Iron-chelating therapy and the treatment of thalassemia

Blood

Volumn 89, Issue 3, 1997, Pages 739-761

  Olivieri, Nancy F ^a   Brittenham, Gary M ^b  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

DEFEROXAMINE;

BODY HEIGHT; ERYTHROCYTE TRANSFUSION; HUMAN; HUMAN CELL; HUMAN TISSUE; INTRAMUSCULAR DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; IRON CHELATION; IRON OVERLOAD; PERCEPTION DEAFNESS; PRACTICE GUIDELINE; PRIORITY JOURNAL; RETINA DISEASE; REVIEW; SPINE DISEASE; SPLENECTOMY; THALASSEMIA;

EID: 0031001278     PISSN: 00064971     EISSN: None     Source Type: Journal    
DOI: 10.1182/blood.v89.3.739     Document Type: Review

References (315)

1. Weatherall DJ, Clegg JB: The Thalassemia Syndromes (ed 3). Oxford, UK, Blackwell Scientific Publications, 1981
2. Cohen AR: Management of iron overload in the pediatric patient. in Hematol Oncol Clin North Am 521, 1987
3. Wolman IJ: Transfusion therapy in Cooley's anemia: Growth and health as related to long range hemoglobin levels. A progress report. Ann NY Acad Sci 119:736, 1964
4. Wolman IJ, Ortolani M: Some clinical features of Cooley's anemia patients as related to transfusion schedules. Ann NY Acad Sci 165:407, 1969
5. Piomelli S, Danoff S, Becker M, Lipera M, Travis S: Prevention of bone malformations and cardiomegaly in Cooley's anemia by early hypertransfusion regimen. Ann NY Acad Sci 165:427, 1969
6. Cazzola M, De Stefano P, Ponchio L, Locatelli F, Dessi C, Beguin Y, Barella S, Dessi C, Cao A, Galanello R: Relationship between transfusion regimen and suppression of erythropoiesis in beta thalassemia major. Br J Haematol 89:473, 1995
7. Cazzola M, Locatelli F, De Stefano P: Deferoxamine in thalassemia major [letter]. N Engl J Med 332:271, 1995
8. Propper RD, Button LN, Nathan DG: New approaches to the transfusion management of thalassemia. Blood 55:55, 1980
9. Piomelli S, Seaman C, Reibman J, Tyrun A, Graziano J, Tabachnik N: Separation of younger red cells with improved survival in vivo: An approach to chronic transfusion therapy. Proc Natl Acad Sci USA 75:3474, 1978
10. Corash L, Klein H, Deisseroth A, Shafer B, Rosen S, Beman J, Griffith P, Neinhuis A: Selective isolation of young erythrocytes for transfusion support of thalassemia major patients. Blood 57:599, 1981
11. Bracey AW, Klein HG, Chambers S, Corash L: Ex-vivo selective isolation of young red blood cells using the IBM-2991 cell washer. Blood 61:1068, 1983
12. Cohen AR, Schmidt JM, Martin MB, Barnsley W, Schwartz E: Clinical trial of young red cell transfusions. J Pediatr 104:865, 1984
13. Marcus RE, Wonke B, Bantock HM, Thomas MJ, Parry ES, Taite H, Huehns ER: A prospective trial of young red cells in 48 patients with transfusion-dependent thalassemia. Br J Haematol 60:153, 1985
14. Kevy SV, Jacobson MS, Fosburg M, Renaud M, Scanlon A, Carmen R, Nelson E: A new approach to neocyte transfusion: Preliminary report. J Clin Apheresis 4:194, 1988
15. Simon TL, Sohmer P, Nelson EF: Extended survival of neocytes produced by a new system. Transfusion 29:221, 1989
16. Collins AF, Dias GC, Haddad S, Talbot R, Herst R, Tyler BJ, Zuber E, Blanchette VS, Olivieri NF: Evaluation of a new neocyte transfusion preparation vs. washed cell transfusion in patients with homozygous beta thalassemia. Transfusion 34:517, 1994
17. Cohen AR, Martin MB, Silber JH, Kim HC, Ohene-Frempong K, Schwartz E: A modified transfusion program for prevention of stroke in sickle cell disease. Blood 79:1657, 1994
18. Berdoukas VA, Kwan YL, Sansotta ML: A study on the value of red cell exchange transfusion in transfusion dependent anemias. Clin Lab Haematol 8:209, 1986
19. Modell B: Total management of thalassaemia major. Arch Dis Child 52:489, 1977
20. Cohen A, Gayer R, Mizanin J: Longterm effect of splenectomy on transfusion requirements in thalassemia major. Am J Hematol 30:254, 1989
21. Olivieri NF: Unpublished observations, November 1996
22. Fosburg M, Nathan DG: Treatment of Cooley's anemia. Blood 76:435, 1990
23. Zurlo MF, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, Di Gregorio F, Burattini MG, Terzoli S: Survival and causes of death in thalassaemia major. Lancet 2:27, 1989
24. Piperno A, Fargion S, D'Alba R: Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection. J Hepatol 16:364, 1992
25. Sher GD, Milone SD, Cameron R, Jamieson FB, Krajden M, Collins AF, Matsui D, Entsuah B, Berkovitch M, Hackman R, Francombe WH, Olivieri NF: Hepatitis C virus infection in transfused patients with β hemoglobinopathies accelerates iron-induced hepatic damage. Blood 82:360a, 1993 (abstr, suppl 1)
26. Lai ME, De Virgilis S, Argiolu F, Farci P, Mazzoleni AP, Lisci V, Rapicetta M, Clemente MG, Nurchis P, Arnone M, Balestrieri A, Cao A: Evaluation of antibodies to hepatitis C virus in a long-term prospective study of posttransfusion hepatitis among thalassemic children: Comparison between first-and second-generation assay. J Pediatr Gastroenterol Nutr 16:458, 1993
27. Tong MT, El-Farra NS, Reikes AR, Co RL: Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med 332:1463, 1995
28. Donohue SM, Wonke B, Hoffbrand AV, Reittie J, Ganeshaguru K, Scheuer PJ, Brown D, Dusheiko G: Alpha interferon in the treatment of chronic hepatitis C infection in thalassaemia major. Br J Haematol 83:491, 1993
29. Clemente MG, Congia M, Lai ME, Killiu F, Lampis R, Frau F, Frau MR, Faa G, Diana G, Dessi C, Melis A, Mazzoleni AP, Cornnacchia G, Cao A, De Virgiliis S: Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C. J Pediatr 125:123, 1994
30. Hershko C, Weatherall DJ: Iron-chelating therapy. CRC Crit Rev Clin Lab Sci 26:303, 1988
31. Halliwell B, Gutteridge JMC: Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 219:1, 1984
32. Slater TF: Free radical mechanisms in tissue injury. Biochem J 222:1, 1984
33. Bacon BR, Tavill AS, Brittenham GM, Park CH, Recknagel RO: Hepatic lipid peroxidation in vivo in rats with chronic iron overload. J Clin Invest 71:429, 1983
34. Heys AD, Dormandy TL: Lipid peroxidation in iron loaded spleens. Clin Sci 60:295, 1981
35. Hershko C, Peto TEA: Annotation: Non-transferrin plasma iron. Br J Haematol 66:149, 1987
36. Sutton HC: Efficiency of chelated iron compounds as catalysts for the Haber-Weiss Reacion. J Free Radical Biol Med 1:195, 1985
37. Hershko C, Graham G, Bates CW, Rachmilewitz EA: Non-specific serum iron in thalassemia: An abnormal serum iron fraction of potential toxicity. Br J Haematol 40:255, 1978
38. Batey RG, LaiChung Fong P, Sherlock S: The nature of serum iron in primary haemachromatosis. Clin Sci 55:24, 1978
39. Anuwatanakulchia M, Pootrakul P, Thuvasethakul P, Wasi P: Non-transferrin plasma iron in β-thalassaemia/HbE and haemoglobin H diseases. Scand J Haematol 32:153, 1984
40. Wagstaff M, Peters SW, Jones BM, Jacobs A: Free iron and iron toxicity in iron overload. Br J Haematol 61:566, 1985
