摘要:

AbstractThe serum concentration of hyaluronan (HYA) was measured in 41 patients with malignant lymphoma, including 21 patients with non‐Hodgkin's malignant lymphoma and 20 patients with Hodgkin's disease. Thirty‐four patients were studied at diagnosis. The remaining 7 patients had relapsing or resistant disease. The patients were categorized into four stages according to conventional staging procedures. The median serum HYA concentration in patients with malignant lymphoma was significantly higher (median 40.7 ng/ml; 95% confidence limits 26.1–57.6 ng/ml) than in an age‐matched healthy reference group (median 14.5 ng/ml, 95% confidence limits 11–19.4 ng/ml) (P= 0.00032). The highest serum HYA levels were found in patients with relapsing/resistant disease, all being in stages III and IV (median 181.5; range 11.9–500 ng/ml), as compared to previously untreated patients (median 29.8; range 9.1–108) (P= 0.0002) and controls (median 14.2; range 6.7–51.2). Decreased uptake and degradation of HYA owing to malignant transformation of lymphatic tissue is the most plausible explanation to

ISSN:0361-8609    

DOI:10.1002/ajh.2830500402

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

年代:1995

数据来源: WILEY

摘要:

AbstractClonal disorders of large granular lymphocytes (LGL) of either CD3‐ (NK cell) or CD 3+ (T‐cell) phenotype have been described. B‐cell malignancies such as hairy cell leukemia and non‐Hodgkin's lymphoma have been observed in association with the T‐cell type of LGL leukemia. Here we report the occurrence of LGL lymphocytosis in four patients with Hodgkin's disease. Immunophenotyping studies showed that these LGL were CD 3‐ in three patients and CD3+ in the other. LGL were polyclonally expanded in both patients in whom clonality could

ISSN:0361-8609    

DOI:10.1002/ajh.2830500403

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe examined red cell fragmentation syndrome (RCFS) induced by mitomycin C (MMC) (13 patients), by thrombotic thrombocytopenic purpura (TTP) (17 patients), and by disseminated intravascular coagulation (DIC) (15 patients). Plasma cytokine levels were increased in the TTP and DIC patients, but not in those whose RCFS was induced by MMC, suggesting that the activation of the immune system plays an important role in the pathogenesis of RCFS due to TTP and DIC but did not in RCFS due to MMC. Plasma thrombomodulin, tissue type plasminogen activator, and plasminogen activator inhibitor‐I levels were increased in all RCFS patients, suggesting that RCFS, whether MMC induced, or due to TTP or DIC, might be associated with vascular endothelial cell injury. In TTP, von Willebrand factor (vWF) antigen and high molecular weight vWF multimer levels were reduced, possibly as a result of microthrombus consumption. The hemostatic data in this study showed that the TTP patients were in a hypercoagulable state without hyperfibrinolysis, and that DIC patients were in both a hypercoagulable and a hyperfibrinolytic state, whereas hemostatic abnormalities were slight in patients with MMC induced RCFS. These findings suggest that vascular endothelial cell injuries might be associated with RCFS, and that those injuries in MMC‐induced RCFS might not be related to microthrombi or an activated immune sys

ISSN:0361-8609    

DOI:10.1002/ajh.2830500404

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe hematologic disorder paroxysmal nocturnal hemoglobinuria (PNH) arises from a somatic mutation within thePigagene important for the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. The PNH defect has been identified in all cells of the myeloerythroid lineage, but involvement of the lymphoid lineage in PNH is more controversial. We therefore analyzed lymphocytes from 22 patients with PNH to characterize phenotypically the GPI‐deficient population, and to investigate the functional consequences of GPI deficiency. GPI‐deficient T lymphocytes, B lymphocytes, and NK cells were identified, but at a lower percentage than granulocytes and erythrocytes. CD8+ lymphocytes were significantly more affected than CD4+ T cells, and CD45RA+ lymphocytes were significantly more affected than CD45RO+ cells. Proliferation assays demonstrated that lymphocytes from PNH patients, either unfractionated or purified GPI‐deficient cells, responded normally to in vitro stimuli. When stimulated with phytohemagglutinin (PHA), naive CD45RA+ GPI‐deficient T lymphocytes acquired the memory CD45RO+ phenotype. In addition, GPI‐deficient T lymphocytes had a relative growth advantage as compared to normal T cells. The results demonstrate that PNH involves the lymphoid as well as the myeloerythroid lineage, and therefore arises from a totipotent bone marrow stem cell. The in vitro growth advantage of GPI‐deficient lymphocytes in PNH may have important implications for the pathogenesis of some puzzling clinical aspects of PNH, including predominance of the PNH clone, defective hematopoiesis, and leu

