cheese. The results obtained on analysis of the urine during this period are given in Table II. The notably increased elimination of the Bence-Jones albumose during this period of high protein feeding indicated that the formation of the pathological metabolism product is indeed greatly affected by the protein contents of the diet. During the first DATE, JAN. Volume, cc.. Sp. gr.. Total N, gm. gm.. Ammonia N, gm. Creatinine N, gm. Creatine N, gm.. Uric acid N, gm. Rest N, gm. Protein.. TABLE II. 25-26 26-27 27-28 28-29 29-30 30-31 31FEB. 1 FEB. 1-2 1140 1570 1190 1310 1600 1150 1050 1300 3.70 5.45 4.39 6.33 5.54 6.10 6.04 5.00 6.57 8.72 9.40 11.50 13.10 15.62 15.71 16.60 5.92 7.85 8.70 10.49 12.22 14.65 14.75 15.80 Ammonia.. Creatinine. Creatine. period we found from 1.76 to 2.8 grams of albumose in urines containing from 5 to 8.5 grams of total nitrogen, while in the second period the albumose elimination rose to 6.5 grams and the total nitrogen to 16 grams. Considered more in detail it is, however, equally clear that there is nothing like a definite or constant relationship between the total nitrogen and the albumose in the urine. The increased albumose elimination during the period of high protein feeding might therefore have been a mere coincidence. THE JOURNAL OF BIOLOGICAL CHEMISTRY, VOL. XVIII, NO. 2 The patient expressed himself as feeling unusually well during the period covered by the low nitrogen feeding experiments, but he had a relapse and felt much worse during the following feeding experiments with a liberal diet. An interesting fact to be noted in this connection is the considerable creatine elimination during the period of high protein feeding. Hopkins and Savory also found creatine in the urine of their patients and seem to consider the creatine elimination a constant phenomenon in multiple myeloma. Creatine has now been found in so many different conditions that its occurrence in this disease is scarcely any more than one should expect. Its occurrence is, however, by no means constant. We found none of it during the first metabolism period, and we are inclined to ascribe the occurrence and the amount of the creatine appearing in the urine as something of an index to the subjective condition of the patient. Because of the condition of the patient we were unfortunately not able to carry out our plan to return to the original low nitrogen diet of the first period. He could not take it, and in fact could take very little food of any kind. During the three days immediately following the high protein feeding we found 6, 7.9 and 4.4 grams respectively of albumose in the urine. The total nitrogen of these days amounted to 13.4, 13.4 and 8.6 grams. In view of these facts we must conclude, as did Hopkins and Savory, that the protein content of the food has no direct bearing or influence on the elimination of the BenceJones albumose. In view of the patient's poor appetite we felt justified in requesting him to abstain from taking any food for a couple of days. He did so and we obtained 5.2 and 5 grams respectively of albumose and 8.8 and 8.4 grams of (non-protein) nitrogen in the urine. In considering the results obtained during this period of starvation it occurred to us that the effect produced on the albumose excretion by the ingestion of food might be studied by examining separately the day and night urines. For a few days the urines were therefore collected in twelve hour periods from 7 a.m. to 7 p.m. and from 7 p.m. to 7 a.m. The last meal of the day, a light one, was given at 5 p.m., and the patient received no food until 8 o'clock the next morning. As will be seen by the figures given in Table III the excretion of protein is practically the same during the two periods. To account for the albumose elimination during these two days of complete starvation following a period of inadequate feeding on the basis of the hypothesis of Magnus-Levy would be rather difficult, unless one is willing to fall back on the dramatic but improbable hypothesis of Freund that in fasting the protein is secreted into the intestine and there digested before being reabsorbed (in the form of amino-acids). Aside from the creatine elimination when the subjective symptoms become severe the protein metabolism in multiple myeloma appears to be normal so far as the ordinary normal nitrogenous metabolism products are concerned. The Bence-Jones albumose is more or less similar to one of the primary peptic digestion products (Meissner's "metapeptone") and is probably formed by internal autolytic digestion since it appears to be independent of the total protein metabolism. From this point of view it would seem not altogether improbable that in some cases of multiple myeloma traces of other albumoses might occur in the urine, but in our case, as in the two cases investigated by Hopkins, no such albumoses were found. Like Hopkins and Savory we have been unable as yet to obtain our Bence-Jones albumose in crystalline condition by means of the method of Gritterink and de Graaff.8 7 Loc. cit. 8 Zeitschr. f. physiol. Chem., xxxiv, p. 393, 1912. THE IMPORTANCE OF THE LIVER IN UREA FORMATION FROM AMINO-ACIDS. BY CYRUS H. FISKE AND JAMES B. SUMNER. (From the Biochemical Laboratory of Harvard Medical School, (Received for publication, June 1, 1914.) The chief methods of attack upon the problem of the site of urea formation have been: (1) comparative determinations of the urea content of blood from various sources and of tissues, and (2) urine analysis (a) after operative procedures which exclude the liver more or less completely from the circulation and (b) in hepatic disease in man. Comparative analyses have yielded no conclusive result, for several reasons. The methods used for the various kinds of material are not known to be comparable, the discrepancies lying chiefly in the completeness of extraction. In addition to, and doubtless largely because of this, the results have never been uniform. Finally, there is no obvious connection between site of formation and site of storage. The question of the amino nitrogen content of the urine in diseases of the liver, especially after the administration of aminoacids, holds at the present day an important position in relation to the functional diagnosis of liver lesions. Here likewise results have varied greatly. Even assuming an excessive excretion of amino nitrogen and a subnormal "assimilation limit" for aminoacids in liver disease, however, there is no proof from this alone that the liver is at all concerned in urea formation.1 The only operative procedures to be considered in this connection are those which exclude the liver completely from the circulation. Operations of this sort are entirely incompatible with prolonged life. Conclusions drawn from urinary changes under such cir 1 This subject has been recently discussed by Fiske and Karsner: this Journal, xvi, p. 399, 1913. |