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Biomedical subjects

Stephen B Hanauer

Publications and source records attributed to Stephen B Hanauer.

At least 73 records · Page 4Linked to original sources
PubMed2004

Therapy of ulcerative colitis.

PURPOSE OF REVIEW: The past year has brought forth several controversies regarding the treatment of ulcerative colitis along with several potentially important clinical advances. The aim of this review is to provide the practicing gastroenterologist with a summation of these recent developments, with particular emphasis on advances that have already moved toward acceptance into clinical practice. RECENT FINDINGS: Controversies remain regarding the optimal formulations and doses of aminosalicylates. At the same time, the potential for chemoprotective effects in patients using maintenance therapy with mesalamine derivatives has been expanded. In addition, advances in biologic therapy for Crohn disease are beginning to be formally evaluated in ulcerative colitis, although the benefits of anti-tumor necrosis factor therapy in this condition remain to be established. Biologic therapies are beginning to be explored as adjunctive therapy for steroid-refractory ulcerative colitis, where trials of calcineurin inhibitors are also advancing clinical practice for this poor prognostic subgroup of patients. Finally, after surgery for ulcerative colitis, the treatment and prevention of pouchitis has become the one established indication for probiotic therapy. SUMMARY: Despite some inroads into the medical therapy of ulcerative colitis, controversies remain regarding the optimal dosing and delivery systems of the most fundamental therapies, and how to optimize therapy for severe ulcerative colitis. Clinical research will continue to investigate new biologic agents that inhibit tumor necrosis factor and other pro-inflammatory cytokines, and ongoing trials with leukocyte apheresis are currently under way.

Journal Article↗
PubMed2004

Crohn's is not a 6-week disease: lifelong management of mild to moderate Crohn's disease.

Crohn's disease is an idiopathic, chronic inflammatory disorder of the digestive tract with heterogeneous clinical presentations. Crohn's is currently not a curable disease, and patients are faced with a lifetime of recurrent disease flare-ups and remissions. Management strategies for Crohn's must therefore be targeted toward lifelong management, taking into consideration not only the short-term but also the long-term aspects of the disease. With this in mind, here we review the classifications and natural history of Crohn's disease and discuss possible predictive factors for the disease evolution in a patient. Here we also evaluate the current preferable treatment practices, based on scientifically valid research and collective clinical experience, for the management of mild to moderate Crohn's disease.

Algorithms↗
PubMed2004

Emerging biologic therapies in inflammatory bowel disease.

Ulcerative colitis and Crohn's disease, the idiopathic inflammatory bowel diseases (IBD), are thought to represent genetically determined, dysregulated immune responses to otherwise innocuous luminal antigens. Although progress in research has advanced our understanding of the immunopathogenesis and begun to elucidate genetic contributions toward susceptibility, limitations of current medical approaches continue to drive the search for better therapeutic agents. Most recently, the introduction of infliximab has heralded a new era of evolving biologically targeted treatments for IBD. Infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulizing Crohn's disease, but ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved in the inflammatory process. Undoubtedly, with the success of infliximab, the role of biologic therapy will continue to expand in the future treatment of IBD.

Antibodies, Monoclonal↗
PubMed2004

Controversies with aminosalicylates in inflammatory bowel disease.

Aminosalicylates have been shown to exhibit a wide range of anti-inflammatory and immunomodulatory properties. Since the discovery of sulfasalazine's efficacy in ulcerative colitis and the subsequent development of sulfa-free mesalamine delivery systems, aminosalicylates have evolved to become an integral part of our therapeutic armamentarium and are now first-line therapies for the treatment of mildly to moderately active inflammatory bowel disease and for maintenance of remissions after successful induction therapy. Despite the substantial body of evidence supporting the use of aminosalicylates in ulcerative colitis and Crohn's disease, gaps in our evidence base and controversies surrounding aminosalicylates clinical application have emerged. In this review, issues of dose response and optimization of the treatment regimen in ulcerative colitis, the discrimination between oral mesalamine formulations in left-sided colitis, and their efficacy in active and quiescent Crohn's disease are discussed.

Aminosalicylic Acids↗
PubMed2004

COLAL-PRED Alizyme.

COLAL-PRED (prednisolone sodium metasulfobenzoate), which is targeted to the colon by COLAL colonic drug delivery technology, is being developed by Alizyme for the potential treatment of inflammatory bowel disease. Alizyme expect to initiate a phase III trial in 2005.

Animals↗
PubMed2004

Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: overview of randomized clinical studies.

The past decade has brought forth a series of novel biologic agents targeting tumor necrosis factor (TNF) for the treatment of Crohn's disease. The introduction of infliximab has paved the way for additional anti-TNF strategies that have the potential to build on that drug's efficacy and safety profile. However, the anti-TNF strategies might not have identical efficacy and safety profiles and might differ in dosing compared with therapy for rheumatoid arthritis. Most recently, adalimumab has been approved by the US Food and Drug Administration for the treatment of rheumatoid arthritis and is undergoing evaluation in Crohn's disease, with promising initial results. This review discusses the results of controlled clinical trials of anti-TNF agents for Crohn's disease.

Adalimumab↗
PubMed2003

Treatment of inflammatory bowel disease: safety and tolerability issues.

