Louise Langmead

Anti‐inflammatory effects of aloe vera gel in human colorectal mucosa in vitro

Background : Oral aloe vera gel is widely used by patients with inflammatory bowel disease and is under therapeutic evaluation for this condition.

Use of complementary therapies by patients with IBD may indicate psychosocial distress.

BackgroundComplementary and alternative medicine (CAM) is used increasingly by patients with chronic diseases. We have assessed the use of CAM in general medicine and gastrointestinal outpatients focusing particularly on factors predisposing to its use in patients with inflammatory bowel disease (IBD). Methods239 consecutive patients attending gastrointestinal and general medical outpatient clinics answered a questionnaire about their use of CAM: patients with IBD also completed a validated disease-specific quality of life (QOL) inflammatory bowel disease questionnaire (IBDQ). Results26% of all patients used CAM, most commonly herbal remedies (43%). CAM was used significantly more by younger than older patients and by single than married or widowed ones. There were no differences by gender or ethnicity. More patients with irritable bowel syndrome used CAM than those with other diagnoses. In IBD patients, CAM users had significantly poorer QOL scores for emotional and social factors than nonusers. 53% of users stated that CAM alleviated their symptoms. ConclusionsUse of CAM is common in gastroenterological outpatients, particularly if they are young, single, or have irritable bowel syndrome (IBS). Most patients deem it helpful. In IBD, poor QOL predisposes to use of CAM. Conversely, use of CAM may serve as a marker of emotional or social unease in these patients. Physicians need to be aware of widespread usage of CAM by their patients.

Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease: an in vitro study

Herbal remedies used by patients for treatment of inflammatory bowel disease include slippery elm, fenugreek, devil’s claw, Mexican yam, tormentil and wei tong ning, a traditional Chinese medicine. Reactive oxygen metabolites produced by inflamed colonic mucosa may be pathogenic. Aminosalicylates (5‐ASA) are antioxidant and other such agents could be therapeutic.

Do antidepressants influence the disease course in inflammatory bowel disease? A retrospective case-matched observational study.

Background: Depression, like adverse events and psychological stress, can trigger relapse in inflammatory bowel disease (IBD); however, the effects of psychoactive drugs on disease course are unclear. Methods: Using retrospective electronic case note review, after exclusion of five patients on low‐dose tricyclic antidepressants we compared the course of IBD in 29 patients (14 ulcerative colitis and 15 Crohns disease), during the years before (year 1) and after (year 2) they were started on an antidepressant for a concomitant mood disorder to that of controls matched for age, sex, disease type, medication at baseline, and relapse rate in year 1. Results: Patients had fewer relapses and courses of steroids in the year after starting an antidepressant than in the year before (1 [0–4] (median [range]) vs. 0 [0–4], P = 0.002; 1 [0–3] vs. 0 [0–4], P < 0.001, respectively); the controls showed no changes between years 1 and 2 in relapses (1 [0–4] vs. 1 [0–3], respectively) or courses of steroids (1 [0–2] vs. 0 [0–3]). Although there were no differences in the use of other relapse‐related medications, outpatient attendances, or hospital admissions, the number of endoscopies fell significantly in the antidepressant group in year 2 compared with year 1 (P < 0.01). No such changes were seen in the controls. Conclusions: Antidepressants, when used to treat concomitant mood disorders in IBD, seem to reduce relapse rates, use of steroids, and endoscopies in the year after their introduction. These results suggest the need for a prospective controlled trial to evaluate their effects on disease course in patients with IBD. (Inflamm Bowel Dis 2011;)

The Effect of Hypnosis on Systemic and Rectal Mucosal Measures of Inflammation in Ulcerative Colitis

OBJECTIVES:Hypnotherapy is effective in several diseases with a psychosomatic component. Our aim was to study the effects of one session of hypnosis on the systemic and rectal mucosal inflammatory responses in patients with active ulcerative colitis (UC).METHODS:In total, 17 patients with active UC underwent a 50-min session of gut-focused hypnotherapy. Before and after each procedure, the systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor-alpha (TNF-α) and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell number, platelet activation, and platelet–leukocyte aggregate formation. Rectal inflammation was assessed by mucosal release of substance P (SP), histamine, IL-13 and TNF-α, reactive oxygen metabolite production, and mucosal blood flow. Eight patients with active UC underwent a control procedure.RESULTS:Hypnosis decreased pulse by a median 7 beats per minute (bpm) (P= 0.0008); it also reduced the median serum IL-6 concentration by 53% (P= 0.001), but had no effect on the other systemic variables assessed. Hypnosis reduced rectal mucosal release of SP by a median 81% (P= 0.001), histamine by 35% (P= 0.002) and IL-13 by 53% (P= 0.003), and also, blood flow by 18% (P= 0.0004). The control protocol had no effect on any of the variables assessed.CONCLUSIONS:Hypnosis reduced several components of the systemic and mucosal inflammatory response in active ulcerative colitis toward levels found previously in the inactive disease. Some of these effects may contribute to the anecdotally reported benefits of hypnotherapy and provide a rationale for controlled trials of hypnotherapy in UC.

