Showing papers by "Fergus Shanahan published in 2008"
TL;DR: Cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS.
Abstract: Host defence against infection requires a range of innate and adaptive immune responses that may lead to tissue damage Such immune-mediated pathologies can be controlled with appropriate T regulatory (Treg) activity The aim of the present study was to determine the influence of gut microbiota composition on Treg cellular activity and NF-κB activation associated with infection Mice consumed the commensal microbe Bifidobacterium infantis 35624 followed by infection with Salmonella typhimurium or injection with LPS In vivo NF-κB activation was quantified using biophotonic imaging CD4+CD25+Foxp3+ T cell phenotypes and cytokine levels were assessed using flow cytometry while CD4+ T cells were isolated using magnetic beads for adoptive transfer to naive animals In vivo imaging revealed profound inhibition of infection and LPS induced NF-κB activity that preceded a reduction in S typhimurium numbers and murine sickness behaviour scores in B infantis–fed mice In addition, pro-inflammatory cytokine secretion, T cell proliferation, and dendritic cell co-stimulatory molecule expression were significantly reduced In contrast, CD4+CD25+Foxp3+ T cell numbers were significantly increased in the mucosa and spleen of mice fed B infantis Adoptive transfer of CD4+CD25+ T cells transferred the NF-κB inhibitory activity Consumption of a single commensal micro-organism drives the generation and function of Treg cells which control excessive NF-κB activation in vivo These cellular interactions provide the basis for a more complete understanding of the commensal-host-pathogen trilogue that contribute to host homeostatic mechanisms underpinning protection against aberrant activation of the innate immune system in response to a translocating pathogen or systemic LPS
355 citations
TL;DR: Identifiable subsets of patients with Crohn9s disease are at risk of exposure to significant amounts of diagnostic radiation, given the background risk of neoplasia and exposure to potentially synergistic agents such as purine analogues and other immune-modulators.
Abstract: Aims: Exposure to diagnostic radiation may be associated with increased risk of malignancy. The aims of this study were: (a) to examine patterns of use of imaging in Crohn9s disease; (b) to quantify the cumulative effective dose (CED) of diagnostic radiation received by patients; and (c) to identify patients at greatest risk of exposure to high levels of diagnostic radiation. Methods: 409 patients with Crohn9s disease were identified at a tertiary centre. CED was calculated retrospectively from imaging performed between July 1992 and June 2007. High exposure was defined as CED>75 milli-Sieverts (mSv), an exposure level which has been reported to increase cancer mortality by 7.3%. Complete data were available for 399 patients. 45 were excluded (20 attended outside study period, 25 primarily managed at other centres). Results: Use of computed tomography increased significantly and accounted for 77.2% of diagnostic radiation. Mean CED was 36.1mSv and exceeded 75mSv in 15.5% of patients. Factors associated with high cumulative exposure were: age 1) surgeries (OR 2.7, CI 1.4-5.4). Conclusions: Identifiable subsets of patients with Crohn9s disease are at risk of exposure to significant amounts of diagnostic radiation. Given the background risk of neoplasia and exposure to potentially synergistic agents such as purine analogues and other immune-modulators, specialist centres should develop low-radiation imaging protocols.
302 citations
TL;DR: While the complexity and heterogeneity of these diseases surely accounts for some of this dilemma, it seems reasonable to ask whether several decades of epidemiological studies have directed or distracted researchers seeking clues to the cause of IBD.
Abstract: Few would contest that advances in uncovering genetic risk factors for Crohn’s disease and ulcerative colitis over the past decade have changed the way we think about inflammatory bowel diseases (IBDs). Perhaps the most important message has been that much of the genetically determined risk lies in how the host interprets its microbial environment.1–3 However, the primacy of environmental factors was already evident from several sources; notably, studies of genetically identical twins showing a relatively low concordance rate for both Crohn’s disease (<50%) and ulcerative colitis (<10%), and the increased frequency of both disorders in many countries during a period too short to involve significant changes in the population gene pool.4 What are the environmental or lifestyle risk factors for IBD? How do they collude with genetic susceptibility?
The lesson of Helicobacter pylori and peptic ulcer disease was that the solution to some chronic disorders cannot be found by studying the human host alone. Rather, the answer may lie at the interface with the microbial environment. A more sobering lesson was the failure of conventional epidemiological studies to recognise that peptic ulcer disease is caused by a transmissible agent. How did disparate epidemiological observations miss this association and fail to guide medical scientists toward this conclusion? Could IBDs (or a subset thereof) be due to an infectious agent, waiting to be identified? Or is the relationship between host susceptibility and the microbial environment a more subtle one? While the complexity and heterogeneity of these diseases surely accounts for some of this dilemma, it seems reasonable to ask whether several decades of epidemiological studies have directed or distracted researchers seeking clues to the cause of IBD.
