Bilirubin Encephalopathy

  • Marilyn Louise Cowger


So-called physiological jaundice is a mild, transient increase in concentration of serum bilirubin of the unconjugated variety seen during the first few days of life of the newborn infant. It occurs regularly and has been recognized for many years. In fact, the first mention of jaundice occurring in the newborn may go back as far as 1473. The very early history of jaundice in the newborn has been reviewed in a number of works, to which the interested reader is referred.(1–4)


Human Serum Albumin Serum Bilirubin Newborn Infant Exchange Transfusion Brain Mitochondrion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    L. K. Diamond, in “Bilirubin Metabolism in the Newborn” (D. Bergsma, D. Hsia, and C. Jackson, eds.) Birth Defects: Orig. Art. Ser 6:3–6 (1970).Google Scholar
  2. 2.
    F. H. Allen and L. K. Diamond, “Erythroblastosis Fetalis,” pp. 6–8, Little, Brown, Boston (1957).Google Scholar
  3. 3.
    A. Claireaux, Hemolytic disease of the newborn, Part 1: A clinical-pathological study of 157 cases, Arch. Dis. Child 25:61–80 (1950).Google Scholar
  4. 4.
    L. K. Diamond, K. D. Blackfan, and J. M. Baty, Erythroblastosis fetalis and its association with universal edema of the fetus, icterus gravis neonatorum and anemia of the newborn, J. Pediat 1:269–309 (1932).Google Scholar
  5. 5.
    P. L. Mollison and M. Cutbush, Haemolytic disease of the newborn: Criteria of severity, Brit. Med. J 1:123–130 (1949).Google Scholar
  6. 6.
    V. C. Vaughan, F. H. Allen, and L. K. Diamond, Erythroblastosis fetalis. IV. Further observations on kernicterus, Pediatrics 6:706–716 (1950).Google Scholar
  7. 7.
    F. H. Allen, L. K. Diamond, and V. C. Vaughan, Erythroblastosis fetalis. VI. Prevention of kernicterus, Am. J. Dis. Child 80:779–791 (1950).Google Scholar
  8. 8.
    D. Y. Y. Hsia, F. H. Allen, S. S. Gellis, and L. K. Diamond, Erythroblastosis fetalis. VIII. Studies of serum bilirubin in relation to kernicterus, New Engl. J. Med 247:668–671 (1952).Google Scholar
  9. 9.
    W. W. Zuelzer and R. T. Mudgett, Kernicterus, etiologic study based on an analysis of 55 cases, Pediatrics 6:452–474 (1950).Google Scholar
  10. 10.
    A. E. Claireaux, P. G. Cole, and G. H. Lathe, Icterus of the brain in the newborn, Lancet 2:1226–1230 (1953).Google Scholar
  11. 11.
    R. L. Day, Inhibition of brain respiration in vitro by bilirubin. Reversal of inhibition by various means, Proc. Soc. Exptl. Biol. Med 85:261–264 (1954).Google Scholar
  12. 12.
    K. Landsteiner and A. S. Wiener, An agglutinable factor in human blood recognized by immune sera for rhesus blood, Proc. Soc. Exptl. Biol. Med 43:223 (1940).Google Scholar
  13. 13.
    H. Wallerstein, Treatment of severe erythroblastosis by simultaneous removal and replacement of the blood of the newborn infant, Science 103:583–584 (1946).Google Scholar
  14. 14.
    R. Finn, C. A. Clarke, W. T. A. Donohoe, R. B. McConnell, P. M. Sheppard, D. Lehane, and W. Kulke, Experimental studies on the prevention of Rh haemolytic disease, Brit. Med. J 1:1486–1490 (1961).Google Scholar
  15. 15.
    A. W. Liley, Intrauterine transfusion of foetus in haemolytic disease, Brit. Med. J 2: 1107–1109 (1963).Google Scholar
  16. 16.
    R. J. Cremer, P. W. Perryman, and D. H. Richards, Influence of light on the hyperbilirubinemia of infants, Lancet 1:1094–1097 (1958).Google Scholar
  17. 17.
    J. Lucey, M. Ferreiro, and J. Hewitt, Prevention of hyperbilirubinemia of prematurity by phototherapy, Pediatrics 41:1047–1054 (1968).Google Scholar
  18. 18.
    R. E. Behrman and D. Y. Y. Hsia, Summary of a symposium on phototherapy for hyperbilirubinemia, J. Pediat 75:718–726 (1969).Google Scholar
  19. 19.
