Ulcerative Colitis: Katz JA

Katz JA. · No affiliation provided · Gastroenterology. · Pubmed #12730892 No free full text.

This publication has no abstract.

Katz JA. · Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, OH 44106-5066, USA. · J Dig Dis. · Pubmed #17532817 No free full text.

Abstract: Optimal care of the inflammatory bowel diseases, Crohn's disease and ulcerative colitis, requires a broad understanding of disease pathophysiology and therapeutic alternatives. The goals of therapy are accurate diagnosis and timely treatment to both induce and maintain a clinical remission and improve patient quality of life. Most patients can be adequately treated using a combination or aminosalicylates, antibiotics, and corticosteroids, though many patients with Crohn's disease will require immunomodulators, such as azathioprine or 6-mercaptopurine. The development of novel biologic therapies, particularly infliximab, have dramatically improved our ability to medically manage more severe Crohn's disease and ulcerative colitis patients. This review will focus on the medical management of inflammatory bowel disease in adults.

Floch MH, Madsen KK, Jenkins DJ, Guandalini S, Katz JA, Onderdonk A, Walker WA, Fedorak RN, Camilleri M. · Yale University School of Medicine, New Haven, CT 06520-8019, USA. · J Clin Gastroenterol. · Pubmed #16633136 No free full text.

Abstract: Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.

Katz JA. · Division of Gastroenterology, Department of Medicine, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106-5066, USA. · Gastroenterol Clin North Am. · Pubmed #15177533 No free full text.

Abstract: Corticosteroids are a mainstay in the treatment of inflammatory bowel disease. Administered topically, orally, or intravenously corticosteroids rapidly and consistently improve moderate to severe active ulcerative colitis and Crohn's disease, although they are ineffective in the maintenance of remission in either illness. The beneficial effects of corticosteroid therapy are counterbalanced by their many side effects. A better understanding of the mechanism of steroid action and toxicity has led to the development of novel corticosteroids that offer the promise of continued efficacy with minimal toxicity. This article reviews the role of conventional and novel corticosteroids in the management of inflammatory bowel disease.

Gurudu S, Fiocchi C, Katz JA. · Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, OH 44106-5066, USA. · Best Pract Res Clin Gastroenterol. · Pubmed #11977930 No free full text.

Abstract: Although inflammatory bowel disease (IBD) usually presents in adolescents and young adults, both ulcerative colitis and Crohn's disease can also present in older adults. The diagnosis of IBD in the elderly is often difficult and can easily be confused with diverticulitis or ischaemic colitis. The symptoms and complications of IBD in the elderly are similar to those found in younger patients. However, when IBD presents later in life the disease is often less extensive and milder. Older IBD patients are treated with the same medications as younger patients, although the risk for drug toxicity is greater, especially with corticosteroid therapy. Comorbid illness in older patients often has a significant impact on the outcome of medical and surgical therapy for IBD but, in the absence of significant co-morbid disease, most elderly IBD patients can expect a good response to therapy.

Katz JA, Pore G. · Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. · Inflamm Bowel Dis. · Pubmed #11383588 No free full text.

Abstract: Most women with inflammatory bowel disease who desire to become pregnant can expect to conceive successfully, carry to term, and deliver a healthy infant. However, the management of inflammatory bowel disease during pregnancy remains challenging, and some women with ulcerative colitis or Crohn's disease will have difficulty becoming pregnant or have increased disease symptoms while pregnant. Control of disease activity before conception and during pregnancy is critical to optimize both maternal and fetal health. The natural history of inflammatory bowel disease during pregnancy will be reviewed and the medical and surgical therapy discussed.

Katz JA. · Division of Gastroenterology, Case Western Reserve University, Cleveland, OH, USA. · Semin Gastrointest Dis. · Pubmed #10706226 No free full text.

Abstract: The management of severe ulcerative colitis and Crohn's colitis remains a challenge, despite significant advances in medical and surgical therapy. Optimal management of the patient with severe colitis requires close collaboration between the gastroenterologist and surgeon. All patients with severe colitis should be hospitalized and treated with intravenous corticosteroids. If significant improvement does not occur within 7 to 10 days, then intravenous cyclosporine therapy or surgery is appropriate. Newer medical therapies, including heparin, tacrolimus, and other immunomodulatory agents, show promise for the treatment of severe colitis. When surgery is necessary, a total abdominal colectomy with ileostomy is the appropriate surgical intervention in most cases. In patients presenting with fulminant colitis, toxic megacolon, or perforation, earlier surgical intervention is indicated. The evaluation of and approach to the medical and surgical management of severe colitis will be reviewed.

