Search

Your search keyword '"Fedorak, Richard N."' showing total 676 results
Start Over Author "Fedorak, Richard N." Publication Type Academic Journals
676 results on '"Fedorak, Richard N."'

6. A randomised phase I study of etrolizumab (rhuMAb β7) in moderate to severe ulcerative colitis

Author

Rutgeerts, Paul J, Fedorak, Richard N, Hommes, Daan W, Sturm, Andreas, Baumgart, Daniel C, Bressler, Brian, Schreiber, Stefan, Mansfield, John C, Williams, Marna, Tang, Meina, Visich, Jennifer, Wei, Xiaohui, Keir, Mary, Luca, Diana, Danilenko, Dimitri, Egen, Jackson, and O'Byrne, Sharon

Subjects
Inflammatory Bowel Disease, Biotechnology, Clinical Trials and Supportive Activities, Clinical Research, Digestive Diseases, Autoimmune Disease, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Adolescent, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Colitis, Ulcerative, Dose-Response Relationship, Drug, Double-Blind Method, Female, Gastrointestinal Agents, Humans, Infusions, Intravenous, Injections, Subcutaneous, Male, Middle Aged, Severity of Illness Index, Treatment Outcome, Young Adult, Etrolizumab, rhuMAb 7, ulcerative colitis, drug development, safety, pharmacokinetics, IBD clinical, IBD basic research, IBD, IBD models, apoptosis, cell cycle, immunology, inflammatory bowel disorders, dendritic cells, Crohn's disease, cytokines, genetics, signal transduction, IBD-genetics, antibody targeted therapy, arthritis, autoimmune disease, integrins, IBD–genetics, rhuMAb β7, Clinical Sciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology
Abstract

ObjectiveEtrolizumab (rhuMAb β7, anti-β7, PRO145223) is a humanised monoclonal antibody targeting the β7 subunit of the heterodimeric integrins α4β7 and αEβ7, which are implicated in leucocyte migration and retention in ulcerative colitis (UC). This randomised phase I study evaluated the safety and pharmacology of etrolizumab in patients with moderate to severe UC.DesignIn the single ascending dose (SAD) stage, etrolizumab (0.3, 1.0, 3.0, 10 mg/kg intravenous, 3.0 mg/kg subcutaneous (SC) or placebo) was administered 4:1 (n=25) in each cohort. In the multiple dose (MD) stage, new patients received monthly etrolizumab (0.5 mg/kg SC (n=4), 1.5 mg/kg SC (n=5), 3.0 mg/kg SC (n=4), 4.0 mg/kg intravenous (n=5)) or placebo (n=5). The pharmacokinetics was studied and Mayo Clinic Score evaluated at baseline, day 29 (SAD), and days 43 and 71 (MD).ResultsIn the SAD stage, there were no dose limiting toxicities, infusion or injection site reactions. Two impaired wound healing serious adverse events occurred in two patients receiving etrolizumab. In the MD stage, there were no dose limiting toxicities, and no infusion or injection site reactions. Headache was the most common adverse event, occurring more often in etrolizumab patients. Antietrolizumab antibodies were detected in two subjects. The duration of β7 receptor full occupancy was dose related. A clinical response was observed in 12/18 patients, and clinical remission in 3/18 patients treated with etrolizumab in the MD stage, compared with 4/5 and 1/5 placebo patients, respectively.ConclusionEtrolizumab is well tolerated in moderate to severe UC. Further investigation is warranted.

Published
2013

8. Metabolomic Profiles Are Gender, Disease and Time Specific in the Interleukin-10 Gene-Deficient Mouse Model of Inflammatory Bowel Disease

Author

Tso, Victor K, Sydora, Beate C, Foshaug, Rae R, Churchill, Thomas A, Doyle, Jason, Slupsky, Carolyn M, and Fedorak, Richard N

Subjects
Medical Biochemistry and Metabolomics, Analytical Chemistry, Biomedical and Clinical Sciences, Chemical Sciences, Autoimmune Disease, Crohn's Disease, Digestive Diseases, Inflammatory Bowel Disease, Aetiology, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Age Factors, Animals, Disease Models, Animal, Female, Inflammatory Bowel Diseases, Interleukin-10, Male, Metabolome, Metabolomics, Mice, Sex Factors, General Science & Technology
Abstract

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies.