Formation of platelet-leukocyte aggregates in inflammatory bowel disease

Objectives:Formation of platelet-leukocyte aggregates (PLAs) is increased in several inflammatory and thrombotic conditions. This may result from and enhance platelet and neutrophil activation and could contribute to the inflammatory process in inflammatory bowel disease (IBD). We investigated platelet-leukocyte aggregation in patients with IBD and its relation to treatment, disease activity and platelet and neutrophil activation. Methods:PLAs, platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression) were assessed 30 and 180 minutes after drawing blood into EDTA/citrate-theophylline-adenosine and dipyridamole, a novel anticoagulant, using fluorescent antibodies to CD45 (for leukocytes), CD42a (for platelets), CD62P (P-selectin) and CD62L (L-selectin) and flow cytometry. Platelet activation was also measured using the ADVIA 120 hematology analyser. Results:Samples from 67 patients with IBD measured within 30 minutes had a higher platelet count (P < 0.001), more platelets expressing P-selectin (P = 0.01), and more PLAs (P < 0.01) than from 20 healthy controls and more PLAs (P < 0.05) than from 9 controls with inflammatory arthropathies. IBD patients on thiopurines had fewer PLAs than those not taking them (P < 0.05); corticosteroids and aminosalicylates had no such effects. Incubation for 180 minutes increased the number of platelets expressing P-selectin (P < 0.0001), and the number of PLAs (P < 0.0001). The PLAs correlated with the number of platelets expressing P-selectin before (r = + 0.40, P < 0.001) and after (r = + 0.66, P < 0.0001) incubation. Conclusions:The number of PLAs is higher in patients with IBD than in healthy and inflammatory controls, but their numbers are lowered by thiopurines. Increased PLA formation may in part be due to increased platelet activation and could be pathogenic in IBD.

High resolution colonoscopy in a bowel cancer screening program improves polyp detection

AIM To compare high resolution colonoscopy (Olympus Lucera) with a megapixel high resolution system (Pentax HiLine) as an in-service evaluation. METHODS Polyp detection rates and measures of performance were collected for 269 colonoscopy procedures. Five colonoscopists conducted the study over a three month period, as part of the United Kingdom bowel cancer screening program. RESULTS There were no differences in procedure duration (χ² P = 0.98), caecal intubation rates (χ² P = 0.67), or depth of sedation (χ² P = 0.64). Mild discomfort was more common in the Pentax group (χ² P = 0.036). Adenoma detection rate was significantly higher in the Pentax group (χ² test for trend P = 0.01). Most of the extra polyps detected were flat or sessile adenomas. CONCLUSION Megapixel definition colonoscopes improve adenoma detection without compromising other measures of endoscope performance. Increased polyp detection rates may improve future outcomes in bowel cancer screening programs.

Bile acid malabsorption in patients with graft-versus-host disease of the gastrointestinal tract.

expected, these patients had more advanced disease and more frequent extranodal localization at presentation. In this study, we demonstrated that the addition of rituximab to CHOP was associated with a reduction in the incidence of secondary CNS involvement. Moreover, compared to the pre-rituximab era, progression during systemic treatment is less frequent, CNS relapses tend to be isolated and, most strikingly, leptomeningeal involvement is uncommon. These findings are similar to the Vancouver group’s study (Villa et al, 2010). The reduced incidence of secondary CNS involvement was also demonstrated by Boehme et al, 2009; and Shimazu et al, 2009;. However, a greater proportion of leptomeningeal relapses in R-CHOP-treated patients was observed in the former study. Conversely, the addition of rituximab did not change the incidence of secondary CNS involvement in the other three studies (Feugier et al, 2004; : Yamamoto et al, 2010; Tai et al, 2011). In contrast to previous studies, our R-CHOP-treated patients with secondary CNS involvement were younger and, probably for that reason, half of them were successfully salvaged with second-line treatment. Zdravko Mitrovic Martin Bast Philip J. Bierman Robert G. Bociek Julie M. Vose Wing C. Chan James O. Armitage Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA, School of Medicine, University of Zagreb, Zagreb, Croatia, and Department of Internal Medicine, Division of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE, USA. E-mail: joarmita@unmc.edu

Herbal therapies used by patients for inflammatory bowel disease are antioxidant in vitro

