A.M.A. Journal of Diseases of Children

AVERY, MARY ELLEN;MEAD, JERE

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010519001pmid: 13649082

Abstract Recent observations suggest that a low surface tension may be an important attribute of the lining of the air passages of the lung.1-4 The purpose of this paper is to present evidence that the material responsible for such a low surface tension is absent in the lungs of infants under 1,100-1,200 gm. and in those dying with hyaline membrane disease. The role of this deficiency in the pathogenesis of the disease is considered. Surface tension operates so as to minimize the area of the surface. In the lungs, where the internal surface (the alveolar lining) is curved concave to the airway, the tendency of the surface to become smaller promotes collapse. Although the forces not only of surface tension but also of the elastic tissue tend to collapse the lungs, their behavior differs in one important respect. When the lung contains only a small volume of air, the elastic References 1. Pattle, R. E.: Properties, Function, and Origin of the Alveolar Lining Layer , Proc. Roy. Soc. London, Ser. B 148:217-240, 1958.Crossref 2. Pattle, R. E.: Properties, Function, and Origin of the Alveolar Lining Layer , Nature , London 175:1125, 1955.Crossref 3. Clements, J. A.: Surface Tension of Lung Extracts , Proc. Soc. Exper. Biol. & Med. 95:170-172, 1957. 4. Brown, E. S.: Lung Area from Surface Tension Effects , Proc. Soc. Exper. Biol. & Med. 95:168-170, 1957. 5. Harkins, W. D.: Physical Chemistry of Surface Films , New York, Reinhold Publishing Corporation, 1952, Chap. 2 . 6. Stacy, R. W.; Williams, D. T.; Worden, R. E., and McMorris, R. O.: Essentials of Biological and Medical Physics , New York, McGraw-Hill Book Company, Inc., 1955, Chap. 8 . 7. Cook, C. D.; Sutherland, J. M.; Segal, S.; Cherry, R. B.; Mead, J.; McIlroy, M. B., and Smith, C. A.: Studies of Respiratory Physiology in the Newborn Infant: III. , J. Clin. Invest. 36: 444-448, 1957. 8. Gitlin, D., and Craig, J. M.: The Nature of the Hyaline Membrane in Asphyxia of the Newborn , Pediatrics 17:64, 1956. 9. Gruenwald, P.: Pathologic Aspects of Lung Expansion in Mature and Premature Newborn Infants , Bull. New York Acad. Med. 32:689-692, 1956. 10. Briggs J. N., and Hogg, G.: Perinatal Pulmonary Pathology , Pediatrics 22:41-48, 1958. 11. Potter, E.: Personal communication to the authors. 12. Silverman, W., and Silverman, R.: Letter to the Editor, Lancet 2:588, 1958. 13. Phillips, L. L., and Skrodalis, V.: Fibrinolytic Enzyme System in Maternal and Umbilical-Cord Blood , Pediatrics 22:715-726, 1958.

