Understanding and managing psychological disorders in patients with inflammatory bowel disease: a practical guide.

Mood disturbances such as anxiety and depression are common in patients with inflammatory bowel disease (IBD), and impact negatively on their quality of life and disease course. An integrated multidisciplinary IBD team, which includes access to psychology and psychiatry opinion, makes possible the prompt recognition and management of psychological disturbance in patients with IBD. Based on our experience and existing literature, including systematic reviews of the effectiveness of available treatment modalities, a stepwise approach to the maintenance and restoration of psychological well-being is recommended, evolving upwards from lifestyle advice, through behavioural therapies to pharmacotherapy.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Association of Genetic Variants in NUDT15 With Thiopurine-Induced Myelosuppression in Patients With Inflammatory Bowel Disease.

Importance: Use of thiopurines may be limited by myelosuppression. TPMT pharmacogenetic testing identifies only 25% of at-risk patients of European ancestry. Among patients of East Asian ancestry, NUDT15 variants are associated with thiopurine-induced myelosuppression (TIM). Objective: To identify genetic variants associated with TIM among patients of European ancestry with inflammatory bowel disease (IBD). Design, Setting, and Participants: Case-control study of 491 patients affected by TIM and 679 thiopurine-tolerant unaffected patients who were recruited from 89 international sites between March 2012 and November 2015. Genome-wide association studies (GWAS) and exome-wide association studies (EWAS) were conducted in patients of European ancestry. The replication cohort comprised 73 patients affected by TIM and 840 thiopurine-tolerant unaffected patients. Exposures: Genetic variants associated with TIM. Main Outcomes and Measures: Thiopurine-induced myelosuppression, defined as a decline in absolute white blood cell count to 2.5 × 109/L or less or a decline in absolute neutrophil cell count to 1.0 × 109/L or less leading to a dose reduction or drug withdrawal. Results: Among 1077 patients (398 affected and 679 unaffected; median age at IBD diagnosis, 31.0 years [interquartile range, 21.2 to 44.1 years]; 540 [50%] women; 602 [56%] diagnosed as having Crohn disease), 919 (311 affected and 608 unaffected) were included in the GWAS analysis and 961 (328 affected and 633 unaffected) in the EWAS analysis. The GWAS analysis confirmed association of TPMT (chromosome 6, rs11969064) with TIM (30.5% [95/311] affected vs 16.4% [100/608] unaffected patients; odds ratio [OR], 2.3 [95% CI, 1.7 to 3.1], P = 5.2 × 10-9). The EWAS analysis demonstrated an association with an in-frame deletion in NUDT15 (chromosome 13, rs746071566) and TIM (5.8% [19/328] affected vs 0.2% [1/633] unaffected patients; OR, 38.2 [95% CI, 5.1 to 286.1], P = 1.3 × 10-8), which was replicated in a different cohort (2.7% [2/73] affected vs 0.2% [2/840] unaffected patients; OR, 11.8 [95% CI, 1.6 to 85.0], P = .03). Carriage of any of 3 coding NUDT15 variants was associated with an increased risk (OR, 27.3 [95% CI, 9.3 to 116.7], P = 1.1 × 10-7) of TIM, independent of TPMT genotype and thiopurine dose. Conclusions and Relevance: Among patients of European ancestry with IBD, variants in NUDT15 were associated with increased risk of TIM. These findings suggest that NUDT15 genotyping may be considered prior to initiation of thiopurine therapy; however, further study including additional validation in independent cohorts is required.

Herbs and Inflammatory Bowel Disease.

Although herbal preparations are widely used by patients with inflammatory bowel disease (IBD), evidence for their efficacy is limited and they may not always be safe. Mainly small studies of varying quality have suggested that several herbal preparations could be of benefit in IBD, but larger better-designed trials are needed to establish their place in inducing and maintaining remission. Patients and health care workers need to be made more aware of the limitations and risks of using herbal products for IBD.

Incidence and Outcome of Clostridium difficile Infection in Hospitalized Patients with Inflammatory Bowel Disease in the UK.

