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Constipation; Intestinal manometry; Intestinal neuropathy Restrenyiment; Manometria intestinal; Neuropatia intestinal Estreñimiento; Manometría intestinal; Neuropatía intestinal Introduction Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. Methods Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. Results The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. Conclusion and Inference Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry. This work was supported by the Instituto de Salud Carlos III and co-financed by the European Union (FEDER/FSE) [PI17/01794]; Spanish Ministry of Economy and Competitiveness (Dirección General de Investigación Científica y Técnica) [SAF 2016-76648-R]; Ciberehd is funded by the Instituto de Salud Carlos III. LA was supported by the Instituto de Salud Carlos III (CM20/00182).

Background We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depends on the characteristics of the meal and the appropriateness of the digestive response. The aim of the present study is to identify metabolomic biomarkers of the cognitive response to meal ingestion. Methods In 18 healthy subjects, the response to a test meal (Edanec, 1 kcal/mL) ingested until maximum satiation (50 mL/min) was assessed. Perception measurements and blood samples were taken before, at the end of the meal, and 20 min after ingestion. The cognitive response and the hedonic dimension were measured on 10 cm scales. Metabolomic analysis was performed using nuclear magnetic resonance (NMR) spectroscopy and values of triglycerides, insulin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were determined using conventional laboratory techniques. Key Results Ingestion up to maximum satiation induced sensation of fullness and decreased digestive well-being. The total amount ingested by each subject correlated with the basal sensation of hunger, but not with other sensations or blood metabolite levels. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043). Twenty-minutes after finalizing ingestion, triglyceride levels had significantly increased which correlated with the recovery in well-being (R = 0.48; p = 0.046) and the decrease in desire to eat a food of choice (R = −0.56; p = 0.016). The increase in lipids inversely correlated with abdominal discomfort (R = −0.51; p = 0.032). Conclusions & Inferences Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites, which may serve as objective biomarkers of perception.

Background Intestinal manometry is the current standard for direct evaluation of small bowel dysmotility. Patients with abnormal motility can either be diagnosed of pseudo-obstruction when there are radiological findings mimicking mechanical intestinal obstruction or of enteric dysmotility when these findings are absent. The aim of the present study was to prospectively compare small bowel manometric abnormalities with histopathological findings in intestinal full-thickness biopsies in patients with severe dysmotility disorders. Methods We investigated 38 patients with intestinal manometry and a subsequent full-thickness intestinal biopsy. Manometric recordings were read by 4 investigators and a diagnostic consensus was obtained in 35 patients. Histopathological analysis, including specific immunohistochemical techniques of small bowel biopsies was performed and compared to manometric readings. Key Results Patients with abnormal intestinal manometry had abnormal histopathological findings in 73% of cases. However, manometric patterns did not match with the specific neuromuscular abnormalities. Among patients with a neuropathic manometry pattern and abnormal histopathology, only 23% had an enteric neuropathy, whereas 62% had neuromuscular inflammation, and 15% an enteric myopathy. On the other hand, patients with a myopathic manometry pattern all had abnormal histopathology, however, none of them with signs of enteric myopathy. Conclusion & Inferences Small bowel dysmotility detected by intestinal manometry is often associated with abnormal neuromuscular findings in full-thickness biopsies. However, there is no correlation between the specific manometric patterns and the histopathological findings.

Background Gut dysfunctions may be associated to digestive symptoms. We hypothesized that the gut can also originate pleasant sensations, and wished to demonstrate the hedonic component of the digestive response to a meal. Methods Healthy subjects (n = 42) were evaluated during basal fasting conditions and during experimentally induced fullness sensation (either by gastric distension or duodenal nutrient infusion). In each set of studies, a 240 mL test meal (12 kcal broth) and water, as inert control meal, were administered on separate days in a randomized, cross-over design. Gastric accommodation, the cognitive response and the hedonic dimension (both by 10 score scales) were measured 9 min before and 60 min after the meal. Key Results In basal conditions, the test meal induced a significantly greater gastric relaxation than the control meal (166 ± 28 mL isotonic volume increase 67 ± 14 mL; p = 0.002). Both meals induced epigastric fullness (3.8 ± 0.7 score and 3.2 ± 0.8 score, respectively; p = 0.740), but contrary to the inert meal, with the active meal this conscious sensation had a pleasant dimension (digestive comfort increase by 1.3 ± 0.6 score with active meal vs −1.1 ± 0.6 decrease with inert meal; p = 0.015). Experimentally induced fullness was associated to a decrease in digestive well-being or abdominal discomfort, which improved only after the active meal but not the inert meal. Conclusions & Inferences When appropriate conditions are met, the response to a meal includes a hedonic dimension involving pleasant sensation of digestive well-being.

BACKGROUND: We previously showed that abdominal distension in patients with functional gut disorders is due to a paradoxical diaphragmatic contraction without major increment in intraabdominal volume. Our aim was to characterize the pattern of gas retention and the abdomino-thoracic mechanics associated with abdominal distension in patients with intestinal dysmotility. METHODS: In 15 patients with manometrically proven intestinal dysmotility, two abdominal CT scans were performed: one during basal conditions and other during an episode of severe abdominal distension. In 15 gender- and age-matched healthy controls, a basal scan was performed. KEY RESULTS: In basal conditions, patients exhibited more abdominal gas than healthy subjects, particularly in the small bowel, and the volume significantly increased during an episode of distension. During episodes of abdominal distension, the increase in abdominal content was associated with increased girth and antero-posterior abdominal diameter, as well as a cephalic displacement of the diaphragm, which reduced the height of the lung. The consequent reduction in the air volume of the lung was attenuated by an increase in the antero-posterior diameter of the chest. CONCLUSIONS & INFERENCES: Abdominal distension in patients with severe intestinal dysfunction is related to marked pooling of gut contents, particularly in the small bowel. This increase in content is accommodated within the abdominal cavity by a global and coordinated abdomino-phreno-thoracic response, involving an accommodative ascent of the diaphragm and a compensatory expansion of the chest wall.