ABALLÍ, ARTURO J.;BANÚS, VALERIANO LÓPEZ;de LAMERENS, SERGIO;ROZENGVAIG, SIMÓN

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010526002

Abstract The term hemorrhagic disease of the newborn was introduced by Townsend1 in 1894 to include a variety of bleeding disorders which occur during this period of infancy unrelated to trauma, infection, or definite disease. The condition was differentiated from hemophilia. In 1910 Schwarz and Ottenberg2 reported a prolonged coagulation time in these cases, and two years later Whipple3 advanced the hypothesis that the condition was due to a lack of prothrombin. Very low values of this factor were reported by Gelston4 and later by Kugelmass et al.,5 but in these studies very inaccurate methods were employed. In 1937 Brinkhous, Smith, and Warner6 with a two-stage technique showed that the defect of coagulation of normal newborn infants was due to a reduction of blood prothrombin. After this, independent publications from different parts of the world established the value of vitamin K in prophylaxis and treatment References 1. Townsend, C. W.: The Hemorrhagic Disease of the Newborn , Arch. Pediat. 11:559, 1894. 2. Schwarz, H., and Ottenberg, R.: The Hemorrhagic Disease of the Newborn with Special Reference to Blood Coagulation and Serum Treatment , Am. J. M. Sc. 140:17, 1910.Crossref 3. Whipple, G. H.: Hemorrhagic Disease: Antithrombin and Prothrombin Factors , Arch. Int. Med. 12:637, 1913.Crossref 4. Gelston, C. F.: On the Etiology of Hemorrhagic Disease of the Newborn , Am. J. Dis. Child. 22:351, 1921. 5. Kugelmass, I. N.: The Management of Hemorrhagic Problems in Infancy and Childhood , J.A.M.A. 99:895, 1932.Crossref 6. Brinkhous, K. M.; Smith, H. P., and Warner, E. D.: Plasma Prothrombin Level in Normal Infancy and in Hemorrhagic Disease of the Newborn , Am. J. M. Sc. 193:475, 1937.Crossref 7. Waddell, W. W., Jr., and Guerry, D., III: The Role of Vitamin K in the Etiology, Prevention and Treatment of Hemorrhage in the Newborn Infant , J. Pediat. 15:802, 1939.Crossref 8. Hellman, L. M., and Shettles, L. B.: Factors Influencing Plasma Prothrombin in the Newborn Infant: Prematurity and Vitamin K , Bull. Johns Hopkins Hosp. 63:138, 1939. 9. Dam, H.; Tage-Hansen, E., and Plum, P.: K-avitaminose hos spaede born som aarsag til hemorrhagisk diathese , Ugesk. læger 101:896, 1939. 10. Nygaard, K. K.: Prophylactic and Curative Effect of Vitamin K in Hemorrhagic Disease of the Newborn , Acta obst. et gynec. scandinav . 19: 361, 1939.Crossref 11. Kato, K., and Poncher, H. G.: The Prothrombin the Blood of Newborn Mature and Inmature Infants as Determined by the Microprothrombin Test , J. A. M. A. 114:749, 1940. 12. Lawson, R. B.: Treatment of Hypoprothrombinemia (Hemorrhagic Disease) of the Newborn Infant , J. Pediat. 18:224, 1941.Crossref 13. Bruchsaler, F. S.: Vitamin K and the Prenatal and Postnatal Prevention of Hemorrhagic Disease in Newborn Infants , J. Pediat. 18:317, 1941.Crossref 14. Toohey, M.: Vitamin K Requirements of the Newborn , Arch. Dis. Childhood 17:187, 1942.Crossref 15. Snelling, C. E.: Vitamin K in Hemorrhagic Disease of the Newborn Infant , J. Pediat. 22:27, 1943. 16. Nygaard, K. K.: Prothrombin Deficiency as Cause of Hemorrhagic Diathesis in the New-Born , Nord. med. 7:1535, 1940. 17. Sells, R. L.; Walker, S. A., and Owen, C. A.: Vitamin K Requirement of the Newborn Infant , Proc. Soc. Exper. Biol. & Med. 47:441, 1941. 18. Hardwicke, S. H.: Studies on the Minimal Effective Dose of a Water-Soluble Vitamin K Substitute in the Prevention of Hypoprothrombinemia in the Newborn Infant , J. Pediat. 24:259, 1944. 19. Fitzgerald, J. E., and Webster, A.: Effect of Vitamin K Administered to Patients in Labor , Am. J. Obst. & Gynec. 40:413, 1940. 20. Mull, J. W.; Bill, A. H., and Skowroska, H.: Effect on Newborn of Vitamin K Administered to Mothers in Labor , J. Lab. & Clin. Med. 26:1305, 1941. 21. Bohlender, G. P.; Rosenbaum, W. M., and Sage, E. C.: Antepartum Use of Vitamin K in the Prevention of Prothrombin Deficiency of the Newborn , J. A. M. A. 116:1763, 1941.Crossref 22. Valentine, E. H.; Reinhold, J. G., and Schneider, E.: The Effectiveness of Prenatal Administration of 2-Methyl 1-4 Naphthoquinone in Maintaining Normal Prothrombin Levels in Infants , Am. J. M. Sc. 262:358, 1941. 23. Hellman, L. M., and Shettles, L. B.: The Prophylactic Use of Vitamin K in Obstetrics , South. M. J. 35:289, 1942.Crossref 24. Fiechter, N.: Hypoprothrombinämia und Hämorrhagische Diathese des Neugeborenen und ihre Beziehungen zum Vitamin K , Monatsschr. Gerburtsh. u. gynäk . 111:1, 1940. 25. Gasser, E.: Die Hypoprothrombinämie und die K Vitamin Prophylaxis , Arch. Kinderh. 129: 161-243, 1943. 26. Larsen, E. H.: Svingningernei Prothrombinaktiviteten hos nyfødte , Copenhagen, Ejnar Munksgaards Forlag, 1952. 27. Parmelee, A. H.: Hemorrhagic Disease of the Newborn , J. Mich. M. Soc. 42:455, 1943. 28. Scobbie, E. B. S.: Haemorrhagic Disease of the Newborn , Arch. Dis. Childhood 17:175, 1942.Crossref 29. Grossman, A. M.: Vitamin K for the Pediatrician , J. Pediat. 19:205, 1941.Crossref 30. Sanford, H. N.; Shmigelsky, I., and Chapin, J. M.: Is Administration of Vitamin K in the Newborn of Clinical Value? J. A. M. A. 118:697, 1942.Crossref 31. Parks, J., and Sweet, L. K.: Does the Antenatal Use of Vitamin K Prevent Hemorrhage in the Newborn Infant? Am. J. Obst. & Gynec. 44:432, 1942. 32. Potter, E. L.: The Effect on Infant Mortality of Vitamin K Administered During Labor , Am. J. Obst. & Gynec. 50:235, 1945. 33. Sanford, H. N.; Kostalik, M., and Blackmore, B.: Prothrombin Studies on the Blood of Premature Infants and the Value of Vitamin K Therapy , Am. J. Dis. Child. 78:686, 1949. 34. Smith, C. A.: The Newborn Patient, Pediatrics 16:254, 1955. 35. Fresh, J. W.; Ferguson, J. H.; Stamey, C.; Morgan, F. M., and Lewis, J. H.: Blood Prothrombin, Proconvertin and Proaccelerin in Normal Infancy: Questionable Relationships to Vitamin K , Pediatrics 19:241, 1957. 36. Dyggve, H. W.: Undersøgelser over K-vitaminets betydning for blødninger hos nyfødte , Copenhagen, Nyt Nordisk forlag-Arnold Busck, 1952. 37. Dyggve, H. W.: Prophylactic Treatment with Vitamin K of 11,000 Newborn Infants Compared with 22,000 Untreated Infants , Sixth International Congress of Pediatrics , Zurich, 1950. 38. Randall, A., IV, and Randall, H. P.: Prothrombin Deficiency of Newborn , Proc. Soc. Exper. Biol. & Med 70:215, 1949. 39. Loeliger, A., and Koller, F.: Behavior of Factor VII and Prothrombin in Late Pregnancy and in the Newborn , Acta haemat. 7:157, 1952. 40. De Nicola, P.: Factor VII (SPCA): Its Physiological Significance , Blood 8:947, 1952. 41. Larrieu, M. J.; Soulier, J. P., and Minkowski, A.: Le Sang du cordon ombilical , Études neonat . 1:39, 1952. 42. Owen, C. A., and Hurn, M.: Changes in Blood Coagulation Factors During the First Week of Life , J. Pediat. 42:424, 1953. 43. Van der Mey, C. A. M., and Ens, J. C.: Proconvertin Content in the Blood of Newborn Full-Term Infants, Nederl , tijdschr. geneesk. 98: 1157, 1954. 44. Van Creveld, S.; Paulssen, M. M. P.; Ens, J. C.; Van der Mey C. A. M., and Versteeg, P.: Proconvertin Content in the Blood of the Newborn Full-Term and Premature Infants , Études neonat. 3:53, 1954. 45. Salazar de Souza, C.: Les Alterations de la coagulabilité chez les nouveau ne , Pédiatrie 9:8, 1954. 46. Passaro, G. P.: Prothrombin, Factors V and VII in the Newborn , Arch. ital. Pediat. e puericolt. 17:59, 1955. 47. Douglas, A. S., and Davies, P. L.: Hypoprothrombinemia in the Newborn , Arch. Dis. Childhood 30:509, 1955.Crossref 48. Van Creveld, S.; Nagel, C. G. M.; Nijenhurs, J. G.; Miranda, S. I., and Tijon, S.: Thromboplastin Formation in the Blood of the Newborn , Études neonat. 3:135, 1954. 49. Van Creveld, S.; Baker, H.; Niegssigt, I.; Sipkemma, J. J., and Smits, C.: Thromboplastin Formation in the Blood of the Newborn Infant , Études neonat. 3:217, 1954. 50. Hartmann, J. R.; Howell, D. A., and Diamond, L. K.: Disorders of Blood Coagulation During the First Week of Life , A. M. A. Am. J. Dis. Child. 90:594, 1955. 51. McElfresh, A. E.; Sharpsteen, J. R., and Akabane, T.: The Generation of Thromboplastin and Levels of Plasma Thromboplastin Component of the Blood of Infants , Pediatrics 17:870, 1956. 52. Fresh, J. W.; Fergusson, J. H., and Lerois, J. H.: Blood Clotting Studies in Parturient Women and the Newborn , J. Obst. & Gynec. 