BACKGROUND AND AIMS: Previous studies have reported that Clostridium difficile infection [CDI] is more common, and has a worse outcome, in patients with inflammatory bowel disease [IBD] than in those without. We have now reassessed the incidence and outcome of CDI in in-patients with and without IBD, and the outcomes of admissions for IBD patients with and without CDI. METHODS: In-patients who had stool samples submitted for C. difficile testing [2007-2013] were collated. Two matched pools were generated: patients with IBD and CDI vs non-IBD patients with CDI [matched for age, sex and date] and patients with IBD and CDI vs IBD patients without CDI [matched for age and IBD type]. For each group, admission details, pre-admission and outcome data were compared. RESULTS: Four per cent [1079/21035] of samples were positive for CDI; 5% [49] of these were from IBD in-patients. The incidence of CDI in IBD patients decreased from 8.7% in 2007/08 to 0.4% in 2012/13 [p < 0.0001]. Length of stay was shorter in IBD patients with CDI than in non-IBD CDI patients (hazard ratio [HR] 0.335 [0.218-0.513]) and was no different between IBD patients with and without CDI (HR 0.661 [0.413-1.06]). IBD patients were diagnosed with CDI earlier in their admission than non-IBD patients (HR 0.182 [0.093-0.246]). No differences in mortality were found. CONCLUSIONS: The incidence of CDI complicating IBD has fallen since 2007. CDI is no longer associated with worse short-term outcomes in patients with IBD than in those without. Patients with CDI and IBD have similar outcomes to those with IBD alone.

Oral Iron Treatment Response and Predictors in Anaemic Adolescents and Adults with IBD: A Prospective Controlled Open-Label Trial.

BACKGROUND: Because of previous concerns about the efficacy and safety of oral iron for treating iron deficiency anaemia in inflammatory bowel disease [IBD], particularly in young people, we compared the effects of ferrous sulphate on haemoglobin response, disease activity and psychometric scores in adolescents and adults with IBD. We also assessed the relation of baseline serum hepcidin to haemoglobin response. METHODS: We undertook a prospective, open-label, 6-week non-inferiority trial of the effects of ferrous sulphate 200 mg twice daily on haemoglobin, iron status, hepcidin, disease activity (Harvey-Bradshaw Index, Simple Colitis Clinical Activity Index, C-reactive protein [CRP]), faecal calprotectin and psychometric scores in 45 adolescents [age 13-18 years] and 43 adults [>18 years]. RESULTS: On intention-to-treat analysis, ferrous sulphate produced similar rises in haemoglobin in adolescents {before treatment 10.3 g/dl [0.18] (mean [SEM]), after 11.7 [0.23]: p < 0.0001} and adults (10.9 g/dl [0.14], 11.9 [0.19]: p < 0.0001); transferrin saturation, ferritin [in adolescents] and hepcidin [in adults] also increased significantly. On per-protocol univariate analysis, the haemoglobin response was inversely related to baseline haemoglobin, CRP and hepcidin. Oral iron did not alter disease activity; it improved Short IBDQ and Perceived Stress Questionnaire scores in adults. CONCLUSION: Oral ferrous sulphate was no less effective or well-tolerated in adolescents than adults, and did not increase disease activity in this short-term study. The inverse relation between baseline CRP and hepcidin levels and the haemoglobin response suggests that CRP or hepcidin measurements could influence decisions on whether iron should be given orally or intravenously. [ClinTrials.gov registration number NCT01991314].

Prevalence and management of anemia in children, adolescents, and adults with inflammatory bowel disease.

