Arden W. Moyer

Action of adrenocorticotropic hormone (ACTH) in experimental allergic encephalomyelitis of the guinea pig.

Summary Timely administration of adequate doses of ACTH shows an inhibiting action upon the occurrence of clinical manifestations and the development of pathological lesions in experimental allergic encephalomyelitis of the guinea pig.

Immunological Response to Trivalent Oral Poliomyelitis Vaccine

A survey of the literature to date on feeding living attenuated polioviruses for the immunization of man reveals that relatively little has been reported on simultaneous feeding of the three types of virus or the use of mixtures of them as a trivalent vaccine. This is apparently due to the fact that certain strains of poliovirus were found to interfere with the establishment and multiplication of other type strains in the human gut. Thus, Koprowski (1955) reported that type I, SM virus, interfered with the immunizing effect of type II, TN strain, when the two were fed simultaneously. In a subsequent study Koprowski et al. (1956) attempted to overcome this interference by feeding much larger doses of type II virus in a mixture with type I. Again interference was found to occur between the two types, though, under the conditions of the latter study, type I strain was not always dominant. In 1955 Sabin stated that simultaneous feeding of approximately 10 million tissue-culture 50%-infective doses (TCD50) of attenuated polioviruses of all three types to chimpanzees completely suppressed the multiplication and immunizing effect of only type III virus. In 1956 Sabin reported that when he fed approximately one million TCDSO of the naturally occurring attenuated strains (P 2149, P 712, and Glenn) simultaneously, he found no significant interference in four volunteers fed a mixture of types I and II, nor in three volunteers fed a mixture of types I and III, nor in three persons fed types II and III, nor in one person fed all three types together. He did note that, in some of the individuals fed, the appearance of antibodies was delayed and titres were in the lower range. In later studies carried out with his optimum single plaque strains, Sabin (1957) reported that the type II strain was the dominant one and that quite often, though not always, it interfered with the multiplication of the other two types when fed as a mixture. This finding prompted him to state that immunization against all three types of poliovirus by a single administration of a mixture of them is not feasible (Sabin, 1958). He therefore recommended that his three optimal strains be fed separately at intervals of thtee weeks in the order of types I, III, and II. In contrast to some of the above findings Smorodintsev et al. (1959), working with some of Sabins earlier strain variants (type I, LS of 22/12/55; type II, P 7121Oab of 5/9/56; and type III, Leon 14ab of 5/4/56), have reported a single experiment in which a trivalent vaccine containing one million TCD50 (a mixture of equal volumes of monovalent strains) was fed to eight staff members of the Institutes Virology Department* and to 29 children, 7 to 15 years old. No comments are made about the serological results obtained in the eight staff members, but the children with low or medium antibody levels before immunization showed an increase in antibodies to all three types of virus. Our interest in the possibility of using a trivalent vaccine for simultaneous immunization of humans against all three types of poliomyelitis by a single feeding was renewed about a year ago, when one of us (M. R.-G.) found that it was possible to maintain a mixed infection of types II and III polioviruses for at least 20 serial passages in monkey-kidney-tissue culture. Both types of virus were present in the stool specimen of a Minnesota child who had been fed the Lederle strains of attenuated polioviruses (Roca-Garcia, unpublished observations). This observation suggested that it might be possible to immunize against the three types of poliomyelitis by feeding the Lederle strains either in the form of capsules taken simultaneously or as a mixture in a stabilized fluid preparation, and a number of studies were initiated. Other studies in this connexion will be reported independently. This paper presents results obtained to date in feeding different dosages of a liquid, trivalent, oral poliomyelitis vaccine to approximately 550 persons-principally employees of Lederle Laboratories, Pearl River, New York, who voluntarily requested the vaccination, and, in a few cases, members of their immediate families. All these individuals live in a semi-urban area located within approximately a 15-mile radius of Pearl River, New York, chiefly Bergen County (northern New Jersey) and Rockland County (southern New York). The study was well controlled, since all persons involved

Assessment of Correlation between certain in vitro Poliovirus Markers and Monkey Neurovirulence.

The availability of proved and stable laboratory assays other than the monkey test for determining the degree of virulence of polioviruses would indeed be of great value. Search for such assays has uncovered in recent years certain in-vitro characteristics, the so-called d, t, and MS markers, which have been proposed as criteria of acceptability of poliovirus strains intended as live oral vaccines (Advisory Committee to the SurgeonGeneral, 1959). But already evidence suggests that at least the d marker is not as well correlated with monkey neurovirulence as was originally thought, and information accumulated about the MS character is as yet insufficient. Consequently, until the value of these markers is definitely established, the residual neurovirulence of a poliovirus strain for monkeys remains its most reliable marker and the most acceptable measure of its attenuation.

