Biomedical subjects

Ayalew Tefferi

Publications and source records attributed to Ayalew Tefferi.

191 records · Page 11Linked to original sources

PubMed2002

The prognostic significance of trisomy 8 in patients with acute myeloid leukemia.

Recent therapeutic outcomes for patients with acute myeloid leukemia and trisomy 8 (+8) who were seen at our institution were investigated. Complete remission was achieved in 85% with isolated +8, 100% with +8 and chromosomal abnormalities predictive of a favorable outcome, and 47% of patients with +8 and other, mostly complex chromosomal abnormalities. Median relapse-free and overall survivals in months were 5.5 and 12 (isolated +8), 20 and 25 (+8 and favorable karyotype), and 7.5 and 6 (+8 and unfavorable karyotype). Despite an encouraging rate of complete remission, the relapse-free and overall survivals for patients with isolated +8 were not significantly different from those of patients with +8 and unfavorable karyotypes. The presence of +8 did not appear to adversely affect the outcome of patients with favorable karyotypes.

Acute Disease↗

PubMed2002

Methotrexate induced seizures associated with acute reversible magnetic resonance imaging (MRI) changes in a patient with acute lymphoblastic leukemia.

A 27-year-old woman with acute lymphoblastic leukemia (ALL) had an episode of generalized tonic-clonic seizure after therapy with intrathecal and intravenous methotrexate (MTX). Magnetic resonance imaging (MRI) of her head showed meningeal, cortical and subcortical enhancement that was new when compared to a study done prior to therapy. Subsequent imaging 10 days later showed partial resolution of these findings. The association of seizures and MTX in ALL and the corresponding MRI changes are discussed.

Adult↗

PubMed2002

A review of angiogenesis and anti-angiogenic therapy in hematologic malignancies.

Tumor angiogenesis is currently not only a concept but has also become a rationale for the therapeutic use of both old and new drugs that might affect new blood vessel formation. There is growing evidence that angiogenesis is as important in hematologic malignancies as it is in solid tumors. Both myeloid and lymphoid disorders may be accompanied by a prognostically detrimental increase in bone marrow microvessel density. In this review, we summarize the current literature as well as our own studies regarding bone marrow angiogenesis and the use of anti-angiogenic treatment in hematologic disorders. Background information on pathogenesis and laboratory methods of quantifying bone marrow angiogenesis is also discussed.

Angiogenesis Inhibitors↗

PubMed2002

Bone marrow angiogenesis in systemic mast cell disease.

Mast cells may participate in tumor angiogenesis through the release of angiogenic cytokines from their secretory granules. To gain additional insight into the role of mast cells in bone marrow angiogenesis, we performed a semiquantitative measurement of bone marrow microvessel density in 52 consecutive adult patients with systemic mast cell disease (SMCD). The results were examined for potential correlations with mast cell expression of angiogenic cytokines and with other histologic features of the bone marrow. Standard immunohistochemical methods were used to visualize bone marrow microvessels (CD34 staining) and mast cell expression of transforming growth factor-beta, basic fibroblast growth factor, and their respective receptors. An increase in microvessel density was demonstrated in 32 of the 52 patients (62%) with SMCD, and the degree of bone marrow angiogenesis did not correlate with either the mast cell expression pattern of the study cytokines or the presence (23 patients) or absence (29 patients) of an associated hematologic disorder. In the 29 patients without an associated hematologic disorder, microvessel density was correlated significantly with the presence of an abnormal pattern of hematopoiesis but not with the degree of bone marrow involvement by mast cells. Furthermore, areas occupied by mast cell lesions were often devoid of neovascularization. We conclude that bone marrow angiogenesis characterizes a percentage of patients with SMCD and that the pathogenesis may not necessarily be linked to the mast cells themselves.

Antigens, CD34↗

PubMed2002

Cytogenetic and molecular genetic aspects of essential thrombocythemia.

