Ralph H. Boots

Effect of adrenocorticotrophic hormone (ACTH) on rheumatoid arthritis

T HIS report deals with observations on eight patients with rheumatoid arthritis who have been treated with adrenocorticotrophic hormone (ACTH). The dramatic symptomatic response of patients with rheumatoid arthritis to the administration of ACTH described by Hench et al.’ has been amply confirmed. An understanding of the mechanism of this response or, in fact, of the mechanism of the activity of rheumatoid arthritis has not yet been found. Before the advent of cortisone and ACTH for clinical usage any decrease in activity of rheumatoid arthritis, when it occurred, took place gradually. With ACTH, and as reported by Hench with cortisone,’ a rapid and complete defervescence of activity takes place and activity usually returns when the medication is discontinued. This type of response suggests that the primary cause of the disease may not be affected by the administration of cortisone or ACTH, the effects being only on those factors which constitute the reaction of the host to the mechanisms that initiate and sustain the disease. These secondary factors constitute what is vaguely termed “activity” of the disease. Some of them are purely subjective, such as pain, easy fatiguability, lassitude and general malaise. Others are objective and capable of measurement, such as the inflammation of the joints, rapid erythrocyte sedimentation rate, fever and anemia. Most of our studies to determine the mode of action of ACTH in rheumatoid arthritis gave negative results. The data are recorded to save repetition on the part of subsequent workers on this problem. A few possible leads as to the mechanism of action are presented but these require more extensive study and confirmation.

Changes in the bacterial flora of the throat and intestinal tract during prolonged oral administration of penicillin

Abstract A bacteriologic study of the throat and intestinal flora of ten patients with arthritis, treated orally with 500,000 to 1,000,000 units of penicillin daily over a prolonged period of time, has been carried out. Upon administration of penicillin there was a sudden change in the bacterial flora of the throat from gram-positive to gram-negative. Coliform bacteria appeared in the throat early in the course of treatment and were present, and often predominant, throughout the course. Subsequent to treatment there was a rapid reappearance of gram-positive cocci in the throat. The coliform organisms disappeared gradually. There was a lower incidence of streptococcus-positive stool cultures during, than prior to or subsequent to penicillin therapy. No difference in the range of penicillin sensitivity of the gram-positive cocci isolated from throat cultures prior to and subsequent to treatment was demonstrated. Penicillin-sensitive organisms were infrequent in the throat and stool cultures during treatment. There was no evidence that bacterial resistance to penicillin developed during the course of therapy.

Studies on the Etiology of Rheumatoid Arthritis. I. Bacteriological Investigations on Blood, Synovial Fluid and Subcutaneous Nodules in Rheumatoid Arthritis.

The clinical evidence pointing to an infective origin of rheumatoid arthritis has led numerous investigators to seek a bacterial agent to which etiological significance could be ascribed. A wide variety of such agents has been reported, but lack of uniformity in the results obtained has confused rather than clarified the issue. Cecil, Nicholls and Stainsby, 1 by the use of a special technique, claim to have demonstrated the presence of streptococci in the blood-stream in 61.5% of a series of 78 cases examined. Because of the unusual nature of this report and the importance of such a finding the present investigation was undertaken. The greatest care was exercised to follow their technique. The type of patient selected in all cases presented the characteristic clinical syndrome of rheumatoid arthritis. Cases of osteo-(hypertrophic, degenerative) arthritis were not included. One hundred and five separate blood cultures were done on 80 patients. In the majority of instances the specimens of blood obtained at each vene puncture were divided into 2 portions so that in all 204 samples of blood were cultured. Eighteen selected patients were cultured on 2 occasions, 3 on 3 occasions and one on 6 occasions. As a control 31 samples of blood were obtained from 16 normal individuals and subjected to similar methods of culture. Sixteen tubes of sterile, autoclaved agar were subjected to the same manipulations and cultured by the same technique. The results may be summarized as follows: (1) In spite of the greatest care to conduct all manipulations under sterile precautions the technique was so involved as to call into serious question the significance of all bacterial growth encountered.