Abstract
Reactive oxygen and nitrogen species are considered to play a major role in the pathogenesis of a wide range of human disorders. This may be a particularly important pathogenetic mechanism in the newborn nursery. The phrase “oxygen radical disease of prematurity” has been coined to collectively describe a wide range of neonatal disorders based on the belief that premature newborns are deficient in antioxidant defenses at a time when they are subjected to acute and chronic oxidant stresses. This belief has led to a number of clinical trials of antioxidant therapies being undertaken in neonatal patients. The realization that reactive oxygen species play a critical role in neonatal illnesses has only recently been paralleled by an increased understanding of their physiologic roles. A major concern is that effective scavenging of reactive oxygen species, to attenuate their toxic effects, will also inhibit essential cellular functions such as growth in potential target organs such as lung, brain, intestine, and retina.
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Abbreviations
- AP-1:
-
activator protein-1
- GSH:
-
reduced glutathione
- H2O2:
-
hydrogen peroxide
- N-AC:
-
N-acetyl-L-cysteine
- ·NO:
-
nitric oxide
- O2−·:
-
superoxide anion
- ·OH:
-
hydroxyl radical
- RNS:
-
reactive nitrogen species
- ROS:
-
reactive oxygen species
- SOD:
-
superoxide dismutase
References
Sullivan JL 1988 Iron, plasma antioxidants, and the ‘oxygen radical disease of prematurity.'. Am J Dis Child 142: 1341–1344
Saugstad OD 1998 Oxygen radical disease in neonatology. Semin Neonatol 3: 229–238
Frank L 1998 Development of the antioxidant defenses in fetal life. Semin Neonatol 3: 173–182
Pitkänen OM, Hallman M 1998 Evidence for increased oxidative stress in preterm infants eventually developing chronic lung disease. Semin Neonatol 3: 199–205
Bast A, Haenen GR, Doelman CJ 1991 Oxidants and antioxidants: state of the art. Am J Med 91: 2S–13S
Halliwell B 1991 Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 91: 14S–22S
Halliwell B, Gutteridge JMC 1999 Free radicals in biology and medicine. Oxford University Press, Oxford.
Freeman BA, Crapo JD 1982 Biology of disease: free radicals and tissue injury. Lab Invest 47: 412–426
Freeman BA 2000 Oxygen: the air-borne nutrient that both sustains and threatens life. Nutrition 16: 478–480
McCord JM, Fridovich I 1969 Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244: 6049–6055
Freeman BA, Topolosky MK, Crapo JD 1982 Hyperoxia increases oxygen radical production in rat lung homogenates. Arch Biochem Biophys 216: 477–484
Jamieson D, Chance B, Cadenas E, Boveris A 1986 The relation of free radical production to hyperoxia. Annu Rev Physiol 48: 703–719
Groneck P, Gotze-Speer B, Oppermann M, Eiffert H, Speer CP 1994 Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics 93: 712–718
Saugstad OD, Tubman TR, Gloppestad K, Halliday HL, Oyasaeter S, Curstedt T, Robertson B 1992 Raised plasma hypoxanthine levels as a prognostic sign in preterm babies with respiratory distress syndrome treated with natural surfactant. J Perinat Med 20: 379–385
Moldeus P, Cotgreave IA 1994 N-acetylcysteine. Methods Enzymol 234: 482–492
Patel RP, McAndrew J, Sellak H, White CR, Jo H, Freeman BA, Darley-Usmar VM 1999 Biological aspects of reactive nitrogen species. Biochim Biophys Acta 1411: 385–400
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA 1990 Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87: 1620–1624
Gutierrez HH, Nieves B, Chumley P, Riviera A, Freeman BA 1996 Nitric oxide regulation of superoxide-dependent lung injury: oxidant-protective actions of endogenously produced and exogenously administered nitric oxide. Free Radic Biol Med 21: 43–52
Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M, Freeman BA 1994 Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem 269: 26066–26075
Landino LM, Crews BC, Timmons MD, Morrow JD, Marnett LJ 1996 Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc Natl Acad Sci U S A 93: 15069–15074