41. Gutteridge JMC, Rowley DA, Griffiths E, Halliwell B: Low-molecular-weight iron complexes and oxygen radical reactions in idiopathic haemochromatosis. Clin Sci 68:463, 1985
42. Wang WC, Ahmed N, Hanna M: Non-transferrin-bound iron in long-term transfusion in children with congenital anemias. J Pediatr 108:552, 1986
43. al-Refaie FN, Wickens DG, Wonke B, Kontoghiorghes GJ, Hoffbrand AV: Serum non-transferrin-bound iron in beta-thalassaemia major patients treated with desferrioxamine and L1. Br J Haematol 82:431, 1992
44. Link G, Pinson A, Hershko C: Heart cells in culture: A model of myocardial iron overload and chelation. J Lab Clin Med 106:147, 1985
45. White GP, Jacobs A, Grady RW, Cerami A: The use of chang cells cultured in vitro to evaluate potential iron chelating drugs. Br J Haematol 33:487, 1976
46. Jacobs A: in Fitzsimons DW (ed): Iron Metabolism: Ciba Foundation Symposium. Amsterdam, The Netherlands, Elsevier, 1977, p 91
47. Guterridge JMC, Halliwell B: Iron toxicity and oxygen radicals. Bailliere's Clin Hematol 2:195, 1989
48. Keberle H: The biochemistry of desferrioxamine and its relation to iron metabolism. Ann NY Acad Sci 119:758, 1964
49. Callender ST, Weatherall DJ: Iron chelation with oral desferrioxamine. Lancet 2:689, 1980
50. Summers MR, Jacobs A, Tudway D, Perera P, Ricketts C: Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects. Br J Haematol 42:547, 1979
51. Pippard M: Desferrioxamine induced iron excretion in humans. Bailliere's Clin Hematol 2:323, 1989
52. Brittenham GM: Disorders of iron metabolism: Deficiency and overload, in Hoffman R, Benz E, Shattil S, Furie B, Cohen H (eds): Hematology: Basic Principles and Practice. New York, NY, Churchill Livingstone, 1994, p 492
53. Willis ED: Lipid peroxide formation in microsomes. The role of non-haem iron. Biochem J 13:325, 1969
54. Morehouse LA, Thomas CE, Aust SD: Superoxide generation of NADPH-Cytochrome P-450 reductase: The effect of iron chelators and the role of Superoxide in microsomal lipid peroxidation. Arch Biochem Biophys 232:366, 1984
55. O'Connell MJ, Ward RJ, Baum H, Peters TJ: The role of iron in ferritin-and haemosiderin-mediated lipid peroxidation in liposomes. Biochem J 229:135, 1985
56. Hershko C, Link G, Pinson A: Modification of iron uptake and lipid peroxidation by hypoxia, ascorbic acid and α-tocopherol in iron-loaded rat myocardial cell cultures. J Lab Clin Med 110:355, 1987
57. Link G, Athias P, Grynberg A, Pinson A, Hershko C: Effect of iron loading on transmembrane potential, contraction and automaticity of rat ventricular muscle cells in culture. J Lab Clin Med 113:103, 1989
58. Sephton-Smith R: Iron excretion in thalassaemia major after administration of chelating agents. Br Med J 2:1577, 1962
59. Bannerman RM, Callender ST, Williams DL: Effect of desferrioxamine and DTPA in iron overload. Br Med J 2:1573, 1962
60. Sephton-Smith R: Chelating agents in the diagnosis and treatment of iron overload in thalassemia. Ann NY Acad Sci 119:776, 1964
61. Barry M, Flynn D, Letsky E, Risdon RA: Long term chelation therapy in thalassemia major: Effect on liver iron concentration, liver histology and clinical progress. Br Med J 2:16, 1974
62. Modell CB, Beck J: Long-term desferrioxamine therapy in thalassaemia. Ann NY Acad Sci 232:201, 1974
63. Propper RD, Shurin SB, Nathan DG: Reassessment of the use of desferrioxamine B in iron overload. N Engl J Med 294:421, 1976
64. Hussain MAM, Flynn DM, Green N, Hussein S, Hoffbrand AV: Subcutaneous infusion and intramuscular injection of desferrioxamine in patients with transfusional iron overload. Lancet 2:1278, 1976
65. Propper RL, Cooper B, Rufo RR, Nienhuis AW, Anderson W, Bunn HF, Rosenthal A, Nathan DG: Continuous subcutaneous administration of deferoxamine in patients with iron overload. N Engl J Med 297:418, 1977
66. Pippard MJ, Callender ST, Weatherall DJ: Intensive iron-chelation therapy with desferrioxamine in iron-loading anaemias. Clin Sci Mol Med 54:99, 1978
67. Pippard MJ, Callender ST, Finch CA: Ferrioxamine excretion in iron loaded man. Blood 60:288, 1982
68. Engle MA, Erlandson M, Smith CH: Late cardiac complications of chronic, severe, refractory anemia with hemochromatosis. Circulation 30:689, 1964
69. Grisaru D, Rachmilewitz FA, Mosseri M, Gotsman, Latair JS, Okon E, Goldfarb A, Hasin Y: Cardiopulmonary assessment in β-thalassemia major. Chest 98:1138, 1990
70. Kremastinos DTh, Tiniakos G, Theodorakis GN, Katritsis DG, Toutouzas PK: Myocarditis in β-thalassemia major: A cause of heart failure. Circulation 91:66, 1995
71. Buja LM, Roberts W: Iron in the heart: Etiology and clinical significance. Am J Med 51:209, 1971
72. MacDonald RA, Mallory GK: Haemochromatosis and haemosiderosis: Study of 21 autopsied cases. Arch Int Med 105:686, 1960
73. Graziano JH, Piomelli S, Hilgartner M, Giardian P, Karpatkin M, Andrew M, Lo Iacomo N, Seaman C: Chelation therapy in β-thalassemia major. III. The role of splenectomy in achieving iron balance. J Pediatr 99:695, 1981
74. Modell B, Letsky EA, Flynn DM, Peto R, Weatherall DJ: Survival and desferrioxamine in thalassaemia major. Br Med J 284:1081, 1982
75. Flynn DM, Hoffbrand AV, Politis D: Subcutaneous desferrioxamine: The effects of three years' treatment on liver iron, serum ferritin, and comments on echocardiography. Birth Defects 18:347, 1982
76. Weatherall DJ, Pippard MJ, Callender ST: Iron loading in thalassemia - Five years with the pump. N Engl J Med 308:456, 1983
77. Pippard MJ, Callender ST: The management of iron chelation therapy. Br J Haematol 54:503, 1983
78. Freeman AP, Giles RW, Berdoukas VA, Walsh WF, Choy D, Murray PC: Early left ventricular dysfunction and chelation therapy in thalassemia major. Ann Intern Med 99:450, 1983
79. Marcus RE, Davies SC, Bantock HM, Underwood SR, Walton S, Huehns ER: Desferrioxamine to improve cardiac function in iron-overloaded patients with thalassaemia major. Lancet 1:392, 1984
80. Anon: High-dose chelation therapy in thalassaemia. Lancet 1:373, 1984
81. Hyman CB, Agness CL, Rodriguez-Funes R, Zednikova M: Combined subcutaneous and high-dose intravenous deferoxamine therapy of thalassemia. Ann NY Acad Sci 445:293, 1985
82. Giardina PJV, Ehlers KH, Engle MA, Grady RW, Hilgartner MW: The effect of subcutaneous deferoxamine on the cardiac profile of thalassemia major: A five-year study. Ann NY Acad Sci 445:282, 1985
83. Wolfe L, Olivieri N, Sallan D, Colan S, Rose V, Propper R, Freedman MH, Nathan DG: Prevention of cardiac disease by subcutaneous deferoxamine in patients with thalassemia major. N Engl J Med 312:1600, 1985
84. Schafer AI, Rabinowe S, LeBoff MS, Bridges K, Cheron RG, Dluhy R: Long-term efficacy of deferoxamine iron chelation therapy in adults with acquired transfusional iron overload. Arch Intern Med 145:1217, 1985