    S. J. Yaffe, G. Levy, T. Matsuzawa, and T. Baliah, Enhancement of glucuronide-conjugating capacity in a hyperbilirubinemic infant due to apparent enzyme induction by phenobarbital, New Engl. J. Med 275:1461–1466 (1966).Google Scholar
  20. 20.
    R. E. Behrman and D. E. Fisher, Phenobarbital for neonatal jaundice, J. Pediat 76: 945–948 (1970).Google Scholar
  21. 21.
    R. A. Ulstrom and E. Eisenklam, The enterohepatic shunting of bilirubin in the newborn infant. 1. Use of an oral activated charcoal to reduce normal serum bilirubin values, J Pediat 65:27–37 (1964).Google Scholar
  22. 22.
    R. Lester, L. Hammaker, and R. Schmid, A new therapeutic approach to unconjugated hyperbilirubinemia, Lancet 2:1257 (1962).Google Scholar
  23. 23.
    R. L. Poland and G. B. Odell, Physiologic jaundice, the enterohepatic circulation of bilirubin, New Engl. J. Med 284:1–6 (1971).Google Scholar
  24. 24.
    R. Brodersen and J. Theilgaard, Bilirubin colloid formation in neutral aqueous solution, Scand. J. Clin. Lab. Invest 24:395–398 (1969).Google Scholar
  25. 25.
    J. D. Ostrow and R. V. Branham, in “Bilirubin Metabolism of the Newborn” (D. Bergsma, D. Hsia, and C. Jackson, eds.) Birth Defects: Orig. Art. Ser 6:93–99 (1970).Google Scholar
  26. 26.
    T. K. With, “Bile Pigments, Chemical, Biological, and Clinical Aspects,” pp. 295–338, Academic Press, New York (1968).Google Scholar
  27. 27.
    R. Brodersen, Bilirubin diglucuronide in normal human blood serum, Scand. J. Clin. Lab. Invest 18:361–379 (1966).Google Scholar
  28. 28.
    C. H. Gray, A. Neuberger, and P. H. A. Sneath, Studies in congenital porphyria. 2. Incorporation of 15N in the stercobilin in the normal and in the porphyric, Biochem. J 47: 87–92 (1950).Google Scholar
  29. 29.
    I. M. London, R. West, D. Shemin, and D. Rittenberg, On the origin of bile pigment in normal man, J. Biol. Chem 184:351–358 (1950).Google Scholar
  30. 30.
    L. G. Israels, J. Skanderbeg, H. Guyda, W. Zingg, and A. Zipursky, A study of the earlylabelled fraction of bile pigment: The effect of altering erythropoiesis on the incorporation of [2-14C] glycine into haem and bilirubin, Brit. J. Haematol 9:50–62 (1963).Google Scholar
  31. 31.
    T. Yamamoto, J. Skanderbeg, A. Zipursky, and L. G. Israels, Early appearing bilirubin: Evidence for two components, J. Clin. Invest 44:31–41 (1965).Google Scholar
  32. 32.
    S. H. Robinson, M. Tsong, B. W. Brown, and R. Schmid, The sources of bile pigment in rat: Studies of “early-labeled” fraction, J. Clin. Invest 45:1569–1586 (1966).Google Scholar
  33. 33.
    G. W. Ibrahim, S. Schwartz, and C. J. Watson, Early labeling of bilirubin from glycine and δ-aminolevulinic acid in bile fistula dogs with special reference to stimulated erythropoiesis, Metabolism 15:1129–1139 (1966).Google Scholar
  34. 34.
    S. H. Robinson, The origins of bilirubin, New Engl. J. Med 279:143–149 (1968).Google Scholar
  35. 35.
    R. Schmid, H. S. Marver, and L. Hammaker, Enhanced formation of rapidly labelled bilirubin by phenobarbital: Hepatic microsomal cytochromes as a possible source, Biochem. Biophys. Res. Commun 24:319–328 (1966).Google Scholar
  36. 36.
    M. F. Vest, in “Bilirubin Metabolism” (I. A. D. Bouchier and B. H. Billing, eds.) pp. 47–53, Blackwell Scientific Publications, Oxford (1967).Google Scholar
  37. 37.
    R. Tenhunen, H. S. Marver, and R. Schmid, Microsomal heme oxygenase. Characterization of the enzyme, J. Biol. Chem 244:6388–6394 (1969).Google Scholar
  38. 38.