Hogg N, Kalyanaraman B 1999 Nitric oxide and lipid peroxidation. Biochim Biophys Acta 1411: 378–384
Russell GA 1994 Antioxidants and neonatal lung disease. Eur J Pediatr 153: S36–S41
Saugstad OD 1997 Bronchopulmonary dysplasia and oxidative stress: are we closer to an understanding of the pathogenesis of BPD?. Acta Paediatr 86: 1277–1282
Saugstad OD 1998 Chronic lung disease: the role of oxidative stress. Biol Neonate 74: 21–28
Phelps DL 1992 Retinopathy of prematurity. Curr Probl Pediatr 22: 349–371
Parks DA, Granger DN 1986 Contribution of ischemia and reperfusion to mucosal lesion formation. Am J Physiol 250: G749–G753
Volpe JJ 1997 Brain injury in the premature infant - from pathogenesis to prevention. Brain Dev 19: 519–534
Inder TE, Volpe JJ 2000 Mechanisms of perinatal brain injury. Semin Neonatol 5: 3–16
Saugstad OD 1988 Hypoxanthine as an indicator of hypoxia: its role in health and disease through free radical production. Pediatr Res 23: 143–150
Frank L 1991 Developmental aspects of experimental pulmonary oxygen toxicity. Free Radic Biol Med 11: 463–494
Frank L 1992 Antioxidants, nutrition, and bronchopulmonary dysplasia. Clin Perinatol 19: 541–562
Frank L, Groseclose EE 1984 Preparation for birth into an O2-rich environment: the antioxidant enzymes in the developing rabbit lung. Pediatr Res 18: 240–244
Tanswell AK, Freeman BA 1984 Pulmonary antioxidant enzyme maturation in the fetal and neonatal rat. I. Developmental profiles. Pediatr Res 18: 584–587
Frank L, Sosenko IR 1991 Failure of premature rabbits to increase antioxidant enzymes during hyperoxic exposure: increased susceptibility to pulmonary oxygen toxicity compared with term rabbits. Pediatr Res 29: 292–296
Fryer AA, Hume R, Strange RC 1986 The development of glutathione S-transferase and glutathione peroxidase activities in human lung. Biochim Biophys Acta 883: 448–453
Strange RC, Cotton W, Fryer AA, Drew R, Bradwell AR, Marshall T, Collins MF, Bell J, Hume R 1988 Studies on the expression of Cu,Zn superoxide dismutase in human tissues during development. Biochim Biophys Acta 964: 260–265
Lavoie JC, Chessex P 1997 Gender and maturation affect glutathione status in human neonatal tissues. Free Radic Biol Med 23: 648–657
Gladstone IM Jr, Levine RL 1994 Oxidation of proteins in neonatal lungs. Pediatrics 93: 764–768
Varsila E, Hallman M, Andersson S 1994 Free-radical-induced lipid peroxidation during the early neonatal period. Acta Paediatr 83: 692–695
The STOP-ROP Multicenter Study Group 2000 Supplemental Therapeutic Oxygen for Prethreshold Retinopathy Of Prematurity (STOP-ROP), a randomized, controlled trial. I: primary outcomes. Pediatrics 105: 295–310
Pitkänen OM, Hallman M, Andersson SM 1990 Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants. J Pediatr 116: 760–764
Nycyk JA, Drury JA, Cooke RW 1998 Breath pentane as a marker for lipid peroxidation and adverse outcome in preterm infants. Arch Dis Child Fetal Neonatal Ed 79: F67–F69
Inder TE, Graham P, Sanderson K, Taylor BJ 1994 Lipid peroxidation as a measure of oxygen free radical damage in the very low birthweight infant. Arch Dis Child Fetal Neonatal Ed 70: F107–F111
Inder TE, Darlow BA, Sluis KB, Winterbourn CC, Graham P, Sanderson KJ, Taylor BJ 1996 The correlation of elevated levels of an index of lipid peroxidation (MDA-TBA) with adverse outcome in the very low birthweight infant. Acta Paediatr 85: 1116–1122
Ogihara T, Hirano K, Morinobu T, Kim HS, Hiroi M, Ogihara H, Tamai H 1999 Raised concentrations of aldehyde lipid peroxidation products in premature infants with chronic lung disease. Arch Dis Child Fetal Neonatal Ed 80: F21–F25
Ogihara T, Okamoto R, Kim HS, Nagai A, Morinobu T, Moji H, Kamegai H, Hirano K, Ogihara H, Tamai H, Mino M 1996 New evidence for the involvement of oxygen radicals in triggering neonatal chronic lung disease. Pediatr Res 9: 117–119
Ogihara T, Kim HS, Hirano K, Imanishi M, Ogihara H, Tamai H, Okamoto R, Mino M 1998 Oxidation products of uric acid and ascorbic acid in preterm infants with chronic lung disease. Biol Neonate 73: 24–33