The Ileo Neo-Rectal Anastomosis (lNRA) is an alternative restorative procedure for patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) and has been developed in order to reduce the high pouch-related complication (15-35%) and failure rate (6.5%) of the Ileo Pouch-Anal Anastomosis (IPAA). In contrast to IPAA the ano-rectum is preserved and the rectal mucosa is excised and replaced by healthy, vascularised, ileal mucosa. The ultimate purpose, establishment of a compliant neo-rectal reservoir with a concordant low defecation frequency and full continence in the long-term is being addressed in this presentation. In 12 patients (10 UC + 2 FAP) an INRA was performed after subtotal colectomy, with a temporary diverting ileostomy for three months. Anorectal function was tested preoperatively and up to a median of 16 months postoperatively (range 12-22 months). The first sensation, urge sensation, capacity, compliance and anorectal electrosensibility were measured. Anal and rectal ultrasound were carried out to assess the transmural architecture of the neo-rectum. Furthermore histological aspects of neo-rectal mucosa ingrowth and maturation were assessed. The INRA procedure was successfully performed in all patients. Ano-rectal function tests revealed no change in anal sphincter resting (median 8 (6-13) kPa) and squeeze pressure (median 18 (7-35) kPa). Rectal capacity temorarily decreased considerably after INRA, but increased up to normal levels in 12 months (median 108 (56-300) vs 157 (130-225) ml, respectively). This is in accordance with increasing compliance of the neorectum and decreasing stoolfrequency. Anal electrosensibility was unchanged after INRA (median 7 (4-14) rnA), but rectal electrosensibility decreased from median 26 rnA (16-75) to 46 rnA (13-99). Ultrasound showed no structural damage to the anal sphincter and an anatomically normal intestinal wall. Histology showed villus atrophy and a mixed active and chronic inflammatory infiltrate at 6 weeks with recovery in time. At 6 months the villus architecture was restored with an intact goblet cell population and brush border and dissapearance of the inflammatory infiltrate. Although during the INRA procedure the anorectum is manipulated to great extend, anorectal function is perserved. Anorectal function, as well as the functional result after INRA are comparable to IPAA. Ileal mucosa transplantation is feasible with development of healthy neorectal mucosa.

Anxiety and psychological stress in acute severe ulcerative colitis: prevalence and effect on outcome

Introduction There is increasing evidence that psychological stress and associated mood disorders are linked with, and adversely affect the course of IBD. The authors hypothesise that: (1) anxiety and stress are more common in acute severe ulcerative colitis (ASUC) than in patients with inactive UC; (2) anxiety and stress are more common in patients presenting for the first time with UC; (3) anxiety and stress worsen outcome in ASUC. Methods 39 ASUC patients (aged 28 (18–74) years (median (range)); disease duration 10 (0–240) months), requiring hospital admission and intravenous hydrocortisone with a Barons sigmoidoscopic score ≥2, completed questionnaires to assess anxiety (Hospital Anxiety and Depression Score (HADS-A)) and stress levels (Perceived Stress Questionnaire: Recent, R-PSQ, General, G PSQ). Outcomes were assessed, using the Travis criteria (day 3) and colectomy rates at day 70, in relation to upper and lower tertiles of the anxiety and stress scores. In addition, the psychometric scores of the ASUC patients were compared to those of 27 outpatients with inactive UC. Results Patients with ASUC had higher stress levels (R-PSQ Index 0.52 (0.03) (mean (SEM)), G-PSQ 0.46 (0.03)) than in patients with inactive UC (0.35 (0.03), p=0.001, 0.39 (0.02), p=0.046, respectively) but there was no difference in anxiety scores (HADS-A 9.6 (0.8), 8.4 (0.7), p=0.9, respectively). However, in patients with ASUC, there was a positive correlation between stress and anxiety scores (R-PSQ, r2=0.27, p=0.0008; G-PSQ, r2=0.14, p=0.02)). Although stress scores were similar, anxiety levels were higher in the 11 newly presenting ASUC patients (12 (1.4)) than in those previously diagnosed (8.6 (0.9), p=0.049). There was no difference in those responding to intravenous hydrocortisone (by Travis criteria) or in day 70 colectomy rates between patients who were highly (upper tertile) anxious (Travis response 8/13, colectomy rate 2/13) or highly (upper tertile) stressed (R-PSQ: Travis response 8/12, colectomy rate 6/13; G-PSQ Travis response 5/13, colectomy rate 4/13) compared to those less (lower tertile) anxious (5/13, 3/13, respectively) or stressed (lower tertile) (R-PSQ, 5/13, 1/13; G-PSQ 5/12, 1/13, respectively). Conclusion Perceived stress levels are greater in patients with ASUC than in those in remission and anxiety scores are highest in patients newly presenting with UC, but neither stress nor anxiety influenced disease outcome.