85. Rahko PS, Salerni R, Uretsky BF: Successful reversal by chelation therapy of congestive cardiomyopathy due to iron overload. J Am Coll Cariol 8:426, 1986
86. Brittenham G, Nienhuis A: Desferrioxamine use protects against heart disease and death from transfusional iron overload in thalassemia major. Blood 72:56a, 1988 (abstr, suppl 1)
87. Aldouri MA WB, Hoffbrand AV, Flynn DM, Ward SE, Agnew JE, Hilson AJW: High incidence of cardiomyopathy in betathalassemia patients reccing transfusion and iron chelation: reversal by intensified chelation. Acta Haematol 84:113, 1990
88. Lerner N, Blei F, Bierman F, Johnson L, Piomelli S: Chelation therapy and cardiac status in older patients with thalassemia major. Am J Ped Hematol Oncol 12:56, 1990
89. Olivieri NF, McGee A, Liu P, Koren G, Freedman MH, Benson LN: Cardiac disease-free survival in patients with thalassemia major treated with subcutaneous deferoxamine. Ann NY Acad Sci 612:584, 1990
90. Ehlers KH, Giardina PJ, Lesser ML, Engle MA, Hilgartner MW: Prolonged survival in patients with beta-thalassemia major treated with deferoxamine. J Pediatr 118:549, 1991
91. Olivieri NF, Nathan DG, MacMillan JH, Wayne AD, Martin M, McGee A, Koren G, Liu PP, Cohen AR: Survival of medically treated patients with homozygous β thalassemia. N Engl J Med 331:574, 1994
92. Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW: Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 331:567, 1994
93. Olivieri NF, Brittenham GM, Matsui D, Berkovitch M, Blendis LM, Cameron RG, McClelland RA, Liu PP, Templeton DM, Koren G: Iron-chelation therapy with oral deferiprone in patients with thalassemia major. N Engl J Med 332:918, 1995
94. Iancu TC, Neustein HB. Ferritin in human liver cells of homozygous β thalassemia: Ultrastructural observations. Br J Haematol 37:527, 1977
95. Tsukamoto H, Horne W, Kamimura S, Niemelä O, Parkkila S, Yiä-Herttula S, Brittenham GM: Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest 96:620, 1995
96. Hoffbrand AV, Gorman A, Laulicht M, Garidi M, Economikdou J, Georgipoulou P, Hussain MAM, Flynn DM: Improvement in iron status and liver function in patients with transfusional iron overload with long-term subcutaneous desferrioxamine. Lancet 1:946, 1979
97. Janka GE, Mohring P, Helmig M, Haas RJ, Betke K: Intravenous and subcutaneous desferrioxamine therapy in children with severe iron overload. Eur J Pediatr 137:385, 1981
98. Cohen A, Martin M, Schwartz E: Response to long-term deferoxamine therapy in thalassemia. J Pediatr 99:689, 1981
99. Cohen A, Martin M, Schwartz E: Depletion of excessive liver iron stores with desferrioxamine. Br J Haematol 58:369, 1984
100. Cohen A, Mizanin J, Schwartz E: Treatment of iron overload in Cooley's anemia. Ann NY Acad Sci 445:374, 1985
101. Aldouri MA, Wonke B, Hoffbrand AV, Flynn DM, Laulicht M, Fenton LA, Scheuer PJ, Kibbler CC, Allwood CA, Brown D, Thomas HC: Iron state and hepatic disease in patients with thalassaemia major treated with long term subcutaneous desferrioxamine. J Clin Pathol 40:1352, 1987
102. Cohen AR, Mizanin J, Schwartz E: Rapid removal of excessive iron with daily, high-dose intravenous chelation therapy. J Pediatr 115:151, 1989
103. Grundy RG, Woods RA, Savage MO, Evans JPM: Relationship of endocrinopathy to iron chelation status in young patients with thalassaemia major. Arch Dis Child 71:128, 1994
104. Kwan EYW, Lee ACW, Li AMC, Tam SCF, Chan CF, Lau YL, Low LCK: A cross-sectional study of growth, puberty and endocrine function in patients with thalassaemia major in Hong Kong. J Paediatr Child Health 31:83, 1995
105. Landau H, Matoth I, Landau-Cordova Z, Goldfarb A, Rachmilewitz EA, Glaser B: Cross-sectional and longitudinal study of the pituitary-thyroid axis in patient with thalassaemia major. Clin Endocrinol 38:55, 1993
106. McIntosh N: Endocrinopathy in thalassaemia major. Arch Dis Child 51:195, 1976
107. Sklar CA, Lew LQ, Yoon DJ, David R: Adrenal function in thalassemia major following long term treatment with multiple transfusions and chelation therapy. Evidence for dissociation of cortisol and adrenal androgen secretion. Am J Dis Child 141:327, 1987
108. Kattamis C, Touliatos N, Haidas S, Matsaniotis N: Growth of children with thalassaemia: Effect of different transfusional regimens. Arch Dis Child 45:502, 1970
109. Costin G, Kogut MD, Hyman CB, Ortega JA: Endocrine abnormalities in thalassemia major. Am J Dis Child 133:497, 1979
110. Maurer HS, Lloyd-Still JD, Ingrisano C, Gonzalez-Crussi F, Honig CR. A prospective evaluation of iron chelation therapy in children with severe β-thalassaemia: A six-year study. Am J Dis Child 142:287, 1988
111. Modell B: Advances in the use of iron-chelating agents for the treatment of iron overload. Prog Hematol 11:267, 1979
112. Modell B, Berdoukas V: The Clinical Approach to Thalassaemia. London, UK, Grune and Stratton, 1984
113. Borgna-Pignatti C, De Stefano P, Zonta L, Vullo C, De Sanctis V, Melevendi C, Naselli A, Masera G, Terzoli S, Gabutti V, Piga A: Growth and sexual maturation in thalassemia major. J Pediatr 106:150, 1985
114. Kattamis C, Liakopoulou T, Kattamis A: Growth and development in children with thalassaemia major. Acta Paediatr Scand 366:111, 1990 (suppl)
115. Kletzky OA, Costin G, Marrs RP, Bernstein G, March CM, Mishell DR Jr: Gonadotropin insufficiency in patients with thalassemia major. J Clin Endocrinol Metab 48:901, 1979
116. Wang C, Tso SC, Todd D: Hypogonadotropic hypogonadism in severe β-thalassemia: Effect of chelation and pulsatile gonadotropin-releasing hormone therapy. J Clin Endocrionol Metab 68:511, 1989
117. Saenger P, Schwartz E, Markenson AL, Graziano JH, Levine LS, New AMI, Hilgartner MW: Depressed serum somatomedin activity in beta-thalassemia. J Pediatr 96:214, 1980
118. Werther GA, Matthews RN, Burger HG, Herington AC: Lack of response of nonsuppressible insulin-like activity to short term administration of human growth hormone in thalassemia major. J Clin Endocrionol Metab 53:806, 1981
119. Herington AC, Werthr GA, Matthews RN, Burger HG: Studies on the possible mechanism for deficiency of nonsuppressible insulin-like activity in thalassemia major. J Clin Endocrinol Metab 52:293, 1981
120. Bergeron C, Kovacs K: Pituitary siderosis: A histologic, immunocytologic, and ultrastructural study. Am J Pathol 9:295, 1978
121. Kelly TM, Edwards CQ, Meikle AW, Kushner JP: Hypogonadism in hemochromatosis: Reversal with iron depletion. Ann Intern Med 101:629, 1984
122. Siemens LJ, Mahler CH: Hypogonadotropic hyogonadism in hemochromatosis: Recovery of reproductive function after iron depletion. J Clin Endocrinol Metab 65:585, 1987
123. Pintor C, Cella G, Manso P, Corda R, Dessi C, Locatelli V, Muller EE: Impaired growth hormone (GH) response to GH-releasing hormone in thalassemia major. J Clin Endocrinol Metab 62:263, 1986
