Accurate and reproducible measurement of M-protQins is essential for managing patients with monoclonal gammopathies, but serum protein electrophoresis, radial immunodiffusion, and electroimmunodiffusion yield comparatively divergent results. We have studied these differences and their causes. Sera from cases of lgGmonoclonal gammopathy, IgA-monoclonal gammopathy, and lgM-monoclonai gammopathy were assayed by each of the three techniques. Results indicated intermethod discrepancies as great as fivefold for all proteins studied. For IgO-monoclonal gammopathy, radial immunodlffuslon values were uniformly higher; electroimmunodiffusion values were less consistently so. For IgA-monoclonal gammopathy, both radial immunodiffusion and electroimmunodiffusion gave lower results than did serum protein electrophoresis. For 1gM-monoclonal gammopathy, results were variable, but values by radial immunodiffusion tended to be higher than, and electroimmunodiffusion comparable to, those for serum protein electrophoresis. The differences were not correlated with protein abundance, serum freshness, immunoglobulin class, light-chain type, ultracentrifugal characteristics, or electrophoretic mobility. Clearly, values for M-protein concentration depend on the techniques used to obtain them. We postulate that subclass differences may contribute to the diversity of radial immunodiffusion results, and that for electroimmunodiffusion the fixed electrophoretlc mobility of M-proteins leads to unpredictable results. We conclude that serum protein electrophoresis is the best of the three assay techniques for M-proteins.

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The therapeutic effectiveness of parenterally administered rabbit antigastrin antibody was evaluated in a patient with the Zollinger-Ellison syndrome who had a fasting serum gastrin level of 3020 pg/ml and a basal gastric acid secretion of 48.9 mEq/hr. Control globulin reduced gastric secretion to 32 mEq/hr. Gastrin antibody reduced it further to 8.7 mEq/hr. Betazole hydrochloride which was given 75 min after administration of gastrin antibody stimulated acid secretion to 57.2 mEq/hr. One day later basal acid secretion was uninhibited although some antibody activity was present in the patient's serum. The results suggested that gastrin antibody acutely inhibited basal but not betazole-stimulated secretion.

Digitoxin interference with radioimmunoassay of digoxin may present a problem in determining digoxin concentrations in the serum of patients treated with digitoxin less than four weeks before digoxin was administered. Digoxin and digitoxin values were determined in the sera of 54 patients who were receiving only digitoxin. Additionally, digoxin was added to aliquots of sera from a patient receiving digitoxin, and digoxin concentrations were determined by radioimmunoassay. Digitoxin interfered with radioimmunoassay of digoxin in that 9% of the digitoxin present was counted as digoxin. The resulting spuriously high value for measured digoxin in patients receiving digoxin, but treated with digitoxin previously, can be corrected by applying the following equation (units: µg/liter): Digoxin (corrected) = digoxin (measured) — [0.09 x digitoxin (measured)]. This correction, which may differ somewhat with batch of antiserum, is applicable for digitoxin concentrations up to about 50 ng/ml. Digoxin does not interfere with the digitoxin assay.

A male infant is described with thymic alymphoplasia; lymphocytopenia; lymphoid tissue hypoplasia; plasmacytosis of lymph nodes and marrow; dys-γ-globulinemia characterized by hyper-γA-, normo-γM-, hypo-γG-, and a-γD- and γE-globulinemia and decreased K- and λ-light chains with an increased K/λ light chain ratio; deficient formation of certain hemagglutinin, precipitin and neutralizing antibodies; the presence of skin-sensitizing, heat-labile reaginic antibodies and severe allergic reactions; normal delayed hypersensitivity; and a Coombs' positive anemia. Subsequently, a lymphoma involving bones, liver, spleen, lung, and kidney developed and terminally Pneumocystis carinii pneumonia appeared. A male sibling who died at age 11 months manifested thymic aplasia, lymphoid tissue hypoplasia, pancytopenia and hypo-γ-globulinemia. The frequency of allergic disorders was increased in family members of these children.

Two brothers with polycythemia rubra vera have been studied: one before treatment and one after many years of treatment. Direct harvests of marrow aspirates from both patients exhibited the presence of the Ph1 chromosome. Moderately increased LAP levels were present in both. Available data do not indicate whether the disease and the chromosomal aberrations in these two brothers are familial or fortuitous.

In cold agglutinin disease the untoward effects can be attributed chiefly to high serum concentration of a macroglobulin with S 20 value of 15 to 19. Treatment, including high environmental temperature, ACTH, and HN 2 has not been rewarding. Another therapeutic approach has been explored. Other investigators demonstrated that macroglobulins are depolymerized by mercaptanes. Therefore, the effect of mercaptanes upon the macromolecular cold agglutinin in idiopathic cold agglutinin disease was examined. The subject of this study was a 65-year-old white man suffering from intermittent severe hemolytic anemia which required frequent transfusions. Serum from this patient contained a cold agglutinin characterized by S 20 value of 15.5; electrophoretic mobility of γ 1 - β 2 -globulin; intense periodic, acid-Schiff staining; negative Sia and formolgel tests; cold agglutinin titer of 1:500,000 to 1:1,000,000 at 5 °C. with thermal amplitude extending to 30 ° or 32 °C. Serum was incubated with cysteamine, vitamin B 6 -SH, penicillamine, and penicillin G for 30 minutes. The titer was substantially lowered in all samples except the control. Penicillamine (500 mg. t.i.d.) was administered orally for 10 days. There followed a marked decrease in the titer of cold agglutinins and acid cold hemolysins, with reduction of thermal amplitude. At cessation of treatment, the titers again rose. Since lowering of cold agglutinin titer corresponds with reduction of thermal amplitude (e.g., 20 °C.) and cold sensitivity, further exploration of this biochemical approach is warranted.

Introduction Macroglobulins have, in recent years, been identified as normal constituents of human blood serum. Macroglobulinemia has been recognized in association with neoplastic, collagen, and chronic infectious diseases. There remains, however, a group of patients with the findings of macroglobulinemia unassociated with these entities. Ultracentrifugal, immunophoretic, and viscosity studies have provided further clarification of this disorder. The patients below illustrate two clinical types of primary macroglobulinemia. Of interest is the fact that the disease developed while both patients were under medical observation. In both, the macroglobulinemia was of the uncommon cryogelglobulinemia variety. Report of Cases Case 1. —A 55-year-old Turkish-born white American seaman was admitted to the U.S. Public Health Service Hospital, Galveston, Texas, on Sept. 17, 1957, with weakness, dyspnea, and cough of one month's duration. There was no associated hemoptysis or pedal edema. There was a past history of asthma and a subtotal gastrectomy and gastrojejunostomy performed in