Varsila E, Pesonen E, Andersson S 1995 Early protein oxidation in the neonatal lung is related to development of chronic lung disease. Acta Paediatr 84: 1296–1299
Winterbourn CC, Chan T, Buss IH, Inder TE, Mogridge N, Darlow BA 2000 Protein carbonyls and lipid peroxidation products as oxidation markers in preterm infant plasma: associations with chronic lung disease and retinopathy and effects of selenium supplementation. Pediatr Res 48: 84–90
Winterbourn CC, Buss IH, Chan TP, Plank LD, Clark MA, Windsor JA 2000 Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients. Crit Care Med 28: 143–149
Buss IH, Darlow BA, Winterbourn CC 2000 Elevated protein carbonyls and lipid peroxidation products correlating with myeloperoxidase in tracheal aspirates from premature infants. Pediatr Res 47: 640–645
Banks BA, Ischiropoulos H, McClelland M, Ballard PL, Ballard RA 1998 Plasma 3-nitrotyrosine is elevated in premature infants who develop bronchopulmonary dysplasia. Pediatrics 101: 870–874
Halliwell B, Chirico S 1993 Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr 57: 715S–724S
Valenzuela A 1991 The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci 48: 301–309
Helbock HJ, Motchnik PA, Ames BN 1993 Toxic hydroperoxides in intravenous lipid emulsions used in preterm infants. Pediatrics 91: 83–87
Vacchiano CA, Tempel GE 1994 Role of nonenzymatically generated prostanoid, 8-iso-PGF2α, in pulmonary oxygen toxicity. J Appl Physiol 77: 2912–2917
Roberts LJ II, Morrow JD 1997 The generation and actions of isoprostanes. Biochim Biophys Acta 1345: 121–135
Heffner JE, Repine JE 1989 Pulmonary strategies of antioxidant defense. Am Rev Respir Dis 40: 531–554
Rice-Evans CA, Diplock AT 1993 Current status of antioxidant therapy. Free Radic Biol Med 15: 77–96
Sies H 1993 Strategies of antioxidant defense. Eur J Biochem 215: 213–219
Tanswell AK, Freeman BA 1995 Antioxidant therapy in critical care medicine. New Horiz 3: 330–341
Rosenfeld WN, Davis JM 1998 Prevention of oxygen radical disease in the newborn: possible therapeutic approaches. Semin Neonatol 3: 239–244
Halliwell B 2000 The antioxidant paradox. Lancet 355: 1179–1180
Crapo JD, DeLong DM, Sjostrom K, Hasler GR, Drew RT 1977 The failure of aerosolized superoxide dismutase to modify pulmonary oxygen toxicity. Am Rev Respir Dis 15: 1027–1033
Turrens JF, Crapo JD, Freeman BA 1984 Protection against oxygen toxicity by intravenous injection of liposome-entrapped catalase and superoxide dismutase. J Clin Invest 73: 87–95
Thibeault DW, Rezaiekhaligh M, Mabry S, Beringer T 1991 Prevention of chronic pulmonary oxygen toxicity in young rats with liposome-encapsulated catalase administered intratracheally. Pediatr Pulmonol 11: 318–327
Matalon S, Holm BA, Baker RR, Whitfield MK, Freeman BA 1990 Characterization of antioxidant activities of pulmonary surfactant mixtures. Biochim Biophys Acta 1035: 121–127
Davis JM, Rosenfeld WN, Sanders RJ, Gonenne A 1993 Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury. J Appl Physiol 74: 2234–2241
Karp WB, Robertson AF 1986 Vitamin E in neonatology. Adv Pediatr 33: 127–147
Johnson L, Bowen FW Jr, Abbasi S, Herrmann N, Weston M, Sacks L, Porat R, Stahl G, Peckham G, Delivoria-Papadopoulos M, et al 1985 Relationship of prolonged pharmacologic serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less. Pediatrics 75: 619–638
Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J 1998 Vitamin C exhibits pro-oxidant properties. Nature 392: 559
Rowe PM 1996 Beta-carotene takes a collective beating. Lancet 347: 249
Lorch V, Murphy D, Hoersten LR, Harris E, Fitzgerald J, Sinha SN 1985 Unusual syndrome among premature infants: association with a new intravenous vitamin E product. Pediatrics 75: 598–602
Lucey JF 1992 Do you remember E-Ferol? The penalty for selling untested drugs in neonatology: Fines and a jail sentence. Pediatrics 89: 159
Rubinstein JD, Lesnefsky EJ, Byler RM, Fennessey PV, Horwitz LD 1992 Trolox C, a lipid-soluble membrane protective agent, attenuates myocardial injury from ischemia and reperfusion. Free Radic Biol Med 13: 627–634
