| 2. |
- Freiburghaus, Christian, et al.
(författare)
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Tolerance induction using the Malmo treatment model 1982-1995
- 1999
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 5:1, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- The ultimate goal in the treatment of haemophilia patients with inhibitors is to eradicate permanently the inhibitor and induce tolerance. Here we summarize our experience at the Malmo centre regarding tolerance induction according to the Malmo Treatment Model. The protocol includes immunoadsorption if needed, neutralization of inhibitor and replacement with factor concentrates, cyclophosphamide intravenously for 2 days (12-15 mg kg-1 bw) and then orally (2-3 mg kg-1 bw) for an additional 8-10 days and intravenous gammaglobulin daily at dosages of 0.4 g kg-1 bw for 5 days. This protocol has been applied in 23 haemophilia patients with inhibitors, 16 haemophilia A patients and seven haemophilia B patients. Altogether 36 attempts have been made to induce tolerance. Ten of the 16 haemophilia A (62.5%) and 6/7 patients with haemophilia B (86%) became tolerant after the treatment. The chances of success or failure are roughly equal, if the series is considered in a historical perspective. The data showed that the chances of success in tolerance induction with the Malmo protocol were best in those patients with low inhibitor titres, with relatively low historical inhibitory peak and with a long interval since the previous replacement therapy. This was especially true where no inflammatory state was present at the start or during tolerance induction. The advantage with this method compared to the high-dose regimen is that in the successful cases tolerance can be achieved within 3-4 weeks.
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| 3. |
- Magnusson, Marie, et al.
(författare)
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Effects of pentoxifylline and its metabolites on platelet aggregation in whole blood from healthy humans
- 2008
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 581:3, s. 290-5
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Tidskriftsartikel (refereegranskat)abstract
- It is known that pentoxifylline inhibits platelet aggregation in vitro, but the effects from pentoxifylline and its main metabolites: 3,7-dimetyl-1(5 hydroxyhexyl)xanthine (R-M1 and S-M1), 3,7-dimetyl -1(4-carboxybutyl)xanthine (M4), 3,7-dimetyl -1(3-carboxypropyl)xanthine (M5), on platelet aggregation in whole blood in vitro and in vivo have not been studied. We found that pentoxifylline, rac-M1, R-M1, S-M1 and M4 significantly inhibit ADP induced platelet aggregation in whole blood in vitro in a concentration-dependent manner, R-M1 being the most potent followed by rac-M1, S-M1, pentoxifylline, and M4. In this series of experiments the effects on aggregation induced ATP-release were less pronounced and were only significant after treatment with pentoxifylline, rac-M1 and R-M1, but the potency order appears to be the same. Since the metabolites are not available for use in humans, and also since each substance would be extensively metabolised in vivo, we made an attempt to estimate the relative contribution of each substance to the total effect of pentoxifylline in vivo. Previously published concentrations of pentoxifylline and these metabolites in humans, after administration of pentoxifylline, were used in combination with the potency ratios from this study. The findings from these calculations were that the main effect in vivo comes from S-M1 followed by pentoxifylline, the other metabolites contribute less than 10% each. In conclusion: in the following potency order R-M1, rac-M1, pentoxifylline, S-M1 and M4 all have significant effects on platelet aggregation in whole blood in vitro. However, it appears that the main effects in vivo are caused by S-M1 and pentoxifylline.
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