| 1. |
- Adrian, Katrin, 1966, et al.
(författare)
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Cytokine release during long-term extracorporeal circulation in an experimental model.
- 1998
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Ingår i: Artificial organs. - 0160-564X. ; 22:10, s. 859-63
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to determine the degree of leukocyte activation, as measured by cytokine release, in circulating blood during experimental extracorporeal circulation. Complete in vitro extracorporeal membrane oxygenation (ECMO) circuits were used, and 9 experiments were performed. Whole blood stored at 37 degrees C was used as the control. Blood samples were withdrawn before the start of perfusion and at 24 h of perfusion. Statistically significant releases of interleukin (IL)-1beta, IL-8, and IL-1 receptor antagonist were observed in the perfusion circuits compared to both the control blood and baseline values. Also, increases in plasma tumor necrosis factor (TNF)alpha and IL-6 were seen after 24 h of perfusion although these changes did not reach statistical significance. These results indicate that extracorporeal circulation induced leukocyte activation and cytokine release. These reactions might, as an additional trauma, deteriorate the situation in an already severely ill patient. A search for methods to counteract this untoward activation seems warranted.
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| 2. |
- Adrian, Katrin, 1966, et al.
(författare)
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The effect of albumin priming solution on platelet activation during experimental long-term perfusion.
- 1998
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Ingår i: Perfusion. - 0267-6591. ; 13:3, s. 187-91
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to evaluate the effect of albumin priming on platelet consumption and activation during long-term perfusion. Two identical in vitro extracorporeal membrane oxygenation circuits were used; one was primed with Ringer's solution containing human serum albumin, the other with Ringer's solution only. Fresh heparinized human blood was pooled, divided between the two systems and circulated for 24 h at 37 degrees C. Platelet count, plasma concentration of betathromboglobulin (BTG), platelet membrane density of glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We found that during the first hour of perfusion, slightly higher platelet counts (p = 0.058) and lower BTG values (p = 0.0005) were observed in the circuits primed with albumin, compared to the control circuits. No statistically significant differences were observed for the platelet membrane expression of GPIb and GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent platelet consumption and activation during long-term perfusion.
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| 3. |
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| 4. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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A transforming growth factor-beta1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura.
- 2000
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Ingår i: Annals of hematology. - 0939-5555. ; 79:9, s. 507-13
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Tidskriftsartikel (refereegranskat)abstract
- Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-beta1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) < 50 x 10(9)/l, (2) 50-150 x 10(9)/l and (3) > 150 x 10(9)/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-beta1 in patients with pltc >150x10(9)/l (23.5+/-2.8ng/ml), compared with patients with pltc <50x10(9)/l (2.3+/-0.6 ng/ml; P<0.0001), patients with pltc 50-150x 10(9)/l (7.2+/-1.7 ng/ml; P<0.0001) and healthy volunteers (9.8+/-1.3 ng/ml; P<0.01). The serum levels of the Thl cytokines interleukin (IL)-2 and interferon (IFN)-y were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50 x 10(9)/l had significantly lower levels (0.6+/-0.1 pg/ml) than both patients with pltc 50-150 x 10(9)/l (1.8 +/- 0.1 pg/ml; P<0.005) and healthy volunteers (1.4+/-0.1 pg/ml; P<0.005). Furthermore, patients with pltc <50 x 10(9)/l and splenectomised patients had significantly higher levels of CD4 + CD25 + activated T cells [26.2 +/- 14.8% (P<0.05) and 26.7+/-11.9% (P<0.005), respectively] than healthy controls (16.5+/-4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150 x 10(9)/l were significantly elevated (26.6+/-16.0%; P<0.05) compared with controls (17.4+/-7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-beta1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-beta1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease.
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| 5. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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Chronic idiopathic thrombocytopenic purpura (ITP): molecular mechanisms and implications for therapy.
- 2004
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Ingår i: Expert reviews in molecular medicine. - 1462-3994. ; 6:24, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Chronic idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder in which platelets are prematurely destroyed in the reticuloendothelial system by platelet autoantibodies. However, it is becoming clear that the pivotal process of the humoral immune response in the pathogenesis of the disorder is a complex interaction between antigen-presenting cells, T cells and B cells. Furthermore, it is increasingly evident that regulatory T cells play an important role and that T-cell-mediated cytotoxicity contributes to the destruction of platelets in ITP. Different new approaches to immunotherapy in chronic ITP have been explored, including use of anti-CD20, anti-CD154 and anti-CD52 antibodies. So far, these therapies have been antigen-nonspecific and the risk of general immunosuppression is a concern. Thus, improving our understanding of the interaction and relative contribution of humoral and cell-mediated mechanisms is essential for developing antigen-specific immunotherapies for the treatment of this disorder. This review aims to elucidate the current status of knowledge of the cellular and humoral immune components of chronic ITP, together with the implications of this knowledge for therapy.