Braughler JM, Hall ED, Jacobsen EJ, McCall JM, Means ED 1989 The 21 aminosteroids: Potent inhibitors of lipid peroxidation for the treatment of central nervous system trauma and ischemia. Drugs Future 14: 144–152
Ehrenkranz RA, Ablow RC, Warshaw JB 1982 Effect of vitamin E on the development of oxygen-induced lung injury in neonates. Ann N Y Acad Sci 393: 452–466
Watts JL, Milner R, Zipursky A, Paes B, Ling E, Gill G, Fletcher B, Rand C 1991 Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight. Eur Respir J 4: 188–190
Saldanha RL, Cepeda EE, Poland RL 1982 The effect of vitamin E prophylaxis on the incidence and severity of bronchopulmonary dysplasia. J Pediatr 101: 89–93
Russell GA, Cooke RW 1995 Randomised controlled trial of allopurinol prophylaxis in very preterm infants. Arch Dis Child Fetal Neonatal Ed 73: F27–F31
Darlow BA, Winterbourn CC, Inder TE, Graham PJ, Harding JE, Weston PJ, Austin NC, Elder DE, Mogridge N, Buss IH, Sluis KB 2000 The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group. J Pediatr 136: 473–480
Davis JM, Richter SE, Biswas S, Rosenfeld WN, Parton L, Gewolb IH, Parad R, Carlo W, Couser RJ, Baumgart S, Atluru V, Salerno L, Kassem N 2000 Long-term follow-up of premature infants treated with prophylactic, intratracheal recombinant human CuZn superoxide dismutase. J Perinatol 20: 213–216
Burdon RH 1995 Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med 18: 775–794
Sohal RS, Allen RG, Nations C 1986 Oxygen free radicals play a role in cellular differentiation: an hypothesis. J Free Radic Biol Med 2: 175–181
Chance B, Sies H, Boveris A 1979 Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527–605
Powis G, Mustacich D, Coon A 2000 The role of the redox protein thioredoxin in cell growth and cancer. Free Radic Biol Med 29: 312–322
Allen RG, Newton RK, Sohal RS, Shipley GL, Nations C 1985 Alterations in superoxide dismutase, glutathione, and peroxides in the plasmodial slime mold Physarum polycephalum during differentiation. J Cell Physiol 125: 413–419
Luo X, Sedlackova L, Belcastro R, Cabacungan J, Lye SJ, Tanswell AK 1999 Effect of the 21-aminosteroid U74389G on oxygen-induced free radical production, lipid peroxidation, and inhibition of lung growth in neonatal rats. Pediatr Res 46: 215–223
Jankov RP, Luo X, Cabacungan J, Belcastro R, Frndova H, Lye SJ, Tanswell AK 2000 Endothelin-1 and O2-mediated pulmonary hypertension in neonatal rats: a role for products of lipid peroxidation. Pediatr Res 48: 289–298
Li N, Oberley TD 1998 Modulation of antioxidant enzymes, reactive oxygen species, and glutathione levels in manganese superoxide dismutase-overexpressing NIH/3T3 fibroblasts during the cell cycle. J Cell Physiol 177: 148–160
Allen RG 1991 Oxygen-reactive species and antioxidant responses during development: the metabolic paradox of cellular differentiation. Proc Soc Exp Biol Med 196: 117–129
Burdon RH, Gill V, Rice-Evans C 1989 Cell proliferation and oxidative stress. Free Radic Res Commun 7: 149–159
Murrell GA, Francis MJ, Bromley L 1990 Modulation of fibroblast proliferation by oxygen free radicals. Biochem J 265: 659–665
Jassal D, Han RN, Caniggia I, Post M, Tanswell AK 1991 Growth of distal fetal rat lung epithelial cells in a defined serum- free medium. In Vitro Cell Dev Biol 27A: 625–632
Christie NA, Slutsky AS, Freeman BA, Tanswell AK 1994 A critical role for thiol, but not ATP, depletion in 95% O2-mediated injury of preterm pneumocytes in vitro. Arch Biochem Biophys 313: 131–138
Nathan C 1992 Nitric oxide as a secretory product of mammalian cells. FASEB J 6: 3051–3064
Ikebuchi Y, Masumoto N, Tasaka K, Koike K, Kasahara K, Miyake A, Tanizawa O 1991 Superoxide anion increases intracellular pH, intracellular free calcium, and arachidonate release in human amnion cells. J Biol Chem 266: 13233–13237
Shibanuma M, Kuroki T, Nose K 1991 Release of H2O2 and phosphorylation of 30 kilodalton proteins as early responses of cell cycle-dependent inhibition of DNA synthesis by transforming growth factor-β1. Cell Growth Differ 2: 583–591
McConkey DJ, Nicotera P, Orrenius S 1994 Signalling and chromatin fragmentation in thymocyte apoptosis. Immunol Rev 142: 343–363