7:117, 1956. 53. Barkham, P.: Christmas Factor Activity of Cord Blood , Brit. J. Haemat. 2:215, 1957. 54. Aballí, A. J.; López Banús, V.; Lamerens, S., and Rozengvaig, S.: Coagulation Studies in the Newborn Period: Alterations of Thromboplastin Generation and Effects of Vitamin K in Full-Term and Premature Infants , A. M. A. J. Dis. Child. 94:594, 1957. 55. Beveridge, R. S.: Haemorrhagic Disease of the Newborn , Arch. Dis. Childhood 3:29, 1928. 56. Clifford, S.: Hemorrhagic Disease of the Newborn , J. Pediat. 14:333, 1939. 57. Rozengvaig, S.: Alteraciones de la prueba de la generación de thromboplastina en un caso de leucemia aguda , Rev. cubana pediat. 30:77, 1958. 58. López Banús, V., and Lamerens, S.: Estudio de la coagulación en el recién nacido a término en nuestro medio hospitalario , Rev. Cubana pediat. 28:381, 1956. 59. Aballí, A. J.; López Banús, V.; Lamerens, S., and Borrajero, I.: Trastornos hemorrágicos en el prematuro , Rev. cubana pediat. 28:651, 1956. 60. Gradwohl, R. B. H.: Clinical Laboratory Methods and Diagnosis , Ed. 5, St. Louis, the C. V. Mosby Company, 1956. 61. Macfarlane, R. G., cited by Van Creveld, S.: Blood Dyscrasias with Hemorrhage , in Brenneman's Practice of Pediatrics , Hagerstown, Md., W. F. Prior Company, Inc., 1948, Vol. 3, Chap. 17. 62. Quick, A.: Quantitative Estimation of Prothrombin , Am. J. Clin. Path. 10:154, 1935. 63. Biggs, R., and Macfarlane, R. G.: Human Blood Coagulation and Its Disorders , Oxford, England, Blackwell Scientific Publications, 1953. 64. Koller, F.; Leliger, A., and Duckert, F.: Experiments on a New Clotting Factor , Acta haemat. 6:1, 1951. 65. Stefanini, M.: Activity of Plasma Labile Factor in Disease , Lancet 1:606, 1951. 66. Leake, C. D., and Guy, E. F.: A Diluting Fluid for Platelet Counting , J. A. M. A. 84:809, 1925. 67. Stefanini, M., and Dameshek, W.: The Hemorrhagic Disorders , New York, Grune & Stratton, 1955. 68. del Bono, N., and Pasaro, G. P.: Metodologie per lo studio delle diatesi emorragiche , Quad. coag. (fasc. 3) p. 96, (March) , 1956. 69. Biggs, R., and Douglas, A. S.: The Thromboplastin Generation Test , J. Clin. Path. 6:23, 1953.Crossref 70. Biggs, R.: Observations on Factor VII Deficiency , Brit. J. Haemat. 2:412, 1956.Crossref 71. López Banús, V.: A Simple Method to Obtain Venous Blood Samples from Premature and Newborn Infants , A.M.A. J. Dis. Child. 94:31, 1957. 72. Aballí, A. J.; Rozengvaig, S.; López Banús, V.; Lamerens, S., and Arrastia, F.: Estudios de la coagulación en el recién nacido: II. Peculiaridades de la actividad tromboplástica del suero , Rev. cubana pediat. 30:337, 1958. 73. Douglas, A. S.: Mode of Action of Coumarin Drugs , Brit. M. Bull. 11:35, 1953. 74. Naeye, R. L.: Plasma Thromboplastin Component: Influence of Coumarin Compounds and Vitamin K on Its Activity on Serum , Proc. Soc. Exper. Biol. & Med. 91:101, 1956. 75. Dyggve, H.: Prothrombin and Proconvertin in the Newborn , Acta paediat. 47:251, 1958. 76. Harrington, W. J.; Sprague, C. C.; Minnich, V.; Moor, C. V., Ahlvin, R. C., and Dubach, R.: Inmunologic Mechanisms in Idiopathic and Neonatal Thrombopenic Purpura , Ann. Int. Med. 38: 433, 1953. 77. MacAlenney, P. F., and Kristan, J. J.: Thrombopenic Purpura in the Newborn , Am. J. Dis. Child. 78:401, 1949. 78. Epstein, R. D.; Lozner, E. L.; Cobbey, T. S., Jr., and Davidson, C. S.: Congenital Thrombocytopenic Purpura: Purpura Hemorrhagica in Pregnancy and in the Newborn , Am. J. Med. 9: 44, 1950. 79. Kugelmass, I. N., and Tritsch, J. E.: Prenatal Prevention of Potential Hemorrhagic Disease of the Newborn , J. A. M. A. 92:531, 1929. 80. Capon, N. B.: Hemorrhagic Disease of the Newborn: A Study of 61 Cases , Lancet 1:431, 1937. 81. Rodda, F. C.: Studies with a New Method for Determining the Coagulation Time of Blood in the New-Born , Am. J. Dis. Child. 19:269, 1920. 82. Leslie, E. I., and Sanford, H. N.: Substances Involved in Coagulation of Blood of Newborn , Am. J. Dis. Child. 51:590, 1936. 83. Wille, H.: Influence of Avitaminosis K on Occurrence of Retinal Hemorrhages in the New Born , Nord. med. (Hospitalstidende) 26:1188, 1945. 84. Koller, F.: Das Vitamin K und seine Klinische Bedeutung , Leipzig, Georg Thieme, 1941. 85. Allen, J. G.: Clinical Value of Liver Function Tests: Review with Special Study of Plasma Prothrombin , Gastroenterology 3:490, 1944. 86. Grossman, B. J.; Heyn, R. M., and Rozenfeld, I. H.: Coagulation Studies in the Newborn Infant , Pediatrics 9:182, 1952. 87. Abt, L.: Melena Neonatorum , J. Pediat. 47:1, 1955. 88. Abt, L., and Downey, W. S., Jr.: Melena Neonatorum: The Swallowed Blood Syndrome , J. Pediat. 47:6, 1955. 89. Solomonsen, L.: On the Prevention of Hemorrhagic Disease of the Newborn by Administration of Cow's Milk During the First Two Days of Life , Acta paediat. 28:1, 1940. 90. Solomonsen, L., and Nygaard, K. K.: The Prothrombin Content in Relation to Early and Late Feeding in the Newborn , Acta paediat. 24:209, 1940. 91. Gellies, S. S., and Lyon, R. A.: The Influence of Diet of the Newborn Infant on the Prothrombin Index , J. Pediat. 19:495, 1941.Crossref 92. Schloss, O. M., and Commiskey, L. J. J.: Etiology and Treatment of So-Called Hemorrhagic Disease of the Newborn , Am. J. Dis. Child. 3:216, 1912. 93. Williamson, H. E.; Stadler, H. E., and Owen, C. A.: Curative Effect of Vitamin K and Whole Blood on Prothrombin Deficiency of Newborn Infant , Proc. Soc. Exper. Biol. & Med. 47: 116, 1941. 94. MacPherson, A. I. S.: Treatment of Hemorrhagic Disease of the Newborn , Brit. M. J. 2: 433, 1941. 95. Aballí, A. J.; Moreno, O.; Fernandez, M.; Toledo, J., and Borrajero, I.: Hemorrhagia interna por ruptura de hematoma subcapsular hepático en el recién nacido , Rev. cubana pediat. 27:651, 1955. 96. Aballí, A. J.: Reporte del V Congreso Pan Americano de Pediatría: Dos sindromes de interés medico quirúrgico en el período neonatal , An. Nestl é 65:38, 1957. 97. Mason Brown, J. J.: Hepatic Hemorrhage in the Newborn , Arch. Dis. Childhood 32:480, 1957. 98. Rosenthal, R. L.; Dreskin, O. H., and Rosenthal, N.: Plasma Thromboplastic Antecedent Deficiency , Blood 10:120, 1955. 99. Ratnoff, O. D., and Calopy, J. E.: A Familiar Hemorrhagic Trait Associated with a Deficiency of a Clot-Promoting Fraction of Plasma , J. Clin. Invest. 34:602, 1955. 100. Jim, R. T. C., and Goldfein, S.: Hageman Trait (Hageman Factor Deficiency) , Am. J. Med. 23:824, 1957. 101. O'Brien, J. R.: Factor V in Blood Coagulation in Vitro and Report of a Case of Factor V Deficiency , Brit. J. Haemat. 4:210, 1958. 102. Spaet, T. H.; Aggeler, P. M., and Kensall, B. G.: A Possible Fourth Thromboplastic Component , J. Clin. Invest. 33:1095, 1954. 103. McElfresh, A. E.: Deficiency of a Previously Unrecognized Serum Coagulation Factor Occurring in 5 Siblings (Society Transactions) , A. M. A. J. Dis. Child. 94:501, 1957. 104. Koller, F.: Le Facteur X , Rev. hémat. 18: 362, 1955. 105. Telfer, T. P.; Denson, K. W., and Wright, D. R.: A New Coagulation Defect , Brit. J. Haemat. 2:308, 1956. 106. Hougie, C.; Barrow, E. B., and Graham, J. B.: Stuart Clotting Defect , J. Clin. Invest. 34: 485, 1957. 107. Bachmann, F.; Duckert, F.; Geiger, M.; Baer, P., and Koller, F.: Differentiation of Factor VII Complex—Studies on the Stuart-Prower Factor , Thrombosis et Diathesis hemorrhagica 1: 168, 1957. 108. Bachmann, F.; Duckert, F., and Koller, F.: The Stuart-Prower Assay and Its Clinical Significance , Thrombosis et Diathesis hemorrhagica 2:24, 1958. 109. Greig, H. B. W., and Tattersal, J. C.: Evidence for the Existence of a Third Serum Clotting Factor , Brit. J. Haemat. 2:421, 1956. 110. Dische, F. E.: Substances with Factor VII Activity , Brit. J. Haemat. 4:202, 1958.Crossref 111. Bachmann, F.; Duckert, F.; Fluckiger, P., and Hitzig, W.: An Unusually Severe Hemorrhagic Diathesis , Proc. 6th Congress European Society Haematology , Copenhagen, 1957. 112. Koller, F.; Duckert, F.; Bachmann, F.; Streuli, F., and Geiger, M.: The Differentiation of Serum Clotting Factors , Proc. 6th European Society Haematology , Copenhagen, 1957. 113. Horder, M. H.: Der Stuart Factor Während der Cumarin Therapie , Thrombosis et Diathesis hemorrhagica 2:170, 1958. 114. Van Creveld, S.; Paulssen, M. M. P., and Teng, S. K.: Prothrombin and Accelerator Globulin in the Plasma of Newborns under Normal and Pathological Conditions , Neonatal Studies 1:1, 1952.

