This study compares different immunosuppressive regimens in the treatment of the lupus-like nephritis of NZB/W mice. Groups of 5-month-old female NZB/W mice were given azathioprine, cyclophosphamide and methylprednisolone in all one-, two-and three-drug regimens, each drug in the relatively low dose of 1.5 mg/kg/day. Treatment for 3 months with one or two drugs resulted in modest suppression of NZB/W disease. Mice receiving all three drugs had significantly less proteinuria, lower titers of anti-DNA antibody and less severe, histologically evident renal involvement than mice treated with one or two drugs. Survival at 1 year was 10% for untreated controls, 44% for one-drug-treated, 37% for two-drugtreated and 86% for the three-drug-treated mice. The survival for the three-drug regimen was significantly longer than any other group ( P < 0.01). The three-drug regimen was synergistic, since mice treated with each drug at three times the dose had significantly more proteinuria after 3 months of treatment and lowered 1 year survival (33%). The beneficial effects of triple-drug therapy were attained without increased toxicity. This study represents the first controlled evaluation of single versus combination therapy in a model of autoimmune disease. Based on these results, a controlled evaluation of triple-drug therapy in human systemic lupus erythematosus appears warranted.Combined immunosuppressive regimens are being used widely to treat malignancies, allograft rejection and immunologically mediated diseases. Encouraging results have been reported in the treatment of some leukemias with combinations of as many as four agents (l), and it is now standard therapy to administer prednisone in combination with azathioprine or cy-
Geophagia has been associated with life-threatening hyperkalemia in five patients with chronic renal failure. All five patients were black and had been born in the southeastern United States. Four had had frequent hyperkalemia requiring at least one hospitalization, and two had had hyperkalemia with serum potassium concentration as high as 9.8 mEq/liter, resulting in cardiac arrest in one and paralysis, disorientation, and cardiac arrythmia in the other. Since riverbed clay contains as much as 100 mEq of potassium in 100 gm of clay, much of which is exchangeable at acid pH, the mechanism of geophagia-induced hyperkalemia appears to be the absorption of potassium released from clay after ingestion. After discontinuing geophagia, no new hyperkalemic episodes occurred in these patients.
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