ISSN:0361-8609    

DOI:10.1002/ajh.2830500405

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

年代:1995

数据来源: WILEY

摘要:

AbstractWe describe a study of the effects of heparin on complement activation through the use of assays for fragment C4d, fragment Bb, and the S‐C5b‐9 complex (S‐MAC). In sera from healthy volunteers, virtually no change was observed in C4d either as a function of time or of heparin concentration, whereas changes in Bb and S‐MAC were biphasic. This observation was explored in greater detail in the heparin concentration range 0.001–5.0 u/ml (5 × 10−3to 25 μg/ml). For both Bb and S‐MAC, a significant (P<0.05) increase in production was noted in the heparin concentration range, 0.01–0.5 u/ml (5 × 10−2to 2.5 μg/ml). At higher heparin concentrations, Bb and S‐MAC production decreased markedly (P<0.05). We reconstituted the alternative pathway amplification cycle (C3, factor B, and factor D) and studied Bb generation. With reactants at concentrations one tenth those of normal serum, we observed a maximum generation of 13.2 μg/ml Bb. Control and heparin at 5 × 10−4μg/ml generated Bb concentrations of 6.8 and 6.1 μg/ml, respectively, for a 2‐min incubation; at 5 × 10−3μg/ml heparin, Bb was increased to 9.8 μg/ml. Using isoelectric focusing to study anionic pI shifts in heparin‐bound factors B and D, it was found that factor B bound heparin only at the highest heparin concentration studied, i.e., 50 μg/ml; factor D, however, bound heparin at a much lower concentration (0.05 μg/ml). We conclude that, at low concentrations, heparin activates complement due to potentiation of the alternative pathwa

ISSN:0361-8609    

DOI:10.1002/ajh.2830500406

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

年代:1995

数据来源: WILEY

摘要:

AbstractThe molecular basis of triosephosphate isomerase (TPI) deficiency was studied in 3 patients from three separate families. In all 3 patients, genomic DNA directly sequenced after amplification by the polymerase chain reaction exhibited the point mutation TPI315Camino acid 104 Glu→Asp. Although other mutations known to cause TPI deficiency have been restricted to single families, the amino acid 104 defect has now been described in nine apparently unrelated families throughout the world and is clearly the most frequently occurring form of the disorder. The basis of the repetitive occurrence of this mutation remains unexplaine

ISSN:0361-8609    

DOI:10.1002/ajh.2830500407

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

年代:1995

数据来源: WILEY

摘要:

AbstractHereditary factor VII deficiency is a rare autosomal recessive condition, usually associated with normal or reduced levels of a functionally defective molecule. The available means of treating this condition in North America presents serious health risks to the patient. Transfusion with fresh frozen plasma carries a risk of volume overload and a significant risk for viral transmission. Sustained prothrombin complex therapy is associated with a high risk for thrombogenic complications. This communication describes the use of Factor VII Concentrate (Human) Immuno, Vapor Heated—an intermediate purity factor VII concentrate from Immuno A.G.—for the treatment of 13 patients with factor VII deficiency. Treatment regimens described include those for long‐term prophylaxis (three children), acute hemorrhages (two children, one adult), peripartum prophylaxis (one patient), and surgical coverage (two children, four adults). Prophylaxis and therapy were successful in all cases, the medication was well‐tolerated, and there were no complications. In the three cases of long‐term prophylaxis in children, doses of 10‐50 lU/kg were given one to three times a week; one patient has undergone long‐term prophylaxis for approximately 8 years, one patient for 1 year, and one patient for 1 1/2 years. Three cases in which Factor VII Concentrate was principally used for treatment of acute episodes of bleeding are described. One infant received Factor VII Concentrate on about 50 occasions for treatment of mucosal bleeding; a correction to 40–100% resulted in cessation of bleeding within 15 min in all cases. For treatment of an episode of intracranial bleeding, an 8‐year‐old boy received a dose of 37 IU/kg Factor VII Concentrate every 6 hr for peak factor VII levels of approximately 100% and troughs as low as 4% over the 11‐day treatment period. A 37‐year‐old adult male with intracranial bleeding received alternating doses of 16 IU/kg and 8 IU/kg every 6 hr for 10 days with peak factor VII levels in the upper thirties (%). The peak favor VII level during surgical coverage with Factor VII Concentrate (neurosurgery, open reduction of ankle bones, dental surgery, pituitary adenoma surgery, closed liver biopsy) was approximately 100% in all cases, with trough levels ranging from 8 to 65% over treatment periods of 24 hr to 16 days using treat