ABALLÍ, ARTURO J.;BANÚS, VALERIANO LÓPEZ;de LAMERENS, SERGIO;ROZENGVAIG, SIMÓN

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010551003

Abstract In a previous publication1 and in the preceding paper2 we have presented evidence indicating that the serum of newborns with hypoprothrombinemia has a marked deficit of another thromboplastic substance besides PTC. Moreover, in mixture experiments with the thromboplastin generation test and the Loeliger-Koller technique for determination of proconvertin, newborns with severe hypoprothrombinemia appeared to have the same defect as patients receiving prolonged treatment with coumarin compounds. The various deficits of these newborns were corrected by means of stored normal serum.1,2 The recently described Stuart factor3,4 is a stable substance adsorbed by barium sulfate, which participates in the first and probably in the second stage of blood coagulation. Its deficiency is associated with a low thromboplastic activity of the serum and a very prolonged one-stage prothrombin time. The use of Russell viper venom (Stypven) also gives an abnormal result. The determination of proconvertin with a substrate plasma References 1. Aballí, A. J.; Rozengvaig, S.; López Banús, V.; Lamerens, S., and Arrastía, F.: Estudios de la coagulación en el recién Nacido: II. Alteraciones de la Actividad Tromboplástica del Suero , Rev. cubana pediat. 30:337, 1958. 2. Aballí, A. J.; López Banús, V.; Lamerens, S., and Rozengvaig, S.: Coagulation Studies in the Newborn Period: III. Hemorrhagic Disease of the Newborn, this issue, p. 24. 3. Hougie, C.C.; Barrow, E. M., and Graham, J. B.: The Stuart Factor: A Hitherto Unrecognized Blood Coagulation Factor—Proc. of the Sixth Congress of the International Society of Blood Transfusions, p. 336, 1958. 4. Hougie, C.; Barrow, E. M., and Graham, J. B.: Stuart Clotting Defect: I. Segregation of a Hereditary Hemorrhagic State from the Heterogenous Group Heretofore Called "Stable Factor" (SPCA—Proconvertin, Factor VII) Deficiency , J. Clin. Invest. 36:485, 1957.Crossref 5. Bachmann, F.; Duckert, F.; Geiger, M.; Bear, P., and Koller, F.: Differentiation of Factor VII Complex: Studies on the Stuart-Prower Factor , Thrombosis et Diathesis hemorrhagica 1: 168, 1957. 6. Dische, F. E.: Substances with Factor VII Activity , Brit. J. Haemat. 4:202, 1958.Crossref 7. Bachmann, F.; Duckert, F., and Koller, F.: The Stuart-Prower Assay and Its Clinical Significance , Thrombosis et Diathesis hemorrhagica 2:24, 1958. 8. Horder, M. H.: Der Stuart Factor Während der Cumarin Therapie , Thrombosis et Diathesis hemorrhagica 2:170, 1958. 9. Lawson, R. B.: Treatment of Hypoprothrombinemia (Hemorrhagic Disease) of the Newborn , J. Pediat. 18:224, 1941.Crossref 10. Aballí, A. J.; López Banús, V.; Lamerens, S., and Rozengvaig, S.: Coagulation Studies in the Newborn Period: Alterations of Thromboplastin Generation and Effects of Vitamin K in Full-Term and Premature Infants , A. M. A. J. Dis. Child. 94:589, 1957.Crossref 11. Shafrir, E., and de Vries, A.: Studies on Clot-Promoting Activity of Glass , J. Clin. Invest. 35:1183, 1956.Crossref 12. Biggs, R.; Sharp, A. A.; Margolis, J.; Hardesty, R. M.; Stewart, J., and Davidson, W. M.: Defects in the Early Stages of Blood Coagulation , Brit. J. Haemat. 4:177, 1958.Crossref

DANOWSKI, T. S.;VAN DIERMEN, J.;HEINEMAN, A. C.;MATEER, F. M.