BACKGROUND: Children and adolescents with inflammatory bowel disease (IBD) are more likely to have Crohn's disease (CD) than ulcerative colitis (UC) and their disease tends to be more extensive and severe than in adults. We hypothesized that the prevalence of anemia would therefore be greater in children and adolescents than in adults attending IBD outpatient clinics. METHODS: Using the WHO age-adjusted definitions of anemia we assessed the prevalence, severity, type, and response to treatment of anemia in patients attending pediatric, adolescent, and adult IBD clinics at our hospital. RESULTS: The prevalence of anemia was 70% (41/59) in children, 42% (24/54) in adolescents, and 40% (49/124) in adults (P < 0.01). Overall, children (88% [36/41]) and adolescents (83% [20/24]) were more often iron-deficient than adults (55% [27/49]) (P < 0.01). Multivariate logistic regression showed that both active disease (odds ratio [OR], 4.7 95% confidence interval [CI], 2.5, 8.8) and attending the pediatric clinic (OR 3.7; 95% CI, 1.6, 8.4) but not the adolescent clinic predicted iron deficiency anemia. Fewer iron-deficient children (13% [5/36]) than adolescents (30% [6/20]) or adults (48% [13/27]) had been given oral iron (P < 0.05); none had received intravenous iron compared with 30% (6/20) adolescents and 41% (11/27) adults (P < 0.0001). CONCLUSIONS: Anemia is even more common in children than in older IBD patients. Oral iron was given to half of adolescents and adults but, despite similar tolerance and efficacy, only a quarter of children with iron-deficient anemia. Reasons for the apparent underutilization of iron therapy include a perceived lack of benefit and concerns about side effects, including worsening of IBD activity.

The influence of stress on the development and severity of immune-mediated diseases.

Evidence that psychological stress can increase inflammation and worsen the course of immune-mediated inflammatory disease (IMID) is steadily accumulating. The majority of data supporting this hypothesis come from studies in patients with inflammatory bowel disease (IBD). While there is no evidence to suggest that stress is a primary cause of IBD, many, although not all, studies have found that patients with IBD experience increased stress and stressful life events before disease exacerbations. Further, the disease itself can cause psychological stress, creating a vicious cycle. In addition to reviewing the epidemiological evidence supporting a stress-IMID relationship, this article also briefly discusses how stress-related changes in neural, endocrine, and immune functioning may contribute to the pathogenesis of immune diseases, IBD in particular. The effects of different pharmacological and nonpharmacological interventions, including stress management and behavioral therapy, on stress, mood, quality of life (QOL), and activity of the underlying IMID are also summarized.

Efficacy and tolerability of intravenous iron dextran and oral iron in inflammatory bowel disease: a case-matched study in clinical practice.

OBJECTIVES: Iron deficiency anaemia is common in inflammatory bowel disease (IBD); however, the optimum route of administration of iron replacement therapy is unclear. As inflammation may limit the absorption and efficacy of oral iron, we hypothesized that in routine clinical practice IV iron would be more effective than oral iron in patients with IBD matched for disease type, extent and activity. METHODS: Thirty-three IBD patients who had received IV iron dextran (Cosmofer) in 2008-2010 were identified and matched for age, sex, diagnosis and baseline disease activity, extent and behaviour to IBD patients given oral iron. RESULTS: Patients given IV iron dextran were more anaemic at baseline than those receiving oral iron. Although haemoglobin (Hb) concentrations were normalized in about a third of patients, and increased significantly in both groups, the mean increase in Hb after 8 weeks was greater in the iron dextran group [2.0 g/dl (0.3) vs. 0.6 g/dl (0.1), P<0.0001]. Response to oral or IV iron was unrelated to age, sex, ethnicity, disease duration, extent or activity. Fifteen percent (five out of 33) patients discontinued oral iron because of gastrointestinal side-effects and a further two out of 35 had anaphylactoid reactions to the IV iron dextran test doses. Neither of the iron formulations worsened disease activity. CONCLUSION: In routine clinical practice, in anaemic patients with IBD of similar type, extent and activity, IV Cosmofer is more efficacious in increasing Hb concentration than oral iron. Active disease does not impair the response to either IV or oral iron in patients with IBD, and neither product itself worsens disease activity.

Tobacco dependence and awareness of health risks of smoking in patients with inflammatory bowel disease.

