In leukemia, where there must be a large destruction of nucleoprotein, as evidenced by a report concerning a patient who eliminated 12 grams of uric acid during the last forty hours of life, there is no gout.1 Folin reports that normal human blood contains about 1.5 to 2.5 milligrams of uric acid per 100 c.c. and that this quantity is exceeded not only in gout but also in leukemia, lead-poisoning, and in nephritis. Folin and Denis2 state that in true gout there is no increase in the quantity of non-protein nitrogen in the blood, though this increase appears in arthritis deformans. They recommend this as a means of differential diagnosis between gout and arthritis.

Magnus-Levy,3 Vogt,4 and Reach5 were the first to discover that the administration of glands rich in nucleoprotein, such as thymus and pancreas, to gouty persons did not cause as large an excretion of uric acid in the urine as when the same amounts of these materials were given to normal individuals.

The work of Soetbeer6 is of the best modern character, and illustrates the retention of uric acid in gout. Soetbeer compared the excretion of uric acid by gouty people during three-hour intervals with that of normal individuals, as observed by Pfeil (p. 542). In one case of long-standing gout, of light character and with long intervals between the attacks, there was little variation from the normal in the uric acid excretion. In another case of gout, a patient who was examined between the attacks showed no increase in uric acid output after changing from a purin-free diet to one containing 320 grams of meat, and showed only a slight increase in elimination after 640 grams of meat were given. These results were obtained six weeks after the last attack and at a time when the patient was entirely free from pain. In still another case 350 grams of meat were given during the attack to a gouty patient who had no fever and whose urine was free from albumin and sugar. The results were as follows:

1 Magnus-Levy: "Virchow's Archiv," 1898, clii, 107.

2 Folin and Denis: "Archives of Internal Medicine," 1915, xvi, 33.

3 Magnus-Levy: "Zeitschr. fur klin. Med.," 1899, xxxvi, 414. 4 Vogt: "Deutsches Arch, fur klin. Med.," 1901, lxxi, 21.

6 Reach: "Munchener med. Wochenschr.," 1902, xlix, 1215.

7 Soetbeer: "Zeitschrift fur physiologische Chemie," 1904, xl, 54.

In this experiment even during the days of purin-free diet there was no "morning rise" noted as a normal incident by Pfeil. The hourly uric acid excretion was very even. The kidney was apparently removing uric acid up to the limit of its capacity.

Hefter1 administered uric acid subcutaneously to a gouty patient and recovered only 11 per cent, of it in the urine in contrast with a recovery of 86 per cent, in the normal individual. Thannhauser and Bommes2 report that although between 75 and 82 per cent, of the purin content of 1 gram of adenosin when subcutaneously administered to normal men appears as uric acid in the urine, and the uric acid content of the blood does not rise, yet in severe gout this procedure is not followed by additional excretion of uric acid, though uric acid does increase in the blood. Three of four gouty patients had attacks of gout after this treatment. The authors state that the conclusion is unavoidable, that gout is due to a disturbance in the elimination of uric acid.

1 Hefter: "Deutsches Archiv fur klin. Med.," 1913, cix, 322. 2 Thannhauser and Bommes: "Zeitschrift fur physiologische Chemie," 1914, xci, 336.

Denis1 finds that there is no increase in the uric acid content of the blood of man after the ingestion of foods rich in purins, except in cases of renal insufficiency.

The drugs which are used in rheumatism, arthritis, and gout, such as salicylate of soda, aspirin, and atophan, cause an increased elimination of uric acid in the urine and a concomitant fall in the quantity of uric acid present in the blood.2 Salicylate of sodium when given in amounts to produce no salicylate intoxication (such as ringing in the ears) has no effect upon the basal metabolism of normal men, though the uric acid and total nitrogen elimination is somewhat increased.3

The discovery of Stanley Benedict of the large amount of uric acid combined in the corpuscles of ox blood lends added significance to the idea of Minkowski that the deposition of urates in gout may be dependent upon some abnormal chemical union of the uric acid which breaks up, yielding urates for the construction of tophi. The possible importance of this factor should not be lost sight of.4

Miller and Jones6 were unable to find any variation from the normal in the distribution of the purin enzymes in the tissues of a gouty individual.

Linser6 tells how a gouty individual suffering from eczema was treated with the Rontgen rays. Although the person was on a purin-free diet, the treatment invariably brought on an attack of gout on account of the increased production of uric acid within the body which normally follows such treatment.

1 Denis: "Journal of Biological Chemistry," 1915, xxiii, 147.

2 Jackson and Blackfan: "Albany Medical Annals," 1907, xviii, 24; Rock-wood: "American Journal of Physiology," 1909-10, xxv, 34; Fine and Chace: "Journal of Biological Chemistry," 1915, xxi, 371; Denis: "Journal of Pharm. and ex. Ther.," 1915, vii, 601.

3 Denis and Means: "Journal of Pharm. and ex. Ther.," 1916, viii, 273.

4 Minkowski: "Zeitschrift fur physiologische Chemie," 1913, lxxxviii, 159. 5 Miller and Jones: Ibid., 1909, lxi, 395.

6 Linser: "Therapie der Gegenwart," 1908, No. 4.

Gudzent1 states that monosodium urate occurs in the blood in two isomeric forms, the more soluble lactam form being readily convertible into the less soluble and more stable lactim form, these having been chemically differentiated by Emil Fischer. While 100 c.c. of blood dissolve 18.4 milligrams of the first salt, they dissolve only 8.4 milligrams of the second. Gudzent2 maintains that the inhalation of radioactive emanations leads to an increased elimination of uric acid in the gouty, due to the conversion of the lactim form of uric acid into the lactam form. However, Wiechowski3 denies the influence of radium upon the solubility of uric acid, though he finds that the emanations bring about a rise in the elimination of uric acid not only in gouty persons but also in normal individuals. He believes with His that the emanations may reduce the inflammatory processes in gout, thereby indirectly favoring more normal conditions and leading to the elimination of uric acid. There is little or no influence exerted by radium emanations upon the respiratory metabolism,4 although it is stated that the ingestion of one hundred times the usual therapeutic dose has caused an increase in metabolism of 17 per cent.6

1 Gudzent: "Zeitschrift fur physiologische Chemie," 1909, lxiii, 455.

2 Gudzent: "Zeitschrift fur klin. Med.," 1910, lxxi, 304; 1913, lxxviii, 266.

3 Knaffl-Lenz and Wiechowski: "Zeitschrift fur physiologische Chemie," 1912, lxxvii, 303.

4 Silbergleit: "Berliner klinische Wochenschrift," 1908, xlv, 13; 1909, xlvi, 1205.

5 von Benczfir and Fuchs: "Zeitschrift fur ex. Path, und Ther.," 1912-13, xii, 564.

6von Noorden and Schliep: "Berliner klinische Wochenschrift," 1905, xlii, 1297.