Dennis M. Donohue

The Use of Chromium as a Red‐cell Tag*

AN effective red-cell tag has important uses in the practice of medicine and in clinical investigation. Such a tag may be employed to measure the circulating red-cell mass and thereby the blood volume, to study circulatory dynamics, to indicate the rate of destruction of a population of transfused cells, and to determine the site of red-cell destruction. A number of substances, each with its own advantages, has been employed. This report deals with the use of 51Cr in the determination of red-cell volume, the measurement of viability of normal, abnormal and stored red cells, and the tissue localization of 51Cr after red-cell breakdown. Results of both human studies and animal experiments are included to delineate the advantages and limitations of this isotope as a red-cell tag.

Erythrokinetics: quantitative measurements of red cell production and destruction in normal subjects and patients with anemia.

To study erythropoiesis and anemia, one must have a firm foundation of indices that accurately measure red blood cell production and destruction. This paper, authored by hematology legends Arno G. Motulsky and Clement A. Finch, provides that foundation. Using methods that would not be approved in todays environment, the authors studied a cohort of normal healthy patients and an equal number of patients with different forms of anemia. The results confirm a reciprocal model of red cell production and destruction, show that anemia can be the result of either underproduction (a regenerative anemia or ineffective erythropoiesis) or increased destruction, and define parameters for distinguishing these 2 possibilities that are still widely used today.

Quantitative Measurement of Hematopoietic Cells of the Marrow

In recent years with the availability of more accurate methods, attention has been directed towards the quantitative aspects of both erythropoiesis and leukopoiesis. It has been difficult to measure the precursor cells in the marrow, and their exact number still remains in question. Previous estimates of total marrow cells have utilized three general methods of approach: a) direct measurements of volume and cellularity of marrow in animals (1); b) calculations based on an assumed maturation time and on the known life span of the erythrocyte (2); and c) calculation based on the frequency and the estimated duration of marrow mitosis (3). The first of these methods imposes formidable technical difficulties and cannot be performed in man; the other two involve assumptions not subject to validation. The present report concerns a direct technique in which the various procedures and assumptions employed are scrutinized. The method employs the eythroid tag Fe59 to relate the cells in an aliquot of marrow to the total marrow, as originally proposed by Suit (4).

ERYTHROCYTE PRESERVATION. VI. THE STORAGE OF BLOOD WITH PURINE NUCLEOSIDES

The addition of adenosine to stored blood results in a chemical restoration of deteriorated erythrocytes and sustains their viability during continued storage (1, 2). This phenomenon has been referred to as the in vitro reversibility of a biochemical lesion of storage. Apart from the implications of this reaction in red cell metabolism (3), it seemed of importance to evaluate the effect of adenosine in the preservation of blood. The present study indicates that adenosine and some related purine nucleosides retard the onset of the storage lesion and extend significantly the period of viability of stored blood. The effective concentration of these supplements, as well as their potential toxicity, is discussed.

Levels of dihydrofolate reductase and the formate-activating enzyme activities in guinea pig tissues before and after amethopterin administration☆

Abstract Formate-activating enzyme activity and dihydrofolate reductase activity have been measured in the tissues of the guinea pig; the highest levels of these enzyme activities occur in the liver and kidney. After the administration of amethopterin, the liver and kidney retained this drug for at least 14 days, while bone marrow, small intestine, and spleen contained amounts not detectable by bioassay methods (less than 1 × 10−7 μmoles/mg protein in lysates). Dihydrofolate reductase activity in liver, kidney, spleen, bone marrow, and small intestine did not increase after amethopterin administration (5 mg/kg body weight given subcutaneously); however, a two- to four-fold increase was observed in circulating erythrocytes 7 to 21 days after the administration of the drug. Dietary deficiency of folate did not produce significant changes in the dihydrofolate reductase activity of liver, bone marrow, erythrocytes, or leukocytes of guinea pigs. The erythrocytes and leukocytes of various animal species have measurable levels of dihydrofolate reductase activity, except the erythrocytes of the dog and the red and white cells of man.

APLASTIC ANAEMIA IN PREGNANCY

IRON deficiency anaemia, megaloblastic anaemia, and hypoplastic anaemia comprise the three common types of true anaemia described as occurring in pregnancy. Even though the coexistence of the anaemia and the pregnancy is frequent, no cause and effect relationship has ever been definitely proved. Any specific anaemia may complicate or be complicated by pregnancy. Again, the effect of the pregnancy in all instances is poorly defined. One of the most serious of this group of anaemias is primary refractory or aplastic anaemia. Although the term “aplastic anaemia” has gained wide acceptance in clinical medicine, it is not precise nor is it really descriptive of any specific feature since anaemia is only one phase of the generalized depression of formed blood elements. The designation is usually applied to cases of severe refractory pancytopenia where gross evidence of increased blood destruction is absent and infiltrative disease of the marrow cannot be demonstrated. The characteristic haematological findings are anaemia, leukopenia and thrombocytopenia. Definite evidence of decreased marrow production of all formed elements of the blood is necessary to support the diagnosis, although this is not invariably confirmed by marrow examination, even in cases with specific aetiology. Such bone marrow depression may be the result of exogenous or endogenous toxic origin. The mechanisms involved in the marrow depression are speculative. The aetiology insofar as a specific causal agent is often obscure and, where such agents are suspect, the aetiological relationship is difficult to establish. Aplastic anaemia is a rare complication of pregnancy. It is noteworthy that the first reported case of aplastic anaemia, described by Ehrlich in 1882, occurred in a young pregnant woman (1888). Although he did not apply any name to the condition he described, he did conclude that the underlying pathology was depression of bone marrow function. Only scattered subsequent reports of cases of pregnancy complicated by aplastic anaemia have appeared in the literature. In 1942 Hurwitt and Field presented a case which terminated fatally. They concluded from the review that pregnancy might play an “etiologic or conditioning” role in the occurrence of this condition in pregnancy and felt that immediate interruption of pregnancy was mandatory. More recently, Lachman, Lund and VintherPaulsen (1954) after a search of the world literature were able to collect twelve cases in which they felt that the diagnosis of aplastic anaemia associated with pregnancy was either “most probable or certain” and to which they added one of their own. Review of the limited data presented by some of these cases leaves the diagnosis in many instances open to question.

An animal assay method for the measurement of post-transfusion survival of stored blood.

A method is described of measuring post transfusion survival of stored blood in the rabbit. Results with blood stored in acid‐citrate‐dextrose and with an experimental preservative have been shown to be comparable to those in man. The harmful effects of plastic bags were also detected by rabbit testing. On the basis of these correlated studies, the rabbit assay is suggested as a suitable method for determination of the viability of stored blood.