Some of the false leads and false promises of epidemiology have been highlighted elsewhere, with the most vigorous attacks in the …
279 citations
TL;DR: The intestinal microbiota and their metabolites are significantly altered in both colorectal cancer and polypectomized subjects compared with controls, and a clear division in the metabonome was observed.
Abstract: A role for the intestinal microbiota is routinely cited as a potential aetiological factor in colorectal cancer initiation and progression. As the majority of bacteria in the gut are refractory to culture we investigated this ecosystem in subjects with colorectal cancer and with adenomatous polyposis who are at high risk of developing colorectal cancer, using culture-independent methods. Twenty colorectal cancer and 20 polypectomized volunteers were chosen for this analysis. An exploration of the diversity and temporal stability of the dominant bacteria and several bacterial subgroups was undertaken using 16S rRNA gene denaturing gradient gel electrophoresis and ribosomal intergenic spacer analysis (RISA). Metabonomic analysis of the distal gut microbiota's environment was also undertaken. A significantly reduced temporal stability and increased diversity for the microbiota of subjects with colorectal cancer and polyposis was evident. A significantly increased diversity of the Clostridium leptum and C. coccoides subgroups was also noted for both disease groups. A clear division in the metabonome was observed for the colorectal cancer and polypectomized subjects compared with control volunteers. The intestinal microbiota and their metabolites are significantly altered in both colorectal cancer and polypectomized subjects compared with controls.
242 citations
TL;DR: The mcrA gene serves as a useful biomarker for meethanogen detection in the human gut and the varying trends of methanogen incidence in thehuman gut could serve as important indicators of intestinal function.
Abstract: The incidence and diversity of human methanogens are insufficiently characterised in the gastrointestinal tract of both health and disease. A PCR and clone library methodology targeting the mcrA gene was adopted to facilitate the two-fold aim of surveying the relative incidence of methanogens in health and disease groups and also to provide an overview of methanogen diversity in the human gastrointestinal tract. DNA faecal extracts (207 in total) from a group of healthy controls and five gastrointestinal disease groups were investigated. Colorectal cancer, polypectomised, irritable bowel syndrome and the control group had largely equivalent numbers of individuals positive for methanogens (range 45–50%). Methanogen incidence in the inflammatory bowel disease groups was reduced, 24% for ulcerative colitis and 30% for Crohn's disease. Four unique mcrA gene restriction fragment length polymorphism profiles were identified and bioinformatic analyses revealed that the majority of all sequences (94%) retrieved from libraries were 100% identical to Methanobrevibacter smithii mcrA gene. In addition, mcrA gene sequences most closely related to Methanobrevibacter oralis and members of the order Methanosarcinales were also recovered. The mcrA gene serves as a useful biomarker for methanogen detection in the human gut and the varying trends of methanogen incidence in the human gut could serve as important indicators of intestinal function. Although Methanobrevibacter smithii is the dominant methanogen in both the distal colon of individuals in health and disease, the diversity of methanogens is greater than previously reported. In conclusion, the low incidence of methanogens in Inflammatory Bowel Disease, the functionality of the methanogens and impact of methane production in addition to competitive interactions between methanogens and other microbial groups in the human gastrointestinal tract warrants further investigation.
177 citations
TL;DR: Despite the expected heterogeneity of the disorder, differences in mucosal chemokine signalling were evident in this cross-sectional study of IBS patients at the level of both gene expression and protein secretion, with IBS Patients demonstrating a consistent deficit in the expression and secretion of chemokines known to play a critical role in mucosa defence.
Abstract: Objective. To systematically examine mucosal biopsies for differences in cytokine gene expression and protein secretion. Material and methods. The study included 59 females with irritable bowel syndrome (IBS) and 39, otherwise healthy, female volunteers presenting for colonoscopy. Colonic biopsies from subsets were studied by microarray analysis (IBS, n=9; controls, n=8), quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (IBS, n=22; controls, n=21), and ex vivo biopsy culture (IBS, n=28, controls, n=10). Biopsies from patients with active colitis were used as inflammatory disease controls. Results. While gene array analysis revealed extensive overlapping between controls and IBS patients, reduced expression of genes linked to chemokine function was evident among the IBS patients alone. Differential expression was confirmed by qRT-PCR or ex vivo biopsy culture for 5 out of 6 selected genes. Reduced secretion of chemokines (IL-8, CXCL-9 and MCP-1) but not pro-inflammatory cytokines (TNF...
163 citations
TL;DR: It is demonstrated that human LPL T cells, triggered by addition of anti‐CD3 and target cells, produce tumour necrosis factor‐alpha and interferon‐gamma, both of which are required for optimal killing of HT‐29.
Abstract: T cell activation can lead to local tissue injury in organ culture studies of human fetal jejunum, either directly through cytotoxicity or indirectly by the release of cytotoxic cytokines. The goal of this study was to establish in vitro whether cytotoxic cytokines can be released by isolated colonic T cells and what cytokine interactions are required for killing of human colonic epithelial cells. Cytokine-containing supernatants were induced by incubating unseparated lamina propria lymphocytes (LPL) or mucosal T cell subpopulations (separated by indirect panning) with anti-CD3 and/or K562 target cells for 18 h at 37 degrees C. Cytokines were measured by cytotoxicity assays using L929 (murine fibroblast) and HT-29 (human colonic tumour) lines as target cells in combination with blocking anti-cytokine antibodies. Supernatants derived from unseparated, CD4+ (greater than 95% pure) and CD8+ (greater than 90% pure) LPL were cytotoxic to L929 targets (350 U/ml, 230 U/ml and 100 U/ml tumour necrosis factor-alpha, respectively). All or nearly all of the cytotoxicity was due to the presence of tumour necrosis factor-alpha (little or no tumour necrosis factor-beta was detected). These same supernatants were cytotoxic (up to 32% lysis at 1/4 dilution) to HT-29 targets in a 48-h 111In release assay. Recombinant tumour necrosis factor-alpha and interferon-gamma alone produced minimal killing of HT-29, but together killed the HT-29 target cells. Anti-tumour necrosis factor-alpha or anti-interferon-gamma alone blocked killing of HT-29 target cells by LPL-derived supernatants, although anti-tumour necrosis factor-beta had no effect upon killing of HT-29. These results demonstrate that human LPL T cells, triggered by addition of anti-CD3 and target cells, produce tumour necrosis factor-alpha and interferon-gamma, both of which are required for optimal killing of HT-29. Simultaneous release of these cytokines in the vicinity of epithelial cells during immune responses could play an important role in the mucosal damage in chronic inflammatory states such as inflammatory bowel disease.
149 citations
TL;DR: IBS and major depression are characterized by a pro-inflammatory profile, whereas IBS patients alone exhibit an exaggerated muscarinic receptor-mediated IL-6 response.
133 citations
TL;DR: The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.
Abstract: Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.
104 citations
TL;DR: The intact vagus has a protective role in acute DSS-induced colitis in mice but not in the chronic T cell transfer model of colitis, but the results interestingly show that, in the T cell, transfer model vagotomy had a biological effect, since it increased the effectiveness of the BI in downregulation of colonic inflammation.
Abstract: The vagus nerve is an important pathway signaling immune activation of the gastrointestinal tract to the brain. Probiotics are live organisms that may engage signaling pathways of the brain-gut axi...
73 citations
TL;DR: Altered central serotonin responses are found in both IBS and in an animal model, and an increased turnover of 5HT was found in the brainstem together with a trend toward increased activity of the SERT gene.
Abstract: Efforts to define either a biomarker for irritable bowel syndrome (IBS) or a valid animal model have proven disappointing. The aims of this study were to determine if buspirone stimulates prolactin release through the 5-hydroxytryptamine (5HT)1a receptor and whether this response is altered in patients with IBS and in the rat maternal separation model. Buspirone (30 mg) was used to stimulate prolactin release in 40 patients with IBS and in 40 healthy controls. In study 1, 10 IBS patients and 10 controls underwent pretreatment with pindolol (5HT1a antagonist) or placebo followed by buspirone. In study 2, 30 patients with IBS and 30 healthy controls had prolactin release stimulated by buspirone. Maternally separated and nonseparated rats were also treated with buspirone and prolactin monitored. Serotonin metabolites were measured together with the expression of the 5HT1a and serotonin transporter (SERT) gene. Pindolol produced a dose-dependent decrease in the buspirone prolactin response. Patients with IBS and maternally separated rats showed an exaggerated release of prolactin in response to buspirone. In the animal model, an increased turnover of 5HT was found in the brainstem together with a trend toward increased activity of the SERT gene. In conclusion altered central serotonin responses are found in both IBS and in an animal model.
