Monocytoid B-cell lymphoma: its evolution and relationship to other low- grade B-cell neoplasms

Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.     

Treatment with interleukin-3 plus granulocyte-macrophage colony- stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts

Hematopoietic growth factors (HGFs) interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) individually have been shown to increase the percentage of acute myeloid leukemia (AML) blasts in S phase and enhance the cytotoxic effects of Ara-C against these blasts in culture. We compared in vitro the effects of a combined treatment with GM-CSF (10 ng/mL) plus IL-3 (10 ng/mL) on the metabolism and cytotoxicity of Ara-C in normal bone marrow mononuclear cells (NBMMC) and AML blasts. NBMMC from six healthy volunteers and AML blasts from 10 patients were incubated for 20 hours with or without IL- 3 plus GM-CSF, followed by a concurrent treatment with Ara-C for 4 additional hours. Exposure to the HGFs and Ara-C produced significantly higher intracellular Ara-CTP levels as well as higher Ara-CTP/dCTP pool ratios in AML blasts as compared with NBMMC. Treatment with HGFs resulted in [3H] Ara-C DNA incorporation that was significantly higher in AML blasts versus NBMMC. This selective improvement of Ara-C metabolism in AML blasts was associated with an enhanced Ara-C-mediated leukemia colony-forming unit (CFU) growth inhibition. In contrast, exposure to HGFs resulted in an improved colony growth of normal CFU granulocyte-monocyte and CFU-granulocyte, erythroid, monocyte, megakaryocyte. These in vitro studies indicate that a combined treatment with IL-3 plus GM-CSF may improve the selectivity of Ara-C against AML blasts.     

Comparison of a parasite lactate dehydrogenase-based immunochromatographic antigen detection assay (OptiMAL) with microscopy for the detection of malaria parasites in human blood samples

Microscopic examination of blood smears remains the gold standard for malaria diagnosis, but is labor-intensive and requires skilled operators. Rapid dipstick technology provides a potential alternative. A study was conducted in The Gambia to compare the performance of OptiMAL, an immunochromatographic antigen detection assay for the diagnosis of malaria using parasite lactate dehydrogenase, against standard microscopy in patients with suspected malaria. For initial diagnosis of Plasmodium falciparum, irrespective of stage, this assay had a sensitivity of 91.3%, a specificity of 92%, a positive predictive value of 87.2%, and a negative predictive value of 94.7%. The sensitivity of the test decreased markedly at parasitemias < 0.01%. This assay can be used for the diagnosis of malaria in areas where microscopy is not available and for urgent malaria diagnosis at night and at weekends, when routine laboratories are closed and when relatively inexperienced microscopists may be on duty.     

Response to Diazepam in Sons of Alcoholics

Alcohol exerts several of its actions via the chloride channel associated with the central GABA-benzodiazepine receptor complex. To explore a possible role for this receptor complex in risk for alcoholism, and to determine whether risk for alcoholism is associated with risk for benzodiazepine abuse, the authors administered intravenous diazepam to 18 sons of male alcoholics (SOAs) and 18 control subjects. Four logarithmically increasing doses of diazepam and matched volumes of placebo were given in randomized order on separate days about 1 week apart. SOAs were significantly more likely than controls to report euphoric responses to diazepam. At some diazepam doses, SOAs were more likely to report feeling "high" and "intoxicated." SOAs and controls did not differ in feeling "drugged." SOAs and controls may differ in expectations regarding the subjective effects of drugs and/or in the function of the central GABA-benzodiazepine receptor complex. These findings also add further evidence for increased pleasurable effects, and thus possibly increased risk for benzodiazepine abuse, in a subgroup of SOAs.     

HbSC hemoglobinopathy suspected by chest x-ray and red blood cell morphology

Thorax scan was performed for elucidation of a pulmonary problem in a Nigerian immigrant. The aspect of the vertebrae suggested sickle cell disease, of course without specification of the genotype. Routine hematological tests seemed compatible with an HbSC disease, showing typical laboratory features, namely a significant proportion of hyperchromic RBC, corresponding to secondary, non hereditary spherocytosis, presence of numerous target cells and occasional HbC crystals on Pappenheim stained blood films. The diagnosis of HbSC disease was confirmed by HPLC, iso-electric focusing and citrate agar electrophoresis of hemoglobin and by reverse phase HPLC of globin-chains. This case illustrates the importance of screening for hemoglobin anomalies as it is performed in a multiethnic country such as the Grand Duchy of Luxembourg     

Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1^T478S, and JAK1^V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.     

Fractography and oxidative analysis of gamma inert sterilized posterior-stabilized tibial insert post fractures: Report of two cases

BackgroundHighly crosslinked ultra-high molecular weight polyethylene (UHMWPE) has shown success in reducing wear in hip arthroplasty but there remains skepticism about its use in Total Knee Replacement (TKR) inserts that are known to experience fatigue loading and higher local cyclic contact stresses.MethodsTwo Legacy Posterior-Stabilized (LPS) Zimmer NexGen tibial implants sterilized by gamma irradiation in an inert environment with posts that fractured in vivo were analyzed. Failure mechanisms were determined using optical and scanning electron microscopy along with oxidative analysis via Fourier Transform Infra-Red (FTIR) spectroscopy.ResultsMicrographs of one retrieval revealed fatigue crack initiation on opposite sides of the post and quasi-brittle micromechanisms of crack propagation. FTIR of this retrieval revealed no oxidation. The fracture surface image of the second retrieval indicated a brittle fracture process and FTIR revealed oxidation in the explant.ConclusionsThese two cases suggest that crosslinking of UHMWPE as a manufacturing process or sterilization method in conjunction with designs that incorporate high stress concentrations, such as the tibial post, may reduce material strength. Moreover, free radicals generated from ionizing radiation can render the polymer susceptible to oxidative embrittlement.Clinical relevanceOur findings suggest that tibial post fractures may be the results of in vivo oxidation and low level crosslinking. These and previous reports of fractured crosslinked UHMWPE devices implores caution when used with high stress concentrations, particularly when considering the potential for in vivo oxidation in TKR.