摘要:

Abstract:We have reviewed the laboratory methods used to diagnose the prethrombotic state, defined as a procoagulant imbalance between the production and inhibition of enzyme activity in the coagulation pathway short of fibrin deposition. One diagnostic approach is that of measuring the plasma levels of activation peptides which are released from the zymogens of the coagulation cascade when they are activated. Another approach is that of measuring the plasma levels of complexes formed in plasma when enzymes of the coagulation cascade are neutralized by their naturally‐occuring inhibitors such as thrombin‐antithrombin complex. The clinical usefulness of these methods still needs to be defined with prospective stud

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00567.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:In a phase II study, 58 patients with resistant multiple myeloma (MM) were treated with a combination chemotherapy (NOP‐bolus regimen) consisting of mitoxantrone (16 mg/m2for the first 25 patients and 12 mg/m2for the subsequent 33), vincristine (2 mg), both as bolus injections on day 1 and prednisone (250 mg/d on d 1–4 and 17–20). In patients>70 years of age, the mitoxantrone dose was reduced to 12 mg/m2or 8 mg/m2, respectively. The treatment was repeated every 4 weeks. A response (>50% reduction in M component) was obtained in 26% of the patients and a minor response (clinical improvement but<50% reduction in M component) in another 21%. Median response duration was 27 wk and median survival for all patients was 25 wk. There were no differences in response rate or duration between patients receiving the high or low mitoxantrone dose, but patients in the low‐dose group had fewer serious inf

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00568.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Between November 1983 and January 1987, 51 consecutive previously untreated adults below 65 years of age were treated for acute lymphoblastic leukaemia with LI or L2 morphology. Induction regimen for the first 15 patients consisted of 4 weekly doses of doxorubicin and vincristine, and of asparaginase and prednisolone. Two more doses of doxorubicin and vincristine were given for refractory disease. Next 36 patients received in addition cyclophosphamide on day 1. Consolidation comprised 17 rotating cycles of three regimens. Three intensification cycles were given, and maintenance treatment lasted until 3 years, or relapse. Median follow‐up time for living patients is 62 months. 82% of the patients achieved remission. Median relapse‐free survival (RFS) was 13 months, and 17% of the patients are in remission at 54 + to 80 + months. Age over 25 yr, a low white blood cell (WBC) count, and a low blast cell count were associated with a longer RFS. Median survival was 24 months, and 33% of the patients lived for 4 yr. Adverse prognostic factors were: age ≤25 of>45 yr, a high WBC count, and a high blast cell count. The results support the policy of concentrating more effort on the initial chemoth

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00569.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Human red blood cells (RBC) are heterogeneous with respect to their size; the physiological significance of this heterogeneity has not yet been fully elucidated. To further investigate this problem, some characteristics of human RBC fractionated according to their mean corpuscular volume (MCV) by counterflow centrifugation were determined. Larger RBC are more prone to hypotonic lysis. The membrane protein content per cell increases with the MCV, but no obvious difference in the distribution of the major proteins can be demonstrated. The lipid content per cell also rises with the RBC size, while the percentages of the main lipid components do not significantly vary. However, the variations of sialic acid content per RBC according to MCV are more important than those of protein or lipid; thus, the sialic acid‐to‐protein ratio gradually increases with the MCV. This indicates that, in spite of the lack of major changes in the membrane composition, some qualitative differences exist between large and small ce

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00570.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Resistance to several cytotoxic agents, including anthracyclines, vinca alkaloids and epipodophylline derivatives (multidrug resistance, or MDR) can develop in tumor cells by overexpression of a 170‐kd glycoprotein (p170) which is an essential component of a membrane transport system leading to increased drug efflux and decreased intracellular drug concentration. By means of a p170‐directed monoclonal antibody (MRK‐16) and immunocytochemistry (alkaline phosphatase anti‐alkaline phosphatase technique), we investigated the expression of p170 in marrow blast cells of 59 cases (38 at diagnosis and 21 in relapse) of acute‐non‐lymphocytic leukemia (ANLL). The proportion of strongly MDR‐positive cells was higher in relapse that at diagnosis (median 15.5% vs 1.5%). Out of 31 patients who were evaluable for the results of first remission induction, failure of first‐line treatment (including Daunorubicin, standard‐dose and high‐dose Arabinosyl Cytosine, and sometimes also Mitoxantrone) occurred in 8/22 MDR‐positive cases and in 1/9 MDR‐negative ones (p = 0.21). Failure of first‐line treatment was always associated with a progressive increase of p170 expression. Total failures (no remission plus early relapse) were more frequent (p = 0.001) among MDR‐positive cases (16/22) than among the others (2/9). These data show that MDR is very frequent in ANLL also at diagnosis and suggest that MDR can contribute to early fa

