The Lancet Article
Dr. McCarty followed up on his important findings in uric acid crystal imaging with his trainee, James S. Faires, MD. Using themselves as the subjects, the two injected uric acid crystals (purified from a gouty tophus and put in solution) into one knee. They injected saline solution without urate crystals into their other knees as a control.1
A few hours later, both experienced excruciating inflammatory gout-like sensations in the knees injected with uric acid crystals. Although they had not initially planned on it, the two ultimately opted to take pain medications and hydrocortisone due to the severity of their symptoms. Follow-up experiments in dogs showed a similar effect.1
The authors noted, “This preliminary work indicates that sodium urate in crystalline form is probably important in the production of acute gouty arthritis. The exact mechanism response for the intense inflammatory arthritis is unknown … The pathogenesis of the acute gouty attack seems to be related to the deposition of sodium-urate crystals in the synovial fluid.”1
The authors also pointed out key questions raised by their work, such as: 1) Why are certain individuals with high uric acid blood levels able to keep their urate in solution? 2) Why are certain tissues in the body more susceptible to deposition? 3) What are the factors responsible for the intense response to sodium urate crystals in synovial fluid?1
JAMA Article
J. Edwin Seegmiller, MD, and his colleagues at the National Institute of Arthritis and Metabolic Diseases of the Public Health Service (est. 1950; later the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Bethesda, Md., published an important, complementary article in JAMA that same year.2
Most previous related work showing an inert inflammatory response to injections had not used crystallized forms of solid sodium urate. In contrast, Dr. Seegmiller and his team injected microcrystalline particulate forms of solid sodium urate into the knees of 12 patient volunteers who had previously had gout disease flares. Each was also injected with an amorphous, non-crystalline solution of sodium urate into the other knee.2
Within a couple of hours, all patients showed signs of pain, warmth and/or effusion in the joints injected with the microcrystalline particulate forms of sodium urate. Several patients described their symptoms as similar to those of a spontaneous gouty attack. Aspirated synovial fluid from the joints was examined under polarized microscopy. This revealed leukocytosis and extensive phagocytosis of the urate crystals.2