TL;DR: Increased LT-Beta gene expression occurs in RA patient synovium and correlates with the degree of inflammation, and may play a role in RA disease pathogenesis by contributing to a more intense inflammatory reaction in thesynovium.
Abstract: Lymphotoxin-Beta (LT-Beta) is implicated in lymphoid follicle development, production of pro-inflammatory cytokines, and can enhance the proliferation of fibroblasts and synoviocytes. The objective of this study was to investigate LT-Beta and LT-BetaReceptor (LT-BetaR) gene expression in RA patient synovium and blood samples compared with control individuals, and correlate with LT-Alpha and TNF-Alpha gene expression and disease parameters. RT-PCR was used to investigate the gene expression of LT-Beta, LT-BetaR, TNF-Alpha and LT-Alpha in the blood and synovium of RA patients and a control group of individuals. LT-Beta gene expression was significantly higher in RA patient synovium compared to control synovium (P = 0.005). There was a significant positive correlation between LT-Beta and LT-Alpha gene expression in both the synovium (P = 0.001) and blood (P = 0.002) of RA patients. LT-Beta gene expression was significantly higher in RA patient synovial samples that were inflamed to a moderately severe degree compared to those inflamed to a minimal degree (P = 0.02). Analysis of clinical variables revealed a significant positive correlation between LT-BetaR gene expression in RA patient synovium and Pain VAS Score (P = 0.01) and also HAQ Score (P = 0.01). Increased LT-Beta gene expression occurs in RA synovium and correlates with the degree of inflammation. LT-Beta may play a role in RA disease pathogenesis by contributing to a more intense inflammatory reaction in the synovium.
Journal Article•
TL;DR: A group of international experts appointed by the World Gastroenterology Organization prepared a practical guideline on the current indications of probiotics and prebiotics in GastroEnterology, which underscores strain-specificity of the clinical effects, and provides precise information on which specific probiotic strains or prebiotic compounds are useful for what particular clinical indications.
Abstract: A century ago, Elie Metchnikoff (Russian scientist, Nobel laureate, and professor at the Pasteur Institute in Paris) postulated that lactic acid bacteria (LAB) offered health benefits leading to longevity. He suggested that "intestinal auto-intoxication" and the resultant aging could be suppressed by modifying the gut microbiota and replacing proteolytic microbes such as Clostridium - which produce toxic substances including phenols, indoles, and ammonia from the digestion of proteins - with useful microbes. He developed a diet with milk fermented with the bacterium he called "Bulgarian bacillus."
TL;DR: It is shown that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E2 (PGE2), plays a role in the upregulation of FasL expression in colon cancer, adding another pro-neoplastic activity to PGE2.
Abstract: Fas ligand (FasL/CD95L) is a member of the tumour necrosis factor superfamily that triggers apoptosis following crosslinking of the Fas receptor. Despite studies strongly implicating tumour-expressed FasL as a major inhibitor of the anti-tumour immune response, little is known about the mechanisms that regulate FasL expression in tumours. In this study, we show that the cyclooxygenase (COX) signalling pathway, and in particular prostaglandin E2 (PGE2), plays a role in the upregulation of FasL expression in colon cancer. Suppression of either COX-2 or COX-1 by RNA interference in HCA-7 and HT29 colon tumour cells reduced FasL expression at both the mRNA and protein level. Conversely, stimulation with PGE2 increased FasL expression and these cells showed increased cytotoxicity against Fas-sensitive Jurkat T cells. Prostaglandin E2-induced FasL expression was mediated by signalling via the EP1 receptor. Moreover, immunohistochemical analysis using serial sections of human colon adenocarcinomas revealed a strong positive correlation between COX-2 and FasL (r=0.722; P<0.0001) expression, and between EP1 receptor and FasL (r=0.740; P<0.0001) expression, in the tumour cells. Thus, these findings indicate that PGE2 positively regulates FasL expression in colon tumour cells, adding another pro-neoplastic activity to PGE2.
01 Jan 2008
TL;DR: This review summarizes the common and important interactions of drugs used in patients with IBD, including some that may be of therapeutic benefit, and pays particular attention to interactions that occur where both drugs are used to treat IBD.
Patent•
30 Sep 2008TL;DR: In this article, a CLA-producing bacterium is selected from one or more of the group consisting of propionibacteria, lactobacilli, lactococci and streptococci, and bifidobacteria.