Essential thrombocythemia (ET) is a chronic myeloid disorder that is characterized by thrombocytosis, thrombohemorrhagic and vasomotor symptoms, a long median survival, and a low risk of transformation to leukemia. ET can be difficult to distinguish from secondary (reactive) thrombocytosis, and the diagnosis of ET can only be made after the exclusion of other marrow disorders with similar features. Although ET has been assumed to be a clonal process, recent studies have suggested that a substantial number of cases classified as ET may actually not be clonal, and nonclonality may be associated with a lower risk of thrombosis. The lack of a characteristic cytogenetic marker for ET confounds analyses of clonality and offers no insight into disease pathogenesis. There is controversy over the proper classification of thrombocytosis associated with the pathological BCR-ABL gene rearrangement; such cases are not clearly distinguishable from chronic myelogenous leukemia (CML) and should be provisionally classified as CML. New insights are emerging into the role of the megakaryocytopoiesis regulator thrombopoietin (TPO) and its receptor, c-Mpl, in ET and related disorders, but TPO-Mpl dynamics appear to be complex. In some familial thrombocythemic syndromes, mutations in the 5' untranslated region of TPO have recently been described, but these have not yet been observed in sporadic ET. In the future, global analysis of gene expression patterns may help overcome diagnostic dilemmas, refine disease classification, and lead to an improved understanding of the pathogenesis of ET.

Chromosome Aberrations↗

PubMed2002

Systemic mast cell disease without associated hematologic disorder: a combined retrospective and prospective study.

OBJECTIVE: To study clinicopathologic correlations and identify prognostically important variables in patients with systemic mast cell disease (SMCD) who have no associated hematologic disorders. PATIENTS AND METHODS: We identified 40 adult patients with SMCD without associated hematologic disorders. Clinical, laboratory, and bone marrow (BM) histologic findings at the time of referral were evaluated (November 1980-February 2001) for possible correlations with a history of aggressive systemic mastocytosis (retrospectively analyzed) as well as survival (prospectively analyzed). RESULTS: The median follow-up time from diagnosis was 108 months and from BM examination was 24 months. A history of aggressive systemic mastocytosis correlated significantly with increased BM mast cell (MC) content, unfavorable MC infiltration pattern, BM eosinophilia, and elevated serum alkaline phosphatase (SAP) level, but not with BM angiogenesis, reticulin fibrosis, or levels of MC mediators. Of these factors, increased BM MC content and elevated SAP level were also associated with shortened survival from time of referral. CONCLUSIONS: This study suggests that the BM MC burden, BM eosinophilia, and SAP level are prognostically important in SMCD without associated hematologic disorders. In contrast, BM angiogenesis, reticulin fibrosis, and levels of MC mediators showed no prognostic relevance.

Adult↗

PubMed2002

Primer on medical genomics. Part IV: Expression proteomics.

Proteomics, simply defined, is the study of proteomes. More completely, proteomics is defined as the study of all proteins, including their relative abundance, distribution, posttranslational modifications, functions, and interactions with other macromolecules, in a given cell or organism within a given environment and at a specific stage in the cell cycle. Proteins carry out the biological functions encoded by genes; hence, once the initial stage of genome sequencing and gene discovery is completed, a study of the proteome must be undertaken to address fundamental biological questions. The 3 broad areas are expression proteomics, which catalogues the relative abundance of proteins; cell-mapping or cellular proteomics, which delineates functional protein-protein interactions and organelle-specific protein distribution; and structural proteomics, which characterizes the 3-dimensional structure of proteins. With these approaches, proteins are studied on a global scale using a synergistic combination of powerful, high-throughput technologies, including 2-dimensional polyacrylamide gel electrophoresis, mass spectrometry, multidimensional liquid chromatography, and bioinformatics. Mass spectrometry, which provides highly accurate molecular mass measurements, has emerged as the analytical technology of choice for protein identification, characterization, and sequencing. This task has been made considerably easier with the availability of complete, nonredundant, and annotated genome sequence databases for many organisms. This article reviews the area of expression proteomics.

Biotechnology↗

PubMed2002

Neutropenic colitis after treatment of acute myelogenous leukemia with idarubicin and cytosine arabinoside.

