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Richard Greil - One of the best experts on this subject based on the ideXlab platform.
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Purine Antagonists for chronic lymphocytic leukaemia
Cochrane Database of Systematic Reviews, 2006Co-Authors: Michael Steurer, Georg Pall, Sue Richards, Guido Schwarzer, Julia Bohlius, Richard GreilAbstract:BACKGROUND Recent trials suggest improved response rates for Purine Antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage. OBJECTIVES To determine if there is any advantage of Purine Antagonists compared to alkylating agents (alone or in combination) in the treatment of patients with previously untreated B-CLL. SEARCH STRATEGY Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and internet-based trial registers were searched electronically and/or by hand (1990-2003). All references were checked for further trial information. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA Randomised controlled trials comparing Purine Antagonists as single agents with alkylator-based regimens in patients with previously untreated B-CLL were included. We included full-text and abstract publications as well as unpublished data. DATA COLLECTION AND ANALYSIS Data extraction and quality assessment were done in duplicate by two independent reviewers. Missing data were obtained from original authors. Endpoints included overall survival, overall response rate, rate of complete remissions, progression-free survival, treatment-related morbidity and mortality. MAIN RESULTS Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with Purine Antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78-1.01], 4 trials, n=1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13-1.31], 5 trials, n=1751) and complete remission (RR 1.94 [95% CI 1.65-2.28], 5 trials, n=1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82], 4 trials, n=1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with Purine Antagonists (RR 1.83 [95% 1.30-2.58], 4 trials, n=1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, n=1620) and therapy-related mortality (RR 0.94 [95% CI 0.45-1.95]). Overall incidence of hemolytic anemia was low, but significantly increased in the Purine antagonist group (RR 3.36 [95% CI 1.27-8.91], 3 trials, n=1258). AUTHORS' CONCLUSIONS Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent Purine Antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of Purine Antagonists also augments the risk for grade III/IV infections and hemolytic anemia.
N. N. Bulaeva - One of the best experts on this subject based on the ideXlab platform.
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Effect of Purine Antagonists on the cAMP level in lymphocytes and bone marrow lymphoblasts
Bulletin of Experimental Biology and Medicine, 1995Co-Authors: A. S. Dukhanin, P. V. Sergeev, L. I. Stankevich, N. N. BulaevaAbstract:The effect of the Purine receptor ligands N-ethylcarboxamide adenine and adenosine and of the Purine Antagonists mercaptoPurine and azathioprine on the intracellular cAMP content in human peripheral blood lymphocytes and bone marrow lymphoblasts was studied. All preparations tested induced an increase in the cAMP level in peripheral blood lymphocytes. The selective immunosuppressive effect of adenosine Antagonists may be due to their ability to modulate the activity of adenylate cyclase in lymphoid cells.
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Comparative study of the interaction of Purine Antagonists with adenosine receptors of bone marrow lymphocytes and lymphoblasts
Biulleten' eksperimental'noi biologii i meditsiny, 1993Co-Authors: A. S. Dukhanin, L. I. Stankevich, N. N. BulaevaAbstract:In this study we used the radiolabeled selective ligand (3H-NECA) of A2-types Purine receptors in order to investigate specific NECA binding with human blood lymphocytes and bone marrow lymphoblasts. Relative affinity of 6-mercaptoPurine and azathioprine for Purine receptors was determined. One type of high affinity NECA binding sites have been shown on the lymphocytes (Kd = 0.57 mkM, Bmax = 0.63 pmol/10(6) cells), which selectively interacted with AZT, but not 6-MP. Relative potencies of substance in competitive radioassay: adenosine > AZT > 6-MP. Two classes NECA binding sites on the lymphoblasts have been identified. One of them corresponds to lymphocyte receptors. The second type of NECA binding sites is characterised by following parameters: Kd = 6.5 mkM and Bmax = 1.5 pmole/10(6) cells. They are selective sensitized to 6-MP. Relative affinity changes in the line: 6-MP > adenosine > AZT.
Bruce E. Sands - One of the best experts on this subject based on the ideXlab platform.
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Review article: practical management of inflammatory bowel disease patients taking immunomodulators.