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010557004

Abstract The administration of methyltestosterone and potassium chloride to patients with muscular dystrophy in an unsuccessful attempt to modify the downward course of the muscle debility provided an opportunity to assess the effects of this androgen upon certain endocrine indices. Materials and Methods Clinical and other pertinent data on the 13 boys and 2 men receiving approximately 10 mg. of methyltestosterone as buccal Linguets and 1 to 3 gm. of potassium chloride per os daily for 12 to 24 months have been presented earlier.1 At the end of the therapeutic trials, and in some instances prior to and during their course, roentgenograms of the sella turcica, the urinary excretion of pituitary gonadotropins,2 17-hydroxycorticosteroids,3,4 and 17-ketosteroids,5,6 the level of serum protein-bound iodine,7,8 the blood and serum solutes, and the responses of the blood sugar and serum inorganic phosphorus to dextrose,9 to insulin,9 and to epinephrine References 1. Van Diermen, J.; Wratney, M. J.; Mateer, F. M., and Danowski, T. S.: Muscular Dystrophy: IX. Body Growth, Muscle Strength, and Serum Solutes During Methyltestosterone-KCl Therapy, A. M. A. J. Dis. Child., to be published. 2. Gorbman, A.: Ultrafiltration of Urine for Collection and Biological Assay of Excreted Hypophyseal Hormones , Endocrinology 37:177-190 ( (Sept.) ) 1945.Crossref 3. Nelson, D. H., and Samuels, L. T.: A Method for the Determination of 17-Hydroxycorticosteroids in Blood: 17-Hydroxycorticosterone in the Peripheral Circulation , J. Clin. Endocrinol. 12:519-526 ( (May) ) 1952.Crossref 4. Silber, R. H., and Porter, C. C.: The Determination of 17, 21-Dihydroxy-20-Ketosteroids in Urine and Plasma , J. Biol. Chem. 210:923-932 ( (Oct.) ) 1954. 5. Holtorff, A. F., and Koch, F. C.: Colorimetric Estimation of 17-Ketosteroids and Their Application to Urine Extracts , J. Biol. Chem. 135:377-392 ( (Sept.) ) 1940. 6. Danowski, T. S.; Bastiani, R. M.; McWilliams, F. D.; Mateer, F. M., and Greenman, L.: Muscular Dystrophy: IV. Endocrine Studies , A. M. A. J. Dis. Child. 91:356-364 ( (April) ) 1956.Crossref 7. Danowski, T. S.; Johnston, S. Y., and Greenman, J. H.: Alterations in Sertun Iodine Fractions Induced by the Administration of Inorganic Iodide in Massive Dosage , J. Clin. Endocrinol. 10:519-531 ( (May) ) 1950.Crossref 8. Danowski, T. S.; Mateer, F.; Weigand, F. A.; Peters, J. H., and Greenman, J. H.: Serum Iodine Fractions in Subjects Receiving Potassium Iodide in Small Dosage , J. Clin. Endocrinol. 10: 532-539 ( (May) ) 1950.Crossref 9. Danowski, T. S.; Gillespie, H. K.; Egan, T. J.; Mateer, F. M., and Leinberger, M. H.: Muscular Dystrophy: V. Blood Sugar and Serum Electrolytes Following Insulin and Dextrose, Alone or in Combination , A. M. A. J. Dis. Child. 91: 429-435 ( (May) ) 1956. 10. Fergus, E. B.; Nichols, W. R.; Horne, L. M., and Danowski, T. S.: Muscular Dystrophy: VI. Diminished Blood Sugar and Serum Electrolyte Responses to Epinephrine , A. M. A. J. Dis. Child. 91:436-441 ( (May) ) 1956. 11. Albright, E. C.; Larson, F. C., and Deiss, W. P.: Thyroxine Binding Capacity of Serum Alpha Globulin in Hypothyroid, Euthyroid, and Hyperthyroid Subjects , J. Clin. Invest. 34:44-47 ( (Jan.) ) 1955.Crossref 12. Keitel, H. G., and Sherer, M. G.: Marked Depression of the Plasma Protein-Bound Iodine Concentration in the Absence of Clinical Hypothyroidism During Testosterone Medication , J. Clin. Endocrinol. 17:854-861 ( (July) ) 1957.Crossref 13. Federman, D. D.; Robbins, J., and Rall, J. E.: Effects of Methyl Testosterone on Thyroid Function, Thyroxine Metabolism, and Thyroxine Binding Protein , J. Clin. Invest. 37:1024-1030 ( (July) ) 1958.Crossref 14. Lewis, L. A., and McCullagh, E. P.: Carbohydrate Metabolism of Animals Treated with Methyl Testosterone and Testosterone Propionate , J. Clin. Endocrinol. 2:502-506 ( (Aug.) ) 1942.Crossref 15. McCullagh, E. P., and Lewis, L. A.: Carbohydrate Metabolism of Patients Treated with Methyl Testosterone: Hypogonadism , J. Clin. Endocrinol. 2:507-510 ( (Aug.) ) 1942.Crossref 16. Talaat, M.; Habib, Y. A., and Habib, M.: The Effect of Testosterone on the Carbohydrate Metabolism in Normal Subjects , Arch. internat. pharmacodyn. 111:215-226, 1957.

FERENCZ, CHARLOTTE;MARKOWITZ, MILTON;BUNIM, JOSEPH J.

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010563005pmid: 13649086

Abstract The introduction of steroids has presented a new therapeutic approach to the treatment of rheumatic fever. This problem has been the subject of extensive studies over the past few years. The detailed observations made in an effort to evaluate the effect of hormone therapy have resulted in a renewed interest in many aspects of this disease. In 1955, when a newly synthesized steroid, prednisone, became available, a study was undertaken to test its effectiveness in children with rheumatic fever. The objectives of this study were (1) to determine the relative anti-inflammatory potency of this new steroid in rheumatic fever; (2) to determine what proportion of children with rheumatic carditis treated early in their first attack with large amounts of prednisone for a prolonged period would escape permanent cardiac damage; (3) to determine whether extension of steroid therapy to 14 weeks, in contrast to the conventional 6 weeks, would reduce the References 1. Greenman, L.; Weigand, F. A., and Danowski, T. S.: Cortisone Therapy in Initial Attacks of Rheumatic Carditis , Ann. Rheumat. Dis. 12:342, 1953. 2. Bunim, J. J.; Pechet, M. M., and Bollet, A. J.: Studies on Metacortandralone and Metacortandracin in Rheumatoid Arthritis: Antirheumatic Potency, Metabolic Effect, and Hormonal Properties , J. A. M. A. 157:311, 1955.Crossref 3. Markowitz, M., and Kuttner, A. G.: The Effect of Intensive and Prolonged Therapy with Cortisone and Hydrocortisone in First Attacks of Rheumatic Carditis , Pediatrics 16:325, 1955. 4. Grollman, A. P., and Gamble, J. L., Jr.: Metabolic Alkalosis: A Specific Effect of Adrenocortical Hormones , A. M. A. J. Dis. Child. 96:494, 1958. 5. Good, R. A.; Vernier, R. L., and Smith, R. T.: Serious Untoward Reactions to Therapy with Cortisone and Adrenocorticotropin in Pediatric Practice: Part I , Pediatrics 19:95, 1957.

