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American Rheumatism Association Ann Rheum Dis: first published as 10.1136/ard.11.4.294 on 1 December 1952. Downloaded from AMERICAN RHEUMATISM ASSOCIATION PROCEEDINGS OF THE ANNUAL MEETING, 1952 The annual meeting of the American Rheumatism The incidence of undesirable side-effects continued to Association was held at Chicago, Illinois, on June 6 be unimportant clinically. There was no greater tendency and 7, 1952. The presidential address was delivered to uric acid stone formation, nor any occasion to discon- by Dr. Charles H. Slocumb of Rochester, Minnesota. tinue therapy in patients in their second year of Benemid. The action of Benemid upon the metabolic pool and Abstracts of the 26 papers and summaries of the turnover rate of uric acid was studied. A depression in discussions thereon are printed below. the metabolic pool persisted while the increase in the One morning session was held jointly with the turnover rate remained within the normal range so long Council on Rheumatic Fever and Congenital Heart as the Benemid regimen was in force. Disease of the American Heart Association, and These studies lend support to the presumption that the a Panel biscussion by the principal investigators of action of Benemid is at the site of the renal tubule and is the United States and United Kingdom Co-operative not concerned with the intermediary metabolism of Rheumatic Fever Study Group was held under purine bodies or of the precursors of uric acid. the chairmanship of Dr. David. D. Rutstein of Boston, Mass. (see p. 318). Discussion.-DR. RICHARD T. SN1rH (Philadelphia, Pa): We have been able to see a number of the results from all over the country on people who have been using Clinical and Metabolic Effects of Benemid. By JOHN H. Benemid. I am continually amazed after sending out TALBoTT, L. MAXWELL LOCKIE, BERNARD M. information about the recommended dosage, to hear NORCROSS, and CHARLES BISHOP, Buffalo, N.Y. that Benemid is not well tolerated because the patient Approximately fifty patients with gout receiving 1-0 cannot keep it in his stomach when he takes 2, 3, andby copyright. or 2-0 g. Benemid daily have been followed for periods 4 g. daily. However, in most instances where the dose ranging from 6 to 24 months. The favourable results is kept no higher than 2 g., it has been well tolerated. the of acute attacks of The diagram (Fig. 1) shows the treatment of a patient reported earlier upon frequency who had had gout for many years and existed by adhering gout are confirmed. A persistent depression of the to a strict gouty diet, abstaining from alcohol, having concentration of uric acid in the serum as well as an physical therapy three times a week, and taking a large increased concentration of uric acid in the urine was -amount of colchicine, cincophen, and other drugs. noted. The body apparently did not develop tolerance On June 15, 1950, he was started on Benemid. We to the pharmacological action of the experimental drug then believed the minimal dose of Benemid to be 2 g. in the period of study. daily. The uric acid decreased immediately to 5*6 mg. per cent. and in 2 months went down to 3 * 6 mg. per cent. 14- The dose was finally reduced to 1 * 5 g. with slightly better http://ard.bmj.com/ 1 1950 tolerance. Between June 15 and August 28, 1950, he had 13 one long interval without an attack. Every time he took colchicine for an acute attack, however, he discontinued Benemid, although told to take it continuously. Between September 1 and November 1, 1950, he had w \/ \ x\ only one attack, and because of his freedom from joint l0* ,X)c disability and gastric intolerance of the drug he discon- -j 0 tinued the medication. We saw no more of him until on September 30, 2021 by guest. Protected 0 09 March 1, 1951, when he was given.1 g. Benemid daily 5 and has continued this dose to the present time. After 4 0 4 months without therapy his blood uric acid level was 8 7- 3 cent. 2 0 only mg. per (. -DATA- % 1951 ' r6 'I Sk (DURINGATTACK) 5. x *- NO DATA ---- uLJ . (I) 4. (DUR ING 3- ATTACK) I. .- .~~~~~~~~~~~1- I FEB MAR APR MAY JUNE JULY AUG. SEPT. OCT. NOV DEC. JAN. FEB. Fig. 1.