Alimentary pharmacology & therapeutics, 2005Co-Authors: Corey A. Siegel, Bruce E. SandsAbstract:Summary Azathioprine, mercaptoPurine, methotrexate, ciclosporin and tacrolimus all have their respective niches in the treatment of inflammatory bowel disease. These immunomodulators are potent and effective medications; however, they potentially have serious toxicity. To maximize benefit and minimize risk, clinicians must understand the mechanism of action, appropriate indications, range of toxicity and proper dosing of these medications. Furthermore, once initiating therapy, patients need to be monitored appropriately for evidence of efficacy and toxicity. This review includes the rationale behind recommendations for the management and monitoring of patients using immunomodulators. For the Purine Antagonists – azathioprine and mercaptoPurine – the evidence for utility of thioPurine methyltransferase testing and mercaptoPurine metabolite monitoring is addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate reductase mutations in patients taking methotrexate are reviewed. With appropriate monitoring, the calcineurin inhibitors – ciclosporin and tacrolimus – can be used safely and effectively. Immunomodulators are important agents for the treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians should be comfortable recognizing both their value and their limitations.
Michael Steurer - One of the best experts on this subject based on the ideXlab platform.
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Purine Antagonists for chronic lymphocytic leukaemia
Cochrane Database of Systematic Reviews, 2006Co-Authors: Michael Steurer, Georg Pall, Sue Richards, Guido Schwarzer, Julia Bohlius, Richard GreilAbstract:BACKGROUND Recent trials suggest improved response rates for Purine Antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage. OBJECTIVES To determine if there is any advantage of Purine Antagonists compared to alkylating agents (alone or in combination) in the treatment of patients with previously untreated B-CLL. SEARCH STRATEGY Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and internet-based trial registers were searched electronically and/or by hand (1990-2003). All references were checked for further trial information. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA Randomised controlled trials comparing Purine Antagonists as single agents with alkylator-based regimens in patients with previously untreated B-CLL were included. We included full-text and abstract publications as well as unpublished data. DATA COLLECTION AND ANALYSIS Data extraction and quality assessment were done in duplicate by two independent reviewers. Missing data were obtained from original authors. Endpoints included overall survival, overall response rate, rate of complete remissions, progression-free survival, treatment-related morbidity and mortality. MAIN RESULTS Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with Purine Antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78-1.01], 4 trials, n=1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13-1.31], 5 trials, n=1751) and complete remission (RR 1.94 [95% CI 1.65-2.28], 5 trials, n=1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82], 4 trials, n=1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with Purine Antagonists (RR 1.83 [95% 1.30-2.58], 4 trials, n=1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, n=1620) and therapy-related mortality (RR 0.94 [95% CI 0.45-1.95]). Overall incidence of hemolytic anemia was low, but significantly increased in the Purine antagonist group (RR 3.36 [95% CI 1.27-8.91], 3 trials, n=1258). AUTHORS' CONCLUSIONS Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent Purine Antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of Purine Antagonists also augments the risk for grade III/IV infections and hemolytic anemia.
A. S. Dukhanin - One of the best experts on this subject based on the ideXlab platform.
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Effect of Purine Antagonists on the cAMP level in lymphocytes and bone marrow lymphoblasts
Bulletin of Experimental Biology and Medicine, 1995Co-Authors: A. S. Dukhanin, P. V. Sergeev, L. I. Stankevich, N. N. BulaevaAbstract:The effect of the Purine receptor ligands N-ethylcarboxamide adenine and adenosine and of the Purine Antagonists mercaptoPurine and azathioprine on the intracellular cAMP content in human peripheral blood lymphocytes and bone marrow lymphoblasts was studied. All preparations tested induced an increase in the cAMP level in peripheral blood lymphocytes. The selective immunosuppressive effect of adenosine Antagonists may be due to their ability to modulate the activity of adenylate cyclase in lymphoid cells.
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Comparative study of the interaction of Purine Antagonists with adenosine receptors of bone marrow lymphocytes and lymphoblasts
Biulleten' eksperimental'noi biologii i meditsiny, 1993Co-Authors: A. S. Dukhanin, L. I. Stankevich, N. N. BulaevaAbstract:In this study we used the radiolabeled selective ligand (3H-NECA) of A2-types Purine receptors in order to investigate specific NECA binding with human blood lymphocytes and bone marrow lymphoblasts. Relative affinity of 6-mercaptoPurine and azathioprine for Purine receptors was determined. One type of high affinity NECA binding sites have been shown on the lymphocytes (Kd = 0.57 mkM, Bmax = 0.63 pmol/10(6) cells), which selectively interacted with AZT, but not 6-MP. Relative potencies of substance in competitive radioassay: adenosine > AZT > 6-MP. Two classes NECA binding sites on the lymphoblasts have been identified. One of them corresponds to lymphocyte receptors. The second type of NECA binding sites is characterised by following parameters: Kd = 6.5 mkM and Bmax = 1.5 pmole/10(6) cells. They are selective sensitized to 6-MP. Relative affinity changes in the line: 6-MP > adenosine > AZT.
