摘要:

AbstractWe studied the effects of azidothymidine (AZT) on rat bone marrow heme metabolism and colony growth as determined by assays of granulocyte‐macrophage (CFU‐GM), erythroid (CFU‐E), burst‐forming erythroid (BFU‐E), and α‐aminolevulinic acid synthase (ALAS), the first enzyme in the heme pathway. In all cases, AZT (1–0.01 μM) was found to be toxic to bone marrow colony growth. When AZT was included in colony assays, 1 μM resulted in 98–100% inhibition, whereas lower concentrations (0.01 μM) inhibited growth by 58–76%. In addition, cultures from AZT‐treated animals had a marked reduction in colony growth as compared with sham controls. In most cases, hemin (10−5M) was found to overcome some of the colony inhibitory effects of AZT. Analysis of heme metabolism indicated that ALAS activity was reduced by 71% in bone marrow cells from treated animals. ALAS activity for control was 204 ± 33 pM ALA formed/4 ± 106cells/hr, whereas ALAS activity from AZT‐treated animals was only 60 ± 3 pM ALA formed/4 ± 106cells/hr. It is considered that AZT toxicity may be due in part to a depression in the pool of available heme, which is requ

ISSN:0361-8609    

DOI:10.1002/ajh.2830350102

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

年代:1990

数据来源: WILEY

摘要:

AbstractResponsiveness of bone marrow erythropoietic stem cells (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh‐Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU‐E and BFU‐E assays. In normals, the CFU‐E numbers reached a plateau of increase at Ep doses of almost 2–5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU‐E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU‐E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU‐E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU‐E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU‐E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB‐T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh‐Ep were suggested to be effective clinically in some patients with aplast

ISSN:0361-8609    

DOI:10.1002/ajh.2830350103

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

年代:1990

数据来源: WILEY

摘要:

AbstractThe aims of the present study are: first, to assess the toxic role of serum from thalassemic patients in phagocytosis of PMN from healthy controls, and second, to seek to determine whether serum and cellular disturbances of polymorphonuclear neutrophils (PMN) phagocytosis, observed in thalassemic patients, can be prevented and/or corrected by use of desferrioxamine (DFX).Two kinds of in vitro incubations–‐without or with DFX–‐were performed. PMN or serum from thalassemic patients or from healthy controls was used. First, a phagocytosis defect of 3 different bacteria species was induced in PMN from healthy controls by incubation in thalassemic serum. Second, DFX could prevent, already at 1 μM, the phagocytic defect induced in normal PMN by the incubation with thalassemic serum, with disappearance of the toxic role of thalassemic serum at higher concentrations. Third, improvement of the phagocytosis defect of PMN from thalassemic patients was also observed at 1 μM of DFX for the 3 bacteria species. Normalization was obtained at higher concentrations for gram‐negative bacteria.In vivo studies revealed, after a 3 hr subcutaneous infusion of DFX into 3 thalassemic patients, an improvement of the phagocytosis results and a decrease of the Prussian Blue reactivity of the PMN.It is concluded first that an iron‐mediated defect in phagocytosis can be induced in normal neutrophils by incubation in serum from thalassemic patients, and second that a precautious and intensive chelation therapy seems to be advantageous for increasing PMN defense against infectious agents. Special care must nevertheless be taken in order to detect rapidly opportunistic (such asYersini

ISSN:0361-8609    

DOI:10.1002/ajh.2830350104

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

年代:1990

数据来源: WILEY

摘要:

AbstractMany patients with thrombotic thrombocytopenic purpura (TTP) fail to respond to daily plasmapheresis and the results of alternative treatments have been inconsistent. Vincristine was given weekly with continued plasmapheresis to eight patients who were refractory to plasmapheresis, antiplatelet agents, and/or corticosteroids. A rapid response to the vincristine occurred in all eight patients in 5 days with a marked rise in the platelet count and resolution of symptoms. The results in these patients suggest that early initiation of vincristine therapy in conjunction with plasmapheresis is useful in TTP.

