Publications
175 results found
Landy J, Wahed M, Peake STC, et al., 2013, Oral tacrolimus as maintenance therapy for refractory ulcerative colitis--an analysis of outcomes in two London tertiary centres., J Crohns Colitis, Vol: 7, Pages: e516-e521
BACKGROUND: The medical management of refractory ulcerative colitis (UC) remains a significant challenge. Two randomised controlled studies have demonstrated tacrolimus therapy is effective for the induction of remission of moderate to severe UC. However, the long term outcomes of UC patients treated with tacrolimus as maintenance therapy are not certain. AIMS: This study aims to assess the efficacy of tacrolimus maintenance therapy for refractory UC. METHODS: A retrospective review of patients with UC treated with tacrolimus at two London tertiary centres was performed. Clinical outcomes were assessed at six months, at the end of tacrolimus treatment, or at the last follow-up for patients continuing tacrolimus treatment. Modified Truelove-Witts score (mTW) and Mayo endoscopy subscores were calculated. RESULTS: 25 patients with UC, treated with oral tacrolimus between 2005 and 2011, were identified. The median duration of tacrolimus treatment was 9 months (IQR 3.7-18.2 months). The median duration of follow-up was 27 months (range 3-66 months). At six months thirteen (52%) patients had achieved and maintained clinical response and eleven (44%) were in clinical remission. The mean mTW score decreased from 10+/-0.5 before therapy, to 5.8+/-0.8 (p≤0.001 95% CI 2.7-5.8) at cessation of treatment or last follow-up. Mayo endoscopy subscore decreased from 2.6+/-0.1 to 1.2+/-0.2 (p≤0.001 mean reduction 1.4, 95% CI 0.8-1.9). Eight patients (32%) subsequently underwent a colectomy within a mean time of 17 months (range 2-45 months). CONCLUSION: Tacrolimus is effective for the maintenance of refractory UC and can deliver sustained improvement in mucosal inflammation.
Al-Hassi HO, Bernardo D, Murugananthan AU, et al., 2013, A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn's disease, Mucosal Immunology, Vol: 6, Pages: 751-761, ISSN: 1933-0219
Dendritic cells (DC) migrate to lymph nodes on expression of C-C motif chemokine receptor 7 (CCR7) and control immune activity. Leptin, an immunomodulatory adipokine, functions via leptin receptors, signaling via the long isoform of receptor, LepRb. Leptin promotes DC maturation and increases CCR7 expression on blood DC. Increased mesenteric fat and leptin occur early in Crohn's disease (CD), suggesting leptin-mediated change in intestinal CCR7 expression on DC as a pro-inflammatory mechanism. We have demonstrated CCR7 expression and capacity to migrate to its ligand macrophage inflammatory protein 3beta in normal human ileal DC but not colonic or blood DC. In CD, functional CCR7 was expressed on DC from all sites. Only DC populations containing CCR7-expressing cells produced LepRb; in vitro exposure to leptin also increased expression of functional CCR7 in intestinal DC in a dose-dependent manner. In conclusion, leptin may regulate DC migration from gut, in homeostatic and inflammatory conditions, providing a link between mesenteric obesity and inflammation.
Yassin NA, Al-Hassi HO, Lee GH, et al., 2013, The Aetiology of Crohn’s and Idiopathic Anal Fistulae - Are There Any Differences in the Dendritic Cells Homing Profile?, ACPGBI
Yassin NA, Al-Hassi HO, Lee GH, et al., 2013, Increased Gut Homing (B7) on Dendritic cells in Fistulating Perianal Crohn’s Disease, ICMI
Yassin NA, Lung PF, Gupta A, et al., 2013, A New 3 Dimentional Model and Volume Assessment Tool for the Surgical and Medical Management of Crohn’s Perianal Fistulae, ACPGBI
Yassin NA, Al-Hassi OH, Lee GH, et al., 2013, The Immune Cell Activation and Homing Profile of Dendritic Cells in Fistulating Perianal Crohn's Disease, DDW
Rahbour G, Al-Hassi HO, Hart AL, et al., 2013, Tumour necrosis factor alpha in non-inflammatory bowel disease enterocutaneous fistulas prospective study, Joint Meeting of the Section-of-Surgery of the Royal-Society-of-Medicine / Annual Meeting of the Society-of-Academic-and-Research-Surgery, Publisher: WILEY-BLACKWELL, Pages: 37-37, ISSN: 0007-1323
Gearry RB, Kamm MA, Hart AL, et al., 2013, Predictors for developing intestinal failure in patients with Crohn's disease, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Vol: 28, Pages: 801-807, ISSN: 0815-9319
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- Citations: 24
Yassin NA, Al-Hassi H, Lee GH, et al., 2013, The aetiology, immune activation and homing profile of dendritic cells in fistulating perianal Crohn's disease, European Crohn's and Colitis Organisation