Tremaine WJ, Brzezinski A, Katz JA, Wolf DC, Fleming TJ, Mordenti J, Strenkoski-Nix LC, Kurth MC, Anonymous00162. · Mayo Clinic, Rochester, MN 55905, USA. · Aliment Pharmacol Ther. · Pubmed #11876693 links to  free full text

Abstract: BACKGROUND: Mast cells isolated from the colonic mucosa in active ulcerative colitis appear to be partially degranulated, suggesting the release of tryptase. AIM: To investigate the safety and activity of APC 2059, a highly specific tryptase inhibitor, in the treatment of ulcerative colitis. METHODS: This was an open-label, Phase 2, multicentre pilot study in patients with mildly to moderately active ulcerative colitis, with a disease activity index of 6-9 on a 12-point scale. Fifty-six adults received 20 mg APC 2059 subcutaneously twice daily and 53 completed 28 days of treatment. The primary end-point was response, defined as a final disease activity index of < or = 3. Supplementary analyses were also performed. RESULTS: Sixteen (29%) of 56 patients responded. Five (9%) showed complete remission (disease activity index=0). Twenty-seven (49%) improved, with a final disease activity index of < or = 3 or a four-point reduction. Improvement or normalization in each category of the disease activity index was as follows: stool frequency, 64%; bleeding, 64%; endoscopy, 50%; physicians' rating, 63%. There were no significant relationships between outcome and pharmacokinetics. The most common adverse events were related to the injection site (32.1%). CONCLUSIONS: In this pilot study, the tryptase inhibitor APC 2059 was safe and there was evidence of activity in the treatment of ulcerative colitis.

Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, Lashner B, Present DH, Chuai S, Ellenberg JH, Nessel L, Wu GD, Anonymous00007. · Division of Gastroenterology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. · Gastroenterology. · Pubmed #18325386 links to  free full text

Abstract: BACKGROUND & AIMS: Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC). METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline, Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC. Disease activity was measured with the Mayo score. The primary end point was clinical response (>/=2-point reduction) at week 12. Clinical remission (Mayo score </=2), endoscopic remission, and quality of life were secondary outcomes. RESULTS: After 12 weeks of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo achieved clinical response (P = .04). Remission was achieved in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8% rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early as 4 weeks after beginning treatment (P = .049). Quality of life was improved significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P = .14). Serious adverse events were rare. CONCLUSIONS: Rosiglitazone was efficacious in the treatment of mild to moderately active UC.

Katz JA. · Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio 44106-5066, USA. · Curr Opin Gastroenterol. · Pubmed #17033318 No free full text.

Abstract: The medical therapy of inflammatory bowel disease (IBD) has advanced significantly over the past year. Serologic markers of IBD have been further investigated and better defined, showing some discriminatory power with potential therapeutic implications. Studies of azathioprine and 6-mercaptopurine metabolites will make it easier and safer to use these effective drugs. Clinical data using other immunomodulators, including 6-thioguanine, mycophenolate mofetil, cyclosporine, and tacrolimus, continue to accrue with positive results. Infliximab has become even more firmly established as a reliable and effective therapy for active and fistulizing Crohn disease and may even be helpful in some patients with resistant ulcerative colitis. However, the recognition of potential complications of infliximab therapy has increased with the accumulated clinical experience. Results from trials of other biologic therapies directed at tumor necrosis factor alpha have been disappointing so far, although preliminary studies with biologics directed at adhesion molecules are encouraging. Growing appreciation of the importance of the enteric microflora in IBD has led to a considerable interest in manipulating intestinal bacteria for therapeutic benefit, and trials of both probiotics and prebiotics show promise.

Katz JA, Itoh J, Fiocchi C. · Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. · Curr Opin Gastroenterol. · Pubmed #17023960 No free full text.

