IX. EFFECTS OF DEFICIENCY 213 



parable to tlu> noiinal rate ol" cxcivtion.''-*^' -''"' These ol)scr\'atioii>s may l)e 

 interpreted as evidence of a defect in PGA metabolism, characteristic of 

 pernicious anemia, which is corrected by supplying a constituent of liver 

 extract, presumably \itamin Bij . 



Is there reason to suppose that any degree of PGA deficiency may be 

 present in pernicious anemia patients who have been receiving, by injection, 

 adequate amt)unts of li\'er extract or \'itamin Bi> for a considerable period 

 of time and whose diets are good? In other words, do these therapeutic 

 agents completely counteract the factors responsible for impaired utiliza- 

 tion of dietary PGA in untreated pernicious anemia? Lack of information 

 prevents categorical replies to these questions. It is true that liver extracts 

 or vitamin B12 constitute apparently complete therapy for pernicious anemia 

 as measured by usual clinical and hematologic criteria. On the other hand, 

 the fact that the dietary supply of PGA is almost never large, and the 

 persistent changes in the alimentary tract characteristic of pernicious ane- 

 mia, including achlorhydria, altered upper intestinal flora, and sometimes 

 motility disturbances, provide grounds for belie\'ing that absorption of 

 food PGA may not be optimal in every case. This conclusion is supported 

 by the impression of some clinicians, including the writer, that supplement- 

 ing adequate livcv extract or vitamin B12 therapy with PGA in daily oral 

 doses of 5 mg. may lead to an increase in sense of well-being and to slight 

 rises in eiythrocj^te values.-*^* However, evidence to the contrary has also 

 been presented.-"' 



In cases of macrocj'^tic anemia associated with chronic partial intestinal 

 obstruction, or anastomoses of the intestine with diminished absorptive 

 surface and possible blind loops, there may be clear evidence of further 

 improvement following administration of PGA after initial response to B12 

 therapy.210 



7. Induced PGA Deficiency in Man 



The administration of PGA antagonists for therapeutic purposes would 

 appear to provide a means of observing the manifestations of pure PGA 

 deficiency under controlled conditions. However, although some clinical 

 entities which respond to PGA therapy bear certain resemblances to the 

 clinical and hematologic picture associated with antagonist administration, 

 there is no close similarity l)etween the two types of deficiency. The ex- 

 planation of these differences undoubtedly lies, in part, in the rapidity with 

 which the effects of such antagonists as 4-aminopteroylglutamic acid 



20S F. H. Bethell, W'Iscon.sin Med. J. 51, 1082 (1952). 

 "« R. B. Chodos and J. F. Ross, Blood 6, 1213 (1951). 



*'» F. H. Bethell, M. E. Swendseid, S. Miller, and A. A. Cintron-Rivcra, Ann. Internal 

 Med.Z5, 518 (1951). 



