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Biomedical subjects

E W BOLAND

Publications and source records attributed to E W BOLAND.

At least 19 recordsLinked to original sources

NONSPECIFIC ANTI-INFLAMMATORY AGENTS. SOME NOTES ON THEIR PRACTICAL APPLICATION, ESPECIALLY IN RHEUMATIC DISORDERS.

A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented. Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases. Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages. Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis.

Adrenal Cortex Hormones↗

16a-Methyl corticosteroids; a new series of anti-inflammatory compounds; clinical appraisal of their antirheumatic potencies.

Four new derivatives of hydrocortisone, each containing in common a methyl grouping at the 16a-carbon position of the steroid molecule, have been synthesized and are being studied in human subjects. The compounds are 16a-methyl 9a-fluoroprednisolone (MK-125: hexadecadrol), 16a-methyl 9a-fluorohydrocortisone (MK-126), 16a-methylprednisolone (MK-110), and 16a-methylhydrocortisone (MK-117). Biologic tests in animals have indicated that these analogues exhibit, in varying degrees, striking alterations of several physiologic properties, including enhanced anti-inflammatory activity unassociated with corresponding disturbance of electrolyte metabolism. In the present study preliminary observations of the effects of the four new compounds were made in patients with rheumatoid arthritis. Clinical estimates of the antirheumatic potencies of the compounds, as compared with prednisolone, were accomplished by determining the milligram dosages required to maintain similar degrees of improvement of active rheumatoid manifestations. The approximate antirheumatic potencies of the compounds, on an average, were gauged as follows: for 16a-methyl 9a-fluoroprednisolone, about seven times greater than prednisolone; for 16a-methyl 9a-fluorohydrocortisone, about three times greater; for 16a-methylprednisolone, approximately one-third greater; and for 16a-methylhydrocortisone, about 70 per cent that of prednisolone. In the dosage used, none of the compounds promoted discernible salt and water retention. These observations would indicate that 16a-methyl 9a-fluoroprednisolone (hexadecadrol) possesses greater anti-inflammatory potency per milligram than any steroid yet produced. The therapeutic efficiency of the compound on longterm administration is being studied.

Animals↗

Effectiveness of antacids in reducing digestive disturbances in patients treated with prednisone and prednisolone.

To appraise the efficiency of complemental antacid administration in preventing and reducing digestive disturbances during prolonged treatment with prednisone and prednisolone, 100 patients with active rheumatoid arthritis who were maintained on combined antacid and prednisone or prednisolone therapy for periods of one year or longer, were studied clinically and roentgenographically. Antacid therapy consisted of 300 mg. of dried aluminum hydroxide gel and 50 mg. of magnesium trisilicate taken with each 2.5 mg. dose of the steroids. Digestive symptoms, such as indigestion, heartburn, sour eructations, gnawing epigastric distress and the like, were experienced by 18 per cent of patients during treatment with prednisone or prednisolone combined with antacids. Among patients who had been maintained on the steroids without antacids beforehand, the incidence of digestive complaints was reduced from 38 per cent to 17 per cent by the addition of alkali therapy, and the severity of the distress decreased in others. Active peptic ulcers were detected roentgenographically in three of the 100 patients. In two instances the ulcers were asymptomatic and in two instances they were considered as reactivations of previously healed lesions. The incidence of active ulcers in this series was substantially lower than that reported by several investigators among patients treated with prednisone and prednisolone without the concomitant administration of alkalis. The size of dosage and individual susceptibility appeared to be important factors in the development of digestive disturbances from steroids. Results of the study indicated that the complemental use of antacids with each divided dose of steroid is highly effective in reducing the frequency and severity of digestive symptoms during prednisone and prednisolone administration. The low incidence (3 per cent) for roentgenographically demonstrable active lesions in the series suggests that the addition of acid-neutralizing agents during prolonged treatment with these steroids may afford at least partial protection against the development and reactivation of peptic ulcers.

Aluminum Hydroxide↗