The former theory as to the production of uric acid in the body was that it represented protein imperfectly oxidized into urea and that the uric-acid diathesis was a condition of sulfoxidation, in which the uric acid acted directly as a toxic agent. This view has been considerably modified and it has even been stated that uric acid and allied purin bodies are entirely independent of the catabolism of protein. Neither uric acid nor any of its congeners are active poisons, but, in excessive amounts, they do exert a detrimental action on the tissues, although xanthin and others of the group seem to be more toxic than uric acid itself. Thus, the general clinical conception of a uric-acid diathesis or better, dys-crasia, may be retained, under the less specific name of purinaemia.

The purin bodies, which are bases with the exception of uric acid, are modifications of the radicle C5 N4. the common ones being hypo-xanthin, xanthin, uric acid, guanin, adenin, caffeine (or theine), and theo-bromine. As a group, they raise blood pressure and tend to produce angiosclerosis and sclerotic changes in the viscera.

In their most complex compounds, the purins are found as nu-cleo-protein, which is split into nuclein and albumin. Nuclein is, itself a compound of albumin and nucleic acid. Nucleic acid is further decomposed into phosphoric acid; a combination of phosphoric acid with a base, nucleotin; a carbohydrate, pentose or xylose; and some modification of the purin radicle. The exact changes of the last are not fully known and differ according to the method of artificial treatment. At any rate, uric acid may be and, in the body, undoubtedly always is to a large degree, produced by the progressive catabolism of nucleo-protein and part of this uric acid is further changed, through the stage of allantoin, into urea.

On the other hand, the system can produce its own nuclein and the higher compounds of nuclein, on a diet free from purins but, of course, containing proteins; and the elimination of purins is somewhat increased by increasing the intake of proteins. On an ordinary mixed diet, about half of the elimination of purins is accounted for by ingestion of more or less combined purins and about half by the metabolism of nuclein-containing structures, such as white blood cells and the cells of viscera, such as the kidneys, liver, pancreas, spleen and thymus, etc.

Thus, the extreme theory that no purin bodies are formed except from purins is false and the older view that uric acid is a precursor of urea is true in a limited sense.

Purins derived from ingesta are termed exogenous (better exogenic) and those from the tissues endogenous (better endogenic). The purin bodies themselves are termed free purins, while nucleic acid, nuclein and nucleo-proteins are termed bound purins.

Purins occur in both animal and plant nitrogenous bodies, in greater amount in the former and obviously, in greater amount in glandular viscera and white blood cells than in muscle and connective tissue cells because of the relative preponderance of nuclei. Vegetable nuclein is mainly derived from yeast cells.

The estimation of purins in the urine cannot be determined by the presence of a precipitate of urates - which is rather due to concentration and cooling - nor even by that of uric acid itself. Urine of high acidity (as determined by titration, not by guess) is usually rich in uric acid, not, however, usually in a free state. The normal elimination of purin bases in the urine is about 0.1 gram daily and of uric acid, about 0.5 or a little more. They may be estimated with sufficient accuracy for clinical purposes quite simply by either of two methods. 100 - 200 c.c. of urine is strongly acidified with hydrochloric acid and allowed to stand for 24 hours, when the uric acid is collected on a filter and its net weight determined by actual weighing. I. Walker Hall's gravity purinometer or It. Harvey Cook's centrifugal method are based on the same principle, the latter being more rapid and probably more accurate. In the centrifugal method, 10 c.c. of urine is cleared of earthy phosphates by adding 1/2 - 1 gram of sodium carbonate and 1 - 2 c.c. of strong ammonia water and the precipitate is separated by centrifuge. The decantate is treated with 2 c.c. of ammoniacal solution of silver nitrate, prepared by adding to a 5% solution of silver nitrate, ammonia water until the precipitate at first formed, redissolves. More ammonia water is added to make the total bulk 15 c.c. A slimy precipitate is produced consisting of purins in combination with silver. Each 1/10 c.c. bulk of this precipitate represents (quite accurately according to Ogden) 117.6 milligrams of uric acid per liter of urine. While commonly termed a test for uric acid, it is, according to Hall, one for purins generally. The Hopkins and similar methods, depending upon precipitation with ammonium chlorid and titration with potassium permanganate solution, are tedious, involve many opportuities for accidental loss, shreds of filter paper or other organic substances swell the readings, and the personal equation is a considerable factor.

Since both "urea" as commonly estimated, and uric acid and other purins, depend upon diet to a very large degree, ther is no such thing as a standard physiologic ratio between urea and uric acid, although it is not incorrect to say that, under ordinary circumstances, this ratio is about 35:1.

Red meats do not, according to the best authorities, contain notably greater quantities of purins or extractives, than white meats so that the use of fish or chicken breast is not to be urged against the preference of a patient for a chop or steak.

A review of the appended table will indicate the method of regulating a diet so as to increase or diminish the intake of purins. A nearly purin-free diet may be based on eggs, milk and its derivatives, preparations of wheat flour, tapioca, and, in general, the purer forms of carbohydrate and fat, and on fruits and vegetables poor in nitrogen.