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00571.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:In patients with previously untreated chronic myelogenous leukaemia (CML) the efficacy of single‐agent interferon (IFN)‐alpha at an initial dose of 4 times 106U/m2(arm A) was compared with the combined administration of the identical dose IFN‐alpha plus a total dose of 50 μg IFN‐gamma (arm B). 51 patients entered this study between April 1987 and October 1989; the analysis was performed in March 1991 and was focused on response rates and toxicity. 54% of patients on arm A and 56% of arm B patients attained haematologic remission. 29% of patients on arm A and 24% of arm B patients had partial haematologic remission. A decrease in Philadelphia chromosome (Ph)‐positive metaphases of more than 10% was only seen in patients who had achieved complete haematologic normalization. In 21% of patients on arm A and 20% of arm B patients, the percentage of Ph‐positive cells declined to less than 35%. Toxicity was different between the two study groups with more pronounced hepatotoxicity observed in patients treated with IFN‐alpha alone. Among the patients receiving both IFNs, alpha and gamma, there were 2 fatal infectious complications. This serious toxicity in conjunction with lack of a clinically meaningful difference between the two treatment schedules has led us to terminate the study. In conclusion, the addition of low‐dose IFN‐gamma failed to improve the efficacy of IFN

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00572.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:To find predictive parameters for development and progression of adult T‐cell leukemia (ATL) in human T‐cell leukemia virus type‐I (HTLV‐I) carriers, we investigated cellular immune responses such as mitogenic responses and natural killer activity of the peripheral blood mononuclear cells (PBMC). And serum or plasma levels of cytokines, including tumor‐necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ) and immunosuppressive acidic protein (IAP), were also measured in patients with ATL, healthy HTLV‐I carriers and healthy HTLV‐I non‐carriers as controls. Results are as follows:(1) increased spontaneous proliferation and decreased mitogenic responses of PBMC already existed in HTLV‐I carriers;(2) IAP was significantly higher in patients with acute/lymphoma type ATL than in those with chronic/smoldering type, HTLV‐I carriers and HTLV‐I non‐carriers. These results suggest that spontaneous proliferation or mitogenic responses and IAP may be useful parameters for the development and progression of ATL from the carriers.Since HTLV‐I carriers already have various grades of immunosuppression, we should seriously try t

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00573.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:In a longitudinal study of a 32‐year‐old male with Ph1+hybrid leukemia we have followed the immunophenotype and configuration of Ig‐and TCR genes during the course of different chemotherapy regimens directed first against the myeloid and later against the lymphoid components of the disease. We identified changes in all parameters, interpretable as an evolution of the malignant clone resulting in a leukemic switch towards a more lymphoid character. Thus, while the expression of the myeloid antigens CD13 and CD33 decreased, that of CD10 (CALLA) and CD20 (B1) increased. Moreover, while the configuration of the Ig heavy and light chain λ genes remained constant during the whole period of treatment, that of the Ig light chain κ gene and TCR (3 gene displayed extensive rearrangements after initiation of ALL therapy. Since this patient represents ade novoacute leukemia as evaluated by location of the translocation‐breakpoint on chromosome 22, our data clearly indicate that Ig‐ and TCR gene rearrangements might prove a valuable addition in monitoring Ph1+hybrid leukemias, providing guidelines for optimizing c

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00574.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:We administered high‐dose mitoxantrone in combination with etoposide to 6 patients with relapsed Hodgkin's disease as the conditioning regimen for autologous bone marrow transplantation. This regimen was well tolerated and no significant cardiotoxicity was observed. Responses of the Hodgkin's disease to this therapy were favourable but short‐lived. Serial measurements of the serum levels of mitoxantrone suggested an open 3‐compartment model of drug distribution. The rapid early phase of drug distribution was followed by an intermediate phase and a slow terminal drug‐elimination phase. However, mitoxantrone was still detected in the serum of all patients 7 days after the last dose of mitoxantrone and on the day of bone marrow re‐infusion. The clinical significance of such findings is unclear but they may suggest a need for the use of other anthracycline‐related cytotoxic agents for the conditioning in autologous bone marrow tran

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00575.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1992.tb00576.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY