OSI-930 and of thyroidectomized animals, the conclusion was drawn that the adrenal cortex plays an important part in the pathogenesis of rheumatic fever and of rheumatoid arthritis in man. Not all workers were able to verify these results. Harrison and Pemberton, Eiman, Patterson, and Stackhous encountered arthritis in a group of rats on standard laboratory rations, in a group on grossly unbalanced diets, and in a group receiving large amounts of deoxycortone by injection. Pemberton and his associates were unable to show that thyroidectomy, adrenalectomy, or gonadectomy influenced the incidence or severity of the arthritis which took the form of focal areas of articular cartilaginous degeneration and ulceration. Many rats, they admitted, were heavily parasitized and controls were poorly defined.
The published illustrations are unconvincing. Pirozynski GS-1101 and Akert repeated Selye,s work. Among seventeen rats no spontaneous deaths occurred during the experiment, after 2 to 3 weeks fifteen showed a subacute non suppurative focal polyarthritis. Controls were not used. Haour considered that the arthritic changes attributed to deoxycortone were not specific. The whole problem of the hormonal production of arthritis was discussed by Justin Besanqon, Rubens Duval, Villiaumey, and Kahn in one of the few reviews of methods for the experimental study of arthritis. In their own work fifty rats were treated in accord ance with Selye,s descriptions and they claimed to have produced a comparable arthritis. Their experiments remain open to criticism, but their review, with 107 references, is valuable.
Siebenmann and Uehlinger agreed with Selye and others in attributing to deoxycortone and salt an inflammatory reaction, but they could not accept the implied analogy with human disease. Salgado referred to earlier work in which only two of 250 rats given deoxycortone developed arthritis detectable clinically, while of 100 rats given somatotrophin none developed arthritis. Smirnov and Beletskaia also found that deoxycortone alone was ineffective. Effect of Adrenal Damage in Deoxycortone Arthritis. Harrison studied the production of arthritis in uninephrectomized rats given deoxycortone and salt. He showed that inadvertent damage to the arterial supply to the left adrenal could cause zonal necrosis, and suggested that this might account for the sensitizing influence of uninephrectomy in Selye,s experiments through diminished secretion of glucocorticoids.
Action of Deoxycortone in Adrenalectomized Rats. The removal of the adrenals was considered by Selye and others and by Tarnopolsky, Schajowicz, Lustig, and Montuori to predispose to joint involvement in animals given deoxycortone, particularly during exposure to cold. However, adrenalectomy in the rat may be an uncertain procedure. Action of Deoxycortone in Thyroidectomized Rats. Selye and others and Pirozynski and Akert considered the influence of thyroidectomy on the evolution of the arthritis caused by deoxycortone. They agreed that thyroidectomy predisposed to arthritis but there was no indication whether this was a specific endocrine effect. Action of Deoxycortone in Thyroparathyroidectomized Rats. Harrison and Barnett treated rats by thyroparathyroidectomy, with or without unin