BACKGROUND AND AIM: Smoking is a risk factor for developing Crohn's disease (CD) and worsens its outcome. Conversely, in ulcerative colitis (UC), the onset may be triggered by the smoking cessation and smoking may be beneficial. To help to ascertain whether patients with inflammatory bowel disease (IBD) would benefit from attending a smoking cessation clinic, we assessed: first, the prevalence of smoking; second, patients' awareness of the effects of smoking, and finally nicotine dependence in IBD patients compared with the healthy and disease-matched controls. METHODS: A total of 246 consecutive IBD outpatients (173 patients with CD, 73 patients with UC) completed a questionnaire on smoking habits and its effect on IBD. Smokers were assessed for dependence using the Fagerstrom test for nicotine dependence (FTND) score and their results were compared with those of age, sex, and ethnicity-matched healthy (five controls for each IBD patient) and asthma controls (one control for each IBD patient) attending a smoking cessation clinic. RESULTS: Thirty five out of 173 patients (20%) with CD and nine out of 73 patients (12%) with UC were current smokers, with 52 out of 173 patients (30%) with CD and 28 out of 73 patients (38%) with UC being ex-smokers. Ninety out of 173 patients (52%) with CD knew that smoking worsens CD, whereas only 15 out of 73 patients (21%) with UC knew of the beneficial effects of smoking on their disease (P=0.032). Knowledge was unrelated to smoking status. In patients with CD, the median (range) FTND score was 3 (0-8) compared with 7 (2-10) in healthy (P<0.001) and 6 (2-9) in asthma controls (P<0.0001). Only seven of the 35 (20%) smoking patients with CD were highly dependent (FTND score ≥6). Similarly, in the patients with UC, the FTND score was 1 (0-4), lower than in healthy, [6 (2-10)], and asthma controls, [7 (4-10); (P<0.004 for both groups)]. CONCLUSION: Patients with CD were better informed about the effects of smoking on their own disease than the patients with UC. Nicotine dependence in IBD patients is lower than in smokers' clinic clients and comparable with that of the general population. Their low nicotine dependence suggests that most IBD patients could be weaned off the smoking habit successfully in the IBD clinic and referral to a smoking cessation clinic was offered to the highly dependent minority and others expressing interest in attending.

Does psychological counseling alter the natural history of inflammatory bowel disease?

BACKGROUND: There is increasing evidence that psychological stress can increase mucosal inflammation and worsen the course of inflammatory bowel disease (IBD). We have now assessed whether psychotherapy by a counselor specially trained in the management of IBD can influence the course of disease. METHODS: Using retrospective case note review, we compared the course of IBD in 24 patients (13 ulcerative colitis; 11 Crohn's disease), during the year before (year 1) and the year after referral (year 2) for supportive outpatient psychotherapy to an IBD counselor, to that of 24 IBD controls who were matched to individual cases for age, sex, disease, duration of disease, medication at baseline, and for relapse rate in year 1. Counselor assessments were made using a visual analog scale 0-6 (0 denotes poor, 6 excellent response to counseling). The results are shown as median (range). RESULTS: Patients were referred for counseling because of disease-related stress (14 patients), work problems (3), concerns about surgery (5), and bereavement (2); they received 6 (1-13) 1-hour sessions in year 2. In the year after starting counseling (year 2), patients had fewer relapses (0 [0-2]) and outpatient attendances (3.5 [1-10]) than in the year before referral (year 1) (2 [0-5], P = 0.0008; and 6.5 [1-17], P = 0.0006, respectively; furthermore, steroid usage (1 course [0-4] before, 0 [0-2] after, P = 0.005) and relapse-related use of other IBD medications declined during psychotherapy (1 drug [0-5] before, 0 [0-2] after, P = 0.002). There were no differences in any of these measures between years 1 and 2 in the control group. Numbers of hospital admissions did not change between year 1 and 2 in either group. In the 20 patients who attended >1 session counseling helped solve stress-related difficulties (counselor's score 4 [3-5]), the counselor scored them 4 (3-6) overall in psychological well-being after the counseling sessions. CONCLUSIONS: IBD-focused counseling may improve not only psychological well-being, but also the course of IBD in individuals with psychosocial stress.

Management of stress in inflammatory bowel disease: a therapeutic option?