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| 6. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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Leukemic transformation of essential thrombocythemia without previous cytoreductive treatment.
- 2000
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Ingår i: Annals of hematology. - 0939-5555. ; 79:1, s. 40-2
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Tidskriftsartikel (refereegranskat)abstract
- Blastic transformation of essential thrombocythemia (ET) preceded by chemotherapy is occasionally described in the literature. In ET as well as in other myeloproliferative disorders the leukemogenic effect of alkylating agents and (32)P is well established, and recent reports also indicate a certain leukemogenic effect of hydroxyurea in these disorders. However, leukemic transformation in untreated ET seems to be a rare event. This is probably due to the fact that, at some time during their clinical course, most ET patients receive chemotherapy and are thereby exposed to leukemogenic challenge. We report on a woman with ET who had not received cytoreductive treatment prior to the development of acute myeloid leukemia, indicating that this transformation was a natural progression of her disorder.
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| 7. |
- Andersson, Per-Ola, 1964, et al.
(författare)
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Reduced transforming growth factor-beta1 production by mononuclear cells from patients with active chronic idiopathic thrombocytopenic purpura.
- 2002
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Ingår i: British journal of haematology. - 0007-1048 .- 1365-2141. ; 116:4, s. 862-7
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Tidskriftsartikel (refereegranskat)abstract
- Chronic idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which activated T-helper (Th) cells and different Th-cell cytokines might play an important role. We have recently reported that chronic ITP patients in remission had elevated plasma levels of the Th3 cytokine transforming growth factor-beta1 (TGF-beta1), possibly as a part of a bystander immune suppression. In the present study we found that, in ITP patients with active disease [platelet count (plc) < 50 x 10(9)/l], mitogen-stimulated peripheral blood mononuclear cells (PBMC) had a significantly reduced production of TGF-beta1 (444 +/- 178 pg/ml; n = 6) compared with patients with plc 50-150 x 10(9)/l (1293 +/- 374 pg/ml; n = 9; P < 0.05), patients with plc >150 x 10(9)/l (1894 +/- 244 pg/ml; n =12; P <0.005) and healthy controls (1698 +/- 241 pg/ml; n = 10; P < 0.01). Nineteen per cent of ITP patients expressed a platelet-induced PBMC proliferation. Surprisingly, 22% of the ITP patients had a PBMC proliferation below the normal range, i.e. a suppressed proliferation in the presence of platelets; five of these six patients had active disease. In summary, this study demonstrated that chronic ITP patients with active disease had reduced PBMC production of the Th3 cytokine TGF-beta1. This result gives further support to the theory that chronic ITP in active phase is associated with a downregulated Th3-response.
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| 8. |
- Andreasson, Björn, et al.
(författare)
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Plasma erythropoietin concentrations in polycythaemia vera with special reference to myelosuppressive therapy.
- 2000
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Ingår i: Leukemia & lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 37:1-2, s. 189-95
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Tidskriftsartikel (refereegranskat)abstract
- In 80 patients with polycythaemia vera (PV) a total of 108 venous blood samples were obtained and analysed for EDTA-plasma erythropoietin (EPO) concentration. At the time of study 21 of the PV patients were newly diagnosed and had prior to blood sampling neither received phlebotomy treatment nor therapy with myelosuppressive agents; these subjects had a mean plasma EPO concentration of 0.5+/-0.9 IU/L. Thirty-seven patients treated with phlebotomy only had a mean plasma EPO concentration of 2.5+/-2.9 IU/L. The mean plasma EPO concentrations for 26 patients treated with hydroxyurea, 13 patients treated with radiophosphorous and 11 patients given a combination of myelosuppressive agents were 8.9+/-8.0, 10.9+/-12.6 and 7.2+/-7.4 IU/L, respectively. Untreated patients and patients on phlebotomy only had significantly lower values for plasma EPO than patients on therapy with myelosuppressive drugs. This finding persisted also after a correction for differences in haemoglobin levels had been introduced. Thereby, the present results would suggest a difference in the EPO feedback system in untreated and phlebotomised PV patients compared to PV patients treated with myelosuppressive agents.