Published
2013

12. The oral toll-like receptor-7 agonist GS-9620 in patients with chronic hepatitis B virus infection

Author

Gane, Edward J., Lim, Young-Suk, Gordon, Stuart C., Visvanathan, Kumar, Sicard, Eric, Fedorak, Richard N., Roberts, Stuart, Massetto, Benedetta, Ye, Zhishen, Pflanz, Stefan, Garrison, Kimberly L., Gaggar, Anuj, Mani Subramanian, G., McHutchison, John G., Kottilil, Shyamasundaran, Freilich, Bradley, Coffin, Carla S., Cheng, Wendy, and Kim, Yoon Jun

Published
2015
Full Text
View/download PDF

14. The Probiotic VSL#3 Has Anti-inflammatory Effects and Could Reduce Endoscopic Recurrence After Surgery for Crohn's Disease

Author

Fedorak, Richard N., Feagan, Brian G., Hotte, Naomi, Leddin, Des, Dieleman, Levinus A., Petrunia, Denis M., Enns, Robert, Bitton, Alain, Chiba, Naoki, Paré, Pierre, Rostom, Alaa, Marshall, John, Depew, William, Bernstein, Charles N., Panaccione, Remo, Aumais, Guy, Steinhart, A. Hillary, Cockeram, Alan, Bailey, Robert J., Gionchetti, Paolo, Wong, Cindy, and Madsen, Karen

Published
2015
Full Text
View/download PDF

19. Methotrexate in Combination With Infliximab Is No More Effective Than Infliximab Alone in Patients With Crohn's Disease

Author

Feagan, Brian G., McDonald, John W.D., Panaccione, Remo, Enns, Robert A., Bernstein, Charles N., Ponich, Terry P., Bourdages, Raymond, MacIntosh, Donald G., Dallaire, Chrystian, Cohen, Albert, Fedorak, Richard N., Paré, Pierre, Bitton, Alain, Saibil, Fred, Anderson, Frank, Donner, Allan, Wong, Cindy J., Zou, Guangyong, Vandervoort, Margaret K., Hopkins, Marybeth, and Greenberg, Gordon R.

Published
2014
Full Text
View/download PDF

38. Clinical Experience with Infliximab for Crohn’s Disease: The First 100 Patients in Edmonton, Alberta

Author

Clifford Sample, Robert J Bailey, Dennis Todoruk, Daniel Sadowski, Gramlich Leah, Mario Milan, Raeleen Cherry, Mang Ma, Eoin Lalor, John McKaigney, Richard Sherbaniuk, Kata Matic, Connie Switzer, and Fedorak Richard N

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

OBJECTIVE: To determine whether the clinical efficacy and safety of infliximab in diverse clinical referral practices was similar to that seen in the randomized, controlled clinical trials.

Published
2002
Full Text
View/download PDF

50. Urinary metabolic profiles of inflammatory bowel disease in interleukin-10 gene-deficient mice

Author

Murdoch, Travis B., Fu, Hao, MacFarlane, Sarah, Sydora, Beate C., Fedorak, Richard N., and Slupsky, Carolyn M.

Subjects
Inflammatory bowel diseases -- Diagnosis, Inflammatory bowel diseases -- Genetic aspects, Interleukin-10 -- Health aspects, Metabolomics -- Research, Urine -- Health aspects, Urine -- Genetic aspects, Chemistry
Abstract

Inflammatory bowel disease (IBD) is a chronic debilitating disorder that is thought to have both genetic and environmental contributors. Commensal microflora have been shown to play a key part in the disease process. Metabolomics, the study of large numbers of small molecule metabolites, has demonstrated that disease and/or changes in gut microbial composition modulate mammalian urine metabolite fingerprints. The aim of this project was to associate the development of IBD with specific changes in a mouse urinary metabolic fingerprint. Interleukin-10 (IL-10) gene-deficient mice were raised alongside age-matched 129/SvEv controls in conventional housing. Urine samples (22 h) were collected at ages 4, 6, 8, 12, 16, and 20 weeks. Metabolite concentrations were derived from analysis of nuclear magnetic resonance spectra, and both multivariate and two-way analysis of variance (ANOVA) statistical techniques were applied to the resulting data. Principal component analysis and partial least-squares-discriminant analysis of urine derived from the control and IL-10 gene-deficient mice revealed that while both groups initially had similar metabolic profiles, they diverged substantially with the onset of IBD as assessed through external phenotypic changes. Several metabolites, including trimethylamine (TMA) and fucose, changed dramatically in the IL-10 gene-deficient mice following 8 weeks of age, concomitant with the known timeline for development of severe histological injury. This study illustrates that metabolomics is effective at distinguishing IBD using urinary metabolite profiles.

Published
2008

Catalog

Books, media, physical & digital resources
See catalog results