摘要:

AbstractDespite hypercellular bone marrows (BM), peripheral cytopenias are the rule in patients with myelodysplastic syndromes (MDS). This study examined the roles played by cell birth and cell death rates in generating this paradox. Cell kinetics from BM biopsies of 35 MDS patients were measured using intravenous infusions of either iododeoxyuridine or bromodeoxyuridine, or both. Degree of apoptosis or programmed cell death (PCD) was estimated using in situ end‐labeling of DNA directly from BM biopsies, which were simultaneously double‐labeled for proliferation/PCD. MDS were found to be highly proliferative disorders with large numbers of myeloid, erythroid, and megakaryocytic cells synthesizing DNA. Median cycling time (Tc) of myeloblasts was more rapid than that of patients with acute myeloid leukemia (44.1 hr vs. 56.0 hr). Interestingly, most marrow cells of all three lineages in 32 of 34 evaluable cases were undergoing PCD. In 19 of 32 patients, greater than 75% cells were apoptotic. Surprisingly, large numbers of S‐phase cells were found to be simultaneously undergoing PCD, as were stromal cells of the BM microenvironment. We conclude that the extensive apoptosis in hematopoietic cells effectively cancels the high birth rate resulting in ineffective hematopoiesis and accounting for deficient bone marrow function. ©1995 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/ajh.2830480302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe myelodysplastic syndromes (MDS) are neoplastic disorders of the hemopoietic system; multilineage involvement is also evidenced by specific cellular dysfunctions. The von Willebrand factor (vWF), synthesized and processed in the megakaryocytes (MK), is stored in the α granules of the platelets. The platelet vWF multimeric pattern was studied in 18 patients with MDS, and in 4 with pernicious anemia (PA), to investigate whether the processing of vWF is abnormal in the megakaryocytic dysplasia. An abnormal multimeric pattern was observed in 10/18 MDS and 4/4 PA patients. The abnormality of this specific protein is the discrete expression of the basic disorder, and is reversible when hemopoiesis is normalized. Although the data do not allow any conclusion, abnormal synthesis is the likely explanation of the abnormality. ©1995 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/ajh.2830480303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractAn initiation codon mutation ATG → ATA of the β‐globin gene was found in seven members of three generations of a family living in northern Sweden. This mutation, which has not previously been described, changes the initiation codon for methionine into a codon for isoleucine and will then result in a β°‐thalassemic phenotype. The affected family members all present hematological findings typical for β‐thalassemic trait, with slight anemia, marked microcytosis, and increased levels of Hb A2. ©1995 Wil

ISSN:0361-8609    

DOI:10.1002/ajh.2830480304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn ten patients with essential thrombocythemia and polycythemia Vera with thrombocytosis we have investigated the therapeutic effect of recombinant α‐2a interferon (Roceron A®) given subcutaneously in a maintenance dosage of 3 million units three times weekly. The aim was to normalize the platelet count (⩽ 400 × 109/L). One of the secondary aims was to study platelet activity measured as β‐thromboglobulin (β‐TG) in urine.All but one patient could administer the injections and in all patients a significant reduction in platelet values was seen. The treatment was discontinued in three patients due to side effects of interferon, two because of hair loss (one with irreversible alopecia), and one because of depression. Three patients developed antibodies to α‐2a interferon and a concomitant rise in the platelet level; in one patient therapy was switched to leukocyte α‐interferon with an excellent response. The initial levels of β‐TG were elevated in 9/10 patients and were significantly reduced at 6 months in 4/5 patients not developing antibodies. Six patient are still on α‐interferon therapy with a long‐term follow‐up of 3‐3.5 years. We conclude that α‐interferon therapy may be an alternative in patients with thrombocytosis and/or complications necessitating

ISSN:0361-8609    

DOI:10.1002/ajh.2830480305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn clinical practice, occasionally some patients show dissociated values of fibrinogen / fibrin degradation products (FDP) and D‐dimer (cross‐linked fibrin degradation products). In an attempt to assess the frequency, clinical backgrounds, and hemostatic states of these cases, FDP and D‐dimer were simultaneously measured together with other hemostatic parameters in 371 samples from patients with various diseases. As a whole, FDP values were positively correlated with D‐dimer values (r = 0.871, P<0.0001), and both were elevated in parallel with the progress of activation of blood coagulation and fibrinolysis. However, in patients with elevated FDP and/or D‐dimer, 11.5% of samples showed relatively lower D‐dimer values than those expected from FDP levels, and these were regarded as an apparently dissociated group. In the dissociated group, activation of coagulation and fibrinolysis occurred to a lesser extent than others. Analysis of these samples suggested that the possible reasons for the dissociation bet ween FDP and D‐dimer values were accelerated fibrinogenolysis with or without secondary fibrinolysis, accelerated fibrinogenolysis by non‐plasmic proteinases, elevated soluble fibrin, and possibly false‐positive FDP levels due to unclottable fibrinogen remaining in the serum samples. In practice, simultaneous measurements of FDP and D‐dimer are useful for more accurate estimation of hyperfibrinolytic states. ©