This is the peer reviewed version of the following article: Bendezú, Á., Mego, M., Monclús, E., Merino, X., Accarino, A., Malagelada, J., Navazo, I., Azpiroz, F. Colonic content: effect of diet, meals, and defecation. "Neurogastroenterology and motility", Febrer 2017, vol. 29, núm. 2, which has been published in final form at [http://onlinelibrary.wiley.com.recursos.biblioteca.upc.edu/doi/10.1111/nmo.12930/full]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. The metabolic activity of colonic microbiota is influenced by diet; however, the relationship between metabolism and colonic content is not known. Our aim was to determine the effect of meals, defecation, and diet on colonic content. Methods: In 10 healthy subjects, two abdominal MRI scans were acquired during fasting, 1 week apart, and after 3 days on low- and high-residue diets, respectively. With each diet, daily fecal output and the number of daytime anal gas evacuations were measured. On the first study day, a second scan was acquired 4 hours after a test meal (n=6) or after 4 hours with nil ingestion (n=4). On the second study day, a scan was also acquired after a spontaneous bowel movement. Results: On the low-residue diet, daily fecal volume averaged 145 ± 15 mL; subjects passed 10.6 ± 1.6 daytime anal gas evacuations and, by the third day, non-gaseous colonic content was 479 ± 36 mL. The high-residue diet increased the three parameters to 16.5 ± 2.9 anal gas evacuations, 223 ± 19 mL fecal output, and 616 ± 55 mL non-gaseous colonic content (P

SUMMARY Background Acute intestinal toxicity is a frequent complication that may lead to interruption of treatment in patients undergoing pelvic radiotherapy. Reliable, non-invasive biological markers to evidence their severity are not yet available. Aim To test faecal DNA and calprotectin as potential biomarkers of intestinal toxicity caused by pelvic radiotherapy. Methods Patients were categorized according to the location of the cancer as nonrectal (n = 25) and rectal (n = 27). Four stool samples were collected at weeks w0, w3, w5 (end of radiotherapy) and w7. Faecal DNA was determined by quantitative PCR and calprotectin by ELISA. Intestinal toxicity was scored according to the Common Toxicity Criteria. Results In the nonrectal group, acute diarrhoea toxicity was present in 80% of patients, faecal DNA increased 10-fold during radiotherapy (1.5 · 10 3 copies ⁄ mg dry weight, 9.5 · 10 2 –8.8 · 10 3 at w0, median and interquartile range vs. 1.3 · 10 4 , 1.9 · 10 3 –3.9 · 10 4 at w5, P < 0.01), but was not recovered at w7 (3.4 · 10 3 , 1.5 · 10 3 –4.1 · 10 4 ) and calprotectin doubled during treatment at w3 and w5. No significant changes in faecal markers were found in the rectal group. Conclusion

The mechanical and secretory factors in the stomach that may be implicated in the production of symptoms are still poorly understood. To determine whether symptoms in response to postcibal gastric distention are associated with increased acid secretion, the relationship between symptoms, acid secretion and intragastric pressure in healthy subjects was investigated. Perception (by a 0–6 score questionnaire) and the gastric secretory response to a glucose test meal (by intragastric titration) was quantified either at low (2 mmHg) or at high (8 mmHg) intragastric pressure levels, maintained by feedback regulation of the air volume within a gastric bag using an electronic barostat. Low intragastric pressure produced a small gastric expansion (87 ± 26 ml; mean ± SE) that was largely unperceived (score 0.7 ± 0.5). High intragastric pressure did not increase acid secretion (15 ± 3 mEq h-1 vs 16 ± 3 mEq h-1 at low pressure), but produced symptomatic perception (score 2.5 ± 0.7) related to a marked gastric expansion (521 ± 92 ml; P < 0.05 vs low pressure for both). It was concluded that postcibal gastric hypertension induces symptoms without affecting the gastric acid secretory response to the meal.

Given the differences that normally exist in jejunal and Heal motility patterns, we wished to determine whether these regions respond differently to acute enteric infections. In 10 patients with acute gastroenteritis induced by Salmonella infection and 12 healthy individuals jejunal and Heal motility was recorded at eight equidistant sites by a manometric system for 6 h during fasting. All were healthy individuals, but only three of 10 patients exhibited the cyclic inter digestive motor complex; 82 ± 9 min duration in healthy individuals (mean ± SE). In the jejenum, patients exhibited short bursts of intense activity (6.3 ± 1.6 bursts/subject in patients vs. 1.8 ± 0.5 in controls; P < 0.05); burst activity was scarce in the ileum. In contrast to healthy subjects, patients exhibited prolonged periods (64 ± 3 min duration) of Heal motor quiescence, that accounted for 32 ± 11% of recording time; such silent periods were not observed in the jejunum. Prolonged propagated ileal contractions were observed only in two healthy subjects, but in seven out of 10 patients. These data indicate that acute Salmonella infection magnifies the motor differences between the jejunum and the ileum; both regions generate aberrant and markedly different dysmotility patterns.

This is the peer reviewed version of the following article: Bendezú, R. A., Barba, E., Burri, E., Cisternas, D., Accarino, A., Quiroga, S., Monclus, E., Navazo, I., Malagelada, J.-R. and Azpiroz, F. (2016), Colonic content in health and its relation to functional gut symptoms. Neurogastroenterol. Motil., 28: 849–854, which has been published in final form at [doi:10.1111/nmo.12782]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving Gut content may be determinant in the generation of digestive symptoms, particularly in patients with impaired gut function and hypersensitivity. Since the relation of intraluminal gas to symptoms is only partial, we hypothesized that non-gaseous component may play a decisive role. Methods: Abdominal computed tomography scans were evaluated in healthy subjects during fasting and after a meal (n = 15) and in patients with functional gut disorders during basal conditions (when they were feeling well) and during an episode of abdominal distension (n = 15). Colonic content and distribution were measured by an original analysis program. Key results: In healthy subjects both gaseous (87 ± 24 mL) and non-gaseous colonic content (714 ± 34 mL) were uniformly distributed along the colon. In the early postprandial period gas volume increased (by 46 ± 23 mL), but non-gaseous content did not, although a partial caudad displacement from the descending to the pelvic colon was observed. No differences in colonic content were detected between patients and healthy subjects. Symptoms were associated with discrete increments in gas volume. However, no consistent differences in non-gaseous content were detected in patients between asymptomatic periods and during episodes of abdominal distension. Conclusions & inferences: In patients with functional gut disorders, abdominal distension is not related to changes in non-gaseous colonic content. Hence, other factors, such as intestinal hypersensitivity and poor tolerance of small increases in luminal gas may be involved.