Abstract: The current invention provides use of a CLA -producing bacterium for the in vivo conversion in the gut of polyunsaturated fatty acids to CLA. The CLA- producing bacterium is selected from one or more of the group consisting of propionibacteria, lactobacilli, lactococci and streptococci, and bifidobacteria.
01 Jan 2008
TL;DR: The previously described covert suppressor function attributed to cells with this phenotype in Crohn's disease was not found to account for diminished B cell responsiveness in vitro and is unlikely to be of major pathophysiologic significance in the majority of patients.
Abstract: An expanded T cell subpopulation (CD8+ Leu-7+) has previously been reported in the peripheral blood of patients with Crohn's disease. This subpopulation of T cells was associated with a 'covert suppressor' function, particularly in patients with mild/early Crohn's disease, suppressing immunoglobulin production in vitro when cultured in the presence of pokeweed mitogen. T cells with the same CD8+ Leu-7+ phenotype have also been shown to exhibit non-major histocompatability complex-restricted cytotoxicity when triggered by anti-CD3 antibodies, and this cytotoxic activity has also been shown to be elevated in patients with Crohn's disease. Because cytotoxic cells can have immunoregulatory properties, we investigated the possible relationship between the cytotoxic and 'covert suppressor' functions of the CD8+ Leu-7+ subset of T lymphocytes in patients with mildly active Crohn's disease. Although the correlation between T cell cytotoxic activity and the CD8+ Leu-7+ cells was confirmed, no evidence for covert suppressor activity was found; there were no significant differences between the amount of IgM secreted by B cells from normal subjects and patients with Crohn's disease when cultured with T cells at increasing T:B ratios. In addition, IgM production by peripheral blood B cells did not correlate with either the number of CD8+ Leu-7+ cells or with the level of cytotoxic T cell activity. Furthermore, when B cells and CD4+ T cells were co-cultured with increasing numbers of CD8+ T cells, there was no evidence for excessive suppressor T cell activity in Crohn's disease. Although some patients exhibited low levels of IgM production, this was due to diminished B cell function, rather than excessive T suppressor activity or defective T helper activity. We conclude that the CD8+ Leu-7+ T cell subset is associated with cytotoxic but not with enhanced or covert suppressor activity in Crohn's disease. The previously described covert suppressor function attributed to cells with this phenotype in Crohn's disease was not found to account for diminished B cell responsiveness in vitro and is unlikely to be of major pathophysiologic significance in the majority of patients.
TL;DR: It is noteworthy that the peak incidence of IBD occurs in an age group that may need special attention to education and the importance of adherence, and that the Crohn’s and Colitis Knowledge Score was developed by Eaden et al to quantify patient knowledge.
Abstract: Patient education is an important determinant of the effectiveness of the doctor–patient relationship, and should perhaps be viewed as an outcome modifier in patients with chronic disease.1 Incorporation of patients’ perspectives into treatment plans, with increased involvement in disease management, has been advocated by several clinicians.2 Adherence to drug regimens is likely to be enhanced when patients are included in clinical decision-making, and when they are required to take some degree of responsibility for their own management (albeit under guidance from their doctor). Poor adherence is common, and is frequently underestimated by the prescribing clinician.3 A diversity of reasons may account for nonadherence, and these include asymptomatic disease (e.g., maintenance of remission in inflammatory bowel disease [IBD]), prolonged therapy, complicated regimens, and most important, fear of the unknown and concern about side effects of medications. In the latest National Health and Nutrition Examination Survey (NHANES-III), only about half of hypertensive patients in the US were being treated and only 34% of those being treated had well-controlled blood pressure.4 One of the major reasons for this is poor adherence or compliance. Although most drugs prescribed today have extensive patient information leaflets and include the commonly encountered side effects, patient confidence has been undermined by recent high-profile examples of pharmaceutical agents withdrawn because of side effects that were unpredictable or unforeseen. As with most chronic disorders, the drug therapy of IBD is complex, with several classes and subclasses of drugs involved. Patient knowledge of the side effects of their prescribed medications is generally disappointing and physician perceptions regarding patient knowledge is often overestimated. Calkins et al5 studied 99 patients and their physicians and enquired about their understanding of the side effects of the patient’s medications. Of the physicians questioned, 89% believed that their patients understood the side effects, in contrast to only 57% of the patients who reported that they understood the side effects. Other studies have confirmed that patients not only do not know the side effects of their drugs, but often are not aware of the identity of the drugs they are consuming.6,7 It is noteworthy that the peak incidence of IBD occurs in an