The clearance curve of 133Xe from canine and human knee joints has two monoexponential components. The rapid half clearance time is designated T1/2F and the slower T1/2S. 133Xe concentration in periarticular tissues was measured; the nuclide was predominately in the intraarticular fat during T1/2S and was distributed between the synovial fluid, synovial membrane and fat during T1/2F. Because of predominant tissue localization of 133Xe during T1/2S and T1/2F, T1/2S is thought to represent clearance from articular fat and T1/2F to represent clearance from synovial fluid and membrane. Use of xenon clearance to calculate the blood flow to synovium or articular fat requires several assumptions that cannot be experimentally verified at this time. Elevation of intraarticular pressure, but not intraarticular volume, decreased 133Xe clearance from both compartments. Crystal‐induced inflammation was usually associated with faster T1/2S, although in one human volunteer T1/2S was slower until a part of the inflammatory exudate was removed. On the other hand, T1/2F was variable.

Sir:With reference to the report of El Attar, Murray and Anderson (Arthritis Rheum 11:178, 1968), it is not surprising that they found no evidence of cortisol metabolism in a rheumatoid knee joint as this has already been reported in ARTHRITIS AND RHEUMATISM by Peterson, Black and Bunim (11:433, 1959) and by Winter, Sandberg, Saroff and Slaunwhite (10:352, 1967). It is likely that metabolites formed in the synovial tissues diffuse into the capillaries and are rapidly washed away, as we have found extensive metabolism of cortisol in rheumatoid synovial tissue cultured in Krebs-Henseleit medium (Murphy and West, J. Endocrinol. 41227, 1968). Eight metabolites have been identified by crystallization with standards to constant specific activity. What is surprising is the marked metabolism they found in an osteoarthritic knee. Our experience of the ability of ethyl acetate that has been on the shelf awhile after redistillation, to transform kg. quantities of cortisol to cortisone, 17-oxosteroids and other substances that have the chromatographic mobilities of cortisol metabolites, has necessitated the use of controls with each study. As they may well have used 20 times as much ethyl acetate for the osteoarthritic synovial fluid as for the rheumatoid, the absence of reported control studies is disturbing. The purpose of this note is to draw attention to the metabolism of cortisol in rheumatoid synovial tissue and to draw to the attention of others who wish to extend these studies the dangers of ethyl acetate.

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