Infliximab induces remission and improves the health-related quality of life (HRQOL) of patients with refractory or fistulous Crohn's disease (CD). However, little information is available as to whether its effect on HRQOL is sustained over time. The objective was to measure the HRQOL of CD patients in long-term clinical remission.Prospective, observational study was undertaken in patients with CD in infliximab-induced clinical remission (Harvey index3) for at least 6 months, and receiving long-term infliximab and azathioprine maintenance therapy. Patients were followed for 4 years or until clinical relapse (Harvey index3). HRQOL was assessed annually using the validated Spanish version of the disease-specific 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) and the EuroQol-5D.Forty-nine patients with CD in stable clinical remission were included at baseline. At 12 months, n = 42 patients remained in remission, at 24 months n = 32 patients, at 36 months n = 13, and in the last visit at 48 months 6 patients remained in clinical remission. The overall score on the IBDQ-36 remained unchanged in patients with stable, inactive CD (median overall score of 6.1 at baseline and 6.5 at 4 years). Scores on all 5 dimensions of the IBDQ-36 remained unchanged over the study period in stable patients. Patients in remission scored highly on the preference value ratings of the EuroQol-5D (scores of 1.0) and remained unchanged in patients who remained in remission.Sustained clinical remission of CD achieved with maintenance treatment maintains HRQOL over long-term follow-up.

Background Expression of acinar cell-specific genes requires the pancreas transcription factor 1 α (Ptf1 α ). p48 is the only component of Ptf1 α that is involved in both acinar gene regulation and pancreatic ontogenesis. Materials and methods To determine whether Ptf1 α /p48 expression is regulated during pancreatitis, acute pancreatitis was induced in rats by repeated caerulein injections; early chronic pancreatitis by the combined administration of caerulein and cyclosporin A; and focal pancreas fibrosis by trinitrobenzene sulfonic acid infusion into the pancreatic duct. AR42J cells were used to examine caerulein effects on acinar cells. Ptf1 α /p48 expression was examined using immunohistochemistry, Western blotting, and qRT-PCR methods. Results In acute pancreatitis, Ptf1 α /p48 decreased markedly within 6 h as determined by Western blotting and immunohistochemistry. After 24 h, Ptf1 α /p48 increased continuously and normalized at day six. In contrast, pancreas amylase reached a nadir at 48 h, when Ptf1 α / p48 had largely recovered. In the early chronic pancreatitis model Ptf1 α /p48 levels did not completely recover even at day 14, and this was associated with a failure to restore normal histology and amylase content. qRT-PCR showed that p48 mRNA were reduced after pancreatitis induction and were followed by a decrease in elastase mRNA. In the focal pancreas fibrosis model, Ptf1 α /p48 expression was undetectable in areas with substantial acinar cell loss and tubular complexes. Caerulein did not affect Ptf1 α /p48 expression in AR42J cells. Conclusions Ptf1 α /p48 protein and mRNA levels are regulated in acute and chronic experimental pancreatitis. Inability to re-express Ptf1 α /p48 after injury may preclude acinar cell differentiation and appropriate pancreatic regeneration.

SUMMARY Background Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. Objective To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. Design Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g ⁄ day) and randomly allocated to receive either oligofructose-enriched inulin (12 g ⁄ day, p.o., n = 10) or placebo (12 g ⁄ day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. Results Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 659 lg ⁄g; day 7: 1033 393 lg ⁄g, P < 0.05) but not in the placebo group (day 0: 5834 1563 lg ⁄g; day 7: 4084 1395 lg ⁄g, n.s.). Changes in faecal concentration of human DNA were not significant. Conclusion In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin.

Preliminary studies suggested that octreotide may be therapeutic in bleeding angiodysplasia. Our aim was to investigate the efficacy of long-term octreotide therapy in the prevention of rebleeding from gastrointestinal angiodysplasia.A cohort of 32 patients diagnosed with bleeding from angiodysplasia was treated with octreotide 50 mu 12 h subcutaneously for a 1-2 yr period. This cohort was compared with an external control group (38 patients who had received placebo [1 tablet/day] in a concurrent randomized clinical trial for the same period.Two patients of the octreotide group were lost to follow-up. Treatment failure occurred in seven of 30 (23%) patients in the octreotide group and in 17 of 35 (48%) in the placebo group (three dropouts before first visit) (P= 0.043). The actuarial probability of remaining free of rebleeding at 1 and 2 yr of follow-up was 77% and 68%, respectively, for the octreotide group and 55% and 36%, respectively, for the placebo group (log rank P= 0.030). Multivariate proportional hazards-regression analysis showed that octreotide therapy and previous bleeding episodes were positive and negative predictors of efficacy, respectively. No significant differences between the groups were observed according to number of bleeding episodes (0.4 +/- 0.7 vs 0.9 +/- 1.5, P= 0.070) and transfusion requirements (1.1 +/- 2.6 vs 0.7 +/- 1.5 units); however, iron requirements were lower in the octreotide than in the placebo group (22 +/- 62 vs 166 +/- 267 units; P0.001). Likewise, major adverse events (1 vs 1) and mortality (0 vs 1) were similar between groups.This study suggests that octreotide treatment may be beneficial in preventing rebleeding from gastrointestinal angiodysplasia.

Background As mean transit time in the colon is longer than the interval between meals, several consecutive meal loads accumulate, and contribute to colonic biomass. Our aim was to determine the summation effect of fermentable food residues on intestinal gas production. Methods In eight healthy subjects, the volume of endogenous intestinal gas produced in the intestine over a 4-h period was measured by means of a wash-out technique, using an exogenous gas infusion into the jejunum (24 mL/min) and collection of the effluent via a rectal Foley catheter. The exogenous gas infused was labeled (5% SF6) to calculate the proportion of endogenous intestinal gas evacuated. In each subject, four experiments were performed ≥1 week apart combining a 1-day high- or low-flatulogenic diet with a test meal or fast. Key Results Basal conditions: on the low-flatulogenic diet, intestinal gas production during fasting over the 4-h study period was 609 ± 63 mL. Effect of diet: during fasting, intestinal gas production on the high-flatulogenic diet was 370 ± 146 mL greater than on the low-flatulogenic diet (p = 0.040). Effect of test meal: on the low-flatulogenic diet, intestinal gas production after the test meal was 681 ± 114 mL greater than during fasting (p = 0.001); a similar effect was observed on the high-flatulogenic diet (599 ± 174 mL more intestinal gas production after the test meal than during fasting; p = 0.021). Conclusions & Inferences Our data demonstrate temporal summation effects of food residues on intestinal gas production. Hence, intestinal gas production depends on pre-existing and on recent colonic loads of fermentable foodstuffs.

Nitric oxide (NO) is implicated in the pathophysiology of intestinal inflammation. Intestinal mast cells may amplify inflammatory response and mucosal injury in inflammatory bowel disease. Our aim was to examine the role of NO and intestinal mast cells by investigating the effects of NO synthase (NOS) inhibitors and a mast cell stabilizer during induction of dextran sulfate sodium (DSS) colitis. Colitis was induced by 4% DSS in drinking water, in rats pretreated with L-NAME or aminoguanidine. In another set of experiments, we investigated the effect of ketotifen in this setting. Inhibition of NO by L-NAME worsened DSS-induced inflammation, however, aminoguanidine had no effect. On the other hand, ketotifen abolished the deleterious effects of L-NAME on colonic inflammation, suggesting that hyperactivation of mast cells by NOS inhibition amplifies mucosal injury induced by DSS. Our results suggest that constitutive isoforms of NOS prevent mast cell activation.

The intestine propels and evacuates large gas loads without detectable phasic contractions by manometry. We hypothesized that intestinal gas motion is produced by changes in gut tone and capacitance. In 13 healthy subjects, changes in duodenal tone were measured by a barostat during continuous perfusion of lipids (Intralipid, 1 kcal min(-1)) into the duodenum for 60 min. In separate groups, the effects of jejunal gas infusion (N2, CO2 and O2 in venous proportions at 12 mL min(-1) starting after 15 min lipid perfusion) and sham infusion were tested. Gas outflow was collected continuously via an intrarectal cannula. Duodenal lipid perfusion produced a rapid duodenal relaxation (volume increased by 48 +/- 18%; P < 0.01 vs basal). Gas infusion increased gas evacuation (184 +/- 59 mL), and this was associated with a tonic contraction of the duodenum (R = 0.86; P < 0.01) that completely reverted the lipid-induced duodenal relaxation (volume decreased by 42 +/- 13%; P < 0.05). During sham infusion only 52 +/- 28 mL of gas were evacuated (P < 0.05 vs gas infusion), and the duodenum remained relaxed due to the effect of lipids (0 +/- 1% volume reduction; ns). In conclusion, intestinal gas propulsion and clearance is associated with a tonic contraction of the gut wall and reduced gut capacitance.

Background: Inflammatory bowel disease impairs patients' perception of health and has a negative impact on health-related quality of life (HRQOL). Most studies include patients from a single hospital. This may bias limit results through the use of small patient samples and/or samples within a restricted disease spectrum. Methods: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's disease (CD) from 9 hospitals located in different geographical areas in Spain using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. Results: The study included 1156 patients (528 patients with UC and 628 with CD; median age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in parallel with disease severity to a similar extent in both UC (IBDQ scores of 6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between clinical activity and quality of life was observed when EuroQol preference values were used. All 5 dimensions of the IBDQ showed significantly lower scores in patients with active UC and CD than in patients in remission. The pattern of scores by IBDQ dimensions differed between patients in relapse (who scored worse on the digestive symptoms dimension) and patients in remission. Variables related with disease activity, time of evolution since diagnosis and female sex, were significantly associated with having a worse perception of HRQOL. The type of disease or geographical area of residence did not influence results on the IBDQ. Conclusions: UC and CD impair patients' HRQOL, and the degree of impairment depends on disease activity but is independent of the type of disease and place of residence.

(2005). Pathogenesis of irritable bowel syndrome: The mast cell connection. Scandinavian Journal of Gastroenterology: Vol. 40, No. 2, pp. 129-140.

Supra-oesophageal manifestations of gastro-oesophageal reflux disease (GERD) are common and often under-appreciated, in part due to the absence of classic symptoms of heartburn and regurgitation. Patients with supra-oesophageal manifestations of GERD may report symptoms involving the pulmonary, otolaryngologic or pharyngeal systems. Endoscopy is often negative and therefore of limited diagnostic value in these patients, and while laryngoscopy and 24 h dual-channel intra-oesophageal pH-metry may have greater yields they are costly, invasive and time-consuming. Therefore, a trial of proton pump inhibitor therapy is now widely considered a first-line diagnostic test in those with suspected GERD-induced supra-oesophageal symptoms. The dose as well as duration of the proton pump inhibitor trial is dependent upon a patient's presenting symptoms. For example, GERD-related non-cardiac chest pain may be relieved with a short-term (e.g. 1 week) treatment with standard doses of a proton pump inhibitor. The use of high-dose twice daily proton pump inhibitor therapy for an extended period (e.g. 2-3 months) may be required before any discernible improvement in pulmonary symptoms or pharyngo-laryngitis is noted. Patients who do not experience symptom improvement following a proton pump inhibitor trial may require further diagnostic evaluations including 24 h oesophageal pH studies, while on acid anti-secretory therapy, to establish the absence of persistent acid reflux. The role of anti-reflux surgical or endoscopic interventions in those with supra-oesophageal manifestations of GERD remains to be established.

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.

Background: Patients describe that body posture may affect their abdominal bloating, distension, and flatulence, but whether changes in position have objectively demonstrable effects, either beneficial or deleterious, has not been investigated. Aim: To determine the effect of body posture, upright versus supine, on intestinal transit of gas loads. Subjects: Eight healthy subjects without gastrointestinal symptoms. Methods: In each subject a gas mixture was continuously infused into the jejunum (12 ml/min) for three hours, and gas evacuation, clearance of a non- absorbable gaseous marker, perception, and abdominal girth were measured. Paired studies were randomly performed in each subject on separate days in the upright and supine positions. Results: In the upright position, intestinal gas retention was much smaller than when supine (13 (52) ml v 146 (75) ml retention at 60 minutes, respectively; p

