Megaloblastosis has been produced in young guinea pigs by feeding them purified diets deficient its pteroylglutamic acid (PGA) or vitamin B12 or both. The withholding of ascorbic acid from the diet did not produce megaloblastosis but it greatly enhanced its development when PGA was also withheld. Spontaneous remission took place in several instances.

The possible role of growth of the animal and changes in the bacterial flora of the gastrointestinal tract has been discussed. Bacteriologic studies appeared to indicate a possible interrelationship between the occurrence of Escherichia coli in the stools of guinea pigs consuming deficient diets and the development of megaloblastosis. Diarrhea and infections are considered important in the pathogenesis of megaloblastic anemia but infections were not observed in animals of the present study. However, diarrhea was a prominent feature and appeared to be a factor associated with megaloblastosis.

Anemia was usually present in association with megaloblastosis; however, megaloblastosis of a mild degree appearing in some of the animals fed the diets deficient in PGA or vitamin B12 was not accompanied by anemia. When ascorbic acid was withheld in addition, then anemia always developed.

A dimorphic picture of macrocytosis and microcytosis was found most commonly in the peripheral blood of animals with megaloblastosis. This has been explained on the basis of regenerative macrocytosis or as a disturbance of the maturation of erythrocytes in such deficiencies.

Data obtained from peripheral blood are not a reliable indicator of megaloblastosis, nor is the clinical condition of the animal indicative of the pathologic state.

One animal which had been fed a diet deficient in vitamin B12 and PGA and which showed megaloblasts in its bone marrow was given injections of vitamin B12. The megaloblastosis was corrected but the animal died on the sixteenth day of treatment.

Two animals fed diets deficient in PGA and ascorbic acid were subsequently given injections of PGA and ascorbic acid. The results demonstrated that administration of ascorbic acid alone did not interrupt the development of severe megaloblastosis in the continuing absence of PGA. When PGA was given, reticuocytosis then ensued and there was a reversal of megaloblastic erythropoiesis.

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