J. Lawrence Naiman

A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction

In the past decade, we have studied four unrelated children with what we believe is a previously unreported disorder affecting the bone marrow and exocrine pancreas. During infancy these patients had the onset of severe, transfusion-dependent, macrocytic anemia plus a variable degree of neutropenia and thrombocytopenia. Their bone marrows had normal cellularity but were characterized by remarkable vacuolization of erythroid and myeloid precursors, hemosiderosis, and ringed sideroblasts. The vacuoles probably represented manifestations of cellular degeneration and death. In two patients, in vitro bone marrow cultures showed abnormal erythroid and myeloid progenitor cell growth and, in one child, abnormal vacuolated erythroid colonies. Family histories were unrevealing, parents were hematologically normal, and both sexes were involved. There was no evidence of specific nutritional deficiencies or exposure to agents associated with marrow vacuolization. A number of therapeutic interventions produced no effect. One child had clinical malabsorption. This child and one other had extensive pancreatic fibrosis at autopsy. The other two patients had findings indicating exocrine pancreatic dysfunction. Two children had splenic atrophy. This new syndrome, with associated bone marrow and exocrine pancreatic dysfunctions, differs in several respects from the syndrome of pancreatic liposis and neutropenia described by Shwachman et all and Bodian et al, and from other conditions with vacuolization of the marrow or sideroblastosis.

Platelet Size and Kinetics in Hereditary and Acquired Thrombocytopenia

Abstract Measurements of platelet size and life-0 span were obtained to classify a variety of thrombocytopenic states. The mean size index in idiopathic thrombocytopenic purpura was significantly increased, whereas platelets in the Wiskott–Aldrich syndrome were small. The platelet defect in a family characterized by thrombocytopenia, sex-linked recessive inheritance, small platelet size and shortened platelet life-span closely resembled that of the Wiskott–Aldrich syndrome, but only mild eczema was present and immunologic abnormalities were absent. In a second family, thrombocytopenia was associated with increased platelet size suggesting a young cell population similar to idiopathic thrombocytopenic purpura. However, autologous platelet life-span was normal. Size measurements are thus useful in the classification of thrombocytopenias. Although in acquired conditions increased platelet size suggests a young platelet population, in hereditary disease platelet size is determined more by the nature of the in...

Possible Graft-versus-Host Reaction after Intrauterine Transfusion for Rh Erythroblastosis Fetalis

Abstract An illness characterized by jaundice, aplastic anemia and striking histiocytic reaction in the bone marrow developed in an eight-week-old infant who survived three intrauterine transfusions for Rh erythroblastosis fetalis. Culture of peripheral blood lymphocytes suggested two populations of lymphocytes based on differences in Y-chromosome length. One of these resembled that of one of the donors of the intrauterine blood transfusions. In spite of initial hematologic improvement the infants condition deteriorated, with multiple infections and progressive weight loss until death at 13 weeks of age. Although lymphoid and thymic atrophy were evident at autopsy these changes were considered to reflect atrophy (secondary to a graft-versus-host reaction) rather than primary immunologic deficiency disease. This observation supports recommendations of others that blood intended for transfusion to the fetus be first rendered free of viable lymphocytes.

Iron deficiency anemia in a newborn infant.

Summary A newborn infant with documented iron deficiency due to protracted fetomaternal hemorrhage is described. The importance of distinguishing acute from chronic loss and the role of iron therapy are discussed.

Digitalis purpurea (Foxglove)

Figure 1. Digitalis purpurea (Foxglove). In 1775 William Withering demonstrated that the leaves of the foxglove plant alleviated certain forms of dropsy (edema), and in 1799 John Ferriar ascribed their beneficial effects to a primary action on the heart. All physicians have learned about digitalis, but few recognize its plant source. Digoxin, the preparation most commonly used in the United States, is derived from related plants, Digitalis lanata and D. orientalis.

Uric Acid Perturbations in the Hemolytic Uremic Syndrome

Although hyperuricemia has been found in a large number of disorders, (1) its occurrence in the hemolytic uremic syndrome (HUS) is not generally appreciated. (2,3) In 1969, while performing studies of the transperitoneal movement of solute (4) (including uric acid) in children undergoing their initial dialysis, we observed marked hyperuricemia disproportionate to the degree of renal failure in two infants with HUS. We have subsequently confirmed these observations in a series of 26 children with HUS and have performed studies in rabbits in an effort to identify the mechanism(s) leading to hyperuricemia. This report has four objectives: 1) to review our experience with and interpretation of uric acid metabolism in patients with HUS, 2) to present data which provide information on possible mechanisms for the hyperuricemia, 3) to consider uric acid metabolism in experimental models of hemolysis and acute and chronic renal failure, and 4) to review available literature on the subject of uric acid metabolism in renal failure.

Large erythrocytes in Down's syndrome: Their significance in relation to enzyme activity, gene dosage, and pyridoxine (B6) metabolism

A significant macrocytosis as reflected by increased packed cell volume and mean corpuscular volume, was found in a group of 12 institutionalized males with Downs syndrome compared to matched controls. There was no evidence of deficiency of vitamin B~, folic acid, pyridoxine, or iron to explain these differences. To determine whether the observed macrocytosis was attributable to a younger mean RBC age, erythrocyte glutamicoxaloacetic transaminase (EGOT) activity was measured. Also, because of previous reports of impaired tryptophane metabolism in Downs syndrome the question of B6 deficiency was investigated by the in vitro B,-stimulated EGOT; this was normal. However, base-line EGOT activity in the Downs syndrome group was significantly elevated when expressed in relation to red cells but not when related to hemoglobin concentration. This difference was present in both washed RBC and whole blood, although greater in the latter and presumably due to leukocytes with increased enzyme activity. Increased EGOT activity in association with macrocytosis suggests a younger mean cell age of the RBC population in Downs syndrome, and adds support to a similar explanation for the increased enzyme activity of WBCs in these patients, rather than the originally proposed gene dosage hypothesis. Failure to appreciate the macrocytosis in this condition may result in erroneous conclusions regarding the relation of RBC enzyme levels to gene dosage.