GLASS, THOMAS G.;FISCHER, ALBERT

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010573006pmid: 13649087

Abstract Widespread interest in parenterally administered proteolytic enzymes in the treatment of trauma is apparent from an examination of the recent literature.1-5 Many enzymes and various routes of administration have been used. Most authors agree that the enzymes are materially beneficial, but their enthusiasm seems to be based on "clinical impressions," clinical observations or subjective improvement. For example, Lichtman6 administered trypsin parenterally to 350 athletes who had sustained bruises, with "excellent" results in 66% of those treated. To either confirm or disprove the reports in the literature, an entirely objective and controlled approach to the problem was essential. Washing machine wringer injuries of the arm in children are common in this area and seemed to present possibilities for a uniformly controlled study, because edema of the arm could be measured accurately, and tenderness could be evaluated objectively. In this series lyophilized trypsin, in 5% aqueous gelatin solution (Parenzyme Aqueous),* References 1. Hopen, J. M., and Campagna, F. N.: Use of Intramuscular Trypsin, in Traumatic, Inflammatory, and Hemorrhagic Ocular Disturbances , Am. J. Ophth. 40:209-214, 1955. 2. Golden, H. T.: Effective Treatment for Traumatic and Inflamed Lesions Using Trypsin , Clin. Med. 2:583, 1955. 3. Moser, J. M.: Intramuscular Injection of Trypsin , New England J. Med. 256:258-263; 303-309, 1957.Crossref 4. Martin, G. J.: Anti-Inflammatory Effect of Trypsin , Ann. New York Acad. Sc. 68:70-88, 1957.Crossref 5. Silbert, N. E.: Enzyme Therapy by Intramuscular Route in Chest Diseases , Dis. Chest 29:520-532, 1956. 6. Lichtman, A. L.: Traumatic Injury in Athletes , Internat. Rec. Med. 170:322-326, 1957. 7. Glass, T. G.: A Simple Method of Elevation of the Arm in Children , Texas J. Med. 53:530-532, 1957. 8. Martin, G. J.: Trypsin, the Pharmacology of the Drug , Exper. Med. & Surg. 13:156-171, 1955. 9. Bogner, R. L.; Edelman, A., and Martin, G. J.: In Vivo Observations with Radioactive Trypsin, Arch. internat. pharmacodyn., to be published. 10. Innerfield, I.; Angrist, A., and Schwarz, A.: Parenteral Administration of Trypsin , J. A. M. A. , 152:597-605, 1953. 11. Menkin, V.: Dynamics of Inflammation , New York, The Macmillan Company, 1950. 12. Spector, W. G.: The Role of Some Higher Peptides in Inflammation , J. Path. & Bact. 63:93-110, 1951. 13. Moss, J. N.; Brendel, R.; Simon, H.; Beiler, J. M., and Martin, G. J.: Effect of Trypsin on Wound Healing , Arch. internat. pharmacodyn. 60:375-379, 1957.

SLUNGAARD, R. K.;JAECK, J. L.

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010577007pmid: 13649088

Abstract Small kidneys may be due to faulty development, as in hypoplasia and aplasia, or the cause may be atrophy secondary to disease in normally developed kidneys. In aplasia, specific renal structures are absent. In hypoplasia renal structures are found but in smaller numbers than usual. While aplasia is incompatible with life for more than a brief duration, hypoplasia may occur in different degrees of severity and thus support life for various periods of time. Atrophy of the kidneys is most often due to pyelonephritis or glomerulonephritis. Frequently, atrophy occurs in hypoplastic kidneys, and it may be exceedingly difficult to decide which is the most important factor in ultimately determining the size of the kidneys. The following case presents this problem along with some marked changes due to chronic renal insufficiency: A 10-year-old boy was seen because of shortness of stature. He was 48 in. tall and weighed 51 lb. as References 1. Mathe, C. P.: Diminutive Kidney , California Med . 84:10 ( (Feb.) ) 1958. 2. Campbell, M. F.: Clinical Pediatric Urology, Philadelphia and London , The W. B. Saunders Company, 1951. 3. Asbeshouse, B. S.: Congenital Renal Aplasia with Calcified Cystic Degeneration , J. Internat. Coll. Surgeons 26:283 ( (Sept.) ) 1956. 4. Caffey, J.: Pediatric X-Ray Diagnosis , Ed. 2, Chicago, The Year Book Publishers, Inc., 1950. 5. Emmet, J. L.; Alvarez-Ierena, J. J., and McDonald, J. R.: Atrophic Pyelonephritis Versus Congenital Renal Hypoplasia , J. A. M. A. 148:1470 ( (April 26) ) 1952.Crossref 6. Bell, E. T.: Renal Diseases , Philadelphia, Lea & Febiger, 1950. 7. Paetzel, W.: Zwergnieren , Chirurg 27:444 ( (Oct.) ) 1956. 8. Kempf, F. K.: Die Nierenaplasie mit Berücksichtigung der Hypoplasie und die Deutung gleichzeitiger cystischer Hamartien im Nieren-lager (Nierenblastemcysten) , Arch. path. Anat. 328:182, 1956.Crossref 9. Herbut, P. A.: Urological Pathology , Philadelphia, Lea & Febiger, 1952. 10. Castelman, B., and Mallory, T. B.: Parathyroid Hyperplasia in Chronic Renal Insufficiency , Am. J. Path. 13:553 ( (July) ) 1937. 11. Albright, F., and Reifenstein, E. C., Jr.: The Parathyroid Glands and Metabolic Bone Disease , Baltimore, The Williams & Wilkins Company, 1948. 12. Wilkins, L.: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence , Ed. 2, Springfield, Ill., Charles C Thomas, Publisher, 1957. 13. Aegerter, E., and Kirkpatrick, J. A., Jr.: Orthopedic Diseases , Philadelphia and London, The W. B. Saunders Company, 1958. 14. McLean, F. C., and Urist, M. R.: Bone: An Introduction to the Physiology of Skeletal Tissue , Chicago, The University of Chicago Press, 1954. 15. Smyth, F. S., and Goldman, L.: Renal Rickets with Metastatic Calcification and Parathyroid Dysfunction , Am. J. Dis. Child. 48:596 ( (Sept.) ) 1934. 16. Albright, F.; Bauer, W.; Claflin, D., and Cockrill, J. R.: Studies in Parathyroid Physiology: The Effect of Phosphate Ingestion in Clinical Hyperparathyroidism , J. Clin. Invest. 11:411 ( (March) )1932.Crossref 17. Jaffe, H. L.; Bodansky, A., and Chandler, J. P.: Ammonium Chloride Decalcification, as Modified by Calcium Intake: The Relation Between Generalized Osteoporosis and Ostitis Fibrosa , J. Exper. Med. 56:823 ( (Dec.) ) 1932.Crossref 18. Park, E. A., and Elliot, M. M.: Renal Hyperparathyroidism with Osteoporosis (Osteitis) Fibrosa Cystica , in Brenneman's Practice of Pediatrics , edited by I. M. McQuarrie, Hagerstown, Md., W. F. Prior Company, Inc., 1936, Vol. 3, Chap. 29. 19. Langmead, F. S., and Orr, J. W.: Renal Rickets Associated with Parathyroid Hyperplasia , Arch. Dis. Childhood 8:265 ( (Aug.) ) 1933.Crossref 20. Pappenheimer, A. M.: The Effect of Experimental Reduction of Kidney Substance upon the Parathyroid Glands and Skeletal Tissue , J. Exper. Med. 64:965 ( (Dec.) ) 1936.Crossref 21. Wintrobe, M. M.: Clinical Hematology , Philadelphia, Lea & Febiger, 1956. 22. Wolff, J. A.: Anemias Caused by Infections and Toxins, Idiopathic Aplastic Anemia and Anemia Caused by Renal Disease , Pediat. Clin. North America 4:469 ( (May) ) 1957.