Cumulative Testing Experience with Consecutive Lots of Oral Poliomyelitis Vaccine

Anderson, J. R., Goudie, R. B., and Gray, K. G. (1959a). Scot. med. J., 4, 64. -(1959b). Lancet, 1, 644. Balfour, B. M., Doniach, D., and Roitt, I. M. (1959). In preparation. Beierwaltes, W. H., Dodson, V. N., and Wheeler, A. H. (1959). J. clin. Endocr., 19, 179. Belyavin, G., and Trotter, W. R. (1959). Lancet, 1, 648. Blizzard, R. M., Hamwi, G. J., Skillman, T. G., and Wheeler, W. E. (1959). New Engl. J. Med., 260, 112. Briinger, H. (1914). Mitt. Grenzgeb. Med. Chir., 28, 213. Buchanan, W. W., Anderson, J. R., Goudie, R. B., and Gray, K. G. (1958). Lancet, 2, 928. Cline, M. J., Selenkow, H. A., and Brooke, M. S. (1959). New Engl. J. Med., 260, 117. Crile, G., jun. (1948). Ann. Surg., 127, 640 and Rumsey, E. W. (1950). J. Amer. med. Ass., 142, 458. Donia:h, D., and Hudson, R. V. (1957). Brit. med. J., 1, 672. (1(959). Proc. roy. Soc. Med., 52, 178. and Roitt, I. M. (1957). J. clin. Endocr., 17, 1293. and Hudson, R. V. (1959). Rev. Maladies du Foie. In press. Druez, G., Hainaut, J., Parmentier, R., and Musin, L. (1958). Acta clin. belg., 13, 280. Eason, J. (1928). Edinb. med. J., 35, Trans. med.-chir. Soc. Edinb., p. 169. Eylan, E., Zmucky, R., and Sheba, C. (1957). Lancet, 1, 1062. Felix-Davies, D. (1958). Ibid., 1, 880. Goudie, R. B., Anderson, J. R., and Gray, K. G. (1959). J. Path. Bact., 77, 389. Clark, D. H., Murray, I. P. C., and McNicol, G. P. (1957). Lancet, 2, 976. Greene, R. (1953). Memoirs Soc. Endocr., 1, 16. Hudson, R. V. (1959). Irish J. med. Sci., p. 149. Joplin, G. F., and Fraser, R. (1959). Proc. roy. Soc. Med., 52, 177. Lee, J. M., and Schneider, H. A. (1957). Proc. 6th int. Congr. Neurol. Brussels, p. 22. McConahey, W. M., and Keating, F. R. (1951). J. clin. Endocr., 11, 1116. Mackay, I. R., and Larkin, Lois (1958). Aust. Annz. Med., 7, 251. Mahaux, J. (1959). Rapports de la Se reunion des endocrinologistes de langue frangaise, Paris. -and Pirart, J. (1959). Acta clin. belg., 14, 59. Morgans, M. E., and Trotter, W. R. (1957). Lancet, 1, 553. (1958). Ibid., 1, 607. Owen, C. A. (1958). J. clin. Endocr., 18, 1015. Owen, S G., and Smart, G. A. (1958). Lancet, 2, 1034. Pasteur, W. (1900). Trans. clin. Soc. Lond., 33, 189. Pulvertaft, R. J. V., Doniach, D., Roitt, I. M., and Hudson, R. V. (1959). Lancet, 2, 214. Robertson, J. D., and Reid, D. D. (1952). Ibid., 1, 940. Roitt, I. M., Campbell, P. N., and Doniach, D. (1958). Biochem. J., 69, 248. and Doniach, D. (1958). Lancet, 2, 1027. -(1959). In Henry Ford Symposium on Mechanisms of Hypersensitivity, p. 325., Little, Brown, Boston. Campbell, P. N., and Hudson, R. V. (1956). Lancet, 2, 820. Trotter, W. R., Belyavin, G., and Waddams, A. (1957). Proc. roy. Soc. Med., 50, 961. Volpe, R., and Johnston, McW. (1957). Canad. med. Ass. J., 77, 297. Waksman, B. (1959). Int. Arch. Allergy, Suppl. to vol. 14. Werner, S. C., and Spooner, M. (1955). Bull. N.Y. Acad. Med., 31, 137. White, R. G. (1957). Proc. roy. Soc. Med., 50, 953. Whitesell, F. B., and Black, B. M. (1949). J. clin. Endocr., 9, 1202. Witebsky, E. (1959). In Seelisberg Symposium on Immunopathology, p. 182. Benno Schwabe, Basel.

Failure of Phenosulfazole (Darvisul) in Treating Experimental Viral Infections

Conclusion Phenosulfazole (Darvisul) showed no beneficial effect in the treatment of mice infected with the Columbia SK virus and other neurotropic viruses, including a rodent adapted strain of poliomyelitis (MEF-1 strain). The lack of therapeutic effectiveness of the drug was also observed in monkeys infected intranasally with the Brunhilde strain of poliomyelitis virus. In other viral and rickettsia1 infections of mice and of developing chick embryos treatment with pheno-sulfazole was of no therapeutic value, with the possible exception of psittacosis in which a slight inhibition of growth in the developing chick embryos was observed. However, even in the latter case the effectiveness of phenosulfazole therapy was of much lower magnitude than that observed with other sulfonamides,4-6 or antibiotics.7