ISSN:0361-8609    

DOI:10.1002/ajh.2830480306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractIn Africa, the β‐globin gene cluster haplotype may be associated with variation of Hb F levels in subjects with sickle cell anemia (SS). These observations have not yet been conclusively confirmed in SS out of Africa, perhaps because of small sample sizes, the predominance of haplotype heterozygotes, and diverse influences, including gender, upon Hb F levels.We studied 384 adult African‐American SS patients (mean age, 31 years) and explored the relationship of gender, β‐globin gene cluster haplotype, and α thalassemia to hematological values and Hb F levels. Both haplotype and gender influenced Hb F concentration. In the total sample, Hb F was higher in females than in males (8.2 vs. 6.5%). In 35 males who were either homozygous for the Senegal chromosome or had the Senegal/Benin haplotype, the mean percent Hb F (8.0%) was equivalent to the Hb F level in females with Benin and Bantu haplotypes (‐7.5%). Both females and males homozygous for the Senegal haplotype chromosome or with the Senegal/Benin combination had a significant increase in Hb F compared to other groups. In 44 Senegal/Senegal or Senegal/Benin females the Hb F was 10.9%, or 1.0 g/dl, the highest value observed in all primary analysis groups. Preliminary analyses suggested that the presence of a Bantu chromosome blunted the gender‐associated difference in Hb F, but Hb F differences between females with the Senegal/Benin haplotype (11.2%) and the Senegal/Bantu haplotype (8.8%) were not statistically significant. Hemoglobin concentrations were higher in males than in females except in subjects with at least one Senegal haplotype chromosome, where hemoglobin levels were equal. As expected, α thalassemia reduced the MCV, increased hemoglobin concentration, and lowered reticulocyte counts, regardless of haplotype. Hb F levels were not affected by the presence of α thalassemia in any group.We conclude that gender and β‐globin gene cluster haplotype interact significantly in the modulation of Hb F and anemia in adults with SS. ©19

ISSN:0361-8609    

DOI:10.1002/ajh.2830480307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractThe Wiskott‐Aldrich syndrome is an X‐linked inherited immunodeficiency disorder characterized by thrombocytopenia, recurrent infections and eczema. Its best management option is HLA‐ldentical bone marrow transplantation; when this is not feasible, splenectomy, followed by continuous prophylactic antibiotics, represents the alternative of choice.The present case report relates the excellent outcome of an adult with the Wiskott‐Aldrich syndrome who suffered his first major complication of the disease at age 33 years, an intracerebral hemorrhage. Since an uneventfull splenectomy, thrombocytopenia has significantly improved, and he has remained free of infections for a follow‐up period of 3 years while being treated with prophylactic antibiotics. ©1995 Wiley

ISSN:0361-8609    

DOI:10.1002/ajh.2830480308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractWe report here two cases of a previously undescribed myeloprollferative disorder. Both were young adult males who presented with generalized lymphadenopathy, splenomegaly, leukocytosis, polycythemia, and persistent thrombocytopenia. The leukocyte alkaline phosphatase (LAP) score was low in both cases, and the bone marrow was hypercellular without dysplasia or fibrosis, but lacked the Philadelphia chromosome, BCR gene rearrangement, or other karyotypic abnormalities. The clinical course was indolent in each case. One patient died from an unusual ‘blast crisis’ after 12 years, while the second patient remains in a complete hematologic remission on hydroxyurea and alpha interferon 4 years from diagnosis. Interestingly, changes in therapy in this patient have consistently resulted in precise and concerted fluctuations in his blood counts, with the red and white cells cycling together and the platelets and mean corpuscular volume (MCV) changing concomitantly but in the opposite direction. This unique myeloproliferative disorder is distinguishable from all previously described forms of chronic myeloid leukemia and other myeloproliferative syndromes. ©1995 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830480309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractSinus histiocytosis with massive lymphadenopathy (SHML) is a rare benign disease of unknown etiology. It is rarely associated with malignant lymphoma. This report documents the first case of a T‐cell lymphoma, which developed in a patient with a 10‐year history of SHML. The disease was complicated by hypereosinophilia and massive retroperitoneal lymphadenopathy. Histological examination of a cervical lymph node biopsy during the terminal phase identified a lymphoma composed of cells with morphological plasmacytoid features. Ultrastructurally, the tumor cells showed poorly developed cytoplasm, nuclei with peripheral chromatin clumping, and inconspicuous nucleoli. Cytogenetic studies showed two related clones. On immunohistochemical staining tumor cells were positive with monoclonal antibodies (mAb) CD3 and CD45RO. Southern blotting analysis identified clonal rearrangements in the T‐cell receptor (TCR) alpha, beta and gamma genes. Thus, T‐cell lineage of the tumor cells was established. In situ hybridization of interleukin‐2 (IL‐2) and interleukin‐5 (IL‐5) cDNA probes on tissue sections identified the synthesis of IL‐5 by the eosinophils, suggesting an autocrine pathway of eosinophilopoiesis leading to hypereosinophilia in this patient. ©19

ISSN:0361-8609    

DOI:10.1002/ajh.2830480310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY

摘要:

AbstractNoninvasive evaluation for iron deficiency is compromised in many individuals due to the presence of chronic inflammatory processes and/or malignancy, thus necessitating bone marrow examination for definitive diagnosis. However, bone marrow aspiration is not obtainable or is inadequate for interpretation (dry tap) in some individuals, and decalcified bone marrow biopsies require 24‐48 hr to prepare, and may falsely indicate absence of iron. We evaluated the accuracy of bone marrow biopsy imprints (touch preparations) compared with aspirate particle smears for semiquantitation of bone marrow iron stores. Results indicate that Prussian blue‐stained bone marrow biopsy imprints accurately reflect the quantity of iron, compared with bone marrow aspirate particle smears, allowing for rapid determination of iron stores in individuals in whom a bone marrow aspirate cannot be obtained. © 1995 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/ajh.2830480311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1995

数据来源: WILEY