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S B Hanauer

Publications and source records attributed to S B Hanauer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Evolving treatment strategies for inflammatory bowel disease.

Crohn's disease and ulcerative colitis are idiopathic inflammatory bowel diseases characterized by dysregulated intestinal immune responses in genetically susceptible hosts. Conventional approaches to the medical therapy of ulcerative colitis and Crohn's disease can now be directed at either induction or maintenance of remission to improve therapeutic efficacy while minimizing complications. Newer approaches have expanded the utility of conventional therapies by improving both safety and efficacy and highlight the importance of specific targets along the immunoinflammatory pathways. The combination of conventional and novel approaches now offers the potential of modifying the natural history of these diseases.

Anti-Bacterial Agents↗
PubMed2001

Update on medical management of inflammatory bowel disease: ulcerative colitis.

Significant advances have been made regarding our understanding of the etiopathogenesis of inflammatory bowel disease. This review focuses on the most recent applications of medical therapy for ulcerative colitis. Therapeutic approaches continue to evolve regarding inductive and maintenance strategies with oral and topical aminosalicylates, systemic and non-systemic corticosteroids, and cyclosporine and alternative immunomodulators. As further investigations continue to discern microbiological and immunoinflammatory targets, future therapies may include both probiotics and novel biological agents.

Adrenal Cortex Hormones↗
PubMed2000

A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators.

BACKGROUND: Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. METHODS: We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea. CONCLUSIONS: In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.

Adult↗
PubMed2000

Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease.

The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.

Chromosomes, Human, Pair 1↗
PubMed2000

Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group.

BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with potent anti-inflammatory properties. We investigated the safety and efficacy of different doses of human recombinant (rhu)IL-10 in patients with Crohn's disease (CD). METHODS: A prospective, multicenter, double-blind, placebo-controlled study was conducted in 329 therapy-refractory patients with CD. Clinical improvement was defined by a reduction of the Crohn's Disease Activity Index (CDAI) by 100 points or more and clinical remission by a decrease of the CDAI to <150 points. At selected centers, patients underwent ileocolonoscopies and activation of the nuclear factor-kappa B (NF-kappa B) system was assessed in biopsy specimens. RESULTS: Subcutaneous treatment with rhuIL-10 over 28 days induced a fully reversible, dose-dependent decrease in hemoglobin and thrombocyte counts but no clinically significant side effects. No differences in the induction of remission were observed between rhuIL-10 groups (1 microg, 18% [9.6-29.2]; 4 microg, 20% [11.3-32.2]; 8 microg, 20% [11.1-31.8]; 20 microg, 28% [18-40.7]; and placebo, 18% [9.6-29.6]). Clinical improvement was observed in 46% (33.7-59) in the 8-microg/kg rhuIL-10 group in comparison with 27% (17-39.6) in patients taking placebo. Responders to rhuIL-10 showed inhibition of NF-kappaB p65 activation in contrast to nonresponders. CONCLUSIONS: Up to 8 microg/kg of rhuIL-10 was well tolerated. A tendency toward clinical improvement but not remission was observed in the 8-microg/kg dose group. Further studies should delineate which subgroups of patients with CD benefit from rhuIL-10 therapy.

Adult↗
PubMed2000

Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group.

BACKGROUND & AIMS: Interleukin 10 (IL-10) is an anti-inflammatory, immunomodulatory cytokine that regulates mucosal inflammation. This study evaluated the safety, tolerance, and efficacy of recombinant human IL-10 (rhuIL-10) for mild to moderately active Crohn's disease. METHODS: We conducted a 24-week multicenter, prospective, randomized, double-blind, placebo-controlled, and sequential-escalating-dose study. Ninety-five patients with Crohn's Disease Activity Index of 200-350, not presently undergoing corticosteroid, mesalamine, or immunosuppressive therapy, were treated with subcutaneous rhuIL-10 (1, 5, 10, or 20 microg/kg) or placebo once daily for 28 consecutive days. Patients were followed up for 20 weeks after treatment. Evaluation of safety and tolerance was the first objective, and efficacy was the second objective. RESULTS: Adverse effects were dose-related, mild-to-moderate in severity, and reversible. Asymptomatic and reversible anemia and thrombocytopenia were observed at higher doses. No withdrawal or delayed adverse effects were evident during 20 weeks of follow-up. At the end of treatment (day 29), intent-to-treat analysis showed that 23.5% (confidence interval [CI], 6.8%-49.9%) of patients receiving 5 micro/kg rhuIL-10 experienced clinical remission and endoscopic improvement; 0% (CI, 0%-14.8%) of patients in the placebo group did. Higher doses of recombinant human IL-10 were less effective than 5 microg/kg. No rhuIL-10 serum accumulation and no antibody against IL-10 were detected after 4 weeks. CONCLUSIONS: Subcutaneous rhuIL-10 administered daily for 28 days to patients with mild to moderately active Crohn's disease is safe, well-tolerated, and shows clinical and endoscopic improvement.