KEITEL, HANS G.;Blakely, Jocelyn

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010585008

Abstract In the present report the plasma potassium concentration of premature infants of varying ages and weight is presented and the range of the "normal" concentrations established, taking into account the effect of the dietary intake and the age of the subjects. The potassium content of a formula for feeding the premature infant was changed by altering the carbohydrate content of the formula and by adding various salts of sodium, potassium, and calcium. The effect of these changes on the plasma concentration of potassium was observed. The data obtained are interpreted to indicate that the factors which affect the plasma concentration of potassium in the premature infant appear similar to those which have been identified in the adult. Patient Material Clinically well infants were studied. Infants weighing less than 5½ lb. (2.5 kg.) at birth were considered to be premature. The temperature of the nursery was maintained between 24 and 27 References 1. Young, W. F.; Hallum, J. L., and McCance, R. A.: The Secretion of Urine by Premature Infants , Arch. Dis. Childhood 16:243, 1941.Crossref 2. Keitel, H. G., and Jones, H., unpublished data. 3. Keitel, H. G.; Berman, H.; Jones, H., and MacLachlan, E.: The Chemical Composition of Normal Human Red Blood Cells, Including Variability among Centrifuged Cells , J. Hemat. 4:370, 1955. 4. Burnell, J. M.; Villamil, M. F.; Uyeno, B. T., and Scribner, B. H.: The Effect in Humans of Extracellular pH Change on the Relationship Between Serum Potassium Concentration and Intracellular Potassium , J. Clin. Invest. 35:935, 1956.Crossref 5. Natelson, S.: Correlation of Clinical and Chemical Observations in the Immature Infant: Manual for Physicians and Chemists , Munson Printing Company, 1952. 6. McCance, R. A., and Young, W. F.: The Secretion of Urine by Newborn Infants , J. Physiol. 99:265, 1941. 7. Edelstein, F., and Ylppö, A.: Passage of Salts Through the Placenta , Ztschr. Kinderh. 27: 79, 1920.Crossref 8. Pincus, J. B.; Gittleman, I. F.; Saito, M., and Sobel, A. E.: A Study of Plasma Values of Sodium, Potassium, Chloride, Carbon Dioxide, Carbon Dioxide Tension, Sugar, Urea and the Protein Base-Binding Power, pH and Hematocrit in Prematures on the First Day of Life, Pediatrics 18:39, 1956. 9. McCance, R. A., and Widdowson, E. M.: The Correct Physiological Basis on Which to Compare Infant and Adult Renal Function , Lancet 2:860, 1952.Crossref 10. Tudvad, F.; McNamara, H., and Barnett, H. L.: Renal Response of Premature Infants to Administration of Bicarbonate and Potassium , Pediatrics 13:4, 1954.

JOHNSON, LOIS;SARMIENTO, FELICITAS;BLANC, WILLIAM A.;DAY, RICHARD

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010593009pmid: 13649090

Abstract This paper describes the occurrence of kernicterus and factors which influence its development in the strain of rats * first studied by Gunn.22,23 The disease of humans designated in 1903 by Schmorl39 as kernicterus has, in our opinion, not been observed or induced in its entirety in animals. Various workers, however, have demonstrated the toxicity of indirect bilirubin.12-15,24,26,44-46 Ernster, Herlin, and Zetterström21 have caused localized pigmentation of the brain of the rabbit by treatment with bilirubin and an S-H blocking agent. Other workers17,19,20 have reported injury of brain tissue in hemolytic anemia of animals, a phenomenon not directly related to the present report, since the rats to be described do not suffer from antibody-antigen disease and have little or no hemolytic Definition of Kernicterus The following criteria are proposed as defining kernicterus: Distinctive evidence of central nervous system dysfunction during life in jaundiced subjects Canary yellow References 1. Arias, I. M., and London, I. M.: Bilirubin Glucuronide Formation in Vitro; Demonstration of a Defect in Gilbert's Disease , Science 126: 563, 1957.Crossref 2. Billing, B. H., and Lathe, G. H.: The Excretion of Bilirubin as an Ester Glucuronide, Giving the Direct van den Bergh Reaction , Biochem. J. 63:6P, 1956. 3. Billing, B. H.; Cole, P. G., and Lathe, G. H.: The Excretion of Bilirubin as as Diglucuronide Giving the Direct van den Bergh Reaction , Biochem, J. 65:774, 1957. 4. Bratton, A. C., and Marshall, E. K.: A New Coupling Component for Sulfanilamide Determination , J. Biol. Chem. 128:537, 1939. 5. Brown, A. K., and Zuelzer, W. W.: Mechanism and Significance of Hyperbilirubinemia in the Newborn with Reference to Kernicterus, read before the 11th Annual Meeting, American Academy for Cerebral Palsy, New Orleans, Nov., 1957. 6. Carbone, J. V., and Grodsky, G. M.: Constitutional Nonhemolytic Hyperbilirubinemia in the Rat: Defect of Bilirubin Conjugation , Proc. Soc. Exper. Biol. & Med. 94:461, 1957. 7. Childs, B., and Najjar, V. A.: Familial Nonhemolytic Jaundice with Kernicterus: a Report of 2 Cases Without Neurologic Damage , Pediatrics 18:369, 1956. 8. Cole, P. G.; Lathe, G. H., and Billing, B. H.: Separation of the Bile Pigments of Serum, Bile and Urine , Biochem. J. 57:514, 1954. 9. Crigler, J. F., and Najjar, V. A.: Congenital Familial Nonhemolytic Jaundice with Kernicterus , Pediatrics 10:169, 1952. 10. Danoff, S.; Boyer, A., and Holt, L. E., Jr.: Observations on the Control of Bilirubinemia, Program of the 28th Annual Meeting of the Society for Pediatric Research, Atlantic City, May 6-7, 1958, Abstract 13, p. 11. 11. Davis, B.: The Binding of Sulfonamide Drugs by Plasma Proteins: A Factor in Determining the Distribution of Drugs in the Body , J. Clin. Invest. 22:753, 1943. 12. Day, R. L.: In Vitro Effect of Bilirubin on Brain Respiration, presented at the 25th Anniversary Celebration of Columbia-Presbyterian Medical Center , Babies Hospital, New York, Oct., 1953. 13. Day, R. L.: Inhibition of Brain Respiration in Vitro by Bilirubin: Reversal of Inhibition by Various Means , Proc. Soc. Exper. Biol. & Med. 85:261, 1954. 14. Day, R.: Kernicterus; Further Observations on the Toxicity of Heme Pigments , Pediatrics 17: 925, 1956. 15. Day, R. L., and Johnson, L.: Kernicterus, to be published. 16. Dameshek, W., and Singer, K.: Familial Nonhemolytic Jaundice , Arch. Int. Med. 67:259, 1941. 17. Dereymaeker, A.: L'ictere nucléaire du nouveau-né , Bruxelles, Editions Arscia, 1949. 18. Dutton, G. J., and Storey, I. D. E.: Uridine Compounds in Gluronic Acid and Metabolism: The Isolation and Structure of Uridine-Diphosphate-Glucuronic Acid , Biochem. J. 59:279, 1955. 19. Eyquem, A.: L'atteinte du systéme nerveux central chez les jeunes animaux présentant une maladie hémolytique expérimentale , Compt. rend. Soc. biol. 142:485, 1948. 20. Eyquem, A.: L'ictére nucléaire expérimental , Acta neurol. et psychiat. belg. 49:965, 1949. 21. Ernster, L.; Herlin, L., and Zetterström, R.: Experimental Studies on the Pathogenesis of Kernicterus , Pediatrics 20:647, 1957. 22. Gunn, C. K.: Hereditary Acholuric Jaundice in a New Mutant Strain of Rats , J. Hered. 29:137, 1938. 23. Gunn, C. K.: Hereditary Acholuric Jaundice in the Rat , Canad. M. A. J. 50:230, 1944. 24. Küster, F., and Krings, H.: Die Bedeutung des Bilirubins für die Pathogenese des Hirnschadens bei der Erythroblastosis fetalis , Ztschr. Kinderh. 67:503, 1950. 25. Karunairatnam, M. C.; Kerr, L. M. H., and Levvy, G. A.: The Glucuronide-Synthesizing System in the Mouse, and Its Relationship to B-Glucuronidase , Biochem. J. 45:496, 1949. 26. Lathe, G. H.: The Chemical Pathology of Bile Pigments: Part I. The Plasma Bile Pigments , Biochemical Society Symposia , No. 12, London, Cambridge University Press, 1954, p. 34. 27. Lathe, G. H., and Walker, M.: An Enzyme Defect in Human Neonatal Jaundice and in Gunn's Strain of Jaundiced Rats , Biochem. J. 67: 9P, 1957. 28. Lathe, G. H., and Walker, M.: The Inhibitory Effect of Human Pregnancy Serum on Bilirubin Conjugation, to be published. 29. Levvy, G. A.: Glucuronide Metabolism with Special Reference to the Steroid Hormones , Vitamins & Hormones 14:267, 1956. 30. Lipschitz, W. L., and Bueding, E.: Mechanism of the Biological Formation of Conjugated Glucuronic Acids , J. Biol. Chem. 129:333, 1939. 31. Malloy, H. T., and Lowenstein, L.: Hereditary Jaundice in the Rat , Canad. M. A. J. 42:122, 1940. 32. Malloy, H. T., and Evelyn, K. A.: The Determination of Bilirubin with the Photoelectric Colorimeter , J. Biol. Chem. 119:481, 1937. 33. Meulengracht, E.: Review of Chronic Intermittent Juvenile Jaundice , Quart. J. Med. 16:83, 1947. 34. Odell, G. B.: In Vitro Studies of the Effect of Sulfonamides on Bilirubin, Program of the 28th Annual Meeting of the Society for Pediatric Research, Atlantic City, May 6-7, 1958, Abstract 156, p. 147. 35. Rosenthal, I. M.; Zimmerman, H. J., and Hardy, N.: Congenital Nonhemolytic Jaundice with Disease of the Central Nervous System , Pediatrics 18:378, 1956. 36. Schmid, R.: Bilirubin Glucuronide, the Direct Reacting Bilirubin, in Serum, Bile and Urine , Science 124:76, 1956. 37. Schmid, R.; Hammaker, L., and Axelrod, J.: The Enzymatic Formation of Bilirubin Glucuronide , Arch. Biochem. 70:285, 1957. 38. Schmid, R.; Axelrod, J., and Hammaker, L.: Congenital Defects in Bilirubin Metabolism , American Society of Clinical Investigation , May, 1957, abstract, p. 63. 39. Schmorl, G.: Zur Kenntnis des Ikterus neonatorum, insbesondere der dabei auftretenden Gehirnveränderungen , Verhandl. deutsch. path. Gesellsch. 15:109-115, 1904. 40. Silverman, W. A.; Andersen, D. H.; Blanc, W. A., and Crozier, D. N.: A Difference in Mortality Rate and Incidence of Kernicterus Among Premature Infants Allotted to Two Prophylactic Antibacterial Regimens , Pediatrics 18:614, 1956. 41. Strominger, J. L.; Kalckar, H. M.; Axelrod, J., and Manvell, E. S.: The Enzymatic Oxidation of Uridine Diphosphate Glucose to Uridine Diphosphate Glucuronic Acid , J. Am. Chem. Soc. 76:6411, 1954. 42. Strominger, J. L.; Maxwell, E. S.; Axelrod, J., and Kalckar, H. M.: The Enzymatic Formation of Uridine Diphosphoglucuronic Acid , J. Biol. Chem. 224:79, 1957. 43. Talafant, E.: Properties and Composition of the Bile Pigment Giving a Direct Diazo Reaction , Nature , London 178:312, 1956. 44. Waters, W. J. W.; Richart, D. A., and Rawson, H. H.: Bilirubin Encephalopathy , Pediatrics 13:319, 1954. 45. Waters, W. J. W., and Britton, H. A.: Bilirubin Encephalopathy: Preliminary Studies Related to Production , Pediatrics 15:45, 1955. 46. Zetterström, R., and Ernster, L.: Bilirubin, an Uncoupler of Oxidative Phosphorylation in Isolated Mitochondria , Nature , London 178:1335, 1956.