ISSN:0361-8609    

DOI:10.1002/ajh.2830350105

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

年代:1990

数据来源: WILEY

摘要:

AbstractBased on in vitro evidence of time‐dependent synergistic kill of HL‐60 leukemia cells exposed to Ara‐C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21–75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara‐C plus daunorubicin. Each dose of Ara‐C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44–68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progessive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug‐induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate‐dose Ara‐C and mitoxantrone is an active and well‐tolerated

ISSN:0361-8609    

DOI:10.1002/ajh.2830350106

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

年代:1990

数据来源: WILEY

摘要:

AbstractMarked thrombocytopenia developed during pregnancy in both identical twins mothers who had systemic lupus erythematosus (SLE) and also type IIB von Willebrand's disease (vWD).The proband's platelet count decreased in the third trimester of pregnancy. Large‐dose γ‐globulin and prednisolone treatments were performed because of the suspicion of immune thrombocytopenic reaction associated with SLE. These treatments were not effective. Her platelet count returned to the normal range immediately after delivery. Postpartum examinations revealed the decreased ristocetin cofactor activity and the deficiency of large von Willebrand factor (vWF) multimers in preserved plasma samples from the third trimester. These abnormal findings improved after delivery. Investigation of family members revealed that the proband had inherited type IIB vWD from her mother.The other twin, who was also under treatment for SLE, became pregnant about 1 year after delivery in the proband and followed almost the same course as that observed in the proband. As bleeding tendency was observed a few days before delivery, a factor VIII concentrate (Haemate P) was administered to compete with her variant vWF. This concentrate could prevent the further decrease in her platelet count, thereby correcting the hemorrhagic tendency. It seems evident that factor VIII concentrate would be effective in treating thrombocytopenia associated with type IIB

ISSN:0361-8609    

DOI:10.1002/ajh.2830350107

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

年代:1990

数据来源: WILEY

摘要:

AbstractA patient with two populations of B cell malignancy in the bone marrow is reported. One population consisted of mature small lymphocytes, expressing surface IgM + D, λ and proliferating very slowly. The other population consisted of abnormal large lymphoid cells, expressing surface IgM, K and proliferating actively. We considered the former as chronic lymphocytic leukemia cells and the latter as malignant lymphoma cells. Therefore, this case was considered as Richter syndrome. The analysis of immunoglobulin heavy chain gene rearrangement showed the different patterns between the two populations. It suggested that the two populations arose from the different origins. We discussed the genetic relationship between the two clones of Richter syndrome referring to other reported cases

ISSN:0361-8609    

DOI:10.1002/ajh.2830350108

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

年代:1990

数据来源: WILEY

摘要:

AbstractA 15 year old girl with aplastic anemia developed a heparin‐like anticoagulant during the course of systemic candidiasis. This was initially detected in the laboratory by an elevation of the thrombin clotting time which corrected with toluidine blue but not by mixing with normal plasma. In vivo and in vitro the anticoagulant was remarkably resistant to neutralization by protamine sulfate. Nevertheless, its heparin‐like nature was confirmed by its sensitivity to heparinase and its dependence on antithrombin

ISSN:0361-8609    

DOI:10.1002/ajh.2830350109

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

年代:1990

数据来源: WILEY

摘要:

AbstractIn this report, we describe a mother with mild incidental thrombocytopenia who delivered a severely thrombocytopenic infant having alloimmune thrombocytopenia. This coincidental association should be considered because the recognition and proper diagnosis of alloimmune neonatal thrombocytopenia is important, not only in the current pregnancy, but also in future pregnancies.

ISSN:0361-8609    

DOI:10.1002/ajh.2830350110

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

年代:1990

数据来源: WILEY

摘要:

AbstractHemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor‐bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet‐aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications.Clinical complications occur in 9–15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor‐related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of

ISSN:0361-8609    

DOI:10.1002/ajh.2830350111

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

年代:1990

数据来源: WILEY