Adult↗
PubMed2000

Linkage heterogeneity for the IBD1 locus in Crohn's disease pedigrees by disease onset and severity.

BACKGROUND & AIMS: There is evidence for the IBD1 Crohn's disease (CD) susceptibility locus on chromosome 16 in several but not all populations studied. Genetic and phenotypic heterogeneity may underlie ability to replicate IBD1. We determined if age and severity stratification could identify a clinical subgroup at risk for IBD1. METHODS: Linkage analysis at microsatellites spanning chromosome 16 was performed in 2 groups of CD pedigrees: group 1, 57 pedigrees with at least one affected relative classified as having "severe" disease, by history of surgical resection or immunomodulator therapy, and with disease diagnosed before age 22; and group 2, 33 pedigrees with no history of early-onset, severe CD. RESULTS: Group 1 pedigrees demonstrated genomewide significant linkage evidence for the IBD1 locus (nonparametric multipoint logarithm of the odds [Mlod], 3.84; P = 1.3 x 10(-5)) with linkage evidence greater than all 90 pedigrees (Mlod, 2.12; P = 9.0 x 10(-4)). Group 2 pedigrees had near zero nonparametric 2-point and Mlod scores for the IBD1 region. Heterogeneity between groups 1 and 2 was significant (P = 0.002). CONCLUSIONS: Presence of early-onset, more severe CD identifies pedigrees at high risk for IBD1. These pedigrees will have more power to refine the IBD1 locus and identify the causative gene.

Adult↗
PubMed2000

Side-to-side isoperistaltic strictureplasty in extensive Crohn's disease: a prospective longitudinal study.

OBJECTIVE: To report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn's disease. METHODS: Between January 1992 and April 1999, the authors operated on 469 consecutive patients for Crohn's disease of the small bowel. Seventy-one patients (15.1%) underwent at least one strictureplasty; of these, 21 (4.5%; 12 men, 9 women; mean age 39) underwent an SSIS. The long-term changes occurring in the SSIS were studied radiographically, endoscopically, and histopathologically. RESULTS: The indication for surgical intervention was symptomatic partial intestinal obstruction in each of the 21 patients. Fourteen SSISs were constructed in the jejunum, four in the ileum, and three with ileum overlapping colon. The average length of the SSIS was 24 cm. Performance of an SSIS instead of a resection resulted in preservation of an average of 17% of small bowel length. One patient suffered a postoperative gastrointestinal hemorrhage. All patients were discharged on oral feedings after a mean of 8 days. In all cases, SSIS resulted in resolution of the preoperative symptoms. With follow-up extending to 7.5 years in 20 patients (one patient died of unrelated causes), radiographic, endoscopic, and histopathologic examination of the SSIS suggests regression of previously active Crohn's disease. CONCLUSIONS: SSIS is a safe and effective procedure in patients with extensive Crohn's disease. The authors' results provide radiographic, endoscopic, and histopathologic evidence that active Crohn's disease regresses at the site of the SSIS.

Adult↗
PubMed2000

Medical therapy for ulcerative colitis.

Last year was not a banner year for developments in medical therapy for ulcerative colitis. In contrast to the expansion of therapies for Crohn disease, treatment for ulcerative colitis was evolutionary, at best, leading many patients to seek alternative medical approaches. Nevertheless, there have been advances in the application of aminosalicylates and immune modifiers for ulcerative colitis. Additional, nonconventional approaches include nicotine, probiotics, dietary therapies, and heparins. Several novel approaches have arisen from animal models, including additional means of inhibiting nuclear factor-kappaB and targeting of tumor necrosis factor-alpha.

