Recovery from aplastic anemia following therapy with antithymocyte globulin.
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Biomedical subjects
Publications and source records attributed to Z Zeigler.
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A 17-year-old female developed severe aplastic anemia following serologically proven infectious mononucleosis. In vitro studies, using the granulocyte colony forming technique, suggested that the aplasia may have resulted from an immune mechanism. The patient's marrow grew no granulocyte colonies and caused inhibition of colony formation when mixed with normal marrows. The patient recovered fully after therapy with antithymocyte globulin and marrow cultures showed disappearance of the inhibitory effect. These observations suggest that the severe aplasia may have resulted from an aberrant immune response which followed infection by EB virus.
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A case of posttransfusion purpura was notable for the manner of antibody detection and response to therapy. The antibody failed to fix complement but was detected by platelet aggregometry studies and confirmed by the chromium 51 release assay. The course was unaffected by plasmapharesis.
A 29-year-old Chinese male developed severe aregenerative anemia. The bone marrow was diffusely hypercellular with increased marrow reticulin and a persistent failure of erythroid differentiation beyond the pronormoblast stage. Although he did not manifest classic features of systemic lupus erythematosus, multiple serologic studies were in accord with this diagnosis. The patient's defect in erythropoiesis was studied by an in vitro technique for the growth of erythroid colonies. Despite the severe erythroid hypoplasia, the patient's marrow yielded abundant large erythroid colonies. Serum erythropoietin activity was high as judged by use of this in vitro assay. Although the patient's native serum did not affect colony formation, a separated IgG fraction was markedly inhibitory to colony growth. This suggests that the erythroid hypoplasia may have resulted from a unique autoantibody. The patient's hematologic abnormalities completely reversed following treatment with corticosteroids.
Microscopic evaluation of apparent platelet size and morphology was examined in a variety of hematologic disorders. The time of preparation of the blood smear was important. An artifactual increase in platelet size was noted on blood films from 20 normal individuals that were prepared either immediately or 180 min after venipuncture. The clearest differentiation of patient categories was obtained with smears prepared 60 min after venipuncture using blood anticoagulated with K3EDTA. Under these conditions, normal size and morphology values were found in thrombocytopenic patients with aplasia or with increased splenic pooling. In contrast, large size values were a reliable finding in idiopathic thrombocytopenic purpura patients, whose platelet counts were less than 50,000/microleter. Large size values were also noted in patients with infiltrated bone marrows or myeloproliferative syndromes regardless of the platelet count. The last two groups usually showed abnormal platelet morphology with greater than 10% hypogranular platelets. Normal platelet size and morphology were observed in patients with iron-deficiency and megaloblastic anemias and in patients with idiopathic thrombocytopenic purpura and systemic lupus erythematosus who had normal platelet counts.
Following extensive bowel resection, a young woman experienced severe malnutrition; subsequent administration of parenteral nutrition precipitated the copper deficiency syndrome. This consisted of hypocupremia, subnormal ceruloplasmin levels, anemia, and severe neutropenia. The bone marrow was megaloblastic, vacuolated, and sideroblastic; granulocytic maturation was not observed beyond the myelocyte stage. Copper sulfate therapy was followed by a marked reticulocytosis, increase in hematocrit, and recovery of neutrophils. Additional studies indicated that both serum and urinary erythropoietin values were low; serum activity increased after copper supplementation. Abnormal granulopoiesis was demonstrated using the in vitro granulocyte colony assay. The patient's granulcoytic stem cells were normal on two occasions; however, mixing studies showed that culture of the patient's copper-deficient marrow with her copper-deficient serum yielded significantly reduced numbers of granulocyte colonies. Thus, copper appears to be a necessary element for normal hematopoiesis; lack of this trace element may result in ineffective erythropoiesis and granulopoiesis.
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Mononuclear cells from seven patients with hairy cells leukaemia were examined for features suggestive of either a lymphocytic or monocytic origin. Immunofluorescent staining of both methanol fixed and incubated cells, using monospecific antisera, revealed a predominant cell-associated immunoglobulin in each case. Three were positive for mu and kappa chains, two for gamma and kappa chains, one for delta and kappa chain determinants and one reacted only with antigamma chain serum. Formation of EAC rosettes, a feature of both B lymphocytes and monocytes, was variable. T cells, as judged by E rosettes, were not elevated in any patient. Phytohaemagglutinin reactivity was normal in six and depressed in one case. With the exception of minimal activity in assays for glass adherence and latex particle phagocytosis, none of the cells showed features typical of monocytes. Hairy cells were negative by peroxidase stain and lacked the electron microscopic characteristics of monocytes. They did not react in either rosette or phagocytic assays with anti-A or anti-D coated erythrocytes nor did they elaborate granulocyte colony stimulating factor, a monocyte-derived in vitro granulopoietin. Although unequivocal classification of these abnormal cells is not possible, the data storngly suggests that this represents a variant of a B lymphocytic neoplasm.
We studied a patient with acute myeloblastic leukemia, hypercalcemia, hypophosphatemia and inappropriately elevated serum parathyroid hormone levels to define the mechanism of the hypercalcemia. On six occasions during two years, hypercalcemia occurred in conjunction with relapses of leukmia. Each time, serum calcium decreased to normal levels in parallel with reduction of the leukemic mass. During two periods of hypercalcemia, immunoreactive parathyroid hormone values were abnormally high. In addition, hormone was detected in vitro after short-term incubation of the leukemic cells (after 24 hours, the patient's cells produced 129 pg of PTH per milliliter, whereas myeloblasts from a normocalcemic patient with leukemia produced only 33 pg). In freeze-thawing experiments, 39 pg of parathyroid hormone was released form 1 x 108 of the patient's myeloblasts; no hormone was released from the normocalcemia cells. These findings suggest that the hypercalcemia resulted from ectopic parathyroid hormone production by leukemic cells.
Three new patients with post-transfusion purpura (PTP) are described. As the manifestations in two differ significantly from those of previously reported cases, they serve to expand the definition of this syndrome. Although all 14 previously reported cases have occurred in Pl-A1-negative females, one of our patients was a Pl-A-negative male. Moreover, a female whose postrecovery platelets possessed the Pl-A1 antigen is described. Antiplatelet antibody activity was detected in all three patients by the 51Cr release test; in contrast, only one reacted in the complement (C) fixation assay. Serum obtained during the acute episode from the PlA1-positive patient reacted against platelets from four of 11 normals by C fixation and against platelets from 48 of 53 normals by 51Cr release, including five of nine Pl-A1-negative platelet samples. This case represents the first instance of PTP in which the platelet isoantibody was not specifically directed against the Pl-A1 antigen. These observations suggest that PTP may be a more heterogeneous disorder than previously realized.