An examination is needed of the potential adverse effects of the agents most commonly used to treat inflammatory bowel disease. Most of these therapies can be used safely to induce or maintain remissions, although some aspects of monitoring for toxicity are necessary. Aminosalicylates, including sulfasalazine and mesalamine delivery systems, are most commonly associated with sulfa-related effects (sulfasalazine) or intolerance, with rare instances of nephritis, pulmonitis, hepatitis, or worsening colitis. The immunomodulators are most commonly associated with bone marrow suppression, hepatitis, and the risk of opportunistic infections. Methotrexate is contraindicated in pregnancy. Antibiotics used for inflammatory bowel disease are generally safe and well tolerated, although metronidazole carries a long-term risk of peripheral neuropathy. The well-recognized multitude of adverse effects from corticosteroids are eliminated or minimized when rapidly metabolized steroids, such as budesonide, are used.

Aminosalicylic Acids↗
PubMed2003

Tacrolimus for the treatment of fistulas in patients with Crohn's disease: a randomized, placebo-controlled trial.

BACKGROUND & AIMS: This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas. METHODS: The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg. kg(-1). day(-1) or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of >/=50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks. RESULTS: Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction. CONCLUSIONS: Oral tacrolimus 0.2 mg. kg(-1). day(-1) is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated.

Adolescent↗
PubMed2003

Crohn's disease: step up or top down therapy.

The concept of a 'step-up' or 'top-down' approach to the treatment of Crohn's disease has evolved from the impact of novel anti-TNF (anti-tumour necrosis factor) therapies that have been effective for patients who are refractory to other medical treatments. In addition, the potential to produce mucosal healing with anti-TNF treatments without the well-recognized systemic complications of glucocorticoid therapy has created debate as to whether earlier, more aggressive, therapies should be advocated. This controversy arises at a time when the concept of sequential therapy to induce and maintain remissions for Crohn's disease has begun to be accepted and precedes our ability to define the concept of disease modification or predict the natural history of Crohn's disease based upon clinical, pathological, molecular orgenetic criteria. Evidence for therapeutic efficacy in Crohn's disease is presented as a prologue to considerations necessary to determine the benefits and risks of early aggressive treatment versus sequential approaches based upon disease severity.

Anti-Inflammatory Agents↗
PubMed2003

A lupus-like syndrome associated with infliximab therapy.

Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's disease. We report in detail an unusual adverse reaction to infliximab therapy, a drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid-dependent Crohn's colitis, successfully managed with maintenance infliximab infusions and methotrexate, developed a lupus-like syndrome eight months after her initial infusion. This was characterized by inflammatory arthritis and an urticarial and papulosquamous rash and was accompanied by high titers of antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and by reduced levels of the C4 component of complement. After discontinuance of infliximab infusions and treatment of symptoms with intermittent courses of prednisone, the patient's arthritis progressively improved, with accompanying decrements in autoantibody titers. One year later, she has minimal joint discomfort and no rash or gastrointestinal symptoms despite also discontinuing prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation.

Antibodies, Monoclonal↗
PubMed2003

Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn's disease phenotypes.

BACKGROUND: Multiple factors, particularly IBD family history, tobacco use, age at diagnosis and recently, NOD2 mutant genotypes may influence Crohn's disease (CD) heterogeneity. METHODS: We performed a multicenter retrospective record analysis of 275 unrelated patients with CD. Age at diagnosis, IBD family history, Jewish ethnicity, tobacco use at diagnosis, surgical history, disease site and clinical behavior were correlated with genotypes for NOD2 mutations, and all risk factors were assessed for independent influence on outcomes of disease site, behavior and surgery free survival. RESULTS: Risk of ileal disease was increased for CD patients with two NOD2 mutations (Odds Ratio, O.R. 10.1), a smoking history (O.R. 2.25 per pack per day at diagnosis) or a younger age at diagnosis (O.R. 0.97 per each increased year). Presence of ileal disease (O.R. 4.8) and carrying one or two NOD2 mutations (O.R. 1.9 and 3.5, respectively) were independent risk factors for stricturing or non-perianal fistulizing behavior. Ileal disease, youthful onset and smoking at diagnosis (but not NOD2 mutations) were risk factors for early surgery. CONCLUSIONS: Carrying two NOD2 mutations predicts youthful onset, ileal disease involvement, and development of stricturing or non-perianal fistulizing complications. Smoking and early onset independently influence ileal site and time to surgery.

Adult↗
PubMed2003

Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation.

OBJECTIVE: Lactoferrin is a glycoprotein expressed by activated neutrophils. The aim of this study was to determine the sensitivity and specificity of fecal lactoferrin concentrations for inflammatory bowel disease (IBD) or irritable bowel syndrome (IBS) versus healthy controls. METHODS: Fresh stool samples were collected from outpatients with ulcerative colitis (UC), Crohn's disease (CD), or IBS. Clinical disease activity for IBD was assessed using a modified Harvey-Bradshaw Activity Index. Fecal lactoferrin concentrations were determined using a polyclonal antibody-based enzyme linked immunoassay. Mean fecal lactoferrin concentrations for each group and sensitivity and specificity of the assay were determined. RESULTS: One hundred-four CD patients, 80 UC patients, 31 IBS patients, and 56 healthy controls were recruited. The mean +/- SE fecal lactoferrin concentration (microg/g fecal weight) was 440 +/- 128 for CD patients, 1125 +/- 498 for UC patients, 1.27 +/- 0.29 for IBS patients, and 1.45 +/- 0.4 for healthy controls. Fecal lactoferrin was 90% specific for identifying inflammation in patients with active IBD. Elevated fecal lactoferrin was 100% specific in ruling out IBS. CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea.

Adolescent↗