OBJECTIVE: To determine the gastrointestinal toxic effects of idarubicin and cytosine arabinoside combination therapy in patients with newly diagnosed acute myelogenous leukemia (AML). PATIENTS AND METHODS: We performed a single-institution retrospective analysis of the incidence of neutropenic colitis in patients with newly diagnosed AML receiving idarubicin and cytosine arabinoside combination therapy. Using pharmacy records, we identified 78 patients who received idarubicin during the study period of January 1997 to September 1998 and who agreed to a review of their medical records. Patients with preexisting bowel conditions were excluded from this analysis. We used a strict definition of neutropenic colitis that included clinical findings (severe abdominal pain, diarrhea, hematochezia, and/or peritoneal signs) plus radiographic evidence of bowel inflammation in the absence of an identified bacterial pathogen. RESULTS: Of the 78 patients receiving idarubicin and cytosine arabinoside for treatment of AML, 65 were included in this study. We observed neutropenic colitis in 10 of these 65 AML patients. This complication was followed by sepsis in 3 patients and was the major cause of death in 4 of the 8 patients who died. CONCLUSION: This analysis suggests that neutropenic colitis is a frequent and serious complication of idarubicin and cytosine arabinoside treatment.

Adult↗

PubMed2002

Primer on medical genomics part II: Background principles and methods in molecular genetics.

The nucleus of every human cell contains the full complement of the human genome, which consists of approximately 30,000 to 70,000 named and unnamed genes and many intergenic DNA sequences. The double-helical DNA molecule in a human cell, associated with special proteins, is highly compacted into 22 pairs of autosomal chromosomes and an additional pair of sex chromosomes. The entire cellular DNA consists of approximately 3 billion base pairs, of which only 1% is thought to encode a functional protein or a polypeptide. Genetic information is expressed and regulated through a complex system of DNA transcription, RNA processing, RNA translation, and posttranslational and cotranslational modification of proteins. Advances in molecular biology techniques have allowed accurate and rapid characterization of DNA sequences as well as identification and quantification of cellular RNA and protein. Global analytic methods and human genetic mapping are expected to accelerate the process of identification and localization of disease genes. In this second part of an educational series in medical genomics, selected principles and methods in molecular biology are recapped, with the intent to prepare the reader for forthcoming articles with a more direct focus on aspects of the subject matter.

Animals↗

PubMed2002

Primer on medical genomics. Part III: Microarray experiments and data analysis.

Genomics has been defined as the comprehensive study of whole sets of genes, gene products, and their interactions as opposed to the study of single genes or proteins. Microarray technology is one of many novel tools that are allowing global and high-throughput analysis of genes and gene products. In addition to an introduction on underlying principles, the current review focuses on the use of both complementary DNA and oligodeoxynucleotide microarrays in gene expression analysis. Genome-wide experiments generate a massive amount of data points that require systematic methods of analysis to extract biologically useful information. Accordingly, the current educational communication discusses different methods of data analysis, including supervised and unsupervised clustering algorithms. Illustrative clinical examples show clinical applications, including (1) identification of candidate genes or pathological pathways (ie, elucidation of pathogenesis); (2) identification of "new" molecular classes of diseases that may be relevant in disease reclassification, prognostication, and treatment selection (ie, class discovery); and (3) use of expression profiles of known disease classes to predict diagnosis and classification of unknown samples (ie, class prediction). The current review should serve as an introduction to the subject for clinician investigators, physicians and medical scientists in training, practicing clinicians, and other students of medicine.

Breast Neoplasms↗

PubMedDate not supplied

Polycythemia vera--a case report and discussion on pathogenic mechanisms of increased thrombosis.

Polycythemia vera is a myeloproliferative disorder characterized by increased red cell mass and frequently complicated by venous and arterial thrombosis. The mechanism underlying the increased incidence of thrombotic events remains illusive. Presented in this report are a case of a 77-year-old man diagnosed with polycythemia vera and a review of the current literature on the mechanisms underlying the increased incidence of thrombotic events in polycythemia vera.

Aged↗