Dr. Ron’s Research Review – November 2, 2016

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This week’s research review focuses on PABA for steroid withdrawal syndrome.

An interesting study was published in the American Journal of the Medical Sciences in 1954. Thirty-one patients with active rheumatoid arthritis were treated with a combination of para-aminobenzoic acid and cortisone acetate for a period of one year or more. Thirty of these patients showed improvement comparable to that obtained with a much larger dose of cortisone acetate alone. The incidence of evidence of hypercorticoidism was negligible. Other known side effects of cortisone therapy were absent. The dose of cortisone acetate was 12.5 mg tid oral. Some received 100 mg im daily for two weeks prior to this. The dose of PABA was 30 cc of a 10% solution one hour before cortisone; increased to 45 cc if the response appeared too slow or inadequate. (Wiesel and Barritt, 1954; Wiesel, 1954)

Phillip S. Hench was the first to administer cortisone to a patient with rheumatoid arthritis (RA). He and his team were awarded the Nobel Prize for medicine. Hench rejected the idea that steroids were of etiological significance for RA, and instead stressed their unique place as a tool for pathological research: “As we have stated repeatedly, the use of these hormones should be considered an investigative procedure, not a treatment. The value of these hormones at present is that their use will permit the study of certain disease mechanisms more carefully than heretofore. We can now repeatedly produce controlled remissions of several diseases, to be followed by more or less controlled relapses, both of which processes can be studied intensively by a variety of clinical, biochemical, and immu- nologic methods. It is hoped and believed that such studies will in time lead to an improved and practical method of treatment. But this present study is to be regarded, not as a report on clinical therapy, but as an investigation in clinical physiology.”  (Neeck, 2002)

 

Dr. Ron


 

Articles

Effect of para-aminobenzoic acid on the metabolism of cortisone in liver tissue.
            (Wiesel, 1954) Download
Para-aminobenzoic acid has been shown to interfere markedly with the rapid reduction of unsaturate conjucated system of the cortisone molecule while permitting more rapid degradation of the side chain.

Long term treatment of rheumatoid arthritis with para-aminobenzoic acid and cortisone acetate.
            (Wiesel and Barritt, 1954) Download
Thirty one patients with active rheumatoid arthritis were treated with a conbination of para-aminobenzoic acid and cortisone acetate for a period of one year or more. Thirty of thes patients showed improvement comparable to that obtained with a much larger dose of cortisone acetate alone. The incidence of evidence of hypercorticoidism was negligble. Other known side effects of cortisone therapy were absent.

Fifty years of experience with cortisone therapy in the study and treatment of rheumatoid arthritis.
            (Neeck, 2002) Download
In 1948 the U.S. rheumatologist Phillip S. Hench administered cortisone for the first time to a patient with rheumatoid arthritis (RA), thereby discovering the therapeutic effects of glucocorticoids. He published this observation together with Kendall, Slocumb, and Polly in 1949, and they received, along with Reichstein and Kendall, the Nobel Prize in Medicine or Physiology in 1950. However, as early as 1949, he rejected the idea that steroids were of etiological significance for RA, and instead stressed their unique place as a tool for pathophysiological research. The discovery of the glucocorticoid receptor and its genomic effects disclosed that there are no qualitative differences between the effects of endogenous cortisol and exogenously applied synthetic glucocorticoids, since all effects are transmitted via the same receptor. Later came the discovery that the hypothalamo-pituitary-adrenal axis is stimulated by cytokines after activation of the immune system. Glucocorticoids are not only the most effective antiphlogistic and immune-suppressive substances with instant effect, but they also show, with low-dosage long-term treatment, clear antiproliferative effects on the cartilage and bone destroying pannus in RA. Little is still known about the precise mechanisms of actions of glucocorticoids in general, and specifically when rheumatic autoimmune diseases are involved. The high effectiveness of these substances and their direct effects via the genomic glucocorticoid receptor allows us to anticipate that uncovering their mechanisms of action will shed deeper insight into the pathomechanisms of these diseases. The use of TNFalpha blockers in the treatment of rheumatoid arthritis and Crohn's disease, with their dramatic immediate effects, comparable with those of the glucocorticoids but without the side effects of the latter, points us in that direction.

 

References

Neeck, G (2002), ‘Fifty years of experience with cortisone therapy in the study and treatment of rheumatoid arthritis.’, Ann N Y Acad Sci, 966 28-38. PubMed: 12114256
Wiesel, LL (1954), ‘Effect of para-aminobenzoic acid on the metabolism of cortisone in liver tissue.’, Am J Med Sci, 227 (1), 80-82. PubMed: 13114218
Wiesel, LL and AS Barritt (1954), ‘Long term treatment of rheumatoid arthritis with para-aminobenzoic acid and cortisone acetate.’, Am J Med Sci, 227 (1), 74-79. PubMed: 13114217