NOORDSIJ, A. J.

1959 A.M.A. Journal of Diseases of Children

doi: 10.1001/archpedi.1959.02070010611010pmid: 13649091

Abstract Administration of γ-globulin to all exposed persons is the only effective means of controlling an epidemic of infectious hepatitis in situations where a group of people live closely together and rigid hygienic standards cannot be maintained. This has been borne out repeatedly in various epidemics since Stokes and Neefe introduced the use of γ-globulin in preventing spread of this disease.1-7 Our recent experience emphasizes once more that under the above-mentioned circumstances the first occurrence of infectious hepatitis is an indication to give γ-globulin to all contacts. The epidemic occurred in the Children's Inpatient Service of a psychiatric hospital which provides in- and outpatient treatment for both adults and children. The Children's Service occupies one wing of the hospital building, so at no time did the children come in contact with the adult patients. However, the personnel of the Children's Service mingle with the personnel of the other services, e. References 1. Stokes, J., Jr., and Neefe, J. R.: The Prevention and Attenuation of Infectious Hepatitis by Gamma Globulin: Preliminary Note , J. A. M. A. 127:144-145 ( (Jan. 20) ) 1945.Crossref 2. Gellis, S. S.; Stokes, J., Jr.; Brother, G. M.; Hall, W. M.; Gilmore, H. R.; Beyer, E., and Morrissey, R. A.: The Use of Human Immune Serum Globulin (Gamma Globulin), in Infectious (Epidemic) Hepatitis in the Mediterranean Theater of Operations: I. Studies on Prophylaxis in 2 Epidemics of Infectious Hepatitis , J. A. M. A. 128:1062-1063 ( (Aug. 11) ) 1945.Crossref 3. Havens, W. P., and Paul, J. R.: Prevention of Infectious Hepatitis with Gamma Globulin , J. A. M. A. 129:270-272 ( (Sept. 22) ) 1945.Crossref 4. Gelperin, A., and Hampton, W.: The Ecology of Infectious Hepatitis , Am. J. Pub. Health 45: 1327-1336, 1955.Crossref 5. Stokes, J., Jr.; Farquhar, J. A.; Drake, M. E.; Capps, R. B.; Ward, C. S., Jr.; Mills, O., and Kitts, A. W.: Infectious Hepatitis: Length of Protection by Immune Serum Globulin (Gamma Globulin) During Epidemics , J. A. M. A. 147:714-719 (Oct. 20) 1951.Crossref 6. Capps, R. B., and Stokes, J., Jr.: Epidemiology of Infectious Hepatitis and Problems of Prevention and Control , J. A. M. A. 149:557-561 (June 7) 1952.Crossref 7. Drake, M. E., and Ming, C.: Gamma Globulin in Epidemic Hepatitis: Comparative Value of 2 Dosage Levels, Apparently Near the Minimal Effective Level , J. A. M. A. 155:1302-1305 ( (Aug. 7) ) 1954.Crossref