摘要:

Abstract:The effect of interleukin‐1 on iron metabolism in rats was evaluated. Plasma iron decreased from 184 ± 16 μg/dl (mean ± SE) to 24 ± 12 at 6 hours after interleukin‐1 intramuscular administration in non‐fasting rats and 109 ± 6 μg/dl to 12 ± 1 μg/dl in fasting rats, which was significantly lower than in control rats. Ferrokinetic studies showed a more rapid disappearance rate and lower iron turnover in interleukin‐1‐injected rats. The release of iron from the mononuclear phagocyte system to plasma was studied at 3 h after interleukin‐1 administration. Although the percent of radioactivity in plasma of the total injected dose was 3.2 ± 0.6% in interleukin‐1, which was significantly lower than in the control rats (5.4 ± 0.6%) at 9 h after intravenous injection of59Fe chondroitin ferrous sulfate, there was no difference between the amount of59Fe released from the mononuclear phagocyte system over the first 9 h in interleukin‐1 and control rats. These data appear to imply that iron release is unimpaired but that, for some reason, there is an enhanced rate of clearance of the59Fe once it has been released from the mononuclear phagocy

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00505.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The pharmacological activity of dipyridamole has been related to its ability to increase intracellular cAMP. Elevated cAMP concentrations can tone down T‐cell effector functions. The aim of this study was to evaluate the dipyridamole effectin vitroon the generation of alloreactive cytotoxic and lymphokine‐activated killer cells in normal T‐cell subpopulations. Dipyridamole suppressed T‐cell cytotoxic functions in a dose‐dependent way. The kinetics of suppression showed that dipyridamole prevented the first step of cytotoxicity, i.e. activation of the lytic program following allogeneic or interleukin‐2 stimulation. The ability of dipyridamole to interact with the immunosuppressive activity of cyclosporine was also investigated. By itself, cyclosporine suppressed the generation of alloreactive cytotoxicity, but not the generation of lymphokine‐activated killer cells. A synergistic immunosuppressive activity between dipyridamole and cyclosporine was observed on the generation of alloreactive cytotoxic

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00506.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:We examined the efficacy and toxicity of recombinant interferon‐alpha2b (rIFN‐α2b) in 10 previously untreated patients with advanced myelodysplastic syndromes. Morphological subtypes were refractory anaemia with excess of blasts (RAEB) in 4, RAEB in transformation (RAEB/T) in 3 and chronic myelomonocytic leukaemia (CMML) in 3 cases. IFN was administered subcutaneously at increasing doses of 1 to 3 times 106IU per day. The median duration of therapy was 6 months (range, 3 to 14). 2 patients, both with a diagnosis of CMML, achieved a complete and partial remission, respectively. In the complete responder, remission could be maintained for 9.5 months by daily administration of 1 times 106IU IFN. The other patients were classified as failures, although in 4 cases a decrease of bone marrow blasts was noted and none of the patients progressed to overt leukaemia while being treated with IFN. During the study, all patients with RAEB and RAEB/T showed a moderate to severe reduction in peripheral leukocyte and platelet counts, requiring premature termination of IFN therapy in 5 cases. Despite adequate supportive measures, 2 patients died of pneumococcal pneumonia and gastrointestinal bleeding, respectively. In 1 patient, IFN therapy had to be stopped because of neurologic toxicity (polyneuropathy). From these data we conclude that rIFN‐α2b at the doses and schedule tried is not a useful treatment for advanced myelodysplastic syndromes. Patients with CMML, however, may be an exception and should further be considered as candidates for therapeutic trials with r

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00507.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The influence of interferon (IFN) on antibody production and viability of malignant cells from patients with multiple myeloma was evaluated. Following incubation of bone marrow cells with IFN‐α (5000 units/ml) for 7 days) a decreased production of monoclonal immunoglobin (mlg) was detected in all experiments except one. IFN induced a>50% decrease in myeloma cell viability in 11 patients and a ≥ 25 % decrease in 4 patients. whereas in myeloma cells from 8 patients IFN had no or only minor effects. The observed effect was not due to an inhibition of proliferation since<5% of the myeloma cells were labeled with [3H]‐thymidine during 7 d of culture. There was no statistically significant correlation between decreases in myeloma cell viability and effects on mlg production, exemplified by the fact that mlg production was decreased also in patients showing no sensitivity to IFN's cytotoxic action. Depletion of autologus T‐cells, NK‐cells and/or monocytes did not abrogate the effects observed. We conclude that IFN can reduce the viability of myeloma cells and the production of Ig from these cells and that the latter can be exerted without an antitu

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00508.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:In order to characterize the effect of T lymphocytes on thein vitrogrowth of erythroid progenitor cells (EPC), we have optimized an assay for evaluating the influence of autologous T‐ lymphocyte clones on BFU‐e, grown from PBMNCs depleted of T lymphocytes. Testing a large number of T‐lymphocyte clones from 2 individuals we found that, irrespective of immunological phenotype, all clones tested were found to enhance the growth of BFU‐e. Thus, no evidence for a functional dichotomy between CD4+ and CD8+ T lymphocytes was found in this system. The enhancing effect worked across a histocompatibility barrier and was, at least in part, mediated by soluble factors. We therefore conclude that the role of the majority of cloned normal T lymphocytes in the regulation of thein vitrogrowth of EPC is a support

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00509.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:The treatment of relapsing or refractory high‐grade malignant non‐Hodgkin lymphoma (NHL) following CHOP chemotherapy remains a challenge for the clinician. In this study, 29 patients with relapsing or refractory high‐ or refractory low‐grade malignant NHL received a combination of mitoxantrone 12 mg/m2i.v. on days 1–2, cytarabine 100 mg/m2i.v., b.d. d 1–2, etoposide 100 mg/m2i.v. d 1–3 and prednisone 100 mg/m2orally d 1–3 (ENAP). An overall response rate of 55% encouraged us to use ENAP alternated with conventional CHOP chemotherapy in 45 previously untreated NHL patients (35 with high‐grade and 10 with “aggressive” low‐grade malignant NHL). All patients responded with a complete remission rate (CR) of (27%) and a partial remission rate (PR) of 73% after only one course of ENAP. After a median number of 3.5 ENAP/CHOP courses, the CR and PR rate was 69 and 22%, respectively. Myelo‐suppression was pronounced and fever of unidentified origin and documented infections followed 59% of all cases given ENAP courses. In the last 19 previously untreated patients mitoxantrone was given at a dose of 10 mg/m2on d 1 and cytarabine 100 mg i.v., b.d. during d 1–2. Non‐hematologic toxicity was mild. We conclude that this novel chemotherapy program is effective both as first‐line and salvage treatment in patients with high‐grade malignant NHL. Furthermore, ENAP appears clinically to be partly non‐cross resistant with CHOP chemotherapy. The dose‐limiting toxicity is myelosuppression. The combination should be explored as primary therapy in combination with other

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00510.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:Among 247 patients with Hodgkin's disease, initial disease presentation was restricted to infradiaphragmatic sites in 17 (6.9%). Advanced age, B symptoms, increased ESR, low lymphocyte and platelet counts, as well as advanced pathological stage and lymphocyte depletion histology were common presenting features of these patients. 7 patients with infradiaphragmatic disease had isolated involvement of inguinofemoral nodes (“peripheral” group) and 10 had only intrabdominal disease (“central” group). Clinical characteristics of patients with “central” forms were different from those with supradiaphragmatic disease, but no differences were observed between “peripheral” infradiaphragmatic and supradiaphragmatic groups. Complete remission was achieved in the 82.2% of patients with infradiaphragmatic disease. Overall survival was 68% at 5 years, and disease‐free survival was 74%. No statistically significant differences were observed in complete remission rates, survival, and disease‐free survival when supradiaphragmatic, “central” infradiaphragmatic and “peripheral” infradiaphr

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00511.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Abstract:In adult neutropenic patients with hematological malignancies, we explored imipenem‐cilastatin as empirical antibiotic therapy in a dose of 500 mg four times daily. Changing to second‐line treatment was only resorted to if clinical deterioration, new infections or recurrence of fever occurred. A clinically or microbiologically documented infection was apparent in 115 of 150 episodes studied (76.7%). Imipenem‐cilastatin was successful in 70.7% of all episodes and in 67.8% of all proven infections. Modification was necessary and successful in 22.0% of all episodes. 11 patients died while still febrile, 6 of them by infection (4%) and 5 because of progressive disease (3.3%). Imipenem‐cilastatin is safe initial therapy in neutropenic febrile p

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00512.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00513.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1991.tb00514.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY