The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

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During the last decade, total appropriations for the NIH have grown in current as well as constant dollars. Constant dollar expenditures for indirect costs and research project grants have increased, as also has the number of the latter, while such expenditures for research centers, training, and research contracts have shrunk. The most impressive redistribution in emphasis has been toward traditional research project grants (R01s). The size of the average R01 award, discounted for inflation, has grown at an annual rate of 1.1% during the last decade and 1.3% since fiscal year (FY) 1970; that of the average research program project (P01) has declined over the same periods, after a slight rise in the early 1970s. Factors contributing to the modest rise in the real (constant-dollar) size of the average R01 are explored. The regularity with which current-services-requirements estimates for the NIH exceed inflation reflects real growth in the program, particularly in the category of research project grants; the artifact of basing calculations on the post-rather than pre-"negotiated" levels of awards in the "current" year; and the extent to which the project periods of awards have been extended. The effect of lengthening project periods is slow to become manifest, but inexorably swells the pool of non-competing awards; decisions in this area undertaken in 1985, and continued at least through FY 1988, could very significantly increase current services requirements in FYs 1991 and 1992.

The renal mechanisms by which urate is excreted have not yet been defined and there still is disagreement on several major points.Previous studies are in accord on one point, that the normal urate clearance in man is only a small fraction of the glomerular filtration rate, usually of the order of 8-10o. Differing explanations for the relatively low clearance have been offered. Patently, the difference between the clearance of urate and the clearance of inulin must be due either to non-filterability of a large fraction of the plasma urate, to tubular reabsorption of a major fraction of the filtered urate, or to some combination of these two.Some observers have reported non-filterability of the plasma urate, presumably due to proteinbinding or polymerization, but the magnitude of the bound fraction, 4-24%o (1), and 23% (2) has not been nearly sufficient to account for the difference between the clearances of urate and inulin. In a number of other studies (3)(4)(5) Despite this evidence of filterability in sitro and, at least in lower vertebrates, in s'ivo, several investigators have held that this is not the situation in man and that the actual amount filtered at the glomerulus is close to the amount excreted. Berglund and Frisk (9) advanced this theory to explain the fairly constant clearance of urate over a moderate range of plasma urate concentrations and a fairly constant ratio of urate to creatinine clearance in a series of patients with a wide range of renal functional impairment. The same hypothesis has been more recently supported by Wolfson and his associates (2, 10, 11), for reasons similar to those of Berglund and Frisk. In addition, it was suggested that the very low cerebro-spinal fluid urate concentration was due to non-filterability in vivo. The latter position, however, is not tenable since the composition of spinal fluid departs in several respects from that of a plasma ultrafiltrate, the concentration of a number of filterable substances in the spinal fluid being appreciably lower than that in plasma water (12, 13). These authors hypothesize that non-filterability of urate is due to polymerization and that urate is excreted by filtration only or by filtration with a small amount diffusing back passively.The most extensive work on the mechanism of uric acid excretion is probably that of Talbott (14) who reported a number of simultaneous determinations of inulin and urate clearances and the effect of various agents on the clearance ratio. Benedict's method (17). No correction for non-uric acid chromogen was made in any of these experiments since all critical data were obtained at times when the plasma concentration and urinary excretion of urate had been greatly increased by the administration of solutions of pure urate. At such times the non-uric acid chromogen is a negligible fraction of the total. Complete diffusibility of the plasma urate has been assumed in all calculations. Toxic reactionsNausea and vomiting occurred in about half of the patients who received infusions of the lithium carbon...

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