    A. J. Levi, Z. Gatmaitan, and I. M. Arias, Two hepatic cytoplasmic protein fractions, Y and Z, and their possible role in the hepatic uptake of bilirubin, sulfobromophthalein, and other anions, J. Clin. Invest 48:2156–2167 (1969).Google Scholar
  39. 39.
    A. J. Levi, Z. Gatmaitan, and I. M. Arias, Deficiency of hepatic organic anion-binding protein, impaired organic anion uptake by liver, and “physiologic” jaundice in newborn monkeys, New Engl. J. Med 283:1136–1139 (1970).Google Scholar
  40. 40.
    S. Sussman, J. V. Carbone, G. Grodsky, V. Hjelte, and P. Miller, Sulfobromophthalein sodium metabolism in newborn infants, Pediatrics 29:899–906 (1962).Google Scholar
  41. 41.
    G. J. Dutton, D. E. Langelaan, and P. E. Ross, High glucuronide synthesis in newborn liver: Choice of species and substrates, Biochem J 93:4p–5p (1964).Google Scholar
  42. 42.
    R. Brodersen, J. Jacobsen, H. Hertz, H. Rebbe, and B. Sørensen, Bilirubin conjugation in the human fetus, Scand. J. Clin. Lab. Invest 20:41–48 (1967).Google Scholar
  43. 43.
    L. Strebel and G. B. Odell, UDP glucuronyl transferase in rat liver: Genetic variation and maturation, Pediat. Res 3:351–352 (1969).Google Scholar
  44. 44.
    M. F. Vest and H. Grieder, Erythrocyte survival in the newborn infant, as measured by chromium51 and its relation to the postnatal serum bilirubin level, J. Pediat 59:194–199 (1961).Google Scholar
  45. 45.
    I. M. Arias, in “Bilirubin Metabolism of the Newborn” (D. Bergsma, D. Hsia, and C. Jackson, eds.) Birth Defects: Orig. Art. Ser 6:55–59 (1970).Google Scholar
  46. 46.
    N. H. Martin, Preparation and properties of serum and plasma proteins. XXI. Interactions with bilirubin, J. Am. Chem. Soc 71:1230–1232 (1949).Google Scholar
  47. 47.
    W. J. Waters, The reserve albumin binding capacity as a criterion for exchange transfusion, J. Pediat 70:185–192 (1967).Google Scholar
  48. 48.
    E. G. Porter and W. J. Waters, A rapid micromethod for measuring the reserve albumin binding capacity in serum from newborn infants with hyperbilirubinemia, J. Lab. Clin. Med 67:660–668 (1966).Google Scholar
  49. 49.
    N. A. Kaufmann, J. Kapitulnik, and S. H. Blondheim, The absorption of bilirubin by Sephadex and its relationship to the criteria for exchange transfusion, Pediatrics 44: 543–548 (1969).Google Scholar
  50. 50.
    W J. Keenan, J. E. Arnold, and J. M. Sutherland, Serum bilirubin binding determined by Sephadex column chromatography, J. Pediat 74:813 (1969).Google Scholar
  51. 51.
    G. B. Odell, S. N. Cohen, and P. C. Kelly, Studies in kernicterus. II. The determination of the saturation of serum albumin with bilirubin, J. Pediat 74:214–230 (1969).Google Scholar
  52. 52.
    R. Schmid, I. Diamond, L. Hammaker, and C. B. Gundersen, Interaction of bilirubin with albumin, Nature 206:1041–1043 (1965).Google Scholar
  53. 53.
    J. D. Ostrow and R. Schmid, The protein-binding of C14-bilirubin in human and murine serum, J. Clin. Invest 42:1286–1299 (1963).Google Scholar
  54. 54.
    G. B. Odell, The distribution of bilirubin between albumin and mitochondria, J. Pediat 68:164–180 (1966).Google Scholar
  55. 55.
    G. B. Odell, Influence of pH on distribution of bilirubin between albumin and mitochondria, Proc. Soc. Exptl. Biol. Med 120:352–354 (1965).Google Scholar
  56. 56.
    R. P. Wennberg and M. L. Cowger, Spectral identification of albumin-bilirubin complexes, Pediat. Res 3:376–377 (1969).Google Scholar
  57. 57.
