IX. EFFKCTS OF DEFICIENCY 205 



.\.ltlu)Uji;h many dI the patients treated hy Wills were pregnant, and so do 

 not fall within the classiUeation of luicomplicated nutritional macrocytic 

 anemia, it seems proper to regard lier cases as primarily attributal)le to 

 dietary lack, and to assign to her priority in demonstrating a clear dis- 

 tinction between the anti-pernicious anemia factor of liver and a hemo- 

 poietic factor which we now recognize as probably PGA. It must, however, 

 l)e borne in mind that nutritional macrocytic anemia varies greatly through- 

 out the world and that the isolated instances of the condition seen in tem- 

 perate zones are (luite different in associated clinical manifestations and 

 probably in pathogenesis from endemic deficiency states. IMoreover, in most 

 of the instances reported, no attempt has been made to establish the pri- 

 mary or major deficiency, whether PGA or vitamin B12 . 



2. Idiopathic Rffractory Megaloblastic Anemia or 

 Achrestic Anemia 



These terms, coined, respectively, by Davis and Davidson"'^ and Israels 

 and Wilkinson, '^2 have been applied to a form of macrocytic anemia with 

 megaloblastic bone marrow for which no dietary or other etiologic explana- 

 tion was discoverable and which failed to respond to purified extracts of 

 li\er. The condition has not been generally recognized in the United States 

 or on the European continent, and its occurrence in Great Britain may 

 possibly be attributed to unknown factors affecting nutrition if not to 

 direct dietary deficiency. The pathogenesis of this type of anemia is prob- 

 ably closely related to the macrocytic anemia of pregnancy on the one 

 hand, and to that associated with idiopathic steatorrhea or the sprue syn- 

 drome on the other. As a rule, such patients respond favorably to the ad- 

 ministration of PGA although they may later relapse while continuing 

 with the medication. In some instances, liver extract injections, although 

 initially ineffective, were later successful in maintaining remission. ^®^ 



3. Megaloblastic Anemia of Pregnancy and the Puerperium 



Mention has already been made of the cases of tropical macrocytic anemia 

 complicated by pregnancy observed by Wills and her associates. In temper- 

 ate climates such anemia, manifested in severe degree, is uncommon, al- 

 though a comparatively high incidence of mild macrocytic anemia has been 

 observed in pregnant women whose diets were habituall}'^ low in protein of 

 good quality and presumably also in PGA and vitamin B12 .'^^' ^®* Yet 

 opinion is divided on the question of the importance of dietary inadequacy 



'" L. J. Davis and L. S. P. Davidson, Quart J. Med. 13, 53 (1944). 



'« M. C. Israels and J. F. Wilkinson, Quart. J. Med. 5, 69 (1936). 



'63 R. H. Girdwood, Edinburgh Med. J. 58, 309 (1951). 



'" F. H. Bethel), /. Am. Med. A.ssoc. 107, 364 (1936). 



'" F. H. Bethell, E. Blecha, and J. H. Van Sant, J. Ani. Dielel. Assoc. 19, 165 (1943). 



