The Experts below are selected from a list of 42 Experts worldwide ranked by ideXlab platform
Thomas J. Degraba - One of the best experts on this subject based on the ideXlab platform.
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Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of Enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study.
Stroke, 2001Co-Authors: Kazuhide Furuya, Hidetaka Takeda, Salman Azhar, Richard M. Mccarron, Yong Chen, Christl A. Ruetzler, Karen M. Wolcott, Thomas J. Degraba, Robert Rothlein, Tony E. HugliAbstract:Background and Purpose— Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. We did a bedside-to-bench study in standardized rat stroke models to explore mechanisms for these untoward results. Methods— After focal brain ischemia in Wistar rats and spontaneously hypertensive rats (SHR), we administered murine anti-rat ICAM-1 antibody (1A29), subclass-matched murine immunoglobulin (IgG1), or vehicle intravenously. To examine whether rat anti-mouse antibodies were generated against the mouse protein and whether these were deleterious, we sensitized Wistar rats with 1A29 or vehicle 7 days before surgery. Infarct volume, tissue myeloperoxidase activity, neutrophil CD11b expression, and microvascular E-selectin, P-selectin, and ICAM-1 expression were examined 48 hours after surgery. Complement activation was serially assessed for 2 hours after a single injection of either 1A29 or vehicle. Results— 1A29 treatment ...
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The role of inflammation after acute stroke : Utility of pursuing anti-adhesion molecule therapy
Neurology, 1998Co-Authors: Thomas J. DegrabaAbstract:A growing body of evidence, primarily from animal models of cerebral ischemia and preliminary human studies, indicates that inflammatory mechanisms contribute to secondary neuronal injury after acute cerebral ischemia. Ischemia followed by reperfusion rapidly leads to the expression of inflammatory cytokines, particularly tumor necrosis factor-α and interleukin-1β, which stimulate a complex cascade of events involving local endothelial cells, neurons, astrocytes, and perivascular cells. A secondary response includes the release of other cytokines, an increase in components of the coagulation system, an upregulation of cell adhesion molecule expression, and changes in the expression of components of the immune response. The net effect of these events is transformation of the local endothelium to a prothrombotic/proinflammatory state and induction of leukocyte migration to the site of injury. A number of studies have shown that leukocyte migration occurs within hours of reperfusion. Leukocytes accumulate in the injured region, where they cause tissue injury by several mechanisms, including occlusion of microvasculature, generation of oxygen free radicals, release of cytotoxic enzymes, alteration of vasomotor reactivity, and increase in cytokine and chemoattractant release. Monoclonal antibodies against leukocyte adhesion molecules have been shown to reduce infarct volume in animal models of ischemia-reperfusion. However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial. A number of factors may complicate the use of antibody directed adhesion molecule blockade in acute stroke and will be discussed in this article. Overall, an increased understanding of inflammatory and immunologic mechanisms still offers great potential for reducing acute stroke injury.
Hanshellmut Neumayer - One of the best experts on this subject based on the ideXlab platform.
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a randomized multicenter trial of the anti icam 1 monoclonal antibody Enlimomab for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation a report of the european anti icam 1 renal transplant study g
Transplantation, 1999Co-Authors: K Salmela, L Wramner, Henrik Ekberg, Ingeborg A Hauser, O Bentdal, Larseric Lins, Helena Isoniemi, Lars Backman, N H Persson, Hanshellmut NeumayerAbstract:Background. T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (Enlimomab), renal allograft survival has been improved and reperfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Transplant Study (EARTS) was a randomized, double-blind, parallel-group, placebo-controlled study lasting 1 year and performed in 10 transplant centers in Europe. Methods. A total of 262 recipients of cadaveric kidneys were given either Enlimomab or a placebo for 6 days and were given triple immunosuppressive therapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, and each event was assessed by a committee including investigators and independent pathologists. Results. There was no significant difference in the incidences of first acute rejection at 3 months between the placebo and Enlimomab groups (39% vs. 45%), and Enlimomab did not reduce the risk of delayed onset of graft function (DGF) (26% vs. 31%). Neither was there a difference in patient survival (95% vs. 91%) or graft survival (89% vs. 84%) at 1 year. Fatal events occurred in 19 (7%) patients (7 placebo, 12 Enlimomab). Clinically, the most important non-fatal adverse events were infections; however, there was no statistically significant difference between the incidences in the two groups (70% vs. 79%). Conclusion. Short term Enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.