124. Shehadeh N, Hazani A, Rudolf MCJ, Peleg I, Benderly A, Hochberg Z: Neurosecretory dysfunction of growth hormone secretion in thalassaemia major. Acta Paediatr Scand 79:790, 1990
125. Postel-Vinay MC, Girot R, Leger J, Hocquette JF, McKelvie P, Amar-Costesec A, Rappaport R: No evidence for a defect in growth hormone binding to liver membranes in thalassemia major. J Clin Endocrinol Metab 68:94, 1989
126. Masala A, Melom T, Gallisai D, Alagna S, Rovasio PP, Rassu S, Milia AF: Endocrine functioning in multitransfused prepubertal patients with homogygous β-thalassemia. J Clin Endocrinol Metab 58:667, 1984
127. Tolis G, Politis C, Kontopoulou I, Poulatzas N, Rigas G, Saridakis C, Athanasiou V, Mortoglou A, Malachtari, Ling N: Pituitary somatotropic and corticotropic function in patients with β-thalassaemia on iron chelation therapy. Birth Defects 23:449, 1988
128. Leger J, Girot R, Crosnier H, Postel-Vinay MC, Rappaport R: Normal growth hormone (GH) response to GH-releasing hormone in children with thalassemia major before puberty: A possible age-related effect. J Clin Endocrinol Metab 69:453, 1989
129. Scacchi M, Danesi L, De Martin M, Dubini A, Forni L, Masala A, Gallisai D, Burrai C, Terzoli C, Marzano C, Cavagnini F: Treatment with biosynthetic growth hormone of short thalassaemic patients with impaired growth hormone secretion. Clin Endocrinol 35:335, 1991
130. Low LCK, Kwan EYW, Lim YJ, Lee ACW, Tam CF, Lam KSL: Growth hormone treatment of short Chinese children with β-thalassaemia major without growth hormone deficiency. Clin Endocrinol 42:359, 1995
131. Bozzola M, Argente J, Cristernino M, Moretta A, Valtorta A, Biscaldi I, Donnadieu M, Evain-Brion D, Severi F: Effect of human chorionic gonadotropin on growth velocity and biological growth parameters in adolescents with thalassaemia major. Eur J Pediatr 148:300, 1989
132. Flynn DM, Fairney A, Jackson D, Clayton BE: Hormonal changes in thalassaemia major. Arch Dis Child 51:828, 1976
133. Arcasoy A, Cavdar A, Cin S, Erten J, Babacan E, Gozdasoglu S, Akar N: Effects of zinc supplementation on linear growth in beta thalassemia (a new approach). Am J Hematol 24:127, 1987
134. Leek JC, Vogler JB, Gershwin ME, Golub MS, Hurley LS, Hendrickx AG: Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects. Am J Clin Nutr 40:1203, 1984
135. Nishi Y, Hatano S, Aihara K, Fujie A, Kihara M: Transient partial growth hormone deficiency due to zinc deficiency. J Am Coll Nutr 8:93, 1989
136. Vassilopoulou-Sellin R, Oyedeji CO, Foster PL, Thompson MM, Saman NA: Haemoglobin as a direct inhibitor of cartilage growth in vitro. Horm Metab Res 21:11, 1989
137. Bronspeigel-Weintrob N, Olivieri NF, Tyler BJ, Andrews D, Freedman MH, Holland FJ: Effect of age at the start of iron chelation therapy on gonadal function in β-thalassemia major. N Engl J Med 323:713, 1990
138. Jensen CE, Tuck SM, Wonke B: Fertility in thalassaemia major: A report of 16 pregnancies, preconceptual evaluation and a review of the literature. Br J Obstet Gynaecol 102:625, 1995
139. Chatterjee R, Katz M, Cox TF, Porter JB: Prospective study of the hypothalamic-pituitary axis in thalassaemic patients who developed secondary amenorrhea. Clin Endocrinol 39:287, 1993
140. De Sanctis V, Katz M, Vullo C, Bagni B, Ughi M, Wonke B: Effect of different treatment regimes on linear growth and final height in β-thalassaemia major. Clin Endocrinol 40:91, 1994
141. Rodda CP, Reid ED, Johnson S, Doery J, Matthews R, Bowden DK: Short stature in homozygous β-thalassaemia is due to disproportionate truncal shortening. Clin Endocrinol 42:587, 1995
142. Piga A, Luzzatto L, Capalbo P, Gambotto S, Tricta F, Gabutti V: High-dose desferrioxamine as a cause of growth failure in thalassaemic patients. Eur J Haematol 40:380, 1988
143. DeVirgilis S, Congia M, Frau F, Argiolu F, Diana G, Cucca F, Varsi A, Sanna G, Podda G, Fodde M, Franco-Piratu G, Cao A: Deferoxamine-induced growth retardation in patients with thalassemia major. J Pediatr 113:661, 1988
144. Olivieri NF, Koren G, Harris J, Khattak S, Freedman MH, Templeton DM, Bailey JD, Reilly BJ: Growth failure and bony changes induced by deferoxamine. Am J Ped Hematol Oncol 14:48, 1992
145. Lassman MN, Genel M, Wise JK, Hendler R, Felig P: Carbohydrate homeostasis and pancreatic islet cell function in thalassemia. Ann Intern Med 80:65, 1974
146. Costin G, Kogut MD, Hyman C, Ortega JA: Carbohydrate metablism and pancreatic islet-cell function in thalassemia major. Diabetes 26:230, 1977
147. Saudek CD, Hemm RM, Peterson CM: Abnormal glucose tolerance in β-thalassemia major. Metabolism 26:43, 1977
148. Zuppinger K, Molinari B, Hirt A, Imbach P, Bugler E, Tönz O, Zurbrügg RP: Increased risk of diabetes melliuts in beta-thalassaemia major. Hel Paediat Acta 4:197, 1979
149. De Sanctis V, D'Ascola G, Wonke B: The development of diabetes mellitus and chronic liver disease in long term chelated β-thalassaemic patients. Postgrad Med J 62:831, 1986
150. De Sanctis V, Zurlo MG, Senesi E, Boffa C, Cavallo L, Di Gregorio F: Insulin dependent diabetes in thalassaemia. Arch Dis Child 63:58, 1988
151. Dandona P, Hussain MAM, Varghese Z, Politis D, Flynn DM, Hoffbrand AV: Insulin resistance and iron overload. Ann Clin Biochem 20:77, 1983
152. Merkel PA, Simonson DC, Amiel SA, Plewe G, Sherwin RS, Pearson HA, Tamborlane WV: Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. N Engl J Med 318:809, 1988
153. Dmochowski K, Finegood DT, Francombe WH, Tyler B, Zinman B: Factors determining glucose tolerance in patients with thalassemia major. J Clin Endocrinol Metab 77:478, 1993
154. Cavello-Perin P, Pacini B, Cerutti F, Bessone A, Condo C, Sacchetti L, Piga A, Pagano G: Insulin resistance and hyperinsulinemia in homozygous β-thalassemia. Metabolism 44:281, 1995
155. Torrance JD, Charlton RW, Schmaman A, Lynch SR, Bothwell TH: Storage iron in 'muscle.' J Clin Path 21:495, 1968
156. Olivieri NF, Ramachandran S, Tyler B, Bril V, Moffatt K, Daneman D: Diabetes mellitus in older patients with thalassemia major: Relationship to severity of iron overload and presence of microvascular complications. Blood 76:72a, 1990 (abstr, suppl 1)
157. Awai M, Yamanoi Y, Kuwashima J, Seno S: Induction mechanism of diabetes by ferric nitriloacetate injection, in Saltman P, Hegenauer J (eds): The Biochemistry and Physiology of Iron. Amsterdam, The Netherlands, Elsevier/North, 1982, p 543
158. Olivieri NF, Snider MA, Nathan DG, Gee B, Muroff A, Martin M, Vichinsky EP, Cohen AR: Survival following the onset of iron-induced cardiac disease in thalassemia major. Blood 86:250a, 1995 (abstr, suppl 1)
159. Perrimond H, Michel G, Orsini A, Kreitman B, Metras D: First report of a cardiac transplantation in a patient with thalassaemia major. Br J Haematol 78:467, 1991
