Abnormal clonogenic potential of T cells from multiple myeloma patients

Peripheral blood lymphocytes (PBLs) from multiple myeloma patients are defective in both proportion and absolute numbers of OKT4+ cells and have a normal proportion but reduced absolute number of OKT8+ cells. To assess the functional capabilities of the T cells in myeloma patients, we cloned the T cells in PBLs using limiting dilution conditions in which 100% of OKT4+ and OKT8+ T cells in normal PBLs are able to form a clone. In contrast, the OKT8+ cells from PBLs of five of seven multiple myeloma patients were severely compromised in their clonogenic potential; only 7% to 25% of OKT8+ T cells appeared to give rise to a clone. Clonogenic potential of the OKT4+ cells in patients was more nearly normal. Analysis of two multiple myeloma patients with abnormally low numbers of T cells in PBLs revealed the existence of abnormalities in the progenitors of T cell clones. In both patients, two to three times as many T cell clones were observed as would have been expected based on the number of PBLs cultured at limiting dilution, indicating that OKT4-8- cells in PBLs are capable of giving rise to OKT4+ and, at lower frequency, to OKT8+ clonal progeny in vitro. We conclude that purely quantitative assessment of T cell subsets should be interpreted with caution, since proportionately normal numbers of OKT8+ cells in patient PBLs are seriously compromised in their ability to give rise to clonal progeny in vitro, and since there appears to be a OKT4-8- population of T cells in PBLs that are committed to become OKT4+ or OKT8+ T cells, but are unable to do so in vivo.     

Amiodarone-associated hypothyroidism--a possible cause of digoxin intoxication

The problem of a possible interaction between amiodarone and digoxin is still unsettled. We have recently treated two patients with digoxin intoxication who had received amiodarone for eight and 36 months respectively. Both developed extreme bradycardia requiring temporary pacemakers. The presence of hypothyroidism was confirmed in both cases by laboratory data. Judging by present knowledge concerning the interaction between amiodarone, thyroid function, and digoxin, it is suggested that digoxin intoxication was not the result of its direct interaction with amiodarone. The possibility that amiodarone-induced hypothyroidism precipitated digoxin intoxication seems to be more plausible. Prevention of digitalis toxicity in amiodarone-treated patients would therefore require monitoring of thyroid function every three to six months. Frequent monitoring of digitalis blood levels is also indicated in patients with amiodarone associated hypothyroidism. Early detection of hypothyroidism and digitalis intoxication is necessary in view of the severity of the course of the disease.