Activated mast cells infiltrate in close proximity to enteric nerves in diarrhea-predominant irritable bowel syndrome.
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Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS). Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves. An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001). MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS. (+info)
Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics.
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BACKGROUND: Various causes of malabsorption syndrome (MAS) are associated with intestinal stasis that may cause small intestinal bacterial overgrowth (SIBO). Frequency, nature and antibiotic sensitivity of SIBO in patients with MAS are not well understood. METHODS: Jejunal aspirates of 50 consecutive patients with MAS were cultured for bacteria and colony counts and antibiotic sensitivity were performed. Twelve patients with irritable bowel syndrome were studied as controls. RESULTS: Culture revealed growth of bacteria in 34/50 (68%) patients with MAS and 3/12 controls (p < 0.05). Colony counts ranged from 3 x 10(2) to 10(15) (median 10(5)) in MAS and 100 to 1000 (median 700) CFU/ml in controls (p 0.003). 21/50 (42%) patients had counts GreaterEqual;105 CFU/ml in MAS and none of controls (p < 0.05). Aerobes were isolated in 34/34 and anaerobe in 1/34. Commonest Gram positive and negative bacteria were Streptococcus species and Escherichia coli respectively. The isolated bacteria were more often sensitive to quinolones than to tetracycline (ciprofloxacin: 39/47 and norfloxacin: 34/47 vs. tetracycline 19/47, <0.01), ampicillin, erythromycin and co-trimoxazole (21/44, 14/22 and 24/47 respectively vs. tetracycline, p = ns). CONCLUSIONS: SIBO is common in patients with MAS due to various causes and quinolones may be the preferred treatment. This needs to be proved further by a randomized controlled trial. (+info)
Systematic review: the economic impact of irritable bowel syndrome.
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BACKGROUND: Although little mortality is associated with irritable bowel syndrome, curative therapy does not exist and thus the economic impact of this disorder may be considerable. METHODS: A systematic review of the literature was performed. Studies were included if their focus was irritable bowel syndrome, and direct and/or productivity (indirect) costs were reported. Two investigators abstracted the data independently. RESULTS: One hundred and seventy-four studies were retrieved by the search; 11 fulfilled all criteria for entry into the review. The mean direct costs of irritable bowel syndrome management were reported to be UK pound sterling90, Canadian$259 and US$619 per patient annually, with total annual direct costs related to irritable bowel syndrome of pound sterling45.6 million (UK) and $1.35 billion (USA). Direct resource consumption of all health care for irritable bowel syndrome patients ranged from US$742 to US$3166. Productivity costs ranged from US$335 to US$748, with total annual costs of $205 million estimated in the USA. Annual expenditure for all health care, in addition to expenditure limited to gastrointestinal disorders, was significantly higher in irritable bowel syndrome patients than in control populations. CONCLUSIONS: Despite the lack of significant mortality, irritable bowel syndrome is associated with high direct and productivity costs. Irritable bowel syndrome patients consume more gastrointestinal-related and more total health care resources than non-irritable bowel syndrome controls, and sustain significantly greater productivity losses. (+info)
Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain A expressed in mouse small intestinal epithelium.
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Expression of a distant homologue MHC class I molecule, MHC class I-related chain A (MICA), has been found to be stress inducible and limited to the intestinal epithelium. This nonclassical MHC molecule is associated with various carcinomas in humans. To understand the biological consequences of MICA expression in the gut, we generated transgenic (Tg) mice (T3(b)-MICA Tg) under the control of the T3(b) promoter. The T3(b)-MICA Tg mice expressed MICA selectively in the intestine and had an increased number of TCRalphabeta CD4CD8alphaalpha, double-positive (DP) intraepithelial lymphocytes (IELs) in the small bowel. These MICA-expanded DP IELs exhibited a bias to Vbeta8.2 and overlapped motifs of the complementarity-determining region 3 region among various Tg mice. Hence, the overexpression of MICA resulted in a clonal expansion of DP IELs. Studies in model of inflammatory bowel disease showed that transgenic MICA was able to attenuate the acute colitis induced by dextran sodium sulfate administration. Therefore, this unique in vivo model will enable investigation of possible influences of stress-inducible MICA on the gut immune surveillance. (+info)
Blockade of B7-H1 suppresses the development of chronic intestinal inflammation.
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A newly identified costimulatory molecule, programmed death-1 (PD-1), provides a negative signal that is essential for immune homeostasis. However, it has been suggested that its ligands, B7-H1 (PD-L1) and B7-dendritic cells (B7-DC; PD-L2), could also costimulate T cell proliferation and cytokine secretion. Here we demonstrate the involvement of PD-1/B7-H1 and B7-DC interaction in the development of colitis. We first examined the expression profiles of PD-1 and its ligands in both human inflammatory bowel disease and a murine chronic colitis model induced by adoptive transfer of CD4(+)CD45RB(high) T cells to SCID mice. Second, we assessed the therapeutic potential of neutralizing anti-B7-H1 and/or B7-DC mAbs using this colitis model. We found significantly increased expression of PD-1 on T cells and of B7-H1 on T, B, and macrophage/DCs in inflamed colon from both inflammatory bowel disease patients and colitic mice. Unexpectedly, the administration of anti-B7-H1, but not anti-B7-DC, mAb after transfer of CD4(+)CD45RB(high) T cells suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced the production of IFN-gamma, IL-2, and TNF-alpha, but not IL-4 or IL-10, by lamina propria CD4(+) T cells. These data suggest that the interaction of PD-1/B7-H1, but not PD-1/B7-DC, might be involved in intestinal mucosal inflammation and also show a possible role of interaction between B7-H1 and an as yet unidentified receptor for B7-H1 in inducing T cell activation. (+info)
Pan-enteric dysmotility, impaired quality of life and alexithymia in a large group of patients meeting ROME II criteria for irritable bowel syndrome.