160. Olivieri NF, Liu PP, Sher GD. Collins AF, McCusker PJ, Levy G, Grieg P, Daley P, Francombe WH, Butany J: Successful combined cardiac and liver transplantation in an adult with homozygous beta-thalassemia. N Engl J Med 330:1125, 1994
161. Pippard MJ: Measurement of iron status. Prog Clin Biol Res 309:85, 1989
162. Finch CA, Bellotti V, Stray SEA: Plasma ferritin determination as a diagnostic tool. West J Med 145:657, 1986
163. Brittenham GM, Danish EH, Harris JW: Assessment of bone marrow and body iron stores. Semin Hematol 18:194, 1981
164. Borgna-Pignatti C, Castriota-Scanderbeg A: Methods of evaluating iron stores and efficacy of chelation in transfusional hemosiderosis. Haematologica 76:409, 1991
165. Brittenham GM, Cohen AR, McLaren CE, Martin MB, Griffith PM, Niehuis AW, Young NS, Allen CJ, Farrell DE, Harris JW: Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major. Am J Hematol 42:81, 1993
166. Finch C: Regulators of iron balance in humans. Blood 84:1697, 1994
167. Worwood M, Cragg SJ, McLaren C, Ricketts C, Economidou J: Binding of serum ferritin to concanavalin A: Patients with homozygous β thalassaemia and transfusional iron overload. Br J Haematol 46:409, 1980
168. Roeser HP, Halliday JW, Sizemore DEA: Serum ferritin in ascorbic acid deficiency. Br J Haematol 45:457, 1980
169. Baynes R, Bezwoda W, Bothwell T, Khan Q, Mansoor N: The non-immune inflammatory response: Serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein. Scand J Clin Lab Invest 46:695, 1986
170. Mitnick JS, Basniak MA, Megibow AJ, Karpatkin M, Feiner HD: CT in beta-thalassemia: Iron deposition in the liver, spleen, and lymph nodes. AJR 136:1191, 1981
171. Long JAJ, Doppman JL, Nienbuis AW, Mills SR: Computed tomographic analysis of beta-thalassemic syndromes with hemochomatosis: Pathologic findings with clinical and laboratory correlations. J Comput Assist Tomogr 4:159, 1980
172. Guyader D, Gandon Y, Deugnier Y, Jouanolle H, Loreal O, Simon M, Bourel M, Carsin M, Brissol P: Evaluation of computed tomography in the assessment of liver iron overload. A study of 46 cases of idiopathic hemochromatosis. Gastroenterology 97:737, 1989
173. Houang MTW, Arozena X, Skalicka A, Huehns ER, Shaw DG: Correlation between computed tomographic values and liver iron content in thalassaemia major with iron overload. Lancet 1:1322, 1979
174. Olivieri NF, Grisaru D, Daneman A, Martin DJ, Rose V, Freedman MH: Computed tomography scanning of the liver to determine efficacy of iron chelation therapy in thalassemia major. J Pediatr 114:427, 1989
175. Wielopolski L, Zaino EC. Noninvasive in-vivo measurement of hepatic and cardiac iron. J Nucl Med 33:1278, 1992
176. Stark DD, Moseley ME, Bacon BR, Moss AA: Magnetic resonance imaging and spectroscopy of hepatic iron overload. Radiology 154:137, 1985
177. Krocker RM, McVeigh ER, Hardy P, Bronskill MJ, Henkelman RM: In-vivo measurement of NMR relaxation times. Magn Reson Med 2:1, 1985
178. Kessing P, Falke T, Steiner R, Bloem H, Peters A: Magnetic resonance imaging in hemosiderosis. Diagn Imaging Clin Med 54:7, 1985
179. Gomori JM, Grossman RI, Drott HR: MR relaxation times and iron content of thalassemic spleens: An in vitro study. AJR 150:567, 1988
180. Hernandez RJ, Sarnaik SA, Lande I, Aisen AM, Glazer GM, Chenevert T, Martel W: MR evaluation of liver iron overload. J Comput Assist Tomogr 12:91, 1988
181. Hardy P, Henkelman RM: Transverse relaxation rate enhancement caused by magnetic particles. Magn Reson Imaging 7:265, 1989
182. Johnston DL, Rice L, Vick GW, Hedrick TD, Rokey R: Assessment of tissue iron overload by nuclear magnetic resonance imaging. Am J Med 87:40, 1989
183. Kaltwasser JP, Gottschalk R, Schalk KP, Hartl W: Non-invasive quantitation of liver iron-overload by magnetic resonance imaging. Br J Haematol 74:360, 1990
184. Bonkovsky HL, Slaker DP, Bills EB, Wolf DC: Usefulness and limitations of laboratory and hepatic imaging studies in iron-storage disease. Gastroenterology 99:1079, 1990
185. Chezmar JL, Nelson RC, Malko JA, Bernadino ME: Hepatic iron overload: Diagnosis and quantification by noninvasive imaging. Gastrointestinal Radiology 15:27, 1990
186. Gomori JM, Horev G, Tamary H, Zandback J, Korneich L, Zaizov R, Freud E, Krief O, Ben-Meir J, Rotem H, Kuspet M, Rosen P, Rachmilewitz EA, Leewenthal E, Gorodetskey R: Hepatic iron overload: Quantitative MR imaging. Radiology 179:367, 1991
187. Chan PCK, Lie P, Cronin C, Heathcote J, Uldall R: The use of nuclear magnetic resonance imaging in monitoring total body iron in hemadialysis patients with hemosiderosis treated with erythropoietin and phlebotomy. Am J Kidney Dis 19:484, 1992
188. Villari N, Caramella D, Lippi A, Guazelli C: Assessment of liver iron overload in thalassemic patients by MR imaging. Acta Radiol 4:347, 1992
189. Liu P, Olivieri N, Sullivan H, Henkelman M: Magnetic resonance imaging in beta-thalassemia: Detection of iron content and association with cardiac complications. J Am Coll Cardiol 21:491, 1993 (abstr)
190. Jenson PD, Jensen FT, Christensen T, Ellegaard J: Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging. Br J Haematol 87:171, 1993
191. Jensen PD, Jensen FT, Christensen T, Ellegaard J: Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients. Br J Haematol 89:880, 1995
192. Olivieri NF, Koren G, Matsui D, Liu PP, Blendis L, Cameron R, McClelland RA, Templeton DM: Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. Blood 79:2741, 1992
193. Liu P, Henkelman M, Joshi J, Hardy P, Butany J, Iwanochko M, Clauberg M, Dhar M, Mai D, Waien S, Olivieri NF: Quantitation of cardiac and tissue iron by
194. Olson LJ, Edwards WD, McCall JT, Ilstrup DM, Gersh BJ: Cardiac iron deposition in idiopathic hemochromatosis: Histologic and analytic assessment of 14 hearts from autopsy. J Am Coll Cardiol 10:1239, 1987
195. Fitchett DH, Coltart DJ, Littler WA, Leyland MJ, Trueman T, Gozzard DI, Peters TJ: Cardiac involvement in secondary haemochromatosis: A catheter biopsy study and analysis of myocardium. Cardiovasc Res 14:719, 1980
196. Fujisawa I, Asato R, Nishimura K, Togashi K, Itoh K, Nakano Y, Itoh H, Hashimoto N, Takeuchi J, Torizuka K: Anterior and posterior lobes of the pituitary gland: assessment by 1.5 T MR imaging. J Comput Assist Tomogr 11:214, 1987
197. Fujisawa I, Morikawa M, Nakano Y, Konishi J: Hemochromatosis of the pituitary gland: MR imaging. Radiology 168:213, 1988
198. Berkovitch M, Milone S, Kucharzyk W, Liu P, Papadouris D, Collins AF, Olivieri NF: Differential iron deposition in the anterior pituitary and liver in homozygous beta-thalassemia: Prediction of gonadal failure by magnetic resonance imaging. Blood 82:359a, 1993 (abstr, suppl 1)
199. Cecchetti G, Binda A, Piperno A, Nador F, Fargion S, Fiorelli G: Cardiac alterations in 36 consecutive patients with idiopathic haemochromatosis: Polygraphic and echocardiographic evaluation. Eur Heart J 12:224, 1991