-Use of Benemid as a uricosuric agent in a 54-year-old patient with gout. 294 Ann Rheum Dis: first published as 10.1136/ard.11.4.294 on 1 December 1952. Downloaded from AMERICAN RHEUMATISM ASSOCIATION 295 The number of acute attacks have decreased, occurring observation. The Arabs used colchicum in dropsy, and only after prolonged severe physical exertion; he eats a Baron von Stoerck, who started the modern era of normal diet, drinks alcohol occasionally, and tolerates colchicum therapy, wrote on its use in dropsical con- Benemid well, and his blood uric acid has remained ditions. Its effect in abnormal water retention has not under 6 mg. per cent. During 1952 his blood uric acid recently been investigated, but warrants further study. has been less than 5 mg. per cent. We believe that Benemid therapy reduces the number DR. WILLIAM D. ROBINSON (Ann Arbor, Mich.): The of gouty attacks, and makes patients comfortable and authors have made an important contribution to the in some able to work. confusing subject of metabolic disturbances in gout and cases resume their possible relationship to endocrine function. I should like to ask whether any determinations of DR. WILLIAM K. ISHMAEL (Oklahoma City, Okla): We 17-ketosteroid excretions were made, and whether the started ten patients only, and it required about 6 months, determinations of the 1 I-oxysteroids made during the using a 1 g. dose of Benemid to achieve a 37- 5 per cent. study showed any suggestion of rebound following drop in the uric acid levels. the withdrawal of hormones. Were the electrolyte changes observed, associated with DR. TALBOrr: I should like to close by stating that expected changes in urine volume ? With the decreased Benemid does not replace colchicine. We have been electrolyte excretion we should expect water retention. using colchicine with but few exceptions in the interval Did this actually occur or was there a discrepancy treatment of all patients with gout. During an acute between electrolyte excretion and total water excretion ? attack colchicine is indicated whether the patient is I ask this last question because some observations receiving Benemid or not. Benemid is merely an suggest the possibility that posterior pituitary factors adjunct and does not replace colchicine, except as an which can alter electrolyte excretion in relation to water urico-suric agent. excretion may be involved in some of these phenomena. I should add that we have found no evidence that colchicine acts through the pituitary adrenal mechanism. Metabolic Studies in Gout with Emphasis on the Role of All the evidence on that point is negative. the Pituitary-Adrenal Axis in Acute Gouty Arthritis. MELVIN H. LEVIN, J. BERNARD Rivo, and DR. WILLIAM R. MERCHANT (Washington, D.C.): By That may be a peripheral action. We have carried out SAMUEL H. BASSErr, Los Angeles, Calif. experiments on albumin for the last 21 years. In using The adrenal function of seven gouty patients has been albumin, we had no results, but with colchicine the studied: eosinophil counts, urinary 11 -oxysteroid excre- clinical results were rather dramatic, and one patient by copyright. tion, serum and urinary uric acid, blood sugar, blood developed renal colic. glutathione, and sweat electrolyte studies were performed DR. LEVIN: In answer to Dr. Robinson, 17-ketosteroid during interval gout, acute spontaneous gouty arthritis, studies were unfortunately not performed during this ACTH and testosterone administration, steroid-induced part of the experiment. We did have a random sampling gout, and colchicine therapy. of 1I-oxysteroid excretion, but it was not made soon Metabolic balances for N, Na, C1, and K were enough after ACTH withdrawal to determine whether performed in one patient for 90 days under the above full rebound activity could be determined by I I-oxy- conditions. A second patient and a normal control were steroid studies as well as by the electrolyte balance. studied for 161 and 59 days respectively, while on a We have data on the water balance with colchicine. balance with observations of serum and Water retention occurred as well as retention of sodium chloride urinary and chloride. uric acid and circulating eosinophils. Basal observations Time did not permit discussion of the possibility of http://ard.bmj.com/ plus the effects of mercurial diuretics and colchicine were this being mediated through an ADH mechanism. An made on the normal control. The effects of mercurial irregular line in the graph at the very end of the. study diuretics, colchicine, ACTH, and pitressin were studied was the effect of 0 5 ml. pitressin tannate in oil given in the gouty patient. intramuscularly. With this came a sharp change in water No evidence was uncovered to corroborate the balance, and a slight change in sodium and chloride hypothesis that acute gout is accompanied by a deficiency balance. With colchicine the opposite is true; here the of adreno-cortical function. The association of acute effect is primarily on the electrolytes. gout with salt diuresis was inconstant. Fever and Lastly, none of our patients had renal colic when given weight colchicine. on September 30, 2021 by guest. Protected changes appeared to influence the electrolyte exchange. The metabolic response to ACTH was within normal Experiments in Repair of Articular Cartilage. By HANS limits. Colchicine regularly produced striking sodium WAINE and VAUGHN W.
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