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| 9. |
- Andreasson, Björn, et al.
(författare)
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The measurement of venous haematocrit in patients with polycythaemia vera.
- 1999
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:3, s. 293-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In clinical practice, patients with polycythaemia vera (PV) are monitored by measurement of venous packed cell volume (PCV). However, whereas treatment recommendations are still based upon studies in which the results were obtained with the centrifuged microhaematocrit, currently in most instances automated blood cell counters are used to calculate PCV. In a group of patients with polycythaemia we therefore compared the results obtained by the microhaematocrit method with PCV calculated by haematology analysers. DESIGN: The study was carried out on a prospective basis. Duplicate venous blood samples were collected. The centrifuged microhaemotocrit was obtained by using an IEC Micro-MB Centrifuge. Depending on different routine methods used in the participating hospitals, the blood cell counter PCV was calculated using Coulter STKS, Bayer Technicon H2 or H3. SETTING: Patients were included from four Swedish university hospitals: Akademiska (Uppsala), Huddinge and Karolinska (Stockholm) and Sahlgrenska (Göteborg). SUBJECTS: Seventy-four patients with PV and 10 patients with secondary polycythaemia were included and a total of 150 duplicate blood samples were analysed from these subjects. RESULTS: In the 150 measurements the mean blood cell counter calculated PCV was 0.448 +/- 0.037; the mean for centrifuged microhaematocrit was 0.467 +/- 0. 037 and the difference between means was highly significant (P = 6.8 x 10-25). The means for centrifuged haematocrit and calculated PCV differed significantly in the groups of PV patients treated with phlebotomy only, hydroxyurea or radiophosphorous (P < 0.0001, respectively). In PV patients treated with alpha-interferon and in patients with secondary polycythaemia the difference in means did not reach statistical significance (P = 0.07 and P = 0.13, respectively). The groups of patients with MCV <80 fL and >/=80 fL both presented significant differences between means for calculated PCV and centrifuged haematocrit. CONCLUSIONS: If PV patients are monitored with blood cell counter calculated PCV it appears that the therapeutic goal should be to maintain the calculated PCV below 0.43, provided the local differences in calculated PCV and centrifuged haematocrit are of the same magnitude as in this study.
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| 10. |
- Andreasson, Björn, et al.
(författare)
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The relation between plasma thrombopoietin and erythropoietin concentrations in polycythaemia vera and essential thrombocythaemia.
- 2001
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Ingår i: Leukemia & lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 41:5-6, s. 579-84
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Tidskriftsartikel (refereegranskat)abstract
- Plasma thrombopoietin (TPO) was measured, by immunoenzymometric assay, in 39 patients with polycythaemia vera (PV), 33 patients with essential thrombocythaemia (ET) and 10 healthy volunteers. The mean TPO concentration was significantly higher in ET patients than in PV patients (p=0.04) and normals (p<0.001). The 6 untreated ET patients had a significantly lower mean TPO concentration compared to the 27 ET patients who were on myelosuppressive regimens (p=0.01). The mean plasma TPO for the 5 PV patients treated with phlebotomy only did not differ significantly from the corresponding mean for the 34 PV patients treated with myelosuppressive agents. Concomitantly, plasma EPO was measured in 25 of the PV patients and in 30 of the ET patients by an immunoradiometric assay with normal reference interval in adults 3.7-16 IU/L. In the 14 PV patients with EPO <3.7 IU/L mean plasma TPO did not differ significantly from the mean for the 11 PV patients with EPO >or=3.7 IU/L; neither of these two groups had plasma TPO concentrations significantly different from the mean for the control subjects. The 7 ET patients with subnormal plasma EPO had significantly lower mean plasma TPO compared to the ET patients with normal and high plasma EPO concentrations (p=0.03 and p=0.02, respectively). Also, the 16 ET patients with normal plasma EPO had significantly lower plasma TPO compared to the 8 patients with high plasma EPO (p=0.04). The mean plasma TPO for each of these three groups of ET patients was significantly higher than the corresponding mean for the controls (p<0.001 for each group). The results of the present study indicate that a relationship between plasma EPO and TPO concentrations may exist and that myelosuppressive treatment affects the TPO concentration in ET but not in PV patients.
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