200. Valdes-Cruz L, Reinenke C, Rutkowski M, Dudell GG, Goldberg SJ, Allen HD, Sahn DJ, Piomelli S: Preclinical abnormal segmental cardiac manifestations of thalassemia major in children on transfusion-chelation therapy: Echographic alteration of left ventricular posterior wall contraction and relaxation patterns. Am Heart J 103:505, 1982
201. Olson LJ, Baldus WP, Tajik AJ: Echocardiographic features of idiopathic hemochromatosis. Am J Cardiol 60:885, 1987
202. Benson L, Liu P, Olivieri N, Rose V, Freedom R: Left ventricular function in young adults with thalassemia. Circulation 80:274, 1989 (abstr)
203. Leon MB, Borer JS, Bacharach SL, Green MV, Benz EJ Jr, Griffith P, Nienhuis AW: Detection of early cardiac dysfunction in patients with severe beta-thalassemia and chronic iron overload. N Engl J Med 301:1143, 1979
204. Spirito P, Lupi G, Melevendi C, Vecchio C: Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. Circulation 82:88, 1990
205. Liu P, Olivieri N: Iron overload cardiomyopathies: New insights into an old disease. Cardiovasc Drugs Ther 8:101, 1994
206. Hou JW, Wu MH, Lin KH, Lue HC: Prognostic significance of left ventricular diastolic Indexes in β-thalassaemia major. Arch Pediatr Adolesc Med 148:862, 1994
207. Lan KC, Li AMC, Hui PW, Yeung CY: Left ventricular function in β-thalassaemia major. Arch Dis Child 64:1046, 1989
208. Overmoyer BA, McLaren CE, Brittenham GM: Uniformity of liver density and nonheme (storage) iron distribution. Arch Pathol Lab Med 111:549, 1987
209. Brittenham GM, Farrell DE, Harris JW, Feldman ES, Danish EH: Magnetic-susceptibility measurement of human iron stores. N Engl J Med 307:1671, 1982
210. Brittenham GM: Noninvasive methods for the early detection of hereditary hemochromatosis. Ann NY Acad Sci 526:199, 1988
211. Pootrakul P, Kitcharoen K, Yansukon P, Wasi P, Fucharoen S, Charoenlarp P, Brittenham G, Pippard MJ, Finch CA: The effect of erythroid hyperplasia on iron balance. Blood 71:1124, 1988
212. Nielsen P, Fischer R, Engelhardt R, Tondüry P, Gabbe EE, Janka GE: Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deteriprone. Br J Haematol 91:827, 1995
213. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo Jr. R, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Stames SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff R: A novel MHC class I-like gene is mutated in patients with hereditary hemochromatosis. Nat Genet 13:399, 1996
214. Cartwright GE, Edwards CQ, Kravitz K, Skolnick M, Amos DB, Johnson A, Buskjaer L: Hereditary hemochromatosis: Phenotypic expression of the disease. N Engl J Med 301:175, 1979
215. Niederau C, Fischer R, Sonnenberg A, Stremmel W, Trampisch HJ, Strohmeyer G: Survival and causes of death in cirrhotic and in noncirrhotic patients with primary hemochromatosis. N Engl J Med 313:1256, 1985
216. Bassett ML, Halliday JW, Powell LW: Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis. Hepatology 6:24, 1986
217. Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G: Long-term survival in patients with hereditary hemochromatosis. Gastroenterology 110:1107, 1996
218. Loreal O, Deugnier Y, Moirand R, Lauvin L, Guyader D, Jouanolle H, Turlin B, Lescoat G, Brissot P: Liver fibrosis in genetic hemochromatosis. Respective roles of iron and non-iron related factors in 127 homozygous patients. J Hepatol 16:122, 1992
219. Olivieri NF, Berriman AM, Davis SA, Tyler BJ, Ingram J, Francombe WH: Continuous intravenous administration of deferoxamine in adults with severe iron overload. Am J Hematol 41:61, 1992
220. Lai E, Belluzzo N, Muraca MF, Daneman R, Cao A, De Virgiliis S, Lisci V, Galanello R, Olivieri NF: The prognosis for adults with thalassemia major: Sardinia, 1995. Blood 86:251a, 1995 (abstr, suppl 1)
221. Angelucci E, Baronciani D, Lucarelli G, Baldassarri M, Galimberti M, Giardini C, Martinelli F, Polchi P, Posizzi V, Ripalti M, Nuretto P: Needle liver biopsy in thalassaemia: Analyses of diagnostic accuracy and safety in 1184 consecutive biopsies. Br J Haematol 89:757, 1994
222. Berkovitch M, Collins AF, Papadouris D, Wesson D, Sirna JB, Brittenham GB, Olivieri NF: Need for early, low-dose chelation therapy in young children with transfused homozygous β thalassemia. Blood 82:359a, 1993 (abstr, suppl 1)
223. DeVirgiliis S: Personal communication. Sardinia, July 1995
224. Porter J, Huehns E: The toxic effects of desferrioxamine. Balliere's Clin Hematol 2:459, 1989
225. Olivieri NF, Buncic R, Chew E, Gallant T, Harrison RV, Keenan N, Logan W, Mitchell D, Ricci G, Skarf B, Taylor M, Freedman MH: Visual and auditory neurotoxicity in patients receiving subcutaneous deferoxamine infusions. N Engl J Med 314:869, 1986
226. Porter JB, Jaswon MS, Huehns ER, East CA, Hazell JWP: Desferrioxamine ototoxicity: Evaluation of risk factors in thalassaemic patients and guidelines for safe dosage. Br J Haematol 73:403, 1989
227. Bloomfield SE, Markenson AI, Miller DR, Peterson CM: Lens opacities in thalassemia. J Pediatr Ophtholmol Strab 15:154, 1978
228. Marsh M, Holbrook I, Clark C, Shaffer J: Tinnitus in a patient with beta thalassaemia intermedia on long term treatment with desferrioxamine. Postgrad Med J 57:582, 1981
229. Porter J, Huehns E: The toxic effects of desferrioxamine. Bailliere's Clin Hematol 2:459, 1989
230. Davies SC, Hungerford JL, Arden GB, Marcus RE, Miller MH, Huehns ER: Ocular toxicity of high-dose intravenous desferrioxamine. Lancet 2:181, 1983
231. Borgna-Pignatti C, De Stefano P, Broglia AM: Visual loss in a patient on high-dose subcutaneous desferrioxamine. Lancet 1:681, 1984
232. Orton R, Veber L, Sulh II: Ocular and auditory toxicity of high dose subcutaneous deferoxamine therapy. Can J Ophthalmol 20:153, 1985
233. Rahi AHS, Hungerford JL, Ahmed A: Ocular toxicity of desferrioxamine: Light microscopic, histochemical and ultrastructural findings. Br J Ophtholmol 70:373, 1986
234. Dickerhoff R: Acute aphasia and loss of vision with desferrioxamine overdose. Am J Ped Hematol Oncol 9:287, 1987
235. De Virgiliis S, Turco MP, Frau F, Dessi C, Argiolu F, Sorcinelli R, Sitzia A, Cao A: Depletion of trace elements and acute ocular toxicity induced by desferrioxamine in patients with thalassaemia. Arch Dis Chil 63:250, 1988
236. Pall H, Blake D, Winyard P, Lunee J, Williams A, Good P, Kritzinger E, Lornish A, Hider R: Ocular toxicity of desferrioxamine: An example of copper promoted auto-oxidative damage. Br J Ophthalmol 73:42, 1989
237. Giardina PJ, Nealon N, McQueen M, Martin M, Schotland D, Cohen A: Sensorimotor neuropathy associated with high dose desferrioxamine. Blood 78:199a, 1993 (abstr, suppl 1)
238. Koren G, Bentur Y, Strong D, Harvey E, Klein J, Baumal R, Spielberg SP, Freedman MH: Acute changes in renal function associated with deferoxamine therapy. Am J Dis Child 143:1077, 1989