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AIM: Psychological factors, altered motility and sensation disorders of the intestine can be variably associated with irritable bowel syndrome (IBS). Such aspects have not been investigated simultaneously. The aim of this paper was to evaluate gastrointestinal motility and symptoms, psychological spectrum and quality of life in a large group of IBS patients in southern Italy. METHODS: One hundred IBS patients (F:M=73:27, age 48+/-2 years, mean+/-SE) fulfilling ROME II criteria matched with 100 healthy subjects (F:M=70:30, 45+/-2 years). Dyspepsia, bowel habit, alexithymia, psycho-affective profile and quality of life were assessed using specific questionnaires. Basally and postprandially, changes in gallbladder volumes and antral areas after liquid meal and orocaecal transit time (OCTT) were measured respectively by ultrasonography and H(2)-breath test. Appetite, satiety, fullness, nausea, and epigastric pain/discomfort were monitored using visual-analogue scales. RESULTS: Compared with controls, IBS patients had increased dyspepsia (score 12.6+/-0.7 vs 5.1+/-0.2, P<0.0001), weekly bowel movements (12.3+/-0.4 vs 5.5+/-0.2, P<0.00001, comparable stool shape), alexithymia (score 59.1+/-1.1 vs 40.5+/-1.0, P=0.001), poor quality of life and psycho-affective profile. IBS patients had normal gallbladder emptying, but delayed gastric emptying (T50: 35.5+/-1.0 vs 26.1+/-0.6 min, P=0.00001) and OCTT (163.0+/-5.4 vs 96.6+/-1.8 min, P=0.00001). Fullness, nausea, and epigastric pain/discomfort were greater in IBS than in controls. CONCLUSION: ROME II IBS patients have a pan-enteric dysmotility with frequent dyspepsia, associated with psychological morbidity and greatly impaired quality of life. The presence of alexithymia, a stable trait, is a novel finding of potential interest to detect subgroups of IBS patients with different patterns recovered after therapy. (+info)
Cluster analysis of symptoms and health seeking behaviour differentiates subgroups of patients with severe irritable bowel syndrome.
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BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous condition which is diagnosed according to specific bowel symptom clusters. The aim of the present study was to identify subgroups of IBS subjects using measures of rectal sensitivity and psychological symptoms, in addition to bowel symptoms. Such groupings, which cross conventional diagnostic approaches, may provide greater understanding of the pathogenesis of the condition and its treatment. METHOD: A K means cluster analysis was used to group 107 clinic patients with IBS according to physiological, physical, and psychological parameters. All patients had severe IBS and had failed to respond to usual medical treatment. Twenty nine patients had diarrhoea predominant IBS, 26 constipation predominant, and 52 had an alternating bowel habit. RESULTS: The clusters were most clearly delineated by two variables: "rectal perceptual threshold (volume)" and "number of doctor visits". Three subgroups were formed. Group I comprised patients with low distension thresholds and high rates of psychiatric morbidity, doctor consultations, interpersonal problems, and sexual abuse. Group II also had low distension thresholds but low rates of childhood abuse and moderate levels of psychiatric disorders. Group III had high distension thresholds, constipation or alternating IBS, and low rates of medical consultations and sexual abuse. CONCLUSION: The marked differences across the three groups suggest that each may have a different pathogenesis and respond to different treatment approaches. Inclusion of psychosocial factors in the analysis enabled more clinically meaningful groups to be identified than those traditionally determined by bowel symptoms alone or rectal threshold. (+info)
Long term benefits of hypnotherapy for irritable bowel syndrome.
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BACKGROUND AND AIMS: There is now good evidence from several sources that hypnotherapy can relieve the symptoms of irritable bowel syndrome in the short term. However, there is no long term data on its benefits and this information is essential before the technique can be widely recommended. This study aimed to answer this question. PATIENTS AND METHODS: 204 patients prospectively completed questionnaires scoring symptoms, quality of life, anxiety, and depression before, immediately after, and up to six years following hypnotherapy. All subjects also subjectively assessed the effects of hypnotherapy retrospectively in order to define their "responder status". RESULTS: 71% of patients initially responded to therapy. Of these, 81% maintained their improvement over time while the majority of the remaining 19% claimed that deterioration of symptoms had only been slight. With respect to symptom scores, all items at follow up were significantly improved on pre-hypnotherapy levels (p<0.001) and showed little change from post-hypnotherapy values. There were no significant differences in the symptom scores between patients assessed at 1, 2, 3, 4, or 5+ years following treatment. Quality of life and anxiety or depression scores were similarly still significantly improved at follow up (p<0.001) but did show some deterioration. Patients also reported a reduction in consultation rates and medication use following the completion of hypnotherapy. CONCLUSION: This study demonstrates that the beneficial effects of hypnotherapy appear to last at least five years. Thus it is a viable therapeutic option for the treatment of irritable bowel syndrome. (+info)