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Although phlorizin has been used mostly in the lower animals, its administration to man is not without precedent; shortly after its isolation by de Koninck (1836a, b), this investigator tried it in the treatment of malaria on the ground that it was bitter, like other remedies which were effective in this disease. The use of the drug in this connection was short-lived, however, and it was not until many years later that v. Mering (1885) discovered that it caused glycuresis and diuresis, observations which initiated its application in the treatment of nephritis, sarcoma, etc., and as a test for renal function in man, in addition to its well known use in studies of metabolism. Since these instances of human administration are of some interest, we have summarized them in Table I Lewis (1913-personal communication) gave 2 grams daily in 10 cc. of sterile olive oil subcutaneously over a period of days. In no instance was permanent injury described.Moderate intravenous doses of the drug produce no unfavorable reactions in the dog, and we decided that the intravenous route would be the most satisfactory for our purposes, particularly since we wished to determine the exact effect of small doses. Our anticipation in this matter has been justified, since we have given phlorizin in doses varying from 2.0 to 65.0 mgm. per kgm. with no unfavorable reactions other than an apparent diminution in glomerular activity with the larger doses. We feel called upon, however, to express a word of caution about the use of the intravenous technique in man and refer the reader to the description of our method of preparation and administration. Previous observations from this laboratory have shown that in the dog adequate doses of phlorizin raise the glucose clearance and lower the creatinine clearance to the level of the xylose clearance (Jolliffe, Shannon and Smith 1083

This report is concerned with the effective renal blood flow and rate of glomerular filtration in normal man, as determined by the diodrast and inulin clearances (26) during diuresis and during the action of phlorizin, adrenin, caffeine, nitrite, and typhoid vaccine. The observations not only throw light on the action of these agents, but also afford information concerning the physiological control of renal blood flow and glomerular activity.Typical data are reported graphically. On the assumption that the diodrast plasma clearance (indicated by D in the figures) is a complete clearance, this value is taken as equal to the effective renal plasma flow, i.e., the flow of plasma to active excretory tissue. To convert this figure to the effective whole blood flow it is only necessary to divide it by the per cent of plasma in the blood. For brevity, the term " effective " will be omitted from the discussion without, however, neglecting the physiological distinction between the diodrast clearance and the actual plasma flow which must be somewhat larger than the former in consequence of the inclusion of inert tissue. The filtration rate has been measured by the inulin clearance (IN). The filtration fraction (FF) (i.e., the apparent fraction of the plasma cleared through the glomeruli) is given directly by the inulin/diodrast clearance ratio. The Inulin, diodrast, and phenol red were given by constant intravenous infusion. The priming infusion consisted of 12 grams of inulin, 1.5 cc. of 10 per cent phenol red, and 1.5 cc. of 35 per cent diodrast solution in 100 cc. of 0.85 per cent saline, given at the rate of 10 cc. per minute. The sustaining infusion consisted of 45 grams of inulin, 10 cc. of phenol red, and 12 cc. of diodrast in 1000 cc. of saline, given at the rate of 4 cc. per minute. All details of technique were the same as those reported in the general description of methods given elsewhere (26). Figure 1 (Subject B. L., 1.83 sq. m., 52 per cent plasma) presents observations on the plasma flow and filtration rate during water diuresis in man. After three control periods, water was administered in four 250 cc. portions at five-minute intervals in order to minimize any disturbance of the systemic circulation. The urine flow, shown graphically, rose from 1.8 cc. to 14.2 cc. per minute. There was no change in the rate of glomerular filtration. The plasma flow decreased slightly, but there is no reason to believe that this circumstance was a result of the administration of water, or that it was causally related to the induction of diuresis. These observations are consonant with the evidence, which has been fully re-683 Water diuresis

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