Mark M. Udden

Donor cell leukemia : Report of a case occurring 11 years after allogeneic bone marrow transplantation and review of the literature

We report the case of a man with chronic myelocytic leukemia (CML) and a 46,XY,t(5;9;22) karyotype who developed acute myelocytic leukemia (AML) with a 45,X,t(8;21) karyotype 11 years after bone marrow transplantation (BMT) from his HLA‐matched sister. Fluorescent in situ hybridization (FISH) studies and molecular analysis using short tandem repeat (STR) sequences proved the new leukemia to be of donor cell origin. Donor cell leukemia (DCL) after BMT is rare. Our review of the literature found 15 cases following BMT for leukemia and 2 cases after BMT for benign hematological disorders. In fewer than half the reported cases were molecular studies available to confirm the cytogenetic evidence for DCL, and the longest previously reported interval between BMT and DCL was 6 years. Am. J. Hematol. 63:46–53, 2000.

Regression of a Plasmablastic Lymphoma in a Patient with HIV on Highly Active Antiretroviral Therapy

We describe an HIV-infected 44-year-old man who presented 1 month after discontinuation of HAART therapy with a large mass extending from the mediastinum, enclosing the heart and extending through the diaphragm to the epigastric region. Biopsies subsequently revealed a highly aggressive non-Hodgkins lymphoma (NHL) producing sheets of cells with an organoid distribution. The cells had abundant basophilic cytoplasm and a plasmacytic appearance. Although immunohistochemistry failed to show either B- or T-cell markers, antigens consistent with plasma cells were found. An immunoglobulin heavy chain clonal rearrangement was identified by PCR analysis. These studies were supportive of a diagnosis of a plasmablastic lymphoma. While awaiting the results of these tests, the patient was reinitiated on his HAART regimen. He was found on follow-up a month later to have complete resolution of his bulky mediastinal mass. He remained free of disease for 3 months with subsequent rectal and abdominal recurrence. Treatment with CHOP chemotherapy with filgrastim support was begun which resulted in another remission. Plasmablastic lymphoma is now reported in some studies to account for 2.6% of all HIV-related NHL. Originally described in 1997 in a series of 16 patients, this entity is highly associated with HIV infection in its later stages. Often, patients present with oral or jaw lesions with a rapidly progressive course. The tumors have the morphologic appearance of a plasmacytoid tumor with high proliferative index. Markers are positive mainly for LCA, CD79a, VS38C, and CD138. Co-infection with HHV-8 and EBV has not been consistently reported. Therapy with standard regimens has variable response. One case has been reported with a 3.5 year disease free survival. The regression of disease after resumption of HAART therapy alone in this patient suggests that HAART has an important role in the treatment of lymphoma in the HIV infected patient.

Danaparoid for heparin‐induced thrombocytopenia: an analysis of treatment failures

Background: Patients with heparin‐induced thrombocytopenia (HIT) (with or without thrombosis) require alternative anticoagulation because of their extreme risk of new thromboembolic complications. The first effective agent for this purpose may be danaparoid, a less‐sulfated low molecular weight heparinoid. Recently, direct thrombin inhibitors have been used.

Rat erythrocyte morphological changes after gavage dosing with 2‐butoxyethanol: a comparison with the in vitro effects of butoxyacetic acid on rat and human erythrocytes

Rats exposed to 2‐butoxyethanol (2‐BE) develop hemolysis preceded by red blood cell swelling and shape changes. In this study effects on red blood cell morphology of dosing rats with 2‐BE by gavage were compared with the effects of incubation of rat erythrocytes in vitro with the principal metabolite of 2‐BE, butoxyacetic acid (BAA). Morphology was assessed by bright‐field and phase microscopy of Wrights stained blood smears and glutaraldehyde‐fixed cells suspended in plasma or buffer. In vivo exposure to 2‐BE resulted in stomatocytosis and spherocytosis in blood smears and cup‐shaped cells and spherocytosis in the fixed samples. In vitro incubation with BAA produced erythrocytes with cup shapes, spherocytosis and red blood cell ghosts in fixed samples. The stomatocytes observed in the blood smears appear to be the morphological equivalents of the cup‐shaped cells observed in fixed samples. A variable degree of echinocytosis was observed in blood smears from animals exposed to 2‐BE and in the in vitro experiments with BAA. Stomatocytes, cup‐shaped cells, and spherocytes are the principal morphological features of erythrocytes from rats exposed to 2‐BE or in vitro exposure to BAA. In comparison, human red blood cells incubated with up to 2.0 mM BAA exhibited none of the morphological changes observed in rat erythrocytes. 2‐Butoxyethanol in vivo and BAA in vitro cause similar changes in rat red blood cell morphology, adding further evidence to support the primary role of BAA in the hemolytic effect of 2‐BE exposure in the rat. Copyright

Bone Marrow Histiocytic Hyperplasia and Hemophagocytosis with Pancytopenia in Typhoid Fever

Typhoid fever was associated with pancytopenia in five patients. Bone marrow examinations revealed histiocytic hyperplasia with marked phagocytosis of platelets, leukocytes, and red blood cells in these individuals. This phagocytosis may contribute to the pancytopenia that occurs in some patients with typhoid fever. The striking degree of the histiocytic hemophagocytosis is reminiscent of the malignant disease, histiocytic medullary reticulosis. The importance of careful exclusion of infectious etiologies in illnesses involving marrow histiocytic proliferation is emphasized.