    R. P. Wennberg and L. Fraser Rasmussen, The influence of albumin on bilirubin distribution, Abst. Forty-first Ann. Meeting Soc. Pediat. Res, p. 182 (1971).Google Scholar
  58. 58.
    W. A. Silverman, D. H. Andersen, W. A. Blanc, and D. N. Crozier, A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens, Pediatrics 18:614–625 (1956).Google Scholar
  59. 59.
    D. Schiff, G. Chan, and L. Stern, Fixed drug combinations and the displacement of bilirubin from albumin, Pediatrics 48:139–141 (1971).Google Scholar
  60. 60.
    L. Johnson, F. Sarmiento, W. A. Blanc, and R. Day, Kernicterus in rats with an inherited deficiency of glucuronyl transferase, Am. J. Dis. Child 97:591–608 (1959).Google Scholar
  61. 61.
    G. B. Odell, The dissociation of bilirubin from albumin and its clinical implications, J. Pediat 55:268–279 (1959).Google Scholar
  62. 62.
    G. Blauer and T. E. King, Interaction of bilirubin with bovine serum albumin in aqueous solution, J. Biol. Chem 245:372–381 (1970).Google Scholar
  63. 63.
    M. L. Cowger, Unpublished data.Google Scholar
  64. 64.
    I. Moriguchi, S. Wada, and T. Nishizawa, Protein bindings. III. Binding of Sulfonamides to bovine serum albumin, Chem. Pharm. Bull 16:601–605 (1968).Google Scholar
  65. 65.
    I. Diamond and R. Schmid, Experimental bilirubin encephalopathy. The mode of entry of bilirubin-14C into the central nervous system, J. Clin. Invest 45:678–689 (1966).Google Scholar
  66. 66.
    R. C. Burnstine and R. Schmid, Solubility of bilirubin in aqueous solutions, Proc. Soc. Exptl. Biol. Med 109:356–358 (1962).Google Scholar
  67. 67.
    W. Haymaker, C. Margoles, A. Pentschew, H. Jacob, R. Lindenberg, L. S. Arroyo, O. Stochdorph, and D. Stowens, in “Kernicterus and Its Importance in Cerebral Palsy,” pp. 21–228, Charles C Thomas, Springfield, Ill. (1961).Google Scholar
  68. 68.
    A. E. Claireaux, in “Kernicterus” (Andrew Sass-Kortsák, ed.) pp. 140–149, University of Toronto Press, Toronto (1961).Google Scholar
  69. 69.
    A. E. Claireaux, Hemolytic disease of the newborn, Part II. Nuclear jaundice (kernicterus), Arch. Dis. Childh 25:71–80 (1950).Google Scholar
  70. 70.
    H. S. Schutta and L. Johnson, Bilirubin encephalopathy in the Gunn rat: A fine structure study of the cerebellar cortex, J. Neuropathol. Exptl. Neurol 26:377–396 (1967).Google Scholar
  71. 71.
    W. A. Blanc and L. Johnson, Studies on kernicterus. Relationship with sulfonomide intoxication, report on kernicterus in rats with glucuronyl transferase deficiency, and review of pathogenes is, J. Neuropathol. Exptl. Neurol 18:165–189 (1959).Google Scholar
  72. 72.
    D. H. Silberberg and H. S. Schutta, The effects of unconjugated bilirubin and related pigments on cultures of rat cerebellum, J. Neuropathol. Exptl. Neurol 26:572–583 (1967).Google Scholar
  73. 73.
    H. S. Schutta, L. Johnson, and H. S. Neville, Mitochondrial abnormalities in bilirubin encephalopathy, J. Neuropathol. Exptl. Neurol 29:296–305 (1970).Google Scholar
  74. 74.
    J. Bernstein and B. H. Landing, Extraneural lesions associated with neonatal hyper-bilirubinemia and kernicterus, Am. J Pathol 40:371–384 (1962).Google Scholar
  75. 75.
    R. L. Day, Inhibition of brain respiration in vitro by bilirubin: Reversal of inhibition by various means, Am. J. Dis. Child 88:504–506 (1954).Google Scholar
  76. 76.
    W. J. Waters and W. R. Bowen, Bilirubin encephalopathy: Studies relating to cellular respiration, Am. J. Dis. Child 90:608 (1955).Google Scholar
  77. 77.
    R. Day, Kernicterus, further observations on the toxicity of heme pigments, Pediatrics 17:925–928 (1956).Google Scholar
  78. 78.
