Cancer of the gastro-intestinal tract accounts for 54 per cent of the total mortality from neoplastic disease in males (1)-an incidence which warrants particularly intensive study of the disorder. The associated metabolic abnormalities are especially important, not only because through them some clue as to etiology may be found, but also to provide information by which the mortality from difficult operative or radiological procedures may be reduced.The results of numerous clinical and experimental studies suggest that dietary factors are important in the maintenance of a normal gastrointestinal mucous membrane (2, 3). Hence, close attention has been given, in the Memorial Hospital, to the study of the nutritional status of patients with intestinal neoplasms. The results of the measurement of levels of vitamin A in the plasma, herein reported, are considered to be of special interest. MATERIALNormal individuals were studied to establish the normal levels of vitamin A, carotene and thiamin in the blood, as well as of riboflavin in the urine. Adult laboratory technicians, house physicians, nurses, and normal young men, all apparently in good health and on adequate diets, were used as subjects.The clinical material upon which this report is based includes six different groups of patients. The first is composed of 51 patients with cancer of the gastro-intestinal tract, selected from 62 consecutive admissions to the gastric and rectal services of the Memorial Hospital. Eleven of the 62 cases were discarded because they were febrile or had received medication which might provide misleading findings.
The methods usually employed at present to ascertain the existence of thiamin deficiency in man are based upon measurements of the amounts of the vitamin in the urine before and after its oral or parenteral administration (1, 2). Evidence is available, however, to indicate that only a fraction of the thiamin ingested in the normal diet is excreted unchanged (3, 4), and hence it is possible that the amount in the urine does not represent the true status of deficiency or sufficiency of the vitamin in the body as a whole. Measurement of the levels of circulating thiamin clearly is preferable, but insufficient information has been available hitherto concerning its distribution between the various constituents of the blood. Due to this fact, the presence of anemia, dehydration, or marked leukocytosis might provide misleading findings if only the levels in whole blood were employed.No method has been at hand for the measurement of the minute amounts of thiamin contained in the cellular elements since neither the technique of Melnick (5), nor the thiochrome method of Hennessy (6) are sensitive enough to be used for this purpose. It has been possible, however, so to adapt the ultramicro-technique of Atkin, Schultz and Frey (7) that thiamin can be determined in either leukocytes or erythrocytes. The method was chosen, not only because of its sensitivity and accuracy, but also because it made possible the measurement of both thiamin and the pyrimidines capable of accelerating yeast fermentation (PAYF) .8From the similarity between the chemical struc- 4). They found that the parenteral administration of 100 mgm. of thiamin resulted in an increased urinary excretion of pyrimidine and concluded that in the normal individual pyrimidine is derived from thiamin. This communication deals with (1) a method for the measurement of the thiamin and the PAYF content of blood cells and urine; (2) the amounts of thiamin and the PAYF compound in leukocytes and platelets, erythrocytes, and the urine of normal individuals; and (3) a study of the metabolism of thiamin by the normal human being. METHODThe techniques used for the quantitative determination of total thiamin and of the pyrimidine compound in the blood and urine are adaptations of the fermentation method of Schultz, Atkin and Frey (7,8). They depend upon the principle that within certain limits both thiamin and PAYF cause a measurable increase in the rate of alcoholic fermentation by yeast of a suitable sugarsalt-buffer mixture.In this communication the term "total thiamin" is employed to include all those substances capable of stimulating fermentation by yeast under the conditions of the experimental procedure.A. Determination of the total thiamin and PAYF in blood cellsTo obtain leukocytes and platelets, 25 ml. of oxalated blood are allowed to settle at room temperature for from 161
In a previous communication' the fact Gas demonstrated that 85% of patients with cancer of the gastrointestinal tract had abnormally low plasma levels of vitamin A. In more than half of the patients this abnormality could not be explained by a deficient ingestion or malabsorption of the vitamin. Since there is considerable evidence to show that the liver is intimately concerned with the storage, distribution, and formation of vitamin A,z it was thought that the low plasma levels of the vitamin probably reflected, in thosc patients, hepatic insufficiency. Subsequently, it was demonstrated that a considerable degree of hepatic dysfunction did exist in patients with gastrointestinal ~a n c e r ,~ but whether that dysfunction had resulted in a decreased capacity of the liver to store vitamin A or to distribute the vitamin properly, still remained unknown.Recently an opportunity was presented to measure in patients with gastrointestinal cancer the vitamin A content of samples of liver removed at the time of laparotomy, and thus to ascertain whether or not the low levels of vitamin A in the plasma of the patients studied were due to decreased hepatic stores or to some other cause.Clinica-l Material. The clinical material studied comprised 2 groups of individuals. The first consisted of 21 adults who wereused as controls, 14 males and 7 females. Of the 21 individuals, death was due to skull fracture in 16, coronary occlusion in 3, gunshot in 1, and stab wound in 1. All these individuals were autopsied and sections of liver were obtained within 24 hours after death. Other than the immediate cause of death no gross pathological changes were noted.* The authors gratefully acknowledge the assistance given by Standard Brands, t Finney-Howell Fellow.
In a previous communication (1) methods were presented for the measurement, in blood cells and urine, of thiamin and of the pyrimidine accelerator of yeast fermentation (PAYF), as well as the results of the application of these methods in a study of the metabolism of the vitamin by the leukocytes and platelets of human beings. It was pointed out that, since thiamin and the PAYF, a probable metabolite of the vitamin, were distributed unequally among the cellular elements of blood, and since the proportions of these elements vary, a comparison of the levels of those substances in the whole blood of normal subjects with those of patients with leukemia would not be valid.The concentrations of free thiamin (2) and of cocarboxylase (3) in the whole blood of leukemic individuals have been reported to be elevated occasionally, even though no corrections were made for the abnormal red or white cell counts. Furthermore, Butler and Cushman have shown that leukemic white cells have an abnormally high content of ascorbic acid (4). Hence, it was deemed important to determine whether or not leukemic white cells contain abnormally high concentrations of thiamin.The study here reported was undertaken, therefore, (1) to compare, by the method described, the levels of thiamin and of the PAYF in unit volumes of leukemic and normal leukocytes and platelets, erythrocytes, and urine, and (2) to compare the metabolism of the vitamin in normal individuals with that in patients with leukemia.
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