Gonzalez-Rubio M, Voit S, Rodriguez-Puyol D, Weber M, Marx M 1996 Oxidative stress induces tyrosine phosphorylation of PDGF -α and -β receptors and pp60c-src in mesangial cells. Kidney Int 50: 164–173
Heffetz D, Bushkin I, Dror R, Zick Y 1990 The insulinomimetic agents H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells. J Biol Chem 265: 2896–2902
Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T 1995 Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270: 296–299
Barrett EG, Johnston C, Oberdorster G, Finkelstein JN 1999 Antioxidant treatment attenuates cytokine and chemokine levels in murine macrophages following silica exposure. Toxicol Appl Pharmacol 158: 211–220
Barrett EG, Johnston C, Oberdorster G, Finkelstein JN 1999 Silica-induced chemokine expression in alveolar type II cells is mediated by TNF-α-induced oxidant stress. Am J Physiol 276: L979–L988
Ohba M, Shibanuma M, Kuroki T, Nose K 1994 Production of hydrogen peroxide by transforming growth factor-β1 and its involvement in induction of egr-1 in mouse osteoblastic cells. J Cell Biol 126: 1079–1088
Suzuki YJ, Forman HJ, Sevanian A 1997 Oxidants as stimulators of signal transduction. Free Radic Biol Med 22: 269–285
Thannickal VJ, Fanburg BL 2000 Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279: L1005–L1028
Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR 1990 Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 85: 632–639
De Keulenaer GW, Ushio-Fukai M, Yin Q, Chung AB, Lyons PR, Ishizaka N, Rengarajan K, Taylor WR, Alexander RW, Griendling KK 2000 Convergence of redox-sensitive and mitogen-activated protein kinase signaling pathways in tumor necrosis factor-α-mediated monocyte chemoattractant protein-1 induction in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 20: 385–391
Schreck R, Rieber P, Baeuerle PA 1991 Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J 10: 2247–2258
Shasby DM, Yorek M, Shasby SS 1988 Exogenous oxidants initiate hydrolysis of endothelial cell inositol phospholipids. Blood 72: 491–499
Sun Y, Oberley LW 1996 Redox regulation of transcriptional activators. Free Radic Biol Med 21: 335–348
Allen RG, Tresini M 2000 Oxidative stress and gene regulation. Free Radic Biol Med 28: 463–499
Anderson MT, Staal FJ, Gitler C, Herzenberg LA 1994 Separation of oxidant-initiated and redox-regulated steps in the NF-κB signal transduction pathway. Proc Natl Acad Sci U S A 91: 11527–11531
Li JJ, Oberley LW, Fan M, Colburn NH 1998 Inhibition of AP-1 and NF-κB by manganese-containing superoxide dismutase in human breast cancer cells. FASEB J 12: 1713–1723
Angel P, Karin M 1991 The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072: 129–157
Abate C, Patel L, Rauscher FJ, Curran T 1990 Redox regulation of fos and jun DNA-binding activity in vitro. Science 249: 1157–1161
Bannister AJ, Cook A, Kouzarides T 1991 In vitro DNA binding activity of Fos/Jun and BZLF1 but not C/EBP is affected by redox changes. Oncogene 6: 1243–1250
Schenk H, Klein M, Erdbrugger W, Droge W, Schulze-Osthoff K 1994 Distinct effects of thioredoxin and antioxidants on the activation of transcription factors NF-κB and AP-1. Proc Natl Acad Sci U S A 91: 1672–1676
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Supported by a Group grant from the Canadian Institutes of Health Research. Dr. Tanswell holds the Women's Auxiliary Chair in Neonatal Medicine. Dr. Jankov is supported by a Clinician-Scientist Training Programme Fellowship from the Hospital for Sick Children Research Institute and a Postdoctoral Fellowship from the Canadian Lung Association and Canadian Institutes of Health Research.
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Jankov, R., Negus, A. & Tanswell, A. Antioxidants as Therapy in the Newborn: Some Words of Caution. Pediatr Res 50, 681–687 (2001). https://doi.org/10.1203/00006450-200112000-00009
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DOI: https://doi.org/10.1203/00006450-200112000-00009
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