Landy J, Hart AL, 2013, Commentary: short-term efficacy of tacrolimus in steroid-refractory ulcerative colitis., Aliment Pharmacol Ther, Vol: 37
Hart AL, 2013, Vitamin D and Inflammatory Bowel Disease: Chicken or Egg?, INFLAMMATORY BOWEL DISEASES, Vol: 19, Pages: 459-460, ISSN: 1078-0998
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- Citations: 4
Landy J, Hart AL, 2013, Commentary: the rising tide of cholecystectomy for biliary dyskinesia, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 37, Pages: 493-494, ISSN: 0269-2813
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- Citations: 3
Tozer P PJ, Balmforth D, Kayani B, et al., 2013, Surgical management of rectovaginal fistula in a tertiary referral centre: many techniques are needed., Colorectal Dis
AIM: Surgery is the mainstay of treatment for rectovaginal fistula (RVF). Published success rates vary with initial success being around 50% rising to 80% with repeated surgery. Fistulas in Crohn's disease are more likely to recur. METHOD: A retrospective study was performed of rectovaginal fistula repair carried out between 2003 and 2008 in a tertiary referral centre . Patients undergoing surgery for a rectovaginal fistula under the senior author during the study period were identified and their clinical notes reviewed. RESULTS: Thirty-five patients underwent 50 operations. The median age was 42 years and 83% were tertiary referrals. Two patients were lost to follow-up. Healing occurred in 19 (58%) of 33 patients after a mean of 1.4 operations. The median time to success was 11 (2.5 - 48) months. The 'curative' group had an overall success of 73% (19 of 26). Seventy-five percent of non-IBD patients and 67% of those with Crohn's disease had successful treatment of the RVF. Twenty-four of thirty-five patients (67%) underwent creation of a stoma. Sixteen of twenty-four (67%) were deemed fit for restoration of continuity. No demographic or disease related factors were found to influence healing. CONCLUSION: Cure of rectovaginal fistula can be achieved by a range of surgical approaches including abdominal and anal. A variety of different anal techniques are necessary, depending on the integrity of the anal sphincter and the presence or absence of perineal descent/internal intussusception. © 2013 The Authors. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.
Mann ER, Landy J, Bernardo D, et al., 2013, Intestinal dendritic cells: their role in intestinal inflammation, manipulation by the gut microbiota and differences between mice and men, Immunology Letters
Peake STC, Bernardo D, Mann ER, et al., 2013, Infliximab induces a dysregulated tissue-homing profile on human T-lymphocytes in-vitro: a novel mechanism for paradoxical inflammation?, J Crohns Colitis
Bernardo D, Mann ER, Al-Hassi HO, et al., 2013, Lost therapeutic potential of monocyte-derived DC through lost tissue homing; stable restoration of gut specificity with retinoic acid, Clinical Experimental Immunology
Peake ST, Hart AL, 2012, Commentary: predicting response to ciclosporin in acute severe ulcerative colitis, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 36, Pages: 1095-1096, ISSN: 0269-2813
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- Citations: 1
Jostins L, Ripke S, Weersma RK, et al., 2012, Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease, NATURE, Vol: 491, Pages: 119-124, ISSN: 0028-0836
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- Citations: 3254
Mann ER, McCarthy NE, Peake STC, et al., 2012, Skin- and gut-homing molecules on human circulating γδ T cells and their dysregulation in inflammatory bowel disease, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, Vol: 170, Pages: 122-130, ISSN: 0009-9104
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- Citations: 24
Rahbour G, Al-Hassi HO, Hart AL, et al., 2012, Tumour necrosis factor alpha in non-inflammatory bowel disease enterocutaneous fistulas prospective study, European Congress of Immunology, Publisher: WILEY-BLACKWELL, Pages: 536-537, ISSN: 0019-2805
Siddiqui MRS, Ashrafian H, Tozer P, et al., 2012, A DIAGNOSTIC ACCURACY META-ANALYSIS OF ENDOANAL ULTRASOUND AND MRI FOR PERIANAL FISTULA ASSESSMENT, GUT, Vol: 61, Pages: A233-A234, ISSN: 0017-5749
Landy J, Peake ST, Akbar A, et al., 2012, TELEMEDICINE SYSTEMS IN IBD MANAGEMENT-ARE PATIENTS READY?, GUT, Vol: 61, Pages: A69-A69, ISSN: 0017-5749
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- Citations: 1
Murugananthan AU, Bernardo DO, Mann ER, et al., 2012, ILEAL AND COLONIC MUCOSAL DENDRITIC CELL CYTOKINE PROFILES DIFFER AT REST AND AFTER IN VITRO BACTERIA AND PRO-BIOTIC CHALLENGE IN POSTOPERATIVE CROHN'S DISEASE PATIENTS, GUT, Vol: 61, Pages: A168-A168, ISSN: 0017-5749