239. Koren G, Kochavi-Atiya Y, Bentur Y, Olivieri NF: The effects of subcutaneous deferoxamine administration on renal function in thalassemia major. Int J Haematol 54:371, 1992
240. Freedman MH, Olivieri NF, Grisaru D, Mcluskey I, Thorner P: Pulmonary syndrome in patients receiving intravenous deferoxamine infusions. Am J Dis Child 144:565, 1990
241. Tenenbein M, Kowalski S, Sienko A, Bowden DH, Adamson IYR: Pulmonary toxic effects of continuous desferrioxamine administration in acute iron poisoning. Lancet 339:699, 1992
242. Brill PW, Winchester P, Giardina PJ, Cunningham-Rundles S: Desferrioxamine-induced bone dysplasia in patients with thalassaemia major. Am J Roentgenol 156:561, 1991
243. Orxincolo C, Scutellari PN, Castaldi G: Growth plate injury of the long bones in treated β-thalassemia. Skeletal Radiol 21:39, 1992
244. Sher GD, Belluzzo N, Babyn P, Collins AF, Bailey JD, Olivieri NF: Improvement in deferoxamine-induced bony abnormalities in transfusion-dependent patients following withdrawal or reduction of deferoxamine and initiation of the oral chelator L1. Blood 82:360a, 1993 (abstr, suppl 1)
245. Hartkamp MJ, Babyn PS, Olivieri NF: Spinal deformities in deferoxamine-treated beta-thalassemia major patients. Ped Radiol 23:525, 1993
246. Hatori M, Sparkman J, Teixeira CC, Grynpas M, Nervina J, Olivieri N, Shapiro IM: Effects of deferoxamine on chondrocyte alkaline phosphatase activity: pro-oxidant role of deferoxamine in thalassemia. Calcif Tissue Int 57:229, 1995
247. Olivieri NF, Basran RK, Talbot AL, Babyn P, Bailey JD: Abnormal growth in thalassemia major associated with deferoxamine-induced destruction of spinal cartilage and compromise of sitting height. Blood 86:482a, 1995 (abstr, suppl 1)
248. De Sanctis V, Pinamonti A, Di Palma A, Sprocati M, Atti G, Ganberini MR, Vullo C: Growth and development in thalassaemia major patients with severe bone lesions due to desferrioxamine. Eur J Pediatr 1996 (in press)
249. O'Brien RT: Ascorbic acid enhancement of desferrioxamine-induced urinary iron excretion in thalassemia major. Ann NY Acad Sci 232:221, 1974
250. Cohen A, Cohen IJ, Schwartz E: Scurvy and altered iron stores in thalassemia major. N Engl J Med 304:158, 1981
251. Chapman RWG, Hussein MAM, Gorman A, Laulicht M, Politis D, Flynn DM, Sherlock S, Hoffbrand AV: Effect of ascorbic acid deficiency on serum ferritin concentrations in patients with β-thalassaemia major and iron overload. J Clin Pathol 35:487, 1982
252. Hussain MAM, Flynn DM, Green N, Hoffbrand AV: Effect of dose, time, and ascorbate on iron excretion after subcutaneous desferrioxamine. Lancet 1:977, 1977
253. Bothwell TH, Bradlow BA, Jacobs P, Keeley K, Kramer S, Seftel H, Zail S: Iron metabolism in scurvy with special reference to erythropoiesis. Br J Haematol 10:50, 1964
254. Bridges KR, Hoffman KE: The effects of ascorbic acid on the intracellular metabolism of iron and ferritin. J Biol Chem 261:14273, 1986
255. Henry W: Echocardiographic evaluation of the heart in thalassemia major. Ann Intern Med 91:892, 1979
256. Nienhuis AW: Vitamin C and iron. N Engl J Med 304:170, 1981
257. McClaren CJ, Bett JHN, Nye JA, Halliday JW: Congestive cardiomyopathy and hemochromatosis - Rapid progression possibly accelerated by excessive ingestion of ascorbic acid. Aust NZ J Med 12:187, 1982
258. Rowbotham B, Roeser HP: Iron overload associated with congenital pyruvate kinase deficiency and high dose ascorbic acid ingestion. Aust NZ J Med 14:667, 1984
259. Olivieri NF, Brittenham GM, Armstrong SAM, Basran RK, Daneman R, Daneman N, Iwanchko RM, Talbot AL, Koren G: First prospective randomized trial of the iron chelators deferiprone and deferoxamine. Blood 86:249a, 1995 (abstr, suppl 1)
260. Piga A, Magliano M, Bianco L, Capalbo P, Baccaccini R, Gabutti V: Compliance with chelation therapy in Torino, in Sirchia G, Zanella A (eds): Thalassaemia Today: Second Mediterranean Meeting on Thalassaemia: Milano, Italy, Policlinico di Milano, 1987, p 141
261. Zani B, Di Palma A, Vullo C: Psychosocial aspects of chronic illness in adolescents with thalassaemia major. J Adolescence 18:387, 1995
262. Borgna-Pignatti C, Cohen AR: An alternative method of subcutaneous deferoxamine administration. Blood 86:483a, 1995 (abstr, suppl 1)
263. Hallaway PE, Eaton JW, Panter SS, Hedlund BE: Modulation of deferoxamine toxicity and clearance by covalent attachment to biocompatible polymers. Proc Natl Acad Sci USA 86:10108, 1989
264. Mahoney JR, Hallaway PE, Hedlund BE, Eaton JW: Acute iron poisoning. Rescue with macromolecular chelators. J Clin Invest 84:1362, 1989
265. Hedlund B: Personal communication, Seattle, WA, December 1995
266. Olivieri NF, Nisbet-Brown E, Srichairatanakool S, Dragsten P, Hallaway P, Hedlund B, Porter JB: Studies of iron excretion and non-transferrin-bound plasma iron following a single infusion of hydroxyethyl starch-deferoxamine: A new approach to iron chelation therapy. Blood 88:310a, 1996 (abstr, suppl 1)
267. Cossu P, Toccafondi C, Vardeu F, Sanna G, Frau F, Lobrano R, Cornacchia G, Nucaro A, Bertolino F, Loi A, DeVergillis S, Cao A: Iron overload and desferrioxamine chelation therapy in beta thalassemia intermedia. Eur J Pediatr 137:267, 1981
268. Pippard MJ, Callender ST, Warner GT, Weatherall DJ: Iron absorption and loading in beta-thalassaemia intermedia. Lancet 2:819, 1979
269. Galanello R: Personal communication, Cagliari, Sardinia, January 1996
270. Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C, Andreani M, Agostinelli F, Albertini F, Clift RA: Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med 329:840, 1993
271. Muretto P, Del Fiasco S, Angelucci E, De Rosa F, Lucarelli G: Bone marrow transplantation in thalassemia: Modifications of hepatic iron overload and associated lesions after long-term engrafting. Liver 14:14, 1994
272. Giardini C, Galimberti M, Lucarelli G, Polchi P, Angelucci E, Baronciani D, Gaziev D, Erer B, La Nasa G, Barbanti I, Muretto P: Desferrioxamine therapy accelerates clearance of iron deposits after bone marrow transplantation for thalassaemia. Br J Haematol 89:868, 1995
273. Brittenham GM: Pyridoxal isonicotinoyl hydrazone: Effective iron chelation after oral administration. Ann NY Acad Sci 612:315, 1990
274. Porter JB, Singh S, Epemolu RO, Ackerman R, Huehns ER, Hider RC: Oral efficacy and metabolism of 1,2-diethyl-3-hydroxypyridin-4-one in thalassemia major. Blood 78:207a, 1991 (abstr, suppl 1)
275. Grady RW, Giardina PJ, Salbe AD, Hilgartner MW: A clinical trial of HBED: An orally effective iron chelator. Blood 82:359a, 1993 (abstr, suppl 1)
276. Hider RC, Kontoghiorghes GJ, Silver J: U.K. Patent: GB-2118176, 1982
277. Kontoghiorghes GJ: The study of iron mobilization from transferrin using α-ketohydroxy heteroaromatic chelators. Biochem Biophys Acta 869:141, 1986