Kyra J Becker - One of the best experts on this subject based on the ideXlab platform.
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Anti-leukocyte antibodies: LeukArrest (Hu23F2G) and Enlimomab (R6.5) in acute stroke.
Current medical research and opinion, 2002Co-Authors: Kyra J BeckerAbstract:An abundance of experimental data show that inflammation contributes to cerebral ischaemic injury and that attenuation of the inflammatory response can improve outcome. The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. The potential reasons for the failure of these trials are discussed.
Enlimomab Acute Stroke Trial Investigators - One of the best experts on this subject based on the ideXlab platform.
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Use of anti-ICAM-1 therapy in ischemic stroke Results of the Enlimomab Acute Stroke Trial
Neurology, 2001Co-Authors: Enlimomab Acute Stroke Trial InvestigatorsAbstract:Background: There has been recent interest in the possible role of reperfusion-induced inflammation with neuronal injury after stroke. Enlimomab, a murine intercellular adhesion molecule-1 (ICAM-1) antibody, reduces leukocyte adhesion and infarct size in experimental stroke studies. The purpose of the current clinical trial was to evaluate the use of Enlimomab after ischemic stroke. Methods: A total of 625 patients with ischemic stroke were randomized to receive either Enlimomab (n = 317) or placebo (n = 308) within 6 hours of stroke onset. Treatment was given over 5 days. Patients were evaluated at baseline and on days 5 and 90 after initiation of treatment; long-term assessments were carried out after 6 and 12 months. The primary efficacy endpoint was the response to therapy at 90 days on the Modified Rankin Scale; other endpoints included Barthel Index (BI) and NIH Stroke Scale and survival. Results: At day 90, the Modified Rankin Scale score was worse in patients treated with Enlimomab than with placebo ( p = 0.004). Fewer patients had symptom-free recovery on Enlimomab than placebo ( p = 0.004), and more died (22.2 versus 16.2%). The negative effect of Enlimomab was apparent on days 5, 30, and 90 of treatment ( p = 0.005). There were significantly more adverse events with Enlimomab treatment than placebo, primarily infections and fever. Patients experiencing fever were more likely to have a poor outcome or die. Conclusions: The authors conclude that anti-ICAM therapy with Enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.
T J Degraba - One of the best experts on this subject based on the ideXlab platform.
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The role of inflammation after acute stroke: utility of pursuing anti-adhesion molecule therapy.
Neurology, 1998Co-Authors: T J DegrabaAbstract:A growing body of evidence, primarily from animal models of cerebral ischemia and preliminary human studies, indicates that inflammatory mechanisms contribute to secondary neuronal injury after acute cerebral ischemia. Ischemia followed by reperfusion rapidly leads to the expression of inflammatory cytokines, particularly tumor necrosis factor-alpha and interleukin-1beta, which stimulate a complex cascade of events involving local endothelial cells, neurons, astrocytes, and perivascular cells. A secondary response includes the release of other cytokines, an increase in components of the coagulation system, an upregulation of cell adhesion molecule expression, and changes in the expression of components of the immune response. The net effect of these events is transformation of the local endothelium to a prothrombotic/proinflammatory state and induction of leukocyte migration to the site of injury. A number of studies have shown that leukocyte migration occurs within hours of reperfusion. Leukocytes accumulate in the injured region, where they cause tissue injury by several mechanisms, including occlusion of microvasculature, generation of oxygen free radicals, release of cytotoxic enzymes, alteration of vasomotor reactivity, and increase in cytokine and chemoattractant release. Monoclonal antibodies against leukocyte adhesion molecules have been shown to reduce infarct volume in animal models of ischemia-reperfusion. However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial. A number of factors may complicate the use of antibody directed adhesion molecule blockade in acute stroke and will be discussed in this article. Overall, an increased understanding of inflammatory and immunologic mechanisms still offers great potential for reducing acute stroke injury.