    W. R. Bowen and W. J. Waters, Bilirubin encephalopathy: Studies related to the site of inhibitory action of bilirubin on brain metabolism, Am. J. Dis. Child 93:21–22 (1957).Google Scholar
  79. 79.
    J. H. Quastel and I. J. Bickis, Metabolism of normal tissues and neoplasms in vitro, Nature (London) 183:281–286 (1959).Google Scholar
  80. 80.
    R. Zetterström and L. Ernster, Bilirubin, an uncoupler of oxidative phosphorylation in isolated mitochondria, Nature (London) 178:1335–1337 (1956).Google Scholar
  81. 81.
    L. Ernster, in “Kernicterus” (A. Sass-Kortsák, ed.) pp. 174–192, University of Toronto Press, oronto (1961).Google Scholar
  82. 82.
    M. L. Cowger, R. P. Igo, and R. F. Labbe, The mechanism of bilirubin toxicity studied with purified respiratory enzyme and tissue culture systems, Biochemistry 4:2763–2770 (1965).Google Scholar
  83. 83.
    M. L. Cowger, Mechanism of bilirubin toxicity on tissue culture cells: Factors that affect toxicity, reversibility by albumin and comparison with other respiratory poisons and surfactants, Biochem. Med 5:1–16 (1971).Google Scholar
  84. 84.
    I. Diamond and R. Schmid, Oxidative phosphorylation in experimental bilirubin encephalopathy, Science 155:1288–1289 (1966).Google Scholar
  85. 85.
    M. Menken and E. C. Weinbach, Oxidative phosphorylation and respiratory control of brain mitochondria isolated from kernicteric rats, J. Neurochem 14:189–193 (1967).Google Scholar
  86. 86.
    S. Schenker, D. W. McCandless, and P. E. Zollman, Studies of cellular toxicity of unconjugated bilirubin in kernicteric brain, J. Clin. Invest 45:1213–1220 (1966).Google Scholar
  87. 87.
    M. T. Vogt and R. E. Basford, The effect of bilirubin on the energy metabolism of brain mitochondria, J. Neurochem 15:1313–1320 (1968).Google Scholar
  88. 88.
    M. G. Mustafa, M. L. Cowger, and T. E. King, Effects of bilirubin on mitochondrial reactions, J. Biol. Chem 244:6403–6414 (1969).Google Scholar
  89. 89.
    I. L. Kahán, M. Timár, and M. Földi, Bilirubin-binding cerebral lipid, Acta Paediat. Acad. Sci. Hung 9:121–131 (1968).Google Scholar
  90. 90.
    M. G. Mustafa and T. E. King, Binding of bilirubin with lipid, a possible mechanism of its toxic reaction in mitochondria, J. Biol. Chem 245:1084–1089 (1970).Google Scholar
  91. 91.
    E. Stenhagen and E. K. Rideal, The interaction between porphyrin, lipoid, and protein monolayers, Biochem. J 33:1591–1598 (1939).Google Scholar
  92. 92.
    R. Lester, R. E. Behrman, and J. F. Lucey, Transfer of bilirubin-C14 across monkey placenta, Pediatrics 32:416–419 (1963).Google Scholar
  93. 93.
    D. Watson, The absorption of bilirubin by erythrocytes, Clin. Chim. Acta 7:733–734 (1962).Google Scholar
  94. 94.
    F. A. Oski and J. L. Naiman, Red cell binding of bilirubin, J. Pediat 63:1034–1037 (1963).Google Scholar
  95. 95.
    N. A. Kaufmann, A. J. Simcha, and S. H. Blondheim, The uptake of bilirubin by blood cells from plasma and its relationship to the criteria for exchange transfusion, Clin. Sci 33:201–208 (1967).Google Scholar
  96. 96.
    W. H. Cheung, A. Sawitsky, and H. D. Isenberg, The effect of bilirubin on the mammalian erythrocyte, Transfusion 6:475–486 (1966).Google Scholar
  97. 97.
    U. Suvansri, W. H. Cheung, and A. Sawitsky, The effect of bilirubin on the human platelet, J. Pediat 74:240–246 (1969).Google Scholar
  98. 98.
    G. B. Odell, J. C. Natzschka, and G. N. B. Storey, Bilirubin nephropathy in the Gunn rat, Am. J. Physiol 212:931–938 (1967).Google Scholar
  99. 99.
