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A case of myoglobinuria of idiopathic origin is described. A diagnostic triad of (1) muscular pseudoparalysis, (2) a highly colored urine containing a benzidine positive pigment, and (3) plasma free from visible discoloration was present. Identification of the urinary pigment as myoglobin was established by spectrophotometry, and the presence of accompanying metmyoglobinuria was detected. Exercise of the lower extremities was the precipitating factor during each attack of myoglobinuria. Attempts to induce attacks by means other than exercise were unsuccessful, and no amelioration of myoglobinuria could be produced by treatment with ascorbic acid or cortisone. The myoglobinopathies are discussed together with the present concept of the physiology of myoglobin. The differentiation of myoglobinurias from hemoglobinuria and porphyrias is readily accomplished by the laboratory procedures indicated above.

Forty-two patients with various diseases of leukocytic proliferation were treated with one or more courses of adrenocorticotropic hormone or cortisone. Of 13 patients with acute or subacute lymphocytic leukemia who received adequate courses of treatment, 9 (69 per cent) developed objective and hematologic evidence of well defined remissions. Remissions were, however, brief, lasting one to ten weeks. Retreatments produced further remissions but a state of refractoriness was eventually reached. Of 5 patients with acute granulocytic leukemia only 1 showed a slight clinical improvement with therapy. An actual acceleration of the process occurred in 2 cases. Two cases of monocytic leukemia showed no response and death seemed to be hastened. In 5 cases of chronic lymphocytic leukemia, distinct improvement occurred in 4, particularly in those showing terminal leukemia with anemia, exfoliative dermatitis, or symptomatic hemolytic anemia. All of 5 cases of lymphosarcoma showed some degree of improvement. Features benefited were organ enlargement, symptomatic hemolytic anemia and anemia. In 5 cases of Hodgkin’s disease, 3 were notably benefited particularly with respect to constitutional symptoms. There was, however, no fundamental alteration of the disease process. Only 1 case of 5 with multiple myeloma showed a favorable response. Hyperglobulinemia decreased to a variable extent in all cases, as did Bence-Jones proteinuria. The characteristics of remission including reticulocytosis, thrombocytosis, white cell response and marrow picture are detailed. The effect of ACTH on the level of serum globulins, the activity of abnormal hemagglutinins, and sedimentation rate are likewise discussed. The nonspecific effects of adrenocorticotropic therapy are indicated. Comment is made of the undesirable effects of ACTH therapy. These included psychoses, fluid retention, hypertension, convulsions, porcine, obesity, acne, hirsutes and diabetes mellitus. The therapeutic effectiveness of ACTH is compared with the existing available methods of therapy in the hematologic conditions under discussion.

Twenty-four cases of malignant lymphocytic disease associated with frank hemolytic anemia are reviewed. Four cases were associated with some form of lymphosarcoma and twenty cases appeared in conjunction with chronic lymphocytic leukemia. In the latter cases, the hemolytic process was detected in eleven patients from one-half to five years after the original diagnosis had been established. In three patients, a positive Coombs’ test antedated the development of any other evidence of a hemolytic process by either several months or a year. In a significant number of cases, x-ray therapy seemed to precipitate the appearance of the abnormal hemolysis. In nine other patients, only when symptoms referable to hemolytic anemia necessitated medical aid, was the lymphocytic leukemia detected. Of the four patients with lymphosarcoma, three presented themselves initially as cases of hemolytic anemia. The primary diagnosis was uncovered only after lymph node biopsy or laparotomy. The physical examination in both disease groups represented a combination of the findings associated with hemolytic anemia and lymphocytic disease. In the cases of chronic lymphocytic leukemia, this led to splenomegaly of unusual degree and disproportionate to the size of the lymphadenopathy. The laboratory findings likewise combined the features of both the primary lymphocytic disorder and hemolytic anemia. Anemia, reticulocytosis, spherocytosis, and bilirubinemia of the indirect type were present, and in the cases of lymphocytic leukemia, elevated white cell counts with diminished platelet counts were found. The bone marrow in many instances represented a "duality of proliferation", hyperplasia of erythroid and lymphoid elements existing side by side. Immunologic studies clearly indicated that the mechanism of hemolysis in these cases differed in no respect from that of "idiopathic" auto-immune hemolytic anemia. The direct Coombs’ test was positive in all twenty cases in which it was employed, and circulating hemagglutinins were demonstrated in eleven of nineteen cases so tested. The multiplicity of laboratory indications of hemolysis, as well as the distinct immunologic mechanism, distinguish these cases of hemolysis from the so-called "occult" hemolytic anemia. The term "overt" hemolytic anemia has been used to emphasize the difference. The role of the lymphoid apparatus in the production of such auto-immune hemolytic anemia is discussed. The bulk of evidence would seem to implicate some cellular component of the lymphoid system, although not the adult lymphocyte, as the producer of antibody. The architectural disruption of this system in malignant lymphocytic disease might well have a functional counterpart with respect to its immunologic duty. The resultant aberration may manifest itself clinically as auto-immune hemolytic anemia. At present the therapy of choice for control of the hemolytic process is ACTH, Compound E or Compound F. Transfusions and splenectomy are useful ancillary measures when hormonal therapy is either partially or totally unsuccessful. The hemolytic component should be treated independently of the lymphocytic proliferation since control of both cannot be established by any one agent currently available.