ISSN:0361-8609    

DOI:10.1002/ajh.2830500408

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

年代:1995

数据来源: WILEY

摘要:

AbstractCarboxyamido‐triazole (CAI), an agent that targets calcium‐sensitive signal transduction pathways, has both antiproliferative and antimetastatic properties. The objective of this study was to evaluate the myelotoxicity of CAI to normal human and murine hematopoietic cells. In vitro toxicity of CAI was determined by inhibition of myeloid [colony‐forming unitgranulocyte/macrophage (CFU‐gm)] and erythroid [burst‐forming unit‐erythroid (BFU‐e)]colony formation in clonal assays. The effects of oral CAI on CD2F1mouse marrow and splenic cellularity, marrow progenitor content, and peripheral blood cell counts were assessed in relation to plasma CAI levels. In vitro, CAI caused a concentration‐dependent inhibition of CFU‐gm and BFU‐e colonies following continuous drug exposure. Murine CFU‐gm and BFU‐e were inhibited>90% by 10 and 15 μg/mL CAI, respectively. However, suppression of human CFU‐gm and BFU‐e did not exceed 65% at the same concentrations. In vivo, CAI reduced the number of CFU‐gm and BFU‐e per femur after the initial dose and through day 4. Variations in colony inhibition paralleled changes in CAI plasma concentrations. While colony inhibition increased in vitro with escalating drug concentrations, this was not observed in vivo with additional CAI doses. The low toxicity of CAI in vivo combined with the significant difference between toxicity for human and mouse progenitors in vitro suggests a relatively low adverse potential to the bone marrow for this new sign

ISSN:0361-8609    

DOI:10.1002/ajh.2830500409

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

年代:1995

数据来源: WILEY

摘要:

AbstractIn order to harmonize the prothrombin time (PT) reporting systems, the World Health Organization, in collaboration with the International Committee on Thrombosis and Hemostasis, and the International Council on the Standardization in Hematology proposed a reporting system, the so‐called international normalized ratio (INR). As the calculation of the INR depends on mathematical formula requiring a special calculator or mathematic tables, its derivation is associated with some difficulties and errors. In this article a nomogram is presented, by which derivation of the INR from different PT reporting methods can be easily done within a few second

ISSN:0361-8609    

DOI:10.1002/ajh.2830500410

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

年代:1995

数据来源: WILEY

摘要:

AbstractA patient with neutropenia and life‐threatening infections secondary to T‐γ lymphoproliferative disease, who did not respond to treatment with recombinant human G‐CSF (filgrastim), was treated with filgrastim plus cyclosporine A (CyA). The patient achieved a good response in the absolute neutrophil count and subsequently required a dose reduction in the filgrastim. The patient was eventually discontinued from the CyA but continues on filgrastim alone. While on therapy, the large granular lymphocytes disappeared from the circulation and the beta‐TCR rearrangement, which was present prior to beginning therapy, became undetectable. The patient had no significant toxicity to the CyA or the filgrastim and he has not experienced any serious infections or required hospitalization. Filgrastim has proven to be relatively nontoxic and of some benefit to patients with this disease and should probably be utilized first when treatment is necessary. However, if improvement is not observed, these findings suggest that a trial of the combination of CyA plus filgrastim may be be

ISSN:0361-8609    

DOI:10.1002/ajh.2830500411

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

年代:1995

数据来源: WILEY