    M. L. Cowger and M. G. Mustafa, Some membrane effects of bilirubin, Pediat. Res 5: 419–420 (1971).Google Scholar
  100. 100.
    A. B. Novikoff, in “Lysosomes” (A. V. S. de Reuck and M. P. Cameron, eds.) Ciba Foundation Symposium, p. 36, Little, Brown, Boston (1963).Google Scholar
  101. 101.
    A. C. Allison, I. A. Magnus, and M. R. Young, Role of lysosomes and of cell membranes in photosensitization, Nature 209:874–878 (1966).Google Scholar
  102. 102.
    M. G. Mustafa and M. L. Cowger, Unpublished data.Google Scholar
  103. 103.
    I. Matsuda, M. Tashimo, and A. Takase, Effects of bilirubin on glucose oxidation in red cells, Experientia 25:865–866 (1969).Google Scholar
  104. 104.
    R. F. Labbe, M. R. Zaske, and R. A. Aldrich, Bilirubin inhibition of heme biosynthesis, Science 129:1741–1742 (1959).Google Scholar
  105. 105.
    M. M. Thaler, in “Bilirubin Metabolism of the Newborn” (D. Bergsma, D. sia, and C. Jackson, eds.) Birth Defects: Orig. Art. Ser 6:128–130 (1970).Google Scholar
  106. 106.
    R. Brodersen and P. Bartels, Enzymatic oxidation of bilirubin, Europ. J. Biochem 10: 468–473 (1969).Google Scholar
  107. 107.
    J. B. Sumner and M. Nyman, The oxidation of bilirubin by peroxidase, Science 102: 209 (1945).Google Scholar
  108. 108.
    I. M. Rosenthal, H. J. Zimmerman, and N. Hardy, Congenital nonhemolytic jaundice with disease of the central nervous system, Pediatrics 18:378–386 (1956).Google Scholar
  109. 109.
    W. A. Gardner and B. W. Konigsmark, Familial nonhemolytic jaundice: Bilirubinosis and encephalopathy, Pediatrics 43:365–376 (1969).Google Scholar
  110. 110.
    J. Dobbing, in “Progress in Brain Research” (A. Lajtha and D. H. Ford, eds.) Vol. 29, pp. 417–427, Elsevier, New York (1968).Google Scholar
  111. 111.
    L. Bakay, Studies on blood-brain barrier with radioactive phosphorus. III. Embryonic development of the barrier, Arch. Neurol. Psychiat 70:30–39 (1953).Google Scholar
  112. 112.
    I. Diamond, Kernicterus: Revised concepts of pathogenesis and management, Pediatrics 38:539–542 (1966).Google Scholar
  113. 113.
    L. Bakay, in “Progress in Brain Research” (A. Lajtha and D. H. Ford, eds.) Vol. 29, pp. 315–319, Elsevier, New York (1968).Google Scholar
  114. 114.
    H. Chen, C.-S. Lin, and I.-N. Lien, Ultrastructural studies in experimental kernicterus, Am. J. Pathol 48:683–711 (1966).Google Scholar
  115. 115.
    B. Rozdilsky, in “Kernicterus” (A. Sass-Kortsák, ed.) pp. 161–166, University of Toronto Press, Toronto (1961).Google Scholar
  116. 116.
    H. Chen, C.-S. Lin, and I.-N. Lien, Vascular permeability in experimental kernicterus, an electron-microscopic study of the blood-brain barrier, Am. J. Pathol 51:69–99 (1967).Google Scholar
  117. 117.
    H. S. Schutta and L. Johnson, Clinical signs and morphologic abnormalities in Gunn rats treated with sulfadimethoxine, J. Pediat 75:1070–1079 (1969).Google Scholar
  118. 118.
    M. Reivich, G. Isaacs, E. Evarts, and S. Kety, The effect of slow wave sleep and REM sleep on regional cerebral blood flow in cats, J. Neurochem 15:301–306 (1968).Google Scholar
  119. 119.
    B. Billing and F. Jansen, Enigma of bilirubin conjugation, Gastroenterology 61:258–260 (1971).Google Scholar

Copyright information

© Plenum Press, New York 1973

Authors and Affiliations

  • Marilyn Louise Cowger
    • 1
    • 2
  1. 1.Albany Medical College of Union UniversityAlbanyUSA
  2. 2.State University of New York at AlbanyAlbanyUSA

Personalised recommendations