摘要:

Abstract:Pentoxifylline (PTX) administered after bone‐marrow transplantation reduces procedure‐related organ damage mediated by TNFα. GM‐CSF is also given post‐transplant to stimulate earlier neutrophil recovery. Because PTX has been shown to inhibit neutrophil function, we sought to determine whether it also inhibited the effects of GM‐CSF on neutrophil activity. The study confirmed that PTX at clinically achievable concentration (5–10 μmol/l) attenuated the responses of human neutrophils to chemotactic peptide, whereas it did not inhibit the effect of GM‐CSF on neutrophil function even at high concentrations. In experiments with human neutrophils, neither the direct effects of GM‐CSF such as stimulation of migration and increased expression of CD11b, nor the priming effects of GM‐CSF on the respiratory burst, were inhibited by PTX. In experiments with monkeys, intravenous administration of PTX did not block subsequent GM‐CSF‐induced neutrophil CD11b upregulation or phagocyte margination, even when near millimolar plasma levels of pentoxifylline were obtained. The retention of cytokine‐stimulated activities suggests that PTX will not compromise the response of neutrophils to sti

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00066.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Elevated concentrations of synovial‐type (group II) phospholipase A2 (PLA2‐II) in serum are associated with septic bacterial infections. We measured the concentrations of PLA2‐II in serum in 24 fever episodes involving patients suffering from haematological malignancies and having fever after cytotoxic treatment. We applied a novel time‐resolved fluoroimmunoassay using a polyclonal antibody raised against recombinant human synovial‐type PLA2. The concentrations of PLA2‐II in serum were 194.7 ± 204.4 μg/l (mean ± SD, median 141.9, range 4.6–931.5 μg/l). The concentrations of PLA2‐II correlated well to the concentrations of C‐reactive protein (CRP) in serum (r = 0.688, p<0.001). The PLA2‐II concentrations increased faster than the corresponding CRP values and began to decrease 12 hours after the beginning of antimicrobial treatment. Inverse correlations were found between the concentrations of PLA2‐II and blood neutrophil and platelet counts. No correlation was found between the concentrations of PLA2‐II and the duration of the time interval from the onset of preceding cytotoxic and corticosteroid treatment to the first blood sample. The concentration of pancreatic PLA2 was within the reference interval in all samples. The present results indicate that PLA2‐II resembles an acute‐phase protein and is not of

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00067.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The effects of zidovudine on the platelet count were studied in 152 patients with HIV‐related thrombocytopenia of severe grade (platelet count<50 × 109/1) and moderate grade (platelet count50 × 109/1). In both groups of patients there was a significant increase in the mean platelet count from the baseline value, after 2 weeks (from 21 × 109/1 to 48 × 109/1 and from 75 × 109/1 to 97 × 109/1) and 3 months of therapy (to 59 × 109/1 and to 144 × 109/1). Sixty‐five and 39 patients were followed up for 12 and 18 months, respectively, and the mean platelet values after 12 and 18 months of therapy were still significantly increased, compared to the respective mean baseline values, in both groups of patients. Clinical progression of the disease was observed in 23 treated patients, none of them showing concomitant reductions of the platelet number. An increase in the mean CD4+cell count after 3 months of therapy was followed by a progressive decline in the 65 patients with a 12‐month follow‐up, while no significant changes of the p24 antigenemia rates were observed after 1 year of therapy in 53 patients evaluated. The long‐term effects of zidovudine on the platelet count, but not on other parameters of clinical outcome, might be explained by the involvement of specific mechanisms in the pathogenesis of this kind of thrombocytopenia and of its respo

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00068.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Cytosine arabinoside (ara‐C) and etoposide are often used in combination in the treatment of acute myelocytic leukemia (AML). The intracellular phosphorylation of ara‐C to its 5′‐triphosphate (ara‐CTP) is a prerequisite for its cytotoxic effects. It has been shownin vitrothat etoposide can impair the formation of ara‐CTP in leukemia cells. The present study was undertaken in order to elucidate whether this interaction may be of clinical importance. Leukemia cells were isolated from 3 patients with acute myelocytic leukemia and incubated in medium (RPMI‐1640) with or without 10% fetal calf serum or in human plasma. When the cells were incubated in RPMI‐1640 with ara‐C (10 μmol/l) and etoposide during 2 h, the formation of ara‐CTP was decreased to 71 ± 18 (mean ± S.D.) and 30 ± 15% of control at 1 and 10 μg/ml etoposide, respectively. When the cells were incubated in human plasma, the formation of ara‐CTP was not influenced by the presence of etoposide (101 ± 6 and 103 ± 20% at 1 and 10 μg/ml etoposide). When incubated in RPMI supplemented with 10% fetal calf serum, the corresponding figures were 81 ± 8 and 70 ± 20%. Six patients with AML were therefore treated with ara‐C 0.5 or 1.0 g/m2as a 2‐h infusion every 12 h and, during 1 h before the second ara‐C infusion, 100 or 200 mg/m2etoposide was administered. The median change in the AUC of cellular ara‐CTP between the first and second ara‐C dose was 0% (‐37 to +21%). The corresponding median change in rate of accumulation of ara‐CTP in leukemia cells was 12% (‐26 to +110%). The concentration of etoposide in plasma during the ara‐C infusion was 18.7 ± 5.1 μg/ml while the non‐protein bound etoposide was 0.73 ± 0.34 μg/ml. Thus, despite exposure to higher etoposide concentrationsin vivothanin vitro, no impairment of ara‐CTP formation was seen in the patients. This corresponds to the results obtained when leukemic cells were incubated in plasma. It is concluded that the inhibition of ara‐CTP formation by etoposide seenin vitrois offset by the high protein binding of etoposide in plasma (96%) and that etoposide does not impair the formation of ara‐CTP in leuke

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00069.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Mononuclear cells from 5 normal men and 5 patients homozygous for hereditary haemochromatosis (HFE) have been incubated for 18 h with or without the addition of sheep red blood cells coated with antibody (SRBC). In the absence of SRBC mean H type ferritin concentrations were greater than L type (normals: mean L type 11.6 ng/106cells, H type 15.5; patients, L type 23.5 ng/106cells, H type 41.6). In the presence of SRBC, monocyte L type ferritin concentrations increased considerably (76 ng/106cells in normals and 141 ng/106cells in patients) but H type ferritin concentrations were the same or decreased compared with incubation in medium only. Incubation with additional iron (ferric ammonium citrate, 2.5 μg Fe/ml) increased both H and L type ferritin concentrations. Erythrophagocytosis thus appears to cause differential regulation of H and L ferritin subunit synthesis or breakdown. Normal subjects and patients do not differ in this response to erythrophagocytosis

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00070.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Pharmacokinetics of recombinant human non‐glycosylated bacterially‐synthesized (E. coli) granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) were studied following single intravenous (i.v.) and subcutaneous (s.c.) bolus injection, and compared to equivalent doses of glycosylated mammalian‐derived CHO‐GM‐CSF. Each route of administration gave a different GM‐CSF concentration‐time profile. The highest peak serum concentrations (Cmax) were observed following i.v. bolus injection. After i.v. administration, a two‐phase decline in concentration was noted for both types of GM‐CSF with a significantly shorter ***t1/2 α of 7.8 minutes for theE. coliGM‐CSF versus 20.0 min for the CHO‐GM‐CSF, while no significant difference was observed for the terminal phase. Following s.c. administration of equivalent doses, a higher peak serum concentration was observed in theE. coli‐treated patients and, again, a faster elimination where pretreatment serum levels were reached after 16–20 h, versus more than 48 h after administration of CHO‐GM‐CSF. Although the non‐glycosylatedE. coliGM‐CSF thus seems to undergo a faster elimination that the glycosylated CHO‐GM‐CSF no significant difference could be demonstrated in thein vivoeffect of corresponding doses of the two compounds with respect to stimulation of granulopoiesis — with reservation for small patient numbe

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00071.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:Twenty‐two patients with non‐Hodgkin's lymphoma (NHL) were treated with a regimen aimed at administering 6–9 cycles at 6‐weekly intervals of oral lomustine (CCNU) 50 mg/m2on day 2, i.v. etoposide 50 mg/m2d 1 and 8, methotrexate 30 mg/m2d 1 and 8, prednisone 60 mg/m2d 1–10 (LEMP). The patients had a median age of 65 years (range 34–81) at diagnosis and comprised 14 males and 8 females. Eighteen patients had had prior chemotherapy (5 patients received more than two combinations). Seven had also received prior radiotherapy. Five patients achieved a complete remission (CR) with a median duration of 18 months (range 4–37). Twelve patients achieved a partial remission with a median survival of 8 months (range 2–45). Responses were seen in 6/6 nodular small cleaved cell, 1/1 diffuse small cleaved cell, 0/2 nodular mixed small and large cell, 3/4 diffuse mixed small and large cell, 7/9 diffuse large cell. One patient with diffuse large cell histology was treated initially with LEMP, achieving and maintaining CR for 18 months. Five patients did not respond to LEMP. This regimen was well tolerated requiring only 2 injections every 6 wk, there was minimal toxicity, no alopecia or cardiotoxicity, and little myelosuppression. There were no treatment‐related deaths. This regimen has a useful role in inducing partial or complete remission in patients who have relapsed or progressed following previous intensive chemotherapy. It may also be used as first‐line therapy in patients who may not tolerate more intensive regimens. These results are encouraging and warrant fu

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00072.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract:The chronic myeloproliferative disorders (MPD) comprise polycythemia vera (PV), idiopathic thrombocythemia (IT), chronic myeloid leukemia (CML) and myelofibrosis/osteomyelosclerosis (MF/OMS). Bone marrow biopsies of 3500 patients with known or suspected MPD were studied, and the clinical and morphologic variables registered were utilized for multivariate data analysis by selected BMD computer programs. The histologic criteria and the histologic subdivisions, as well as the evolution and prognosis of disease are outlined for each of the clinical entities. The results show that a bone marrow biopsy provides independent diagnostic and prognostic data in this group of hematologic malignancies and therefore constitutes an additional parameter in the diagnostic investigation of patients with suspected or established MPD.

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00073.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00074.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1993.tb00075.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY