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  • 1
    Electronic Resource
    Electronic Resource
    Anaemia of chronic disease in rheumatoid arthritis (1990)
    Springer
    Rheumatology international 10 (1990), S. 127-130 
    Details
    ISSN: 1437-160X
    Keywords: Rheumatoid arthritis ; Anemia ; Erythroid colony growth ; Interleukin-6 ; IL-6 ; anti-IL-6
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum and bone marrow from 21 patients with rheumatoid arthritis (RA) were studied in order to establish the pathogenetic role of interleukin-6 (IL-6) in anemia of chronic disease (ACD). Erythroid colony growth, using burst forming units of erythroblasts (BFUe) as a parameter, was impaired in ACD and not in nonanemic RA controls. Serum IL-6 was elevated in ACD and it correlated well with parameters of disease activity such as erythrocyte sedimentation rate and C-reactive protein. IL-6 addition to bone marrow cultures had inconsistent effects while anti-IL-6 addition resulted in impaired erythroid colony growth, suggesting stimulatory effects of IL-6 produced in the medium, which may be masked by simultaneous production of cytokines with suppressive effects. It was concluded that elevated serum IL-6 in ACD reflects disease activity. It probably plays no pathogenetic role in ACD. Its stimulatory effects on erythroid growth might counteract suppressive effects of other interleukins.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02274827
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  • 2
    Electronic Resource
    Electronic Resource
    Transferrin microheterogeneity in rheumatoid arthritis (1992)
    Springer
    Rheumatology international 12 (1992), S. 195-199 
    Details
    ISSN: 1437-160X
    Keywords: Transferrin ; Glycosylation ; Disease activity ; Acute phase response ; Erythroblast iron availability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the relation between disease activity in rheumatoid arthritis (RA) and the microheterogeneity of transferrin. Using crossed immuno isoelectric focusing, transferrin microheterogeneity patterns were analyzed in sera of healthy individuals, nonanemic RA patients, iron deficient RA patients and RA patients with the anemia of chronic disease (ACD). In all RA groups a significant shift in the microheterogeneity pattern was observed, reflecting increased synthesis of transferrins with highly branched glycan chains. Increased disease activity correlated with both the induction of ACD and the change in transferrin glycosylation, which was, therefore, most pronounced in ACD. Generally, an increased synthesis of glycoproteins is accompanied by alterations in their glycosylation pattern. Since transferrin is a negative acute phase protein, our results indicated that changes in synthetic rates and changes in glycosylation induced in the acute phase response are regulated independently.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00302152
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  • 3
    Electronic Resource
    Electronic Resource
    Anaemia in rheumatoid arthritis: pathogenesis, diagnosis and treatment (1990)
    Springer
    Rheumatology international 9 (1990), S. 243-257 
    Details
    ISSN: 1437-160X
    Keywords: Anaemia ; Rheumatoid arthritis ; Pathogenesis ; Iron metabolism ; interleukins ; diagnosis, treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The pathogenesis, diagnosis and treatment of the anaemia of chronic disorders (ACD) in rheumatoid arthritis (RA) were reviewed. Causes of anaemia other than ACD frequently present in RA. Decreased iron absorption was shown to be the result of active RA rather than a cause of ACD or iron deficiency. It has been hypothesized that bone morrow iron availability decreases due to decreased iron release by the mononuclear phagocyte system or that the anaemia in ACD is due to ineffective erythropoiesis; these remain controversial theories. Studies considering a decreased erythropoietin responsiveness have not produced consistent results. Erythroid colony growth is suppressed in vitro by interleukins and tumour necrosis factor but their role in vivo in ACD is unknown. The diagnosis of ACD is made by exclusion. Iron deficiencyis detected by transferrin, ferritin, and cellular indices after adaption of their normal values. Treatment of the anaemia consists merely of antirheumatic treatment. Iron administration is counterproductive since iron chelators or exogenous erythropoietin administration might increase erythropoiesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541320
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  • 4
    Electronic Resource
    Electronic Resource
    Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures (1999)
    Springer
    Rheumatology international 18 (1999), S. 201-206 
    Details
    ISSN: 1437-160X
    Keywords: Key words Rheumatoid arthritis ; Anaemia ; Erythropoietin ; Quality of life ; Utility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Treatment with recombinant human erythropoietin (r-hu-Epo) in patients with rheumatoid arthritis (RA) and anaemia of chronic disease (ACD) resulted in improvement of both anaemia and disease activity. Utilities represent a generic and comprehensive quality of life measure, capable of integrating domain-specific information into one overall value which a patient assigns to his state of health. Therefore, the effect of r-hu-Epo on quality of life was studied by measuring utilities, derived from the rating scale and standard gamble, in a 52-week placebo-controlled randomised double-blind study with r-hu-Epo in 70 patients with active RA and ACD. Furthermore, the relation between anaemia as assessed by haemoglobin levels (Hb), disease activity as assessed with the Disease Activity Score (DAS), and utilities was investigated. Compared to the placebo group, significant improvement of Hb (P〈0.001), DAS (P = 0.01) and rating scale utilities (P = 0.002), but not of standard gamble utilities, was observed in the Epo group. Rating scale utilities correlated strongly with DAS (r = –0.47, P〈0.01), Hb (r = 0.37, P〈0.01) and changes in both DAS (r = –0.74, P〈0.01) and Hb (r = 0.44, P〈0.01). Both DAS and Hb contributed significantly to the variance in rating scale utilities (21% and 3% respectively) and to changes in rating scale utilities (43% and 3% respectively). Standard gamble utilities correlated less well with clinical disease variables than rating scale utilities did. These results indicate, that r-hu-Epo improves utility-derived health-related quality of life, most probably by improving both disease activity and anaemia. Utilities, particularly rating scale utilities, correlated well with conventional disease activity variables and proved sensitive to change. Utilities may be a useful tool for investigating quality of life in RA-patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002960050085
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  • 5
    Electronic Resource
    Electronic Resource
    R-h-erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis (1994)
    Springer
    Rheumatology international 14 (1994), S. 109-113 
    Details
    ISSN: 1437-160X
    Keywords: TNF ; Anaemia of chronic disease ; Erythroid progenitors ; Erythropoietin ; Rheumatoid arthritis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anaemia of chronic disease (ACD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFα) plays an important role in the development of ACD. The objective of the present study was to assess inhibition of in vitro colony-forming unit erythrocyte (CFUe) and blast-forming unit erythrocyte (BFUe) growth by TNFα and to examine whether this suppression could be counteracted by adding increasing concentrations of recombinant human erythropoietin (EPO) (r-h-EPO) to bone marrow cultures of RA patients with ACD and without anaemia (controls). Bone marrow cells of RA patients with ACD and control patients were cultured. The cultures were incubated with increasing concentrations of r-h-EPO (0.25; 0.5; 1; 2 U/ml), each in combination with increasing quantities of TFNα (0; 50; 100; 200; 400 U/ml). CFUe and BFUe were assessed after 7 and 14 days, respectively. Dose-dependent inhibition of BFUe and CFUc by increasing concentrations of TNFα was observed in ACD and controls. Regarding CFUe (ACD patients) incubated with 0.25 U/ml EPO, 50 U/ml TNFα caused 28% suppression compared to cultures without TNFα. Increasing the concentration of r-h-EPO from 0.25 U/ml to 2 U/ml completely restored the number of CFUe. A similar pattern was observed in BFUe growth in both groups. These data demonstrated the suppressive effects of TNFα on erythropoiesis in vitro and that the suppresed erythropoiesis could be partly corrected by the addition of excess r-h-EPO to the cultures. No significant differences were observed between ACD and control RA patients. This in vitro model may help explain the clinical response to r-h-EPO therapy as documented in RA patients with ACD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00300811
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  • 6
    Electronic Resource
    Electronic Resource
    Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial (1996)
    Springer
    Annals of hematology 73 (1996), S. 247-252 
    Details
    ISSN: 1432-0584
    Keywords: Key words Transfusion iron overload ; Hemosiderosis ; Deferiprone ; Myelodysplastic syndrome ; Thalassemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We performed an open, nonrandomized, multicenter phase-II trial to evaluate the efficacy and toxicity of 1 year of treatment with the oral iron chelator deferiprone in 38 mainly nonthalassemic patients with transfusional iron overload. Initial serum ferritin varied between 996 and 11.644 μg/l. Patients were treated with 3–6 g of deferiprone daily. Mean urinary iron excretion (UIE) in 36 evaluable patients was 21.0 mg/24 h and was significantly higher in the patients with thalassemia than in those with myelodysplasia. Negative iron balance was achieved in 20 patients (56%). The median duration of treatment was 10 months; due to side effects and other causes only 20 patients completed 1 year of treatment. Mean serum ferritin levels decreased from 3563 μg/l at the start of the trial to 2767 μg/l at 6 months (26 patients, p〈0.004) and to 2186 μg/l at 12 months (20 patients, p〈0.005). Serum ferritin levels normalized in two patients who were no longer transfusion dependent. Deferiprone was clearly not effective in three patients (two with myelofibrosis, one with myelodysplasia). One patient with myelodysplasia developed agranulocytosis after 12 months of treatment; this was rapidly reversible after stopping deferiprone. Three patients had a mild and transient decrease in white blood cell count. Other side effects leading to withdrawal from the trial consisted mainly of nausea (3 patients), arthralgia (2), and skin rash (1). No clinical signs of zinc deficiency were seen, although zinc excretion was increased in three patients. No changes were seen in liver enzymes, creatinine, antinuclear factor, T-cell subsets, cardiac function, visual acuity, and audiogram. Although our results confirm deferiprone as an effective iron chelator in patients with thalassemia and in some patients with other forms of iron overload, there is still some concern about the safety of this drug, which therefore, at this time, should be used exclusively in well-controlled clinical trials.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050236
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  • 7
    Electronic Resource
    Electronic Resource
    Itraconazole and multidrug resistance: Possible effects on remission rate and disease-free survival in acute leukemia (1993)
    Springer
    Annals of hematology 67 (1993), S. 107-109 
    Details
    ISSN: 1432-0584
    Keywords: Itraconazole ; Acute leukemia ; Diseasefree survival ; Multidrug resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Itraconazole, a triazole antifungal agent, has been reported to reverse drug resistance against daunorubicin in acute leukemia. In a subanalysis from a double-blind, placebo-controlled trial examining the effects of itraconazole on the prevention of fungal infections in neutropenic patients, we studied the effects of itraconazole on remission rate and disease-free survival in patients with acute lymphoblastic (ALL) and acute myelogenous leukemia (AML) receiving remission induction treatment schedules containing daunorubicin (DNR). Eleven ALL and 17 AML patients received itraconazole and 12 ALL and 25 AML patients were given placebo. Among AML patients the remission rate was slightly higher in the itraconazole group, whereas the disease-free survival was higher mong ALL patients given itraconazole. In AML patients DFS was comparable in both groups but the number of high-risk patients in the itraconazole group was higher. These preliminary results may suggest a role for itraconazole in reversing multidrug resistance. Larger trials, however, are required to substantiate these findings and to correlate them with its in vitro effects on multidrug resistance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01701730
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  • 8
    Electronic Resource
    Electronic Resource
    Phase-II trial with M-CAVe-CEC as a salvage chemotherapeutic regimen for early relapsed or primary refractory Hodgkin's disease (1994)
    Springer
    Annals of hematology 69 (1994), S. 303-306 
    Details
    ISSN: 1432-0584
    Keywords: Hodgkin's disease ; Salvage chemotherapy ; Early relapse ; Primary refractory disease ; Overall and failure-free survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A substantial number of patients with Hodgkin's disease (HD) do not respond adequately to standard therapy. Patients who relapse later than 1 year after completion of treatment have a good chance of achieving a second complete remission (CR). The prognosis of patients with primary refractory HD or relapse within 1 year, however, is poor. The long-term results of autologous bone marrow transplantation (ABMT) in these patients have not yet been established. Therefore, we conducted a phase-II study among 15 patients with primary refractory or early relapsed HD, in which they were treated with a two-drug sequential regimen not cross-resistant with MOPP. The patients received two to six courses of methotrexate, cyclophosphamide, adriamycin, vinblastine, CCNU, etoposide, and chlorambucil (M-CAVe-CEC). Seven patients (47%) achieved a CR, including a patient with additional radiotherapy. Actuarial overall survival was 58 and 41%, respectively, and failure-free survival 38% at 2 and 5 years. Gastrointestinal toxicity was acceptable. Dose reductions were necessary in up to 60% of courses given. These preliminary results suggest that the M-CAVe-CEC regimen may be a more effective salvage regimen as compared with other regimens for primary refractory or early relapsed HD. Larger studies, possibly with hematopoietic growth factors, are required to determine its value in comparison to ABMT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01696559
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  • 9
    Electronic Resource
    Electronic Resource
    Iron stores and serum transferrin receptor levels during recombinant human erythropoietin treatment of anemia in rheumatoid arthritis (1992)
    Springer
    Annals of hematology 65 (1992), S. 265-268 
    Details
    ISSN: 1432-0584
    Keywords: Erythropoietin ; Recombinant human ery thropoietin ; Anemia ; Rheumatoid arthritis ; Iron stores ; Transferrin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ten rheumatoid arthritis (RA) patients with anemia of chronic disorders (ACD) were treated with recombinant human erythropoietin (r-Hu-Epo) using a dose of 250 U/kg s.c. 3 times a week for 6 weeks, in order to evaluate its effects on the anemia, iron stores, and serum-soluble transferrin receptor (sTfR) levels. All patients showed a rise in hemoglobin (Hb). Median Hb increased from 5.9 (5.5–7.0) at baseline to 6.7 (5.8–7.8) at 3 weeks and to 7.2 (5.9–8.5) mmol/l at 6 weeks during treatment. Ferritin levels decreased significantly during the 6 weeks, and five patients were iron deficient after 6 weeks of treatment. TfR levels increased significantly at 3 and 6 weeks during treatment. These preliminary findings may indicate that r-Hu-Epo is effective in improving ACD in RA. The sTfR rise may be explained by an increase in erythroid precursor cell mass or increased TfR expression and a decrease in tissue iron stores, although direct effects of Epo on TfR regulation cannot be excluded. Large double-blind studies with r-Hu-Epo in patients with RA and ACD are warranted.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01836071
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  • 10
    Electronic Resource
    Electronic Resource
    Molecular mimicry in diabetes mellitus: the homologous domain in coxsackie B virus protein 2C and islet autoantigen GAD65 is highly conserved in the coxsackie B-like enteroviruses and binds to the diabetes associated HLA-DR3 molecule (1998)
    Springer
    Diabetologia 41 (1998), S. 40-46 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Coxsackie B virus ; peptide binding ; HLA-DR ; molecular mimicry ; IDDM.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been proposed that molecular mimicry between protein 2C (p2C) of coxsackie virus B4 and the autoantigen glutamic acid decarboxylase (GAD65) plays a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In this study we show that the amino acid sequence of p2C which shares homology with a sequence in GAD65 (PEVKEK), is highly conserved in coxsackie virus B4 isolates as well as in different viruses of the subgroup of coxsackie B-like enteroviruses. These are the most prevalent enteroviruses and therefore exposure to the mimicry motif will be a frequent event throughout life. Presentation of the homologous peptides by HLA molecules is essential for T-cell reactivity. Therefore, we tested whether the PEVKEK motif can bind to the IDDM-associated HLA-DR1, -DR3 and -DR4 molecules. Synthetic peptides with sequences derived from p2C and GAD65 did bind to HLA-DR3 but not to HLA-DR1 or -DR4. Replacement of amino acids within the motif showed that the PEVKEK motif binds specifically to HLA-DR3. Moreover, both p2C and GAD65 peptides bind in the same position within the peptide binding groove of the DR3 molecule which is an essential requirement for T-cell cross-reactivity. The results support molecular mimicry between p2C of coxsackie B-like enteroviruses and GAD65. However, this molecular mimicry may be limited to the HLA-DR3 positive subpopulation of IDDM patients. [Diabetologia (1998) 41: 40–46]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050864
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