Inhibition of lymphoproliferation by hyperlipoproteinemic plasma.

Plasma for patients with primary type IV or V hyperlipoproteinemia inhibited [3H]thymidine incorporation by cultured mononuclear leukocytes. This previously unreported abnormality affected mononuclear leukocytes from patients with type IV or V hyperlipoproteinemia and from normal subjects. Patient cells incorporated [3H]thymidine normally when washed and incubated in medium containing normal plasma. Both spontaneous incorporation and stimulated incorporation in response to various mitogens and antigens were inhibited. The inhibitory effect was identified with the chylomicron and very low density lipoprotein fractions isolated from plasma and was concentration-dependent. Lectin used to stimulate cultured cells and [3H]thymidine used to measure responses were not bound to the lipoproteins in appreciable amounts. [3H]-Thymidine incorporation correlated well with morphologic evidence of lymphoproliferation. The mechanism of the inhibitory effect of type IV or V hyperlipoproteinemic plasma upon the response tested was not identified by may be related to interaction between lipoproteins and the cell membranes. We suggest that these lipoproteins may also interfere with the function of other cells.

Acquired Pelger-Huët nuclear anomaly with tuberculosis.

Karel Pelger described an abnormality of granulocyte nuclear segmentation in the context of advanced tuberculosis, but G. Huët questioned this association. It is now recognized that the Pelger-Huët nuclear anomaly (PHNA) can be either hereditary or acquired with systemic diseases, commonly hematologic dysplasias. An association with tuberculosis has never been well verified. The man described in our study had cachexia, high fevers, severe hypoproliferative anemia, and acquired PHNA. At autopsy, an overwhelming tuberculosis was discovered in the absence of any other underlying disease. Acquired PHNA may serve as a diagnostic and prognostic indicator in tuberculosis.

Chronic myelogenous leukemia. Association with 45 XO Philadelphia chromosome karyotype and prolonged survival.

A 42-year-old man with chronic myelogenous leukemia for ten years was found to have a 45 XO Philadelphia chromosome karyotype in myeloid cells with normal 46 XY pattern in peripheral blood lymphocytes. This chromosome pattern has been postulated to be associated with delay in onset of blastic transformation. The prolonged survival of this patient, with only minimal initial chemotherapy and lack of symptoms for ten years, lends support to the concept that the missing Y chromosome may be associated with a favorable prognosis in Philadelphia chromosome-positive men with chronic myelogenous leukemia.

Thrombotic thrombocytopenic purpura complicating Legionnaires' disease.

A case of Legionella pneumophila infection complicated by thrombotic thrombocytopenic purpura (TTP) was confirmed at autopsy by the demonstration of the organism in lung tissue, and by the finding of widespread intravascular and subendothelial thrombi associated with microinfarctions in all major organs examined. In addition to the typical hematologic abnormalities of TTP, the patient was found to have a low serum C3 level and elevated levels of immune complexes as measured by the liquid phase C1q binding assay. We suggest that the L pneumophilia infection caused endothelial damage and/or platelet aggregation, perhaps as a consequence of complement activation, thus initiating the sequence of events leading to extensive microvascular thromboses.

Polycythemia rubra vera and artifactual hypoglycemia.

A patient with polycythemia rubra vera had had a leukocyte count between 55,000 and 86,000/cu mm and had had serum glucose levels as low as 8 mg/dL. Despite these low serum glucose values, the patient was asymptomatic, and a more careful investigation disclosed that the hypoglycemia was artifactual. This phenomenon, reported in other leukemic states, to our knowledge, has not been previously described in patients with polycythemia rubra vera. Our case broadens the spectrum of the causes of artifactual low serum glucose concentration due to excessive glucose consumption by the WBCs. This phenomenon is related to extreme leukocytosis, regardless of the underlying disease. Unnecessary workup for hypoglycemia can be avoided if its artifactual nature is suspected in any patient with a reported low serum glucose level and high WBC count.

Smoldering acute granulocytic leukemia. Observations on its natural history and morphologic characteristics.

In this prospective study, 24 patients with smoldering acute granulocytic leukemia received no specific treatment. Median survival duration from diagnosis was 9.29 months. Fourteen patients died of infection, four died of hemorrhage, two (8%) progressed to aggressive acute leukemia, and three remain alive at 36, 32, and 10 months. No survival predictions could be made from the severity of leukopenia, thrombocytopenia, or both. Neither sepsis nor hemorrhage, as causes of death, segregated into short- or long-term survivors (9.0 and 8.75 months' median survival, respectively). Thirteen patients (59%) had French, American, and British M2 subclassification of acute granulocytic leukemia. The following marrow findings distinguished this entity from preleukemia and other dysplastic states: clustering of stem cells; percentage usually between 20% and 40%; and Auer rods. The use of aggressive chemotherapy v only supportive measures in this condition remains unsolved.

Basophils in peripheral blood and bone marrow. A retrospective review.

The records on 375 consecutive bone marrow aspirations were reviewed to establish the incidence and association of peripheral and bone marrow basophilia. Seventeen cases of peripheral basophilia were identified (4.5 percent incidence) and were associated with iron deficiency (five cases), lung carcinoma (four cases), anemia of undetermined cause (four cases), and chronic myelogenous leukemia, myelodysplasia, chronic renal failure, and acute myelogenous leukemia (one case each). There were six cases of marrow basophilia, including iron-deficiency anemia (two cases), sideroblastic anemia with myelodysplasia, mild dyspoiesis, anemia of chronic disease, and acute erythroleukemia. Marrow basophilia was significantly associated with myelodysplasia and sideroblastic anemia, but was not found in 37 patients with lymphoproliferative disorders. There were no instances of simultaneous marrow and peripheral basophilia. These data support the concept that marrow basophilia is a specific, although not sensitive, marker of disruption of the normal marrow maturation controls.

Hairy cell leukemia associated with focal vascular damage.

In a patient with hairy cell leukemia, segmental vascular alterations developed in many of the larger visceral arteries. In previously reported instances of this association, the vasculitis resembled polyarteritis nodosa. In contrast, in the present case the vessels did not show the typical necroses, polymorphonuclear infiltrates, and aneurysmal changes. Instead, vascular alterations consisted of edema, fibrosis, and infiltration by tumor cells. A possible pathogenetic mechanism for these findings may be a local immunologic interaction of tumor cells and vessels, suggesting a direct relation between hairy cell leukemia and vascular damage.

Crisis in sickle cell trait.

A 34-year-old black male with hemoglobin AS was admitted for renal failure, polydipsia, hypertension, schizophrenia, mental confusion, and visual hallucinations. Abnormal electrolytes were corrected by dialysis, but blood specimens were reported as hemolyzed with hyperkalemia. Peaked T waves on electrocardiographic analysis were followed by cardiac arrest. An autopsy revealed sickled cells in the visual cortex and other symptomatic organs, but normal erythrocytes in most of the vascular tree. These findings suggest true progressive sickle cell crisis in a hemoglobin AS patient.

Serum folate levels. Comparison of microbiologic assay and radioisotope kit methods.

Serum folate levels were measured prospectively in 72 patients and six normal controls using the Lactobacillus casei microbiologic method and a commercially available sequential-binding radioassay kit method. Values between 0 and 14 ng/ml (0 and 31.78 nmol/l) (clinically significant range) obtained by the microbioassay and sequential-binding radioassay were analyzed statistically. The data suggest that comparable values are obtained by the two technics (Y = 0.9 X where Y = radioassay value). Data obtained by the sequential-binding radioassay and a competitive protein-binding radioassay kit were then compared and subjected to statistical analysis. Values obtained by the two radioassay methods were found to be comparable clinically, but significantly different statistically. The authors conclude that these commercially available radioassay kits for measuring serum folate yield reliable values that can be applied to the clinical evaluation of patients with anemia, and can be readily performed in a clinical radioisotope laboratory.

Acute myeloblastic leukemia following chemotherapy for mycosis fungoides.

The development of acute myeloblastic leukemia following therapy for malignant disorders is being recognized with increasing frequency. Acute myeloblastic leukemia (erythroleukemic variant) developed in a patient with mycosis fungoides following three years of chemotherapy with a variety of antineoplastic drugs. The patient demonstrated a hypodiploid chromosomal abnormality with a missing C group chromosome.

Abnormal platelet function in myeloproliferative disorders.

Platelet aggregation and circulating platelet aggregates (CPAs) were evaluated in 18 patients with myeloproliferative disorders, both with and without thrombocytosis. No specific patterns of platelet aggregation were detected, but 11 of 18 patients demonstrated abnormal aggregation to epinephrine, nine of 18 had abnormal aggregation to adenosine diphosphate, and seven of 18 had abnormal aggregation to collagen. There was no definitive correlation of bleeding episodes with abnormal aggregation. However, significant bleeding was observed in a patient with a platelet count of 1,500,000/cu mm and abnormal aggregation. The aggregation defects persisted despite lowering of platelet count. Evidence of increased circulating platelet aggregates and normal platelet aggregation was seen in two patients, one of whom had transient cerebral ischemic attacks relieved by antiplatelet therapy, with return of the CPA index to normal. In two patients with digital ischemia, claudication, and angiographic evidence of peripheral vascular disease, no laboratory evidence of increased circulating platelet aggregates was observed, but one patient had regression of symptoms with antiplatelet therapy.

The lupus anticoagulant in 14 male patients.

Fourteen male patients examined for a prolonged partial thromboplastin time were found to have the lupus anticoagulant. In contrast to previous reports, there was no increased incidence of false-positive results of serological tests for syphilis. In only two patients was systemic lupus erythematosus confirmed, although two additional patients had a positive result of a test for antinuclear antibody. Other clinical diagnoses included peripheral vascular disease, cardiac disease, pulmonary disease, and schizophrenia. Prothrombin times were distinctly abnormal in only two patients. Bleeding was rarely encountered in these patients, including ten who underwent surgical procedures or some type of hemostatic challenge. Thrombocytopenia was not associated with bleeding but was present in two patients who had thrombotic events.

Idiopathic thrombocytopenic purpura occurring in Hodgkin disease after splenectomy: report of two cases and review of the literature.

The occurrence of idiopathic thrombocytopenic purpura (ITP) in Hodgkin disease is uncommon. Even more unusual is the development of ITP in Hodgkin disease following splenectomy. This report describes two patients with Hodgkin disease who developed severe ITP with negative platelet antibody studies very soon after splenectomy (20 days in one and three months in the other). A review of the literature of 21 other patients with well-documented ITP and Hodgkin disease indicated that ITP occurring in Hodgkin disease may be more severe and refractory to therapy than ITP unassociated with Hodgkin. Nodular sclerosis or mixed cellularity histologic types of Hodgkin disease were present in all but one of the patients with ITP and Hodgkin disease, and males constituted 65% of cases. There appeared to be no correlation between the onset of ITP and activity of Hodgkin disease. Of five splenectomized patients with Hodgkin disease who developed ITP and were treated with immunosuppressive drugs for thrombocytopenia, three had an excellent response and two had a good response, suggesting that the combination of corticosteroids and immunosuppressive drugs may be indicated at the outset in patients with Hodgkin disease who develop ITP following splenectomy.

Erythrocytosis and marked leukocytosis in overlapping myeloproliferative diseases.

We describe two patients who had similar features of erythrocytosis and marked leukocytosis but who were subsequently classified as having chronic myelogenous leukemia and polycythemia vera, respectively, using leukocyte alkaline phosphatase scores and cytogenetic studies to detect the Philadelphia chromosome. The patient diagnosed as having polycythemia vera had a leukocyte count of 164,000/cu mm, which remained at similar levels when the patient was not in remission. We believe this is the first well documented case of PV with a leukocyte count above 150,000/cu mm.

Plasma prekallikrein (Fletcher factor) deficiency in a patient with chronic lymphocytic leukemia.

We have described the first patient to be reported in whom plasma prekallikrein (Fletcher factor) deficiency and chronic lymphocytic leukemia were both present. This most likely represents a coincidental occurrence, but the markedly elevated peripheral blood lymphocyte count and the detection of the defect using ellagic acid are unique for Fletcher factor deficiency.

Acquired factor VIII inhibitor in a patient with mycosis fungoides.

Acquired factor VIII inhibitors have been noted in patients with hemophilia A (factor VIII deficiency), in nonhemophilic individuals with various collagen-vascular diseases, in certain normal women following parturition, and occasionally in elderly individuals with no underlying diseases. This study describes the first reported instance of a factor VIII inhibitor in a patient with mycosis fungoides who had bleeding manifested by gross hematuria. Treatment with corticosteroids and cryoprecipitate was followed by cessation of hematuria within two weeks. The patient had one episode of shoulder pain presumably related to hemarthrosis. Immunosuppressive therapy with cyclophosphamide was instituted in an attempt to decrease antibody production and control skin involvement of mycosis fungoides. Factor VIII inhibitor level rose to 100 Bethesda units without further serious bleeding. There was no peripheral blood evidence of Sézary syndrome. It is possible that some patients with cutaneous T-cell lymphomas, such as mycosis fungoides and Sézary syndrome, may have an increase in helper T-cells which may lead to excessive B-cell activity and overproduction of antibodies.

Selective uptake of 75Se-selenomethionine by thymoma with pre red cell aplasia.

Red cell aplasia and an enlarging anterior mediastinal mass developed in a patient being followed for thyroid carcinoma. Differential diagnosis included thymoma and metastatic thyroid carcinoma. Preoperative scanning demonstrated significant uptake of 75Se-selenomethionine whereas 67Ga-galiium citrate failed to visualize the mass. Subsequent thoracotomy revealed a lymphocytic thymoma which was resected, resulting in reversal of the red cell aplasia. The use of 75Se-selenomethionine scanning maybe a useful adjunct in the preoperative evaluation of suspected thymomas.