278. Kontoghiorghes GJ: Iron mobilization from ferritin using oxohydroxy heteroaromatic chelators. Biochem J 233:299, 1986
279. Porter JB, Morgan J, Hoyes KP, Burke LC, Huehns ER, Hider RC: Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice. Blood 76:2389, 1990
280. Kontoghiorghes GJ: New orally active iron chelators. Lancet 1:817, 1985
281. Kontoghiorghes GJ, Hoffbrand AV: Orally active α-ketohy-droxypyridine iron chelators intended for clinical use: In vivo studies in rabbits. Br J Haematol 62:607, 1986
282. Venkataram S, Rahman YE: Studies of an oral iron chelator: l,2-dimethyl-3-hydroxypyrid-4-one. I. Iron excretion in rats: Development of a new rapid microwave method for iron analysis in faeces. Br J Haematol 75:274, 1990
283. Hershko C, Link G, Pinson A, Avramovici-Grisaru S, Sarel S, Peter HH, Hider RC, Grady RW: New orally effective iron chelators: animal studies. Ann NY Acad Sci 612:351, 1990
284. Porter JB, Hoyes KP, Abeysinghe RD, Brooks PN, Huehns ER, Hider RC: Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4-one iron chelators in iron overloaded and nonoverloaded mice. Blood 78:2727, 1991
285. Zevin S, Link G, Grady RW, Hider RC, Peter HH, Hershko C: Origin and fate of iron mobilized by the 3-hydroxypyridin-4-one oral iron chelators: Studies in hypertransfused rats by selective radioiron probes of reticuloendothelial and hepatocellular iron stores. Blood 79:248, 1992
286. Bergeron RJ, Streiff RR, Weigand J, Luchetta G, Creary EA, Peter HH: A comparison of the iron-clearing properties of 1,2-dimethyl-3-hydroxypyrid-4-one, 1,2-diethyl-3-hydroxypyrid-4-one, and deferoxamine. Blood 79:1882, 1992
287. Olivieri NF, Koren G, Hermann C, Bentur Y, Chung D, Klein J, St Louis P, Freedman MH, McClelland RA, Templeton DM: Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients. Lancet 336:1275, 1990
288. Kontoghiorghes GJ, Aldouri MA, Sheppard LN, Hoffbrand AV: l,2-dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload. Lancet 1:1294, 1987
289. Brittenham GM: Development of iron-chelating agents for clinical use. Blood 80:569, 1992
290. Collins AF, Fassos FF, Stobie SS, Lewis N, Shaw D, Fernandes D, Fry M, Templeton DM, Koren G, Olivieri NF: Iron balance and dose response studies of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease. Blood 83:2329, 1994
291. Kontoghiorghes GJ: Effective chelation of iron in β thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Br J Med 295:1509, 1987
292. Tondury P, Kontoghiorghes GJ, Ridolfi-Luthy AR, Hirt A, Hoffbrand AV, Lottenbach AM, Sonderegger T, Wagner HP: L1(1,2-dimethyl-3-hydroxypyrid-4-one) for oral iron chelation in patients with beta-thalassaemia major. Br J Haematol 76:550, 1990
293. Agarwal MB, Viswanathan C, Ramanathan J, Massil DE, Shah S, Supte SS, Vasandani D, Puniyani RR: Oral iron chelation with L1. Lancet 335:601, 1990
294. Kontoghiorghes GJ, Bartlett AN, Hoffbrand AV, Goddard JG, Sheppard L, Barr J, Nortey P: Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). Br J Haematol 76:295, 1990
295. Al-Refaie FN, Wonke B, Hoffbrand AV, Wickens DG, Nortey P, Kontoghiorghes GJ: Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major. Blood 80:592, 1992
296. Agarwal MB, Gupte SS, Viswanathan C, Vasandani D, Ramanathan J, Desai N, Puniyani RR, Chhablani AT: Long-term assessment of efficacy and safety of L1, an oral iron chelator, in transfusion-dependent thalassaemia: Indian trial. Br J Haematol 82:460, 1992
297. Kontoghiorghes GJ: Design, properties, and effective use of the oral chelator L1 and other α-ketohydroxypyridines in the treatment of transfusional iron overload in thalassemia. Ann NY Acad Sci 612:339, 1990
298. Porter JB, Hoyes KP, Abeysinghe R, Huehns ER, Hider RC: Animal toxicology of iron chelator L1 [letter]. Lancet 2:156, 1989
299. Biesemeier JA, Laveglia J: 14-day oral toxicity study in dogs with 1,2-dimethyl-3-hydroxypyrid-4-one (DMHP, L1). Food and Drug Research Laboratories, Waverly, NY, Contract No NO1-DK-4-2255, NIDDK, NIH, USA, 1991
300. Berkoukas VA, Bentley P, Frost H, Schnebli HP: Toxicity of oral iron chelator L1 [letter]. Lancet 341:1088, 1993
301. Berkovitch M, Laxer RM, Inman R, Koren G, Pritzker KP, Fritzler MJ, Olivieri NF: Arthropathy in thalassemia patients receiving deferiprone. Lancet 343:1471, 1994
302. Hoffbrand AV, Bartlett AN, Veys PP, O'Connor NTJ, Kontoghiorghes GJ: Agranulocytosis and thrombocytopenia in patient with Blackfan-Diamond anaemia during oral chelator trial [letter]. Lancet 2:457, 1989
303. Goudsmit R, Kersten MJ: Long term treatment of transfusion hemosiderosis with the oral chelator L1. Drugs of Today 28:133, 1992 (suppl A)
304. Agarwal MB, Gupte SS, Viswanathan C, Vasandani D, Desai N, Chablani AT: Long term efficacy and toxicity of L1-oral chelator in transfusion dependent thalassaemics over the last three years. Abstracts of the Fifth International Conference on Thalassaemias and Haemoglobinopathies, Nicosia, Cyprus, 1993, p 192
305. al-Refaie FN, Wonke B, Hoffbrand AV: Deferiprone-associated myelotoxicity. Eur J Haematol 53:298, 1994
306. Hoffbrand AV: Oral iron chelators. Semin Hematol 33:1, 1996
307. Mehta J, Singhal S, Chablani A, Revankar R, Walvalkar A: L1-induced systemic lupus erythematosus. Indian J Hematol Blood Transf 9:33, 1991
308. Mehta J, Singhal S, Revankar R, Walvalkar A, Chablani A, Mehta BC: Fatal systemic lupus erythematosus in patient taking oral iron chelator L1 [letter]. Lancet 337:298, 1991
309. Pattanapanyasat K, Webster HK, Tongtawa P, Kongcharoen P, Hider RC: Effect of orally active hydroxypyridinone iron chelators on human lymphocyte function. Br J Haematol 82:431, 1992
310. Mehta J, Singhal S, Mehta BC: Deaths in patients receiving oral iron chelator L1 [letter]. Br J Haematol 85:430, 1993
311. Agarwal MB, Gupte SS, Viswanathan C, Vasandani D, Ramanathan J, Desai N, Puniyani RR, Chhablani AT: Deaths in patients receiving oral iron chelator L1 [letter]. Br J Haematol 85:430, 1993
312. al-Refaie FN, Wonke B, Wickens DG, Aydinok Y, Fielding A, Hoffbrand A: Zinc concentration in patients with iron overload receiving oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one or desferrioxamine. J Clin Pathol 47:657, 1994
313. al-Refaie FN, Hershko C, Hoffbrand AV, Kosaryan M, Olivieri NF, Tondury P, Wonke B: Results of long-term deferiprone (L1) therapy. A report by the International Study Group on Oral iron Chelators. Br J Haematol 91:224, 1995
314. Olivieri NF for the Toronto Iron Chelation Group: Long-term followup of body iron in patients with thalassemia major during therapy with the orally active iron chelator deferiprone (L1). Blood 88:310a, 1996 (abstr, suppl 1)
315. Olivieri NF for the Toronto Iron Chelation Group: Randomized trial of deferiprone (L1) and deferoxamine in thalassemia major. Blood 88:651a, 1996 (abstr, suppl 1)