Landy J, Al-Hassi HO, Peake ST, et al., 2012, INAPPROPRIATE INFLAMMATORY RESPONSES IN THE ILEUM OF ULCERATIVE COLITIS PATIENTS, GUT, Vol: 61, Pages: A222-A222, ISSN: 0017-5749
Murugananthan AU, Bernardo DO, Tozer P, et al., 2012, CLINICAL RISK FACTORS FOR CROHN'S DISEASE POSTOPERATIVE RECURRENCE ARE REFLECTED IN ALTERATIONS IN MUCOSALLY ADHERENT MICROBIOTA AT SURGICAL RESECTION, GUT, Vol: 61, Pages: A168-A168, ISSN: 0017-5749
Siddiqui MRS, Ashrafian H, Tozer P, et al., 2012, A Diagnostic Accuracy Meta-analysis of Endoanal Ultrasound and MRI for Perianal Fistula Assessment, DISEASES OF THE COLON & RECTUM, Vol: 55, Pages: 576-585, ISSN: 0012-3706
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- Citations: 104
Bernardo D, Mann ER, Al-Hassi HO, et al., 2012, Human gut-specific homeostatic dendritic cells are generated from blood precursors by the gut microenvironment., Inflammatory Bowel Diseases, Vol: 7, Pages: 1275-1286
BACKGROUND: Dendritic cells (DC) dictate not only the type of T-cell immunity, but also homing patterns of T cells in mice. In humans, we characterized normal human gut DC and tested whether gut-specific homeostatic DC could be generated from blood precursors by factors in the gut microenvironment.METHODS: We characterized the phenotype and function of healthy human gut DC compared with blood and skin DC, and studied whether conditioning of blood DC in the presence of colonic biopsy supernatants (Bx-SN) induced gut-like phenotype and functions.RESULTS: Blood DC mostly expressed both gut and skin homing markers, indicating potential to migrate to both major immune surface organs, and induced multi-homing T cells. However, DC within gut or skin did not demonstrate this multi-homing phenotype, were tissue-specific, and induced tissue-specific T cells. Human gut DC were less stimulatory for allogeneic T cells than their dermal and blood counterparts. Human blood DC cultured in vitro lost homing marker expression. Conditioning of human enriched blood DC with colonic Bx-SN from healthy controls induced a gut-homing phenotype and a homeostatic profile. Moreover, Bx-SN-conditioned DC demonstrated a restricted T-cell stimulatory capacity and preferentially induced gut-specific T cells. Retinoic acid and transforming growth factor beta (TGF-β) mediated the acquisition of the gut-homing and homeostatic properties, respectively, induced by colonic Bx-SN on blood enriched DC.CONCLUSIONS: Tissue-specific factors manipulate immunity via modulating characteristics of DC and may provide tools to generate tissue-specific immunotherapy. (Inflamm Bowel Dis 2011;).
Benhorin S, Hart A, 2012, Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response, Inflammatory Bowel Diseases
Louis E, Baumgart D, Ghosh S, et al., 2012, What changes in inflammatory bowel disease management can we implement today?, Journal of Crohn's and Colitis
Bernardo D, Al-Hassi HO, Mann ER, et al., 2012, T-cell proliferation and FoxP3 expression in human T-cells are dependent on T-cell density: physics of a confined space?, Human Imunology
T-cell proliferation rates in vitro depend on factors including initial T-cell number, dose of stimulus, culture time, and available physical space. The role of forkhead box P3 (FoxP3) in the identification of T cells with a regulatory phenotype remains controversial in humans. Through 5-carboxyfluorescein diacetate succinimidyl ester labeling of human T cells and subsequent culture of different numbers of T cells and antigen-presenting cells (APC), we studied proliferative T-cell responses and FoxP3 expression in divided T cells. T-cell proliferation rates depended on initial T-cell/APC numbers. Proliferation rates decreased when high initial T-cell numbers were increased. FoxP3 expression was expressed exclusively in virtually all divided T cells cultured at high T-cell densities, irrespective of their CD4 nature or cytokine content, and was coexpressed with T-bet. However, when T cells were cultured on larger surfaces or at lower initial numbers, FoxP3 expression was not induced in divided T cells, even when most of the cells had undergone cell division. FoxP3(+) T cells generated at high cell densities did not elicit a suppressive phenotype and FoxP3 expression was subsequently lost in time when the stimulus was removed. Therefore, caution should be observed in the use of FoxP3 expression to identify regulatory T cells in humans because its expression may be only a consequence of activation status in a restricted environment.
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