Ulcerative Colitis: Korzenik JR

Korzenik JR. · IBD Center, Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. · J Clin Gastroenterol. · Pubmed #15758661 No free full text.

Abstract: While tremendous advances have improved the understanding of inflammatory bowel disease, with regard to environmental risk factors as well as the biochemical nature of the inflammatory process, a determination of primary etiology remains elusive. Numerous theories have been proposed in the past century concerning the cause of Crohn's disease and ulcerative colitis with implications for specific therapies. On further study, most of these ideas and therapies have failed to be accurate in theory or therapeutic approach. Others remain untested or are the focus of current investigation and controversy. This paper reviews the dominant theories of primary etiology. These hypotheses include infectious causes such as Mycobacteria paratuberculosis and measles. Allergic and nutritionally related causes have been the focus of considerable research. Microparticles, which is part of the concept behind toothpaste as a cause, have been suggested more broadly to be the principal factor initiating Crohn's disease. Several of these concepts rely on the idea that there is an increased intestinal permeability that is the central defect leading to Crohn's disease. Rather than being an excessive T cell driven process, Crohn's has been suggested to be an innate immune deficiency, leading to the use of colony stimulating factors to augment the intestinal barrier function and innate immunity. A variety of changes in the gut flora, ranging from a basic dysbiosis to the absence of helminths, have been proposed as the root cause of inflammatory bowel disease.

Lam MY, Lee H, Bright R, Korzenik JR, Sands BE. · MGH Crohn's & Colitis Center and Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. · Inflamm Bowel Dis. · Pubmed #19023897 No free full text.

Abstract: BACKGROUND: The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a written, self-administered instrument measuring quality of life in IBD. We assessed the validity of an interactive voice response system (IVRS) as a new mode of administering the SIBDQ. METHODS: An IVRS was designed using prerecorded questions to collect data via touchtone telephone. Subjects with Crohn's disease (CD) or ulcerative colitis (UC) were randomized into 2 groups with different orders of administration: written, self-administered followed by IVRS (S-I) or IVRS followed by written, self-administered (I-S). Half of the S-I group was also randomized to receive a second IVRS. Sixty-four subjects were studied: 30 in S-I, 34 in I-S. RESULTS: The mean SIBDQ scores were not different between written and IVRS modes (P = 0.26) with r = 0.93. IVRS scores were lower in active than inactive CD (36.1 +/- 9.6 versus 54.7 +/- 8.6, P < 0.001) and lower in active than inactive UC (40.8 +/- 9.6 versus 59.8 +/- 10.0, P < 0.001). Mean scores correlated highly with disease activity indices, and were not different between first and second IVRS administrations (P = 0.85) with r = 0.92. IVRS had excellent internal consistency (Cronbach alpha = 0.90). CONCLUSIONS: IVRS administration of the SIBDQ yields results similar to written self-administration, with excellent procedural validity, test-retest reliability, and internal consistency.

Dieckgraefe BK, Korzenik JR, Anant S. · Division of Gastroenterology, Siteman Cancer Center, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. · Ann N Y Acad Sci. · Pubmed #17057209 No free full text.

Abstract: On the basis of several studies that have been completed to date, some growth factors appear promising for the treatment of inflammatory bowel disease: keratinocyte-like growth factor-2 (KGF-2), epidermal growth factor (EGF) enemas used in combination with oral mesalamine, somatropin (human growth hormone), and sargramostim (recombinant human GM-CSF). The results of these studies are highlighted and suggest that new insights into the regulation of intestinal immunity may provide effective synergistic or single-agent treatment alternatives to immunosuppression for inflammatory bowel disease. These data focus on the reparative components of mucosal homeostasis.

Dieckgraefe BK, Stenson WF, Korzenik JR, Swanson PE, Harrington CA. · Division of Gastroenterology, Department of Surgical Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. · Physiol Genomics. · Pubmed #11074008 No free full text.

Abstract: DNA arrays capable of simultaneously measuring expression of thousands of genes in clinical specimens from affected and normal individuals have the potential to provide information about disease pathogenesis not previously possible. Few studies have applied mRNA profiling to diseases involving complex tissues like the intestinal mucosa, reflecting the unique challenges inherent to this type of analysis. We report the analysis of mucosal gene expression in ulcerative colitis (UC) patients and inflamed and noninflamed control specimens. Genes can be used as markers for cell recruitment, activation, and mucosal synthesis of immunoregulatory molecules. Self-organizing maps were applied to cluster and analyze gene expression patterns and were paired with histopathological scores to identify genes associated with increased disease activity. Clustering was achieved on the basis of differences in expression levels across individual specimens. Several inflammatory mediators were identified as likely determinants of characteristic histological features of active UC. These results provide proof of principle for application of functional genomics to larger inflammatory bowel disease populations for gene discovery, to facilitate identification of disease subgroups on the basis of gene expression signatures, and for prediction of disease behavior or optimal therapeutic intervention.