Abstract: In spite of expanding knowledge of cellular and molecular mechanisms of intestinal inflammation, the etiology and pathogenesis of inflammatory bowel disease (IBD) remain obscure. The link between the environment and IBD is still circumstantial, but definite progress is occurring in defining genetic susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The notion that normal enteric flora play a role in initiating or maintaining IBD is gaining momentum. Some components of the flora may act as noxious agents, whereas others (probiotics) seem to have a protective effect. The importance of the mucosal immune system to IBD is established, and evidence is accumulating that nonimmune components, such as epithelial, mesenchymal, and endothelial cells, also contribute to gut inflammation. The effect of cytokines in intestinal immunity is being elucidated by studies on their molecular mechanism, particularly the activation of nuclear factor (NF)-kappaB. Finally, the beneficial effects of cytoprotective prostaglandins and cell adhesion molecule (CAM) blockade promise novel therapeutic opportunities derived from an improved understanding of IBD pathogenesis.

Katz JA. · Department of Medicine, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio 44106-5066, USA. · Curr Opin Gastroenterol. · Pubmed #15703660 No free full text.

Abstract: PURPOSE OF REVIEW: Inflammatory bowel disease commonly affects women during the childbearing years, and young couples are often concerned about the potential effects of inflammatory bowel disease on fertility, pregnancy, and the fetus. This review will critically consider advances over the past 2 years in our knowledge of the effects of inflammatory bowel disease on fertility and pregnancy outcome and the safety and efficacy of medical therapy in the pregnant woman with inflammatory bowel disease. RECENT FINDINGS: The past several years have witnessed significant additions to our knowledge of the effects of ulcerative colitis and Crohn disease on fetal outcome. In addition, important studies have added to the growing database pointing to the overall safety of medical therapy with aminosalicylates and immunomodulators during pregnancy. Limited new data also suggest that inadvertent exposure to infliximab appears not to be harmful to the fetus. SUMMARY: Women with Crohn disease appear to be at risk for early delivery and low birthweight infants, and women with ulcerative colitis may be at increased risk for giving birth to children with congenital abnormalities. The clinical significance of these results may be diluted, however, by inability to adequately assess the confounding influence of disease activity or drug treatment. Despite lingering concerns, the most recent data support the overall safety of the 5-aminosalicylate drugs as well as azothiaprine/6-mercaptopurine during pregnancy. Despite these advances, the potential complications of inflammatory bowel disease and its therapies during pregnancy continue to require careful discussion with each individual couple before conception.

Danese S, Katz JA, Saibeni S, Papa A, Gasbarrini A, Vecchi M, Fiocchi C. · Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine Cleveland, Ohio 44106-4952, USA. · Gut. · Pubmed #12970136 links to  free full text

Abstract: BACKGROUND: The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. AIMS: To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. PATIENTS: CD, UC, and normal control subjects were studied. METHODS: The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). RESULTS: Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. CONCLUSIONS: Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Soweid AM, Chak A, Katz JA, Sivak MV. · Divisions of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106-1736, USA. · Gastrointest Endosc. · Pubmed #10385720 No free full text.

Abstract: BACKGROUND: Use of an echocolonoscope to examine patients with inflammatory bowel disease is technically difficult. Catheter probe assisted endoluminal ultrasonography (US) may be a feasible alternative. METHODS: Determination of demographic information and clinical disease activity was followed by colonoscopy with biopsy. Catheter probe assisted endoluminal US was performed with measurements of thickness of the intestinal wall and evaluation of the structure of the sonographic layers. RESULTS: Twenty-eight patients, 7 with ulcerative colitis, 11 with Crohn's disease, and 10 healthy control subjects participated in a prospective study. Mean colonic wall thickness was 2.2 +/- 0.1 mm (controls) compared with 4. 1 +/- 0.4 mm (ulcerative colitis) (p < 0.001) and 4.4 +/- 0.4 mm (Crohn's disease) (p < 0.001). Among patients with ulcerative colitis, colonic wall thickness correlated with severity of colonoscopic changes (r = 0.84, p = 0.02). Among patients with Crohn's disease, loss of endosonographic layer structure correlated with disease activity score (r = 0.8, p = 0.003), and colonic wall thickness correlated with the severity of histologic changes (r = 0. 62, p = 0.04). CONCLUSIONS: Catheter probe assisted endoluminal US is technically feasible in the care of patients with inflammatory bowel disease. Endosonographic measurements of colonic wall thickness and layer structure provide clinically significant information.