There is increasing evidence that psychological stress and associated mood disorders are linked with, and can adversely affect the course of, inflammatory bowel disease (IBD). Unfortunately, owing to methodological difficulties inherent in undertaking appropriately targeted and blinded trials, there are limited high-quality data regarding the effects on IBD of interventions aimed to ameliorate stress and mood disorders. Nevertheless, patients want psychological intervention as well as conventional medical strategies. Emerging trial evidence supports the suggestion that psychologically orientated therapy may ameliorate IBD-associated mood disorders, but there are no strong data as of yet to indicate that stress management has a beneficial effect on the activity or course of IBD. As yet, which, when and how interventions targeted at psychological stress and mood disturbances should be offered to individual patients with IBD is not clear.

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-alpha) 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-alpha, 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.

Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis.

BACKGROUND AND AIMS: Inflammation and thrombosis are closely related processes, which may play a role in the pathogenesis, as well as complications, of inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte aggregation are increased and platelet aggregation is known to occur in the mesenteric vasculature in IBD. The aims of this study were to test the hypotheses that platelet-leucocyte aggregation, platelet activation and neutrophil activation occur in the mesenteric vessels of patients with ulcerative colitis (UC). PATIENTS AND METHODS: Platelet-leucocyte aggregates (PLAs), platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression, which decreases on neutrophil activation) were assessed flow cytometrically in mesenteric arterial, and venous blood sampled in eight patients with UC and eight controls with colonic carcinoma undergoing intestinal resections. RESULTS: In the patients with UC, the number of PLAs in the mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02). In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) x 10(9)/l versus venous 0.26 (0.09-1.6) x 10(9)/l (P=0.02). The median percentage increase was 45%. Mesenteric PLA formation did not occur in patients with colonic carcinoma [arterial 0.06 (0.03-0.49) x 10(9)/l vs. venous 0.05 (0.02-0.35) x 10(9)/l; P=0.55]. The median percentage change was +45% for UC patients and -5% for controls. No arteriovenous gradient was observed in P-selectin expression, but L-selectin expression (arbitrary units), increased in the mesenteric vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035); P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous 850 (546-957); P=0.04]. The median percentage change was +4% for UC and -7% for controls. CONCLUSION: The finding of increased numbers of PLAs in the venous mesenteric circulation supports the hypothesis that activated vascular endothelium stimulates PLA formation in UC.

Drug interactions in inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) often require a combination of drugs, some of which are taken for many years, to control their disease. Some of these drugs have potentially serious side effects, which may be initiated or exacerbated by interaction with other agents used to treat IBD. Furthermore, patients with IBD may take treatment for other, unrelated conditions. It is important for doctors who manage patients with IBD to be aware of, and thereby minimize, the dangers presented by such drug interactions. In this review, we summarize the common and important interactions of drugs used in patients with IBD, including some that may be of therapeutic benefit. Particular attention is paid to interactions that occur where both drugs are used to treat IBD.

Functional modulation of Crohn's disease myofibroblasts by anti-tumor necrosis factor antibodies.

BACKGROUND & AIMS: Infliximab induces immune cell apoptosis by outside-to-inside signaling through transmembrane tumor necrosis factor-alpha (mTNF). However, in inflamed gut, myofibroblasts also produce TNF-alpha, and the affects of anti-TNF antibodies on these structural cells are unknown. We investigated the action of infliximab on apoptosis, the production of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP)-1, and migration of Crohn's disease (CD) myofibroblasts. METHODS: Colonic myofibroblasts were isolated from patients with active CD and controls. mTNF was evaluated by Western blotting and flow cytometry. Infliximab-treated myofibroblasts were analyzed for apoptosis by Annexin V staining and caspase-3. TIMP-1 and MMPs were measured by Western blotting, and fibroblast migration was assessed by using an in vitro wound-healing scratch assay. RESULTS: CD myofibroblasts showed higher mTNF expression than control myofibroblasts. Infliximab had no effect on CD myofibroblast apoptosis, caspase-3 activation, and production of MMP-3 and MMP-12. However, infliximab induced a significant dose-dependent increase in TIMP-1 production, which was inhibited by the p38 mitogen-activated protein kinase inhibitor SB 203580. The anti-TNF agents adalimumab, etanercept, and p55 TNF-receptor-human IgG fusion protein also increased TIMP-1 production. The migration of CD myofibroblasts was enhanced significantly by infliximab and recombinant human TIMP-1, and infliximab-induced migration was inhibited by anti-TIMP-1 neutralizing antibody. Infliximab also decreased CD myofibroblast collagen production. CONCLUSIONS: Our findings show a novel therapeutic pathway for anti-TNF therapies in enhancing TIMP-1 production and myofibroblast migration, which may reduce MMP activity and facilitate the wound healing.