Journal Article↗
PubMed2000

Smoking and inflammatory bowel disease.

It is well established that smoking cigarettes is associated with Crohn's disease (CD) and that non-smoking is associated with ulcerative colitis (UC). Furthermore, there is convincing evidence that smoking cigarettes has a negative effect on the course of CD, and that smoking cigarettes may improve the disease severity or have a 'protective' effect in some patients with UC. Despite these well-described associations, the mechanism by which cigarette smoking affects CD and UC is not known. Researchers have studied the systemic effects, cellular and humoral immune effects, mucosal changes, and the intestinal permeability changes with inflammatory bowel disease (IBD) and smoking. To date, none of these studies adequately explains the observed clinical patterns. It has been assumed that nicotine is the active agent in these associations, but clinical trials of nicotine chewing gum and transdermal nicotine in UC have shown limited benefit, and have been complicated by significant side-effects. Topical delivery systems for nicotine therapy are currently under development and await future clinical trials.

Comorbidity↗
PubMed2000

A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998.

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.

Adult↗
PubMed2000

A meta-analysis and overview of the literature on treatment options for left-sided ulcerative colitis and ulcerative proctitis.

OBJECTIVES: Therapeutic trials in left-sided ulcerative colitis (L-UC) and ulcerative proctitis (UP) have lacked control for medication type, dose, delivery, and duration of therapy. METHODS: All published therapeutic articles and abstracts in L-UC or UP from 1958-1997 were reviewed. Improvement, remission rates, and adverse events were recorded for all (ALL), placebo-controlled (PC) studies, and for PC studies passing quality assessment (QA) scoring. Meta-analysis was used where appropriate. RESULTS: Left-sided UC: For active disease, 67 studies (17 PC; 10 QA) were identified. Mesalamine enemas achieved remission in a duration but not a dose response (QA), with higher remission rates than steroid enemas (ALL) and clinical improvement rates superior to oral therapies (QA, ALL). Remission maintenance: 17 (six PC, six QA) studies were identified. Mesalamine therapies had comparable remission rates at 6 months, with a possible dose but not delivery effect. Mesalamine enema dosing intervals between QHS to Q3 days maintained efficacy. Reported adverse events were most common with oral sulfasalazine and dose-independent for mesalamine. Withdrawals from therapy were less than placebo, or < or =3%. Ulcerative proctitis: For active disease, 18 (nine PC, three QA) studies were identified. Mesalamine suppositories achieved clinical improvement and remission in a duration but not dose response, with higher rates of remission than topical steroids (ALL). Remission maintenance: three (three PC, two QA) studies were identified. Remission ranged from 75% to 90% (6 months) and 61-90% (12 months) for mesalamine agents. Reported adverse events were most common for mesalamine foam (8%). Withdrawals from therapy were <2%. CONCLUSIONS: In L-UC and UP, the efficacy and side-effect profile of topical mesalamine are dose independent and superior to oral therapies and topical steroids. Economic analysis suggests that use of these agents will also result in an overall decrease in patient costs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Medical therapy to reduce postoperative Crohn's disease recurrence.

Clinical recurrence of Crohn's disease after surgical resection is a significant problem, with reported rates as high as 55% at 5 yr and 76% at 15 yr. Specific factors that predispose to postoperative recurrence of Crohn's disease have not been well defined. In addition, the underlying pathophysiology of recurrent disease and the reason for its localization to the neoterminal ileum are not well understood. Various operative techniques have been evaluated but none, aside from formation of an ostomy, has been shown to reduce the risk of recurrence. In contrast, there is increasing evidence that postoperative medical therapy has the potential to decrease the risk of postoperative recurrence. Historically, sulfasalazine may have a modest effect on reducing postoperative recurrence of ileal or ileocolonic disease. However, 5-ASA preparations that can selectively deliver mesalamine to the small bowel or anastomotic margin should be more effective. Indeed, in several studies and as confirmed by a meta-analysis, mesalamine has been demonstrated to reduce significantly postoperative recurrence of Crohn's disease. Metronidazole and 6-mercaptopurine or azathioprine also seem to be of benefit in postoperative prophylaxis of disease recurrence, but additional controlled studies are required to define better the efficacy and dose-response of these agents. Corticosteroids are ineffective at reducing postoperative recurrence.

Anti-Infective Agents↗