Treatment of refractory thrombotic thrombocytopenic purpura with N-Acetylcysteine: A case report

Thrombotic thrombocytopenic purpura (TTP) is a life‐threatening disease resulting in systemic microvascular thrombosis. The disease is caused by excessive platelet (PLT) adhesion to ultra‐large (UL) von Willebrand factor (VWF) multimers inadequately cleaved by the processing enzyme ADAMTS‐13. While many cases respond to plasma exchange performed with or without concurrent corticosteroids, treatment of the 10% to 20% of patients with refractory disease is difficult. Experimental studies demonstrating that N‐acetylcysteine (NAC) inhibits PLT binding to endothelial cell–secreted and anchored UL VWF multimers suggest that NAC may be useful in the treatment of TTP.

Carboxyhemoglobin Levels in Patients with Sickle-Cell Anemia: Relationship to Hemolytic and Vasoocclusive Severity

Background: When carbon monoxide binds to hemoglobin, it increases the affinity of hemoglobin for oxygen and shifts the oxygen dissociation curve to the left. The resulting decrease in sickling tendency could have clinical benefit, and carbon monoxide has been suggested as a treatment for sickle‐cell disease. Furthermore, in sickle‐cell disease, as in other hemolytic diseases, endogenous carbon monoxide production is increased because of increased heme catabolism. Methods: In the present study, we measured carboxyhemoglobin levels in sickle‐cell patients and compared them with estimates of the hemolytic and the vaso‐occlusive severity of the disease. Results: Significant correlation was found between carboxyhemoglobin (HbCO) levels and hematocrit, reticulocyte count, unconjugated bilirubin level, and percentage of irreversibly sickled cells. However, there was no significant correlation between carboxyhemoglobin levels and measures of the vaso‐occlusive severity of the disease. Conclusions: The correlations between HbCO levels and measures of hemolytic severity are best explained by the known relationship between hemoglobin catabolism and CO production. The lack of correlation with vaso‐occlusive severity may be due to the complex changes involved and the difficulty of quantifying vaso‐occlusive severity.

Reduced erythrocyte deformability associated with calcium accumulation

Abstract Erythrocytes exposed to subhemolytic shear stress in vitro exhibit decreased deformability as determined by a filtration method. Intracellular calcium content of these cells has been measured by atomic absorption spectroscopy and found to be 35 and 55% higher than controls (0.0157 μmol/ml packed red blood cells) after shear stress levels of 100 and 130 N/cm 2 , respectively. These alterations occur without significant changes in ATP level, intracellular magnesium content, cell volume, or morphology, and without large associated sodium and potassium fluxes. Results indicate that calcium may be responsible for or associated with changes in the viscoelastic properties of the red cell membrane caused by sublytic mechanical trauma.

Pure red cell aplasia associated with hepatitis C infection.

We report the case of a 34-year-old woman with recurrent pure red cell aplasia and evidence of hepatitis B and C infection. Review of the English literature identified 19 prior cases in which pure red cell aplasia was associated with hepatitis. This case is the first in which serologic evidence of hepatitis C infection was documented. This patient also had porphyria cutanea tarda and marked hepatic siderosis but no active hepatitis or cirrhosis. Treatment with cyclophosphamide and prednisone produced complete remission of the pure red cell aplasia. Erythroid colony formation (colony-forming unit-erythroid and erythroid burst-forming unit) was reduced in cultures of bone marrow obtained during relapse but was normal in remission marrow. However, addition of the patient serum, whether collected during relapse or remission, inhibited erythroid colony formation by her bone marrow. These observations, and the known extrahepatic immunologic manifestations of hepatitis C infection, suggest that the pure red cell aplasia occurred because of autoimmune mechanism provoked by the infection.

Internal Medicine Clerkship Characteristics Associated With Enhanced Student Examination Performance

Purpose To determine which internal medicine (IM) clerkship characteristics are associated with better student examination performance. Method The authors collected data from 17 U.S. medical schools (1,817 students) regarding characteristics of their IM clerkships, including structural characteristics, pedagogical approaches, patient contact, and clinical teacher characteristics. Outcomes of interest were postclerkship National Board of Medical Examiners (NBME) subject examination score, United States Medical Licensing Examination (USMLE) 2 score, and change in score from USMLE 1 to 2. To examine how associations of various clerkship characteristics and examination performance may differ for students of different prior achievement, the authors categorized students into those who scored in the top ¼ of the cohort on USMLE 1 and the bottom ¼. The authors conducted analyses at both the school and the individual student levels. Results In school-level analyses (using a reduced four-variable model), independent variables associated with higher NBME subject examination score were more small-group hours/week and use of community-based preceptors. Greater score increase from USMLE 1 to 2 was associated with students caring for more patients/day. Several variables were associated with enhanced student examination performance at the student level. The most consistent finding was that more patients cared for per day was associated with higher examination performance. More structured learning activities were associated with higher examination scores for students with lower baseline USMLE 1 achievement. Conclusion Certain clerkship characteristics are associated with better student examination performance, the most salient being caring for more patients per day.