Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease

Present, Daniel H.; Rutgeerts, Paul; Targan, Stephan R.; Hanauer, Stephen B.; Mayer, Lloyd; Hogezand, R. A. van; Podolsky, Daniel K.; Sands, Bruce E.; Braakman, T; DeWoody, Kimberly; Schaible, T.; Deventer, S. J. H. Van

doi:10.1056/nejm199905063401804

Cited by 2,498 publications

(1,683 citation statements)

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“…Using flow cytometric detection of intracellular leukocyte cytokine production, we have shown that steroids inhibit Th1 and inflammatory cytokine production while upregulating IL-10 synthesis (4). The importance of inflammatory cytokines is evident from the successful and safe therapeutic use of antibodies against TNF-␣ in bringing Crohn's disease into remission (5,6). The nonspecific anti-inflammatory treatment being used in the conventional management of patients with IBD (apart from those mentioned) has not changed much since the 1970s and new therapeutic agents are keenly sought.…”

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confidence: 99%

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease

2002

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BackgroundCytokines involved in inflammatory bowel disease (IBD) direct a predominantly cell‐mediated T‐ helper‐1 (Th1) immune response. The nonspecific anti‐inflammatory treatment being used in the management of patients with IBD has not changed much since the 1970s and new therapeutic agents are keenly sought. Several compounds isolated from Allium sativum (garlic) modulate leukocyte cell proliferation and cytokine production.MethodsTo investigate the possible therapeutic effects of garlic in the treatment of patients with IBD, whole blood and peripheral blood mononuclear cells (PBMCs) were stimulated in the presence of various concentrations of garlic extract and the effect on leukocyte cytokine production was determined in vitro using multiparameter flow cytometry.ResultsMonocyte interleukin (IL)‐12 production was inhibited significantly in the presence of low concentrations of garlic extract (≥0.1 μg/ml total protein). Monocyte IL‐10 production increased significantly and monocyte tumor necrosis factor‐alpha (TNF‐α), IL‐1α, IL‐6, IL‐8, T‐cell interferon‐gamma (IFN‐γ), IL‐2, and TNF‐α decreased significantly in the presence of ≥10 μg/ml garlic extract. Twenty to fifty percent of the immunomodulatory activity of garlic extract on cytokine production was acid labile. The inhibitory activity of methylprednisolone, a commonly used anti‐inflammatory in IBD, with garlic on leukocyte cytokine production was additive.ConclusionsBy inhibiting Th1 and inflammatory cytokines while upregulating IL‐10 production, treatment with garlic extract may help to resolve inflammation associated with IBD. An in vivo animal model study needs to be undertaken to determine the significance of these in vitro findings. Cytometry 48:209–215, 2002. © 2002 Wiley‐Liss, Inc.

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Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease

2002

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“…Neutralization of tumor necrosis ␣ has potent antiinflammatory and disease-modifying effects in an expanding list of immune-mediated disease, including Crohn's disease, rheumatoid arthritis, psoriasis, and ankylosing spondylitis. [5][6][7][8][9] These results have led to a widespread echoed belief that increased production of TNF-␣, a molecule known to cause inflammation and cell death, is a common pathogenic pathway in immune-mediated diseases, and consequently the development of TNFinhibiting antibodies, proteins, peptides, and small molecules has become a cottage industry.…”

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Transmembrane TNF-α, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn's disease

Deventer

2001

Gastroenterology

113

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“…Advances in the medical therapy of fistulating perianal Crohn's disease have been boosted by large RCTs8 78, 79. The present study has highlighted a number of important features regarding surgical interventions.…”

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“…Since 1995, supporting medical therapy has changed significantly8. MEDLINE, Embase and Cochrane Library databases were searched using a predefined and registered (PROSPERO database, CRD42016050316) search protocol.…”

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Systematic review of surgical interventions for Crohn's anal fistula

Lee

Heywood²,

Adegbola

et al. 2017

BJS Open

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BackgroundAnal fistula occurs in approximately one in three patients with Crohn's disease and is typically managed through a multimodal approach. The optimal surgical therapy is not yet clear. The aim of this systematic review was to identify and assess the literature on surgical treatments of Crohn's anal fistula.MethodsA systematic review was conducted that analysed studies relating to surgical treatment of Crohn's anal fistula published on MEDLINE, Embase and Cochrane databases between January 1995 and March 2016. Studies reporting specific outcomes of patients treated for Crohn's anal fistula were included. The primary outcome was fistula healing rate. Bias was assessed using the Cochrane ROBINS‐I and ROB tool as appropriate.ResultsA total of 1628 citations were reviewed. Sixty‐three studies comprising 1584 patients were ultimately selected in the analyses. There was extensive reporting on the use of setons, advancement flaps and fistula plugs. Randomized trials were available only for stem cells and fistula plugs. There was inconsistency in outcome measures across studies, and a high degree of bias was noted.ConclusionData describing surgical intervention for Crohn's anal fistula are heterogeneous with a high degree of bias. There is a clear need for standardization of outcomes and description of study cohorts for better understanding of treatment options.

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Infliximab for the Treatment of Fistulas in Patients with Crohn's Disease

Cited by 2,498 publications

References 23 publications

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease

Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: Potential therapeutic use in the treatment of inflammatory bowel disease

Transmembrane TNF-α, induction of apoptosis, and the efficacy of TNF-targeting therapies in Crohn's disease

Systematic review of surgical interventions for Crohn's anal fistula

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