age group (15 and 25 years) that may need special attention to education and the importance of adherence. In a study of adolescents, a very poor understanding of the potential hazards of over-the-counter medications was found.8 The Crohn’s and Colitis Knowledge Score (CCKNOW) was developed by Eaden et al12 to quantify patient knowledge. This showed the variable level of basic disease understanding among patients, and that the level of knowledge was independent of disease duration. Of 354 respondents to the questionnaire, only 60% understood the role of immunosuppressive drugs. A similar proportion understood the role of sulphasalazine in the reduction of relapse, but only 26% knew that it can reversibly reduce male fertility. More important, 56% of patients believed that side effects from steroids occur immediately even after a small dose, and that the side effects disappeared promptly on discontinuing the steroid. Others have confirmed the confusion among patients regarding their medications and the concerns surrounding toxicity.10,11 It is this confusion and lack of knowledge of medications that results in noncompliance and patients turning to alternative remedies. Hilsden et al9 surveyed 2847 members of the Crohn’s and Colitis Foundation of Canada and found that over 23% of them were actively using complementary and alternative medicines. Efforts to improve this knowledge gap by membership in patient advocacy groups including Crohn’s & Colitis societies, and use of information leaflets, have led to improved knowledge scores.13 A predischarge interview improves patient knowledge and reduces the risk of stopping a medication.14 However, as in other spheres, educational strategies for patients with IBD need continual reinforcement. Indeed, for some patients with Crohn’s disease, there is a curiously ambiguous response to information about drugs. It is not uncommon for patients to express concern about the longterm side effects of a prescribed medication, yet blissfully consume a nonprescribed drug (cigarette smoking) which they know damages their general health and aggravates the clinical course of their disease! This paradox needs to be directly addressed repeatedly by the attending clinician, beFrom the Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Copyright © 2008 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20620 Published online in Wiley InterScience (www.interscience.wiley.com).
TL;DR: This column explores the links and synergies between medicine influencing good practice, are to be found in drama, poetry fiction, biography, electronic fora and film?
Abstract: This column explores the links and synergies between medicine influencing good practice, are to be found in drama,poetry fiction, biography, electronic fora and film? The editors would be pleased to receive short papers, ranging from 500-1,000 words, on relevant topics.Those interested in contributing should email brian hurvokd ac.uk or neil.vickers@kel.ac.uk
TL;DR: The results indicate an increased sensitivity to IFN-γ in the regulation of tryptophan catabolism in IBS, which may predispose to the increased rate of Kyn production observed in severe IBS cases and to the high co-morbidity with depressive and anxiety disorders in this group.
01 May 2008
TL;DR: The aim of the study was to compare dietary intakes and body composition of a group of adult patients with long-standing Crohn’s disease, currently in remission, with that of a groups of ageand gender-matched healthy control subjects.
Abstract: Weight loss and low body fat have been reported in adult patients with Crohn’s disease (CD). In addition, deficiencies in several nutrients have also been reported in patients with CD, but it is not clear whether these deficiencies arise as a consequence of inadequate intake and/or poor intestinal absorption and increased requirement, as a result of disease. The aim of the study was to compare dietary intakes and body composition of a group of adult patients with long-standing CD, currently in remission, with that of a group of ageand gender-matched healthy control subjects. Forty adult patients with CD (eighteen men and twenty-two women), currently in remission and with long-standing (>5 years) disease, were recruited from the Inflammatory Bowel Disease Clinic of Cork University Hospital. Remission was defined at the time of study as the absence of gastrointestinal symptoms and not requiring therapeutic doses of corticosteroids. Forty ageand gender-matched healthy control subjects were recruited from the Cork City area. Dietary intake was estimated using a 7-day diet history and analysed for nutrients using WISP (Weighted Intake Software Program) (Tinuviel Software, Warrington, UK). All statistical analysis was carried out using SPSS version 15.0 (SPSS Inc., Chicago, IL). There was a significant (P<0.01) difference in the proportion of patients with CD and healthy controls that were classified (on basis of BMI) as being underweight, normal weight, overweight or obese. There were no significant differences in waist circumference (P = 0.41), hip circumference (P = 0.63), percentage body fat (P = 0.1) mid-arm muscle area (P = 0.27), biceps (P = 0.55) and subscapular (P= 0.22) skinfold thickness measurements in either group. Skinfold thickness measurements at the supra-iliac and triceps sites were significantly (P = 0.03) and borderline significantly (P = 0.08) different respectively between patients with CD and healthy matched controls.