One of the most useful methods available for the quantitative measurement of hemolytic rates in clinical subjects and for the evaluation of red cell viability after storage is based on the survival of transfused erythrocytes. Access to such data, however, has been restricted because of limitations in the methods hithertofore available for measuring red cell survival in vivo.The differential agglutination method of counting donor cells, the procedure most commonly employed, has limitations in that large transfusions are required;* the donor blood must be devoid of all antigenic isoagglutinins which are not likewise possessed by the recipient; the recipient's cells must contain agglutinogen A or B or M or a combination of the three agglutinogens which is not contained in the donor blood; and, finally, this method excludes the use of autotransfusion, which would eliminate the risk of transmission of hemologous serum jaundice.The labelling of donor cells with radioactive iron (Fe55) permits the conduct of survival studies on a short term basis (1-3) but re-utilization of radioactive iron released from hemolyzed donor cells and the subsequent incorporation of this label in the recipient's red cells preclude its use in studies extending for periods longer than 24 to 48 hours.

1. Combinations of effective agents produce at least an additive increase in complete remission rates over that which can be achieved when the agents are used individually. 2. Patients who do not achieve complete remission with initial treatment have a significantly shorter survival. 3. Alternating MTX and 6-MP at 28-day intervals during remission does not prolong the duration of remission over that of combined concurrent 6-MP and MTX. 4. The administration of folic acid antagonists intrathecally at 28-day intervals during antimetabolite maintained remission did not prolong the duration of remission. Meningeal leukemia, however, occurred significantly less frequently in these patients. 5. The duration of combined 6-MP and MTX maintained remission is not greater than that of 6-MP maintained remission. 6. The toxicity of 6-MP and MTX in combination in patients in remission is additive. The above conclusions were drawn from this comparative study of combinations of chemotherapeutic agents in children with acute lymphocytic leukemia.

The efficacy of three therapeutic programs for acute leukemia were compared. These programs included (1) Methotrexate (Phase I) followed by 6-mercaptopurine (Phase II); (2) 6-mercaptopurine (Phase I) followed by Methotrexate (Phase II); and (3) Combination Therapy, i.e., 6-mercaptopurine given in combination with Methotrexate. In children with acute lymphocytic leukemia the remission rate was 59 per cent for combination therapy, 47 per cent for 6-mercaptopurine, and 29 per cent for Methotrexate. The better remission rate for combination therapy is consistent with that predicted if it is assumed that 6-mercaptopurine and Methotrexate act independently. The median duration of complete remissions for the three treatments was not different (4 to 5 months). However, long lasting remissions were more frequent in patients receiving combination therapy. The median survival from the onset of therapy to death was 9 months. There were no differences between the three treatment programs as regards survival. In adults the remission rate was 15 per cent for combination therapy, 21 per cent for 6-mercaptopurine and 7 per cent for Methotrexate. As regards survival in adults, early deaths were more common in patients who received MTX as initial therapy, whereas after 5 months survival was somewhat better in those patients receiving combination therapy. In both children and adults there was no evidence that prior treatment with one of the antimetabolites altered response to the other antimetabolite. This result differs from those in animal models, and its effect on our concept of the mechanism of resistance is discussed. Responsiveness to the second course of antimetabolite therapy (Phase II) was as good as that to the first course of treatment. This was true for the remission rate, remission duration, and even for survival when appropriate corrections were made. Thus, responsiveness to drug therapy is maintained as the disease progresses temporally. It may be concluded therefore that new agents can be effectively studied in patients with "late" disease. Responsiveness to Phase II therapy was independent of responsiveness to Phase I. The most common and severe toxic manifestations related to the bone marrow and gastrointestinal tract. There were no major differences quantitatively in the toxicity for the three treatment programs in children in spite of the fact that the drugs were given in full dosage in the combination program. Oral ulcers and a generalized erythematous rash occurred significantly more frequently in patients receiving Methotrexate. Jaundice was significantly more frequent in adults and in patients receiving 6-MP.

Eight to 25 per cent of intravenously injected Na2Cr51O4 binds firmly with erythrocytes of the chicken, pigeon and duck. Calculation of the maximum life span of these avian red cells was made from the disappearance time of circulating radioactivity. The maximum life span of the chicken erythrocyte was found to be 35 days, of the pigeon erythrocyte 35-45 days, and the duck erythrocyte 42 days. Comparing the life span of avian erythrocytes with those of other animal species, the rate of red cell turnover in the mammals, birds, and reptile (turtle) was found to correlate directly with basal heat production per kilogram body weight. Using erythrocytes tagged with Na2Cr51O4 in vitro, the total red blood cell volume was found to be 17-24 ml. per Kg. body weight in the rooster, 9-12 ml. per Kg. in the hen, 25-31 ml. per Kg. in the duck, and 31-34 ml. per Kg. in the pigeon. These values proved somewhat lower than those obtained from the indirect estimates of red cell volume, using plasma volume figures and periphera blood hematocrit.

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397fied cholesterol, and showed a diminution in the further esterification of cholesterol upon incubation, than the pre-adsorbed plasma. Although the meaning of this is unclear at this time, the apparent removal of some cho-present, affording further evidence of its similarity to or identity with post-heparin factor. Plasma cholesterol ester and cholesterol esterase is also apparently decreased in the post-adsorptive sample. lesterol esterase activity by tricalcium phosphate gel, a known heparin and prothrombin adsorbent, raises the possibility of some relationship between these substances. Unfortunately determinations of total cholesterol before and after adsorption were not done.Summary. Tricalcium phosphate gel removes all or the major portion of post-heparin clearing factor activity from plasma but does not decrease the activity of human pancreatic lipase. It is therefore a useful agent in identifying heparin lipoprotein lipase. Endogenous plasma lipolytic activity is completely or nearly completely removed after gel adsorption in almost all subjects in whom it is 1. Nilsson, I. M., and Wenckert, A., Acta M e d .2. Nikkila, E. A., and Pesola, R., Acta Chenz.3. Engelberg, H., A m .

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