediatr 71:425-430, 1967.Crossref 48. Lipschitz DA, Dugard J, Simon MO, et al: The site of action of deferoxamine . Br J Haematol 20:395-404, 1971.Crossref 49. Misra AL, Hunger A, Keberle H: The passage of drugs across the rat intestine in vitro . J Pharm Pharmacol 18:246-251, 1966.Crossref 50. Balcerzak SP, Jensen WN, Pollack S: Mechanism of action of deferoxamine on iron absorption . Scand J Haematol 3:205-212, 1966.Crossref 51. Bannerman RM, Malpas JS: Studies on deferoxamine in relation to absorption of iron . Br J Haematol 11:15-20, 1965.Crossref 52. Hwang YF, Brown EB: Effect of deferoxamine on iron absorption . Lancet 50:135-137, 1965.Crossref 53. Tripod J: A pharmacological comparison at the binding of iron and other metals , in Gross F (ed): Iron Metabolism: International Symposium on Iron Metabolism . Berlin, Springer-Verlag, 1964, pp 503-524. 54. Peters G, Keberle H, Schmid K, et al: Distribution and renal excretion of desferrioxamine and ferrioxamine in the dog and in the rat . Biochem Pharmacol 15:93-109, 1966.Crossref 55. Brown EB, Hwang YF, Allgood JW: Studies on the site of action of deferoxamine . J Lab Clin Med 69:382-404, 1967. 56. Meyer-Brunot HG, Keberle H: The metabolism of deferoxamine-B and ferrioxamine-B . Biochem Pharmacol 16:527-535, 1967.Crossref 57. Hosking CS: A pharmacologic investigation of acute iron poisoning and its treatment . Aust Paediatr J 6:92-96, 1970. 58. Diplock AT, Green J, Bunyan J, et al: Vitamin E and stress: Iron overloading and the metabolism of D-alpha-tocopherol in the rat . Br J Nutr 21:725-730, 1967.Crossref 59. Goldberg L, Smith JD: Vitamin A and E deficiencies in relation to iron overloading in the rat . J Pathol Bacteriol 80:173-180, 1960.Crossref 60. Cambridge GW, McDonald FF: The influence of diet on the acute toxicity of injectable iron preparations in the mouse . Br J Pharm Chemother 27:114-119, 1966.Crossref 61. King JT, Lee YCP, Visscher MB: Relationship between vitamin E and dietary minerals in mouse 'paralysis' . Proc Soc Exp Biol Med 88:406-409, 1955. 62. Tollerz G, Lanner N: Protection against iron toxicity in vitamin E deficient piglet and mice by vitamin E and synthetic antioxidants . Nature 201:846-847, 1964.Crossref 63. Green J: Vitamin E and the biological antioxidant theory . Ann NY Acad Sci 203:29-44, 1972.Crossref 64. Goldberg L, Smith JP: Changes associated with the accumulation of excessive amounts of iron in certain organs of the rat . Br J Exp Pathol 39:59-73, 1958. 65. Spencer IOB: Ferrous sulfate poisoning in children . Br Med J 2:1112-1117, 1951.Crossref 66. Matthew H, Lawson AAH: Treatment of Common Acute Poisonings . London, Churchill Livingstone, 1975, pp 93-95. 67. Helfer RE, Rodgerson DO: The effect of deferoxamine on the determination of serum iron and iron binding capacity . J Pediatr 68:804-806, 1966.Crossref 68. Gesvirtz NR, Wasserman LR: The measurement of iron and iron binding capacity in plasma containing deferoxamine . J Pediatr 68:802-804, 1966.Crossref 69. Propper RD, Shurin SB, Nathan DG: Reassessment of the use of deferoxamine B in iron overload . N Engl J Med 294:1421-1423, 1976.Crossref

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: Sep 1, 1980

References