XI. PATHOLOGY 490 



origin. It has been shown that indol has a hemolytic effect in dogs main- 

 tained on a diet deficient in B vitamins but not in dogs on an adecjuate 

 diet.''- The report of the therapeutics efficacy of aureomycin in pernicious 

 anemia"** has been confirmed by the writer and his associates, who have 

 also obtained responses to the administration of terramycin and chloram- 

 phenicol. The effects of these agents are slow and prolonged and may be 

 enhanced by the supplemental oral administration of B12 in small doses 

 such as 2 to 5 7 daily. 



The action of antibiotics in pernicious anemia may be due either to the 

 elimination of organisms which require B12 for growth and so deprive the 

 host of the vitamin or to the removal of bacteria which elaborate the pos- 

 tulated injurious substance(s). The latter explanation has some indirect 

 evidence in its support, since the mechanism of injury associated with such 

 bacterial products may include both hemolysis of circulating red cells and 

 inhibition of normal erythropoiesis. A hemolytic effect of plasma from un- 

 treated pernicious anemia patients has been reported by De Gowin and 

 associates,"*^ and reference has been made to the existence of an erythro- 

 I)oietic inhibitor in the serum of such patients. In the present state of our 

 knowledge, it seems probable that whatever injurious influences may be 

 present in pernicious anemia are counteracted by B12 and that the action 

 of antibiotics, in inducing remission, is concerned chiefly with making B12 

 available to the organism. It should be mentioned, however, that an alter- 

 native explanation of the effect of antibiotics in pernicious anemia has been 

 suggested as a possibility by Lichtman and associates*' and is favored by 

 Welch and Heinle.*^ In their view, such drugs as aureomycin probably in- 

 duce hemopoietic responses by producing alterations in intestinal flora with 

 the establishment of species "which synthesize and release significant 

 amounts of readily absorbable PGA or related compounds. Welch and 

 Heinle cite the observations of Foy and associates*^ on the effectiveness of 

 penicillin in a case of megaloblastic anemia of pregnancy as evidence in 

 support of their contention that antibiotics operate by making PGA rather 

 than B12 available. There is, however, no evidence that PGA is produced 

 in greater abundance or is absorbed more efficiently in the alimentary tract 

 of patients who are receiving antibiotics. 



In the foregoing discussion B12 has been identified as the dietary ex- 

 trinsic factor of Castle as well as the substance in liver which is chiefly, if 



'2 C. P. Rhoads, W. H. Barker, and D. K. Miller, /. Exptl. Med. 67, 299 (1938). 

 "H. Lichtman, V. Ginsberg, and J. Watson, Proc. Soc. Exptl. Biol. Med. 74, 884 



(1950). 

 ** E. L. De Gowin, H. K. Hamilton, R. F. Sheets, C. D. Janney, and J. A. Ellis, /. 



Lab. Clin. Med. 40, 790 (1952). 

 '' A. D. Welch and R. W. Heinle, Pharm. Revs. 3, 345 (1951). 

 "« H. Foy, A. Kondi, and A. Hargreaves, Brit. Med. J. I, 1108 (1951). 



