G. H. Whipple

Radioiron Excretion by the Skin and Kidney of Dogs

Summary Following intravenous or oral administration of single doses of radioiron to dogs, little or no radioiron can be washed from the skin and hair, thus indicating that no significant amounts of iron are excreted through the skin in 1 to 7 days.

Effects of inflammation (turpentine abscess) on iron absorption.

Summary The radioactive isotope of iron shows that iron absorption from the gastrointestinal tract of the dog is impaired by the presence of a sterile abscess in subcutaneous tissue.

BLOOD REGENERATION IN SEVERE ANEMIA

A liver extract No. 343, N.N.R. known to be fully potent in pernicious anemia shows but 10 to 20 per cent of the potency of whole liver feeding in severe continuous secondary anemia due to bleeding in dogs. There are wide individual variations which are not noted with whole liver feeding. Supplementing this liver extract with whole bile does not modify the reaction. Supplementing this liver extract with liver ash or apricot ash shows the sum of the two expected feeding reactions. When we supplement this liver extract with small amounts of whole liver (50 to 100 gm.) we may observe hemoglobin and red cell production in excess of the sum of the expected separate reactions. Whether the liver extract increases the potency of the whole liver feeding or vice versa, it suggests similar possibilities in various human secondary anemias. Liver and kidney fractions of varied types deserve much study to ascertain their effect upon widely divergent types of human anemias.

Blood Regeneration in Severe Experimental Anemia. Influence of Inorganic Elements.

We have recently reported in these Proceedings 1 a rather startling reaction to the inorganic ash of liver, kidney and apricots. This ash incorporated in a standard anemia diet 2 given to dogs kept constantly anemic by bleeding will effect a notable increase in blood hemoglobin production above control periods. This may amount to 30 to 50 gm. hemoglobin per 2-week period. We have made various analyses of these ashes and from such data have made various synthetic ash compounds, but such synthetic mixtures so far have not proved to be potent. These experimental data will be published in due time. We wish to report briefly our findings when these dogs are given various simple salts added to the standard ration. It is apparent that in the doses given iron is more potent than either copper or zinc. These observations dealing with copper salts are of considerable interest when contrasted with the recent reports of Hart, S teen-bock, Waddell and Elvehjem, 3 who report a distinctly favorable reaction to copper salts and a negative reaction to iron salts. These distinct differences between our experiments and those of the Wisconsin investigators must be explained on the basis of animal differences or anemia differences. They use rats made anemic by faulty diets and we use dogs made anemic by constant bleeding to a standard anemia level. Early in our anemia experiments (1923) Robscheit-Robbins and Whipple observed that an excess of a salt mixture (McCollum and Simmonds 4 minus iron) caused a distinct increase in hemoglobin production over control periods. The control bread ration contained these same salts but a large excess added would cause an increased hemoglobin output. It could not be that these salts were incorporated in the hemoglobin molecule, so this reaction might be called “catalytic.” We feel that these large doses of iron reported here, which are probably 10 times or more in excess of the body needs, cause a similar salt reaction of “catalytic” nature. There must be a readjustment of the internal protein metabolism so that much more hemoglobin is produced, there being an excess of iron at all times.

Blood Regeneration in Severe Anemia--Influence of Inorganic Ash of Liver, Kidney and Apricots.

In some of the early anemia work at the University of California Robscheit-Robbins and Whipple observed an unusually favorable reaction to the feeding of dried peaches in short term anemia experiments in dogs. Repitition of this apricot and peach diet in severe anemia in dogs shows clearly that the original observations were correct. 1 The addition of 200 gm. of this cooked fruit to the daily standard diet may cause an average output of 40 to 45 gm. hemoglobin per 2-week period over and above the standard control period. All of this work indicated clearly that the inorganic elements of this fruit should be tested. We have recently reported2,3 experiments dealing with various fractions of extracts of beef liver. It is to be kept clearly in mind that our experiments deal with the simplest form of anemia, due to withdrawal of blood. One must be cautious in comparing simple anemias of this sort with fasting or nutritional anemias. Different animals may react quite differently to various diets—for example, the herbivora may utilize the chlorophyll of green vegetables to build hemoglobin whereas dogs cannot do so. 4 We are greatly interested in a recent preliminary report of Waddell, Elvehjem, Steenbock and Hart 5 which indicates that the ash of beef liver has a favorable effect upon certain nutritional anemia of rats. It is probable that some differences will come out as we learn more about this nutritional anemia as compared with simple anemia due to hemorrhage. The various samples of inorganic ash were prepared in the following manner: Fresh beef liver, pig kidney, or dried apricots are weighed and placed in a large fire brick container. Free flames from several blow-torches are played on this material until it is redwed to a black carbon mass.,4t this point a stream of oxygen is directed into the hot material burning it down to a white, gray, or bluish brown, glassy ash.