New flow cytometric technique for the evaluation of circulating endothelial progenitor cell levels in various disease groups.

Circulating endothelial progenitor cells (EPC) localise to sites of ischaemia and play a role in vascular repair and re-endothelialisation of injured blood vessels. Low levels of EPCs are associated with cardiovascular disease (CVD) in the general population. It is not clear at present whether and how the numbers of circulating EPCs vary in diseases other than CVD. We have enumerated EPCs by the flow cytometric analysis of whole blood by using a novel cocktail of monoclonal antibodies. This consisted of CD2FITC, CD13FITC and CD22FITC to eliminate non-progenitor cells and VEGFR2PE and CD133-streptavidin-PeCy7 to include only EPCs. We analysed 250 patients with varying stages of uraemia, 36 patients with inflammatory bowel disease (IBD) and 9 patients with acute respiratory distress syndrome and compared this to 74 healthy controls. Using flow cytometry we were able to measure the circulating levels of EPCs, with a result available within hours of the sample being obtained. Circulating EPC numbers vary in different patient groups and healthy controls. In uraemic patients, irrespective of disease severity, there are lower numbers of circulating EPC numbers compared to normal controls (46.6+/-3.7 vs. 66.1+/-4.7; p=0.03). This new technique provides a means of monitoring patients and shows a reduction in circulating EPCs in uraemic patients; this abnormality may be a target of novel therapies.

The effect of acute psychologic stress on systemic and rectal mucosal measures of inflammation in ulcerative colitis.

BACKGROUND & AIMS: Recent studies suggest that life events and chronic stress increase the risk of relapse in inflammatory bowel disease. Our aim was to study the effects of acute psychologic stress on systemic and rectal mucosal inflammatory responses in patients with inactive ulcerative colitis (UC). METHODS: Twenty-five patients with inactive UC and 11 healthy volunteers (HV) underwent an experimental stress test. Ten patients with UC and 11 HV underwent a control procedure. Before and after each procedure, systemic inflammatory response was assessed by serum interleukin (IL)-6 and IL-13 concentrations, tumor necrosis factor (TNF)-alpha and IL-6 production by lipopolysaccharide (LPS)-stimulated whole blood, leukocyte count, natural killer (NK) cell numbers, platelet activation, and platelet-leukocyte aggregate (PLA) formation. In patients with UC, rectal mucosal inflammation was assessed by TNF-alpha, IL-13, histamine and substance P release, reactive oxygen metabolite (ROM) production, mucosal blood flow (RMBF) and histology. RESULTS: Stress increased pulse (P < .0001) and systolic BP (P < .0001). In UC, stress increased LPS-stimulated TNF-alpha and IL-6 production by 54% (P = .004) and 11% (P = .04), respectively, leukocyte count by 16% (P = .01), NK cell count by 18% (P = .0008), platelet activation by 65% (P < .0001), PLA formation by 25% (P = .004), mucosal TNF-alpha release by 102% (P = .03), and ROM production by 475% (P = .001) and reduced rectal mucosal blood flow by 22% (P = .05). The control protocol did not change any of the variables measured. There were no differences between the responses of the patients with UC and HV. CONCLUSIONS: Acute psychologic stress induces systemic and mucosal proinflammatory responses, which could contribute to exacerbations of UC in ordinary life.