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Your search keyword '"Melton-Celsa, Angela"' showing total 18 results
Start Over Author "Melton-Celsa, Angela" Publisher american society for microbiology
18 results on '"Melton-Celsa, Angela"'

7. Multicenter Evaluation of a Sequence-Based Protocol for Subtyping Shiga Toxins and Standardizing Stx Nomenclature

Author

Scheutz, Flemming, primary, Teel, Louise D., additional, Beutin, Lothar, additional, Piérard, Denis, additional, Buvens, Glenn, additional, Karch, Helge, additional, Mellmann, Alexander, additional, Caprioli, Alfredo, additional, Tozzoli, Rosangela, additional, Morabito, Stefano, additional, Strockbine, Nancy A., additional, Melton-Celsa, Angela R., additional, Sanchez, Maria, additional, Persson, Søren, additional, and O'Brien, Alison D., additional

Published
2012
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18. Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal antibody c alpha Stx2 administered intravenously to healthy adult volunteers.

Author

Dowling TC, Chavaillaz PA, Young DG, Melton-Celsa A, O'Brien A, Thuning-Roberson C, Edelman R, and Tacket CO

Subjects
Adult, Alanine Transaminase blood, Animals, Antibodies, Monoclonal administration & dosage, Area Under Curve, Aspartate Aminotransferases blood, Dose-Response Relationship, Drug, Half-Life, Humans, Injections, Intravenous, Mice, Recombinant Fusion Proteins immunology, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal pharmacokinetics
Abstract

Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that has neutralizing activity in a mouse model was produced and tested in healthy adult volunteers. In this phase I dose escalation study, c alpha Stx2 was generally well tolerated. Pharmacokinetic studies indicated that clearance was stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 +/- 0.023 ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 +/- 0.078 ml/kg/h), suggesting saturable elimination. A similar nonlinear trend was observed for the volume of distribution, where average values ranged from 0.064 +/- 0.015 liter/kg for the 1.0- to 10-mg/kg doses and 0.043 +/- 0.005 for the 0.01-mg/kg dose. The relatively small volume of distribution suggests that the antibody is limited to the vascular (plasma) compartment. The mean half-life was 165 +/- 66 h, with lowest values observed for the 0.1-mg/kg dose (56.2 +/- 9.7 h) and the highest values reported for the 10.0-mg/kg dose (206.4 +/- 12.4 h). Future studies are needed to confirm the safety of this c alpha Stx2, and innovative clinical trials will be required to measure its efficacy in preventing or treating HUS.

Published
2005
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