Background: The precise relation of intestinal gas to symptoms, particularly abdominal bloating and distension remains incompletely elucidated. Our aim was to define the normal values of intestinal gas volume and distribution and to identify abnormalities in relation to functional-type symptoms. Methods:Abdominal computed tomography scans were evaluated in healthy subjects (n = 37) and in patients in three conditions: basal (when they were feeling well; n = 88), during an episode of abdominal distension (n = 82) and after a challenge diet (n = 24). Intestinal gas content and distribution were measured by an original analysis program. Identification of patients outside the normal range was performed by machine learning techniques (one-class classifier). Results are expressed as median (IQR) or mean ± SE, as appropriate. Key Results: In healthy subjects the gut contained 95 (71, 141) mL gas distributed along the entire lumen. No differences were detected between patients studied under asymptomatic basal conditions and healthy subjects. However, either during a spontaneous bloating episode or once challenged with a flatulogenic diet, luminal gas was found to be increased and/or abnormally distributed in about one-fourth of the patients. These patients detected outside the normal range by the classifier exhibited a significantly greater number of abnormal features than those within the normal range (3.7 ± 0.4 vs 0.4 ± 0.1; p < 0.001). Conclusions & Inferences: The analysis of a large cohort of subjects using original techniques provides unique and heretofore unavailable information on the volume and distribution of intestinal gas in normal conditions and in relation to functional gastrointestinal symptoms.

Background and aims: Tumour necrosis factor α (TNF-α) plays a key role in the pathogenesis of intestinal inflammation in Crohn’s disease. The effect of bacteria on TNF-α release by intestinal mucosa was investigated. Methods: Ileal specimens were obtained at surgery from 10 patients with Crohn’s disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-α were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry. Results: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-α by inflamed Crohn’s disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-α expression among intraepithelial lymphocytes from Crohn’s disease mucosa. None of the bacteria induced changes in non-inflamed mucosa. Conclusions: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.

Using a disease specific instrument to measure the health related quality of life (HRQOL) of patients with inflammatory bowel disease (IBD), it has been shown that their perceived HRQOL worsens during active disease. The precise factors involved in HRQOL changes reported by these patients are largely unknown. Our aim was to elucidate which socio-demographic and health status variables are related with HRQOL in IBD patients. To this end, 354 patients with IBD were interviewed. To quantify the impairment in the HRQOL, the 36-item version of the inflammatory bowel disease questionnaire (IBDQ) was administered to all patients. To explore the relation of each individual variable on the HRQOL an univariate analysis by using the Spearman correlation, the Mann–Whitney or the Kruskal–Wallis test was performed when necessary. Factors significant at the univariate analysis were assessed using multiple linear regression modeling with global IBDQ score as the dependent factor. Results: Disease type did not predict IBDQ score in the univariate nor in the multivariate analysis. Consequently, statistical analysis was performed in the global group of 354 patients independently of the type of disease. Lower recurrence/year index, longer disease duration, higher level of education, symptom activity, male gender and non-necessity of hospitalization all predict a better HRQOL (p < 0.05). Factors which remained significant (p < 0.05) in the multiple regression modeling were gender, need of hospitalization, symptomatic activity, recurrence/year index and education level. Conclusions: Symptomatic activity and socio-demographic variables such as gender and education are the most important factors involved in the impairment of HRQOL in patients with IBD.

Cystic fibrosis is a hereditary disease well known to paediatricians. Over recent years, its prevalence among the adult population has dramatically increased; thus becoming a disease increasingly seen in adult practice. Cystic fibrosis is a multi-organ disease, with a wide spectrum of clinical manifestations involving many organs. The aim of this article is to review the digestive system manifestations of this disease: the involvement of the gastrointestinal tract, liver, biliary system and pancreas, with a special emphasis on the adult population.

Background Patients with functional gut disorders frequently complain of gas-related symptoms, but the role of intestinal gas in this context is not clear, because intestinal gas homeostasis is incompletely understood. Our aim was to compare the proportion of the gas produced by colonic fermentation that is evacuated per anus and that eliminated via alternative pathways. Methods In 20 healthy subjects, gas evacuated per anus was collected for 4 h after a standard flatulogenic test meal. Paired studies were performed without and with high-rate infusion of exogenous gas (24 mL/min) into the jejunum to wash-out of the gut the endogenous gas produced by bacterial fermentation. The exogenous gas infused was labeled (5% SF6) to calculate the proportion of endogenous gas evacuated. Key Results In the experiments with gaseous wash-out, 1817 ± 139 mL of endogenous gas was produced over the 4-h study period. However, in the experiments without wash-out (basal conditions), 376 ± 43 mL were evacuated, indicating that only 23 ± 3% of the gas produced was finally eliminated per anus, while the rest (77 ± 3%) had been previously eliminated via alternative pathways. Conclusions & Inferences Intestinal gas homeostasis is a highly dynamic process by which a large proportion of the gas produced by bacterial fermentation of meal residues is rapidly absorbed into the blood and/or metabolized by gas-consuming microorganisms, and only a relatively modest proportion is eliminated per anus. These data contribute to clarify the complex dynamics of intestinal gas and may help interpret the pathophysiology of gas-related symptoms.

The aim of this study was to determine the relationship between colonic symptoms, radiological abnormal- ities, and anorectal dysfunction in patients with Chagas disease. We performed a cross-sectional study of untreated patients diagnosed with Chagas disease. All patients were evaluated clinically (by a questionnaire for colonic symptoms based on Rome III criteria) and underwent a barium enema and anorectal manometry. A control group of patients with functional constipation and without Chagas disease was included in the study. Overall, 69 patients were included in the study: 42 patients were asymptomatic and 27 patients had abdominal symptoms according to Rome III criteria. Anorectal manometry showed a higher proportion of abnormalities in symptomatic patients than in asymptomatic ones (73% versus 21%, respectively; P < 0.0001). Megarectum was detected in a similar proportion in the different subgroups regardless of the presence of symptoms or abnormalities in anorectal functions. Among non-Chagas disease patients with functional constipation, 90% had an abnormal anorectal manometry study. Patients with Chagas disease present a high proportion of constipation with dyssynergic defecation in anorectal manometry but a low prevalence of impaired rectoanal inhibitory reflex, although these abnormalities may be nonspecific for Chagas disease. The presence of megarectum is a nonspecific finding.

Background & Aims: The efficacy of hormonal therapy for recurrent bleeding from gastrointestinal angiodysplasia remains uncertain. We investigated the efficacy of long-term estrogen-progestagen therapy in the prevention of rebleeding from gastrointestinal angiodysplasia. Methods: Seventy-two noncirrhotic patients bleeding from gastrointestinal angiodysplasia confirmed by endoscopy or angiography were randomized to receive in double-blind conditions treatment with ethinylestradiol (0.01 mg) plus norethisterone (2 mg) (1 tablet/d), or placebo (1 tablet/d) for a minimum period of 1 year (range: 1-2 years). Results: Four patients could not be assessed because they did not attend the first follow-up visit. Failure of treatment occurred in 13 of 33 (39%) patients in the treatment group and in 16 of 35 (46%) patients in the placebo group ( P = NS). No significant differences between groups were found according to number of bleeding episodes (0.7 ± 1.0 vs. 0.9 ± 1.5) and transfusional requirements (0.9 ± 1.9 vs. 0.7 ± 1.5 units). Treatment received was not an independent predictor for rebleeding prevention in the multivariate regression analysis. Severe adverse events (2 vs. 1) and mortality (0 vs. 1 patient, respectively) were similar between the treatment and placebo groups. Conclusions: Continuous estrogen-progestagen treatment is not useful in the prevention of rebleeding from gastrointestinal angiodysplasia. GASTROENTEROLOGY 2001;121:1073-1079

BACKGROUND AND AIMS—Altered intestinal permeability is a key pathogenetic factor of idiopathic bowel inflammation. We investigated in the rat if changes in the composition of the bowel flora can alter colonic permeability. METHODS—A colonic segment was surgically excluded from faecal transit and brought out as a loop to the abdominal wall through two colostomies. The loop was used for colonisation with specific bacterial strains after eradication of the native flora with antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and mannitol (molecular weight 182) was measured in rats recolonised with a single bacterial strain from rat colonic origin, and in control rats whose colonic loop was kept free of bacteria by antibiotics. Actual colonisation was confirmed by culture of segment effluents. RESULTS—Colonisation with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen to blood clearance of mannitol. Colonisation with Lactobacillus brevis had the opposite effect and reduced permeability to mannitol. Bacteroides fragilis did not induce significant changes. Permeability to dextran was not altered by any of the strains tested. CONCLUSIONS—Certain commensal bacteria can modify colonic wall permeability to luminal substances. Keywords: bacteria; dextran; intestinal permeability; mannitol; rat

Up to one fifth of celiac disease patients are diagnosed after the age of 60. The hydrogen breath test with d-xylose as substrate (xylose-BT) has proved useful for the diagnosis of adult celiac disease. Our aim was to determine the potential influence of age-related intestinal mucosal changes on the reliability of this test. We reviewed the results of the xylose-BT in 50 patients with clinical celiac disease in whom the diagnosis was confirmed by histology. A control group of 53 patients with various diarrheal disorders and without jejunal mucosal atrophy at biopsy was similarly studied. Both celiac patients and controls were divided into adults (age ≤60 years) and elderly (age >60 years). Seven of the 50 celiacs and 8 of the 53 controls were in the elderly category (P = NS). In the celiac disease group, no differences were observed between the elderly and adult patient subgroups for basal H2 excretion (22.4 ± 42 vs 9.7 ± 11 ppm), delta increase (56 ± 43 vs 53 ± 36 ppm), or area under the curve (7452 ± 5546 vs 6739 ± 5951 ppm × min). The false negative rate was similar for celiac adult (7/43) and elderly (2/7, P = ns) patients. Sensitivity of the xylose-BT was 0.83 in adults and 0.71 in the elderly, and specificity 0.51 in adults and 0.50 in the elderly. In conclusion, the results of the xylose-BT in celiac patients are not influenced by age. The xylose-BT is as valuable a tool for the screening of celiac disease in the elderly as it is in younger patients.

Background—Patients with irritable bowel syndrome (IBS) frequently complain of excessive gas but their fasting volume of intestinal gas is apparently normal. We hypothesised that the pathophysiological mechanism involved may be impairment of intestinal gas transit. Aim—To investigate intestinal gas transit and tolerance in IBS patients compared with healthy subjects. Methods—A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the jejunum of 20 patients with IBS and 20 healthy controls at 12 ml/min for four hours. Gas evacuation, initially flatus from the anus (two hours) and then intrarectally (two hours), was continuously recorded. Symptom perception (0-6 scale) and abdominal distension were measured at 10 minute intervals. Results—After two hours of external gas (flatus) collection, 18 of 20 IBS patients had developed gas retention (>400 ml), increased gastrointestinal symptoms (score >3), or abdominal distension (>3 mm girth increment) compared with only four of 20 control subjects. During intrarectal gas collection, 13 of 17 patients still exhibited abnormal responses. Conclusion—A large proportion of patients with IBS can be shown to have impaired transit and tolerance of intestinal gas loads. This anomaly may represent a possible mechanism of IBS symptoms, specifically pain and bloating. Keywords: intestinal gas; irritable bowel syndrome; intestinal transit; visceral sensitivity; abdominal distension

The diagnosis of colonic angiodysplasia is often challenging and relies on endoscopy or catheter angiography. We investigated whether computed tomographic angiography (CTA) contributes to the diagnosis of colonic angiodysplasia.Twenty-eight patients with suspected bleeding from colonic angiodysplasia were prospectively evaluated. Gastrointestinal bleeding was investigated by colonoscopy plus visceral angiography and by CTA. The level of agreement between CTA and the former procedures was determined.CTA images of diagnostic quality were obtained in 26 patients. Eighteen patients were diagnosed with colonic angiodysplasia by colonoscopy plus visceral angiography, and 14 by CTA (kappa = 0.68; P0.001). Sensitivity, specificity, and positive predictive values of CTA for detection of colonic angiodysplasia were 70%, 100%, and 100%, respectively. CTA signs including accumulation of vessels in the colonic wall, early filling vein, and supplying enlarged artery were present in 55%, 50%, and 22% of cases, respectively. None of these signs were present in the 8 patients with obscure gastrointestinal bleeding and negative diagnostic investigation of the digestive tract.CTA is a sensitive, specific, well-tolerated, and minimally invasive tool for the diagnosis of colonic angiodysplasia.

Background Successful eradication ofHelicobacter pyloriinfection clearly modifies the natural history of peptic ulcer disease and prevents further recurrences of duodenal and gastric ulcers. However, there are few prospective studies about actual rates of rebleeding afterH. pylorieradication, a highly relevant aspect of management as re-infection, relapse of ulcer disease for other reasons (i.e. antiinflammatory agents) or idiopathic ulcers unrelated toH. pylorimay develop and cause further bleeding episodes. Objective To determine the incidence of bleeding episodes after eradication ofH. pyloriinfection in patients who had bled from anH. pylori-positive peptic ulcer. Participants and interventions H. pylori-positive patients who bled from a gastric or duodenal ulcer were treated with appropriate triple and/or quadruple therapy.H. pylorieradication was confirmed by urea breath test 4 weeks after treatment. Patients received no further treatment but were followed clinically and additional urea breath tests were performed every 6 months. Endoscopy with antral and corpus biopsies and urea breath test were repeated as soon as patients manifested any dyspeptic symptoms that might signal recurrence. Results A total of 103 patients with bleeding duodenal ulcer were included in the study;H. pyloriwas successfully eradicated in 93 of these patients, who were followed for a median interval of 27 months. The yearly re-infection rate was calculated to be 0.6%. There were no instances of rebleeding in any patients during the follow-up period. Conclusions Even after prolonged follow-up, successfulH. pylorieradication prevents rebleeding.Eur J Gastroenterol Hepatol12:733-737

Several major management guidelines on dyspepsia (upper abdominal pain or discomfort) recommend an initial ‘test-and-treat’ policy (non-invasive Helicobacter pylori testing with eradication therapy if positive) in uninvestigated patients less than about 45 years old. However, the evidence that this is the optimal strategy is limited. Data from the few available randomized controlled trials provide evidence that this policy improves symptomatology more than a ‘test-and-endoscope’ approach (in which only H. pylori-positive patients undergo early endoscopy) in those with upper abdominal pain. The balance of cost-effectiveness data from clinical studies and decision analyses indicates that both ‘test-and-treat’ and empirical anti-secretory therapy approaches are more cost-effective than the ‘test-and-endoscope’ strategy. Therefore, given concerns about the safety of widespread H. pylori eradication, initial empirical anti-secretory therapy may be a cost-effective alternative to the ‘test-and-treat’ policy in some younger dyspeptic patients. The effectiveness of such an empirical approach might well be improved by symptom-guided therapy and there is growing evidence that the predominant dyspeptic symptom may provide this guide. The diagnostic, therapeutic and economic utility of this approach merits further clinical investigation.

Achalasia presenting as acute airway obstruction is an uncommon complication. We report the case of an elderly woman with previously undiagnosed achalasia who presented with acute respiratory distress due to megaesophagus. Emergency endotracheal intubation and insertion of a catheter into the esophagus, with continuous aspiration was required. Upon introduction of the esophageal catheter an abruptand audible air decompression occurred, with marked improvement of the clinical picture. Endoscopic injection of botulinum toxin was chosen as the definitive treatment with good clinical result. The pathophysiology of the phenomenon of esophageal blowing in achalasia is unclear, but different hypothetical mechanisms have been suggested. One postulated mechanism is an increase in upper esophageal sphincter (UES) residual pressure or abnormal UES relaxation with swallowing in achalasia patients. We reviewed the UES manometric findings in 50 achalasia patients and compared it with measurement performed in 45 healthy controls. We did not find any abnormalities in UES function in any of our achalasia patients group, or in the case under study. An alternative hypothesis postulates that airway compromise in patients with achalasia results from the loss UES belch reflex (abnormal UES relaxation during esophageal air distension), and in fact, an abnormal UES belch reflex was evidenced in our case.

La intencion del tratamiento quirurgico es diferente en la colitis ulcerosa (CU) y en la enfermedad de Crohn (EC). En la CU es mas agresiva y curativa, mientras que en la EC es mas conservadora. Objetivo . Valorar la opinion que el paciente intervenido por enfermedad inflamatoria intestinal tiene de la cirugia a largo plazo y sobre el momento adecuado para su realizacion. Material y metodos . Se han estudiado 50 pacientes (36 con EC y 14 con CU) intervenidos al menos un ano antes. Se evaluaron las caracteristicas clinicas y quirurgicas de los pacientes. Se realizo una entrevista personal y se les pregunto sobre su estado clinico actual, las secuelas posteriores a la cirugia y su opinion sobre la idoneidad del momento de la intervencion. Resultados . La cirugia de la CU consistio en colectomia total en el 85% de los pacientes, siendo urgente en el 43% de ellos. En la EC la intervencion consistio en reseccion intestinal o colonica parcial, practicandose de forma urgente en el 22% de los casos. La aparicion de complicaciones postoperatorias fue mas frecuente en la CU que en la EC (50% frente a 20%; p Conclusiones . La cirugia de la CU tiene una apreciable tasa de complicaciones, pese a lo cual satisface la expectativa de la mayoria de los pacientes al controlar la enfermedad a largo plazo. En la EC el cumplimiento de las expectativas fue inferior al de la CU.

The hydrogen breath test (H2BT) with d-xylose has proven valid in both early recognition and follow-up of intestinal malabsorption. To further evaluate the specificity of the H2BT with d-xylose in the diagnosis of intestinal malabsorption as compared to the conventional urinary d-xylose test, we analyzed the result in 49 patients referred to our unit with a clinical diagnosis of intestinal malabsorption. These patients had an abnormal 25-g d-xylose H2BT but a normal conventional urinary d-xylose test. Jejunal biopsy with Watson capsule was performed in all patients. H&E staining was prepared from each biopsy specimen, and histological changes were classified according to the Marsh criteria. Jejunal biopsy showed mucosal atrophy in 5 patients (10%), hyperplastic lesion in 11 (22.5%), infiltrative lesion in 14 (28.5%), and normal appearance in 19 (39%). G. lamblia infection was additionally diagnosed in two patients. Histological changes were independent of the presence of diarrhea, weight loss, abdominal pain, or anemia. H2 excretion, assessed as increase over baseline and area under the curve, was similarly independent of the histological pattern. In conclusion, performance of a d-xylose H2BT in patients with a normal urinary test reveals a significant number of patients with intestinal mucosal atrophy who might otherwise remain undiagnosed.

Fundamento Investigar la presencia de infeccion colonica por citomegalovirus (CMV) en piezasde colectomia de pacientes con colitis ulcerosa (CU) que han precisado tratamiento quirurgicopor refractariedad al tratamiento medico o complicaciones de la enfermedad. Pacientes y metodos Se incluyen 39 pacientes (26 varones y 13 mujeres) colectomizados porCU refractaria o complicada. Se han analizado las caracteristicas clinicas y farmacologicas quepudieran predisponer a la infeccion por CMV. En todos los casos se practico inmunohistoquimicaespecifica para CMV en cortes obtenidos de bloques parafinados. Resultados La inmunohistoquimica fue positiva para CMV en 7 de los 39 pacientes. Desde1985 hasta 1994 solo hubo un caso de CMV, mientras que de 1995 a 1998 se detectaron 6(p Conclusiones La infeccion por CMV en pacientes con CU de curso complicado destaca tantopor su frecuencia como por su gravedad. En los ultimos anos se aprecia un aumento de la prevalenciade infeccion por CMV, que no parece atribuible a diferencias en el tratamiento inmunodepresorrecibido.

BACKGROUND—Food allergy is a common complaint among patients with a broad spectrum of abdominal and extra-abdominal symptoms that must be distinguished from other more common non-immunological food intolerances. AIMS—To investigate whether human intestinal hypersensitivity reactions are associated with detectable release of inflammatory mediators from activated cells, which may serve as a biological marker of true allergic reactions. PATIENTS/METHODS—In eight patients with food allergy and seven healthy volunteers, a closed-segment perfusion technique was used to investigate the effects of jejunal food challenge on luminal release of tryptase, histamine, prostaglandin D2, eosinophil cationic protein, peroxidase activity, and water flux. RESULTS—Intraluminal administration of food antigens induced a rapid increase in intestinal release of tryptase, histamine, prostaglandin D2, and peroxidase activity (p

This review describes the basis for development of clinical pharmacology models of irritable bowel syndrome (IBS) and presents a critical analysis of current models. IBS is becoming a more circumscribed diagnosis by improved symptom criteria and this is perceived as helpful progress for the development of suitable models. Concepts about the aetiopathogenesis and pathophysiology of IBS are also evolving. Different models have been established to study specific derangements in motor function, visceral reflexes and conscious perception of gut stimuli. The review also focuses on specific examples of drug evaluation using appropriate and validated models.

Esophageal motility is often disturbed in patients with myotonic dystrophy. The esophageal motor derangement pattern and its correlation with esophageal and peripheral motor symptoms is not well defined. Our aims were to evaluate: 1) pharyngo-esophageal motor abnormalities in these patients; 2) the relationship between motor involvement and clinical manifestations; and 3) the correlation between pharyngo-esophageal motility abnormalities and peripheral neuromuscular involvement.We compared data from 18 patients and 18 healthy controls. Neuromuscular affectation was quantified with a five-point muscular disability rating scale. Pharyngo-esophageal symptoms were assessed with a directed questionnaire, whereas motility was evaluated by means of manometry.Myotonic dystrophy patients had diminished pharyngeal contraction amplitude, upper esophageal sphincter basal pressure, and esophageal body contraction amplitude compared with the control group (P0.001). No signs of esophageal myotony were evident. Simultaneous esophageal waves after more than 40% of liquid swallows were found in 80% of patients. No relationship between esophageal manometric alteration and esophageal or peripheral motility symptoms was elicited.In patients with myotonic dystrophy pharyngo-esophageal motility is severely deranged in both amplitude and coordination. These abnormalities may be present even if symptoms referred by the patient or the severity of the disease is not remarkable.

Thrombotic thrombocytopenic purpura (TTP) constitutes a poorly understood multisystemic disease of vascular origin that may involve any organ by thrombotic occlusions of the small vessels. Treatment with plasmapheresis is the best therapeutic option at this present moment. Involvement of the pancreas is a well established feature of this disease, which has generally been interpreted as a consequence of pancreatic vascular compromise. However, there are a few cases in the literature in which the clinical signs of TTP developed well after the clinical and laboratory demonstration of acute pancreatitis (AP). Therefore, the possibility of pancreatic inflammation as a triggering factor of TTP may need to be considered. This cause-effect relationship between AP and TTP remains unclear. We report a patient with chronic pancreatitis presenting with two episodes of TTP, triggered by acute relapses of pancreatitis. TTP may, thus, constitute a hematological complication of AP. We discuss the pathophysiological aspects of this association, along with therapeutical options.

The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.

Background Inhibitory neuromuscular transmission in the human colon is due to nitrergic and purinergic (P2Y1-mediated) inputs. The aim of this study was to determine the mechanisms of neuromuscular transmission in different regions of the human small intestine. Methods Ileal (n = 6) and jejunal (n = 6) samples underwent histological examination and were studied using sharp microelectrodes in smooth muscle cells and conventional muscle bath techniques. Electrical field stimulation (EFS) was used to stimulate inhibitory neurons. Key Results No histological abnormalities were found. Resting membrane potential was −39.7 ± 1.5 and −45.5 ± 2.1 mV in the jejunum and ileum, respectively. Slow waves and spontaneous contractions were recorded at a frequency of about 8–9 and 6–7 cpm in the jejunum and ileum, respectively. In non-adrenergic, non-cholinergic conditions, EFS caused an inhibitory junction potential and mechanical relaxation. Both responses were blocked by tissue incubation with the nitric oxide synthase inhibitor (Nω-nitro-l-arginine 1 mM) and the P2Y1 receptor blocker 2′-deoxy-N6-methyladenosine 3′,5′-bisphosphate tetrasodium salt (MRS2179; 10 μM). Both exogenous addition of sodium nitroprusside (1 μM) and the preferential P2Y1 receptor agonist ADPβS (1 μM) hyperpolarized and relaxed smooth muscle cells. MRS2179 (10 μM) blocked ADPβS-induced responses. Conclusions & Inferences Similar to colon, inhibitory neurotransmission in the human small intestine is mainly mediated by purinergic (via P2Y1 receptors) and nitrergic inhibitory neurotransmission. Similar mechanisms of inhibitory neurotransmission are present in different regions of the human intestine.

Our aim was to investigate in humans the gastrogastric reflexes that regulate gastric tone and their relationship to perception. In nine healthy subjects, liquid distension (in 100-ml steps), warm stimuli (in 3 degrees C increments), and cold stimuli (in 6 degrees C decrements) were randomly applied in the stomach for 3 min at 8-min intervals. Gastric tone was measured as isobaric volume changes of air by a barostat, and perception was scored by a graded (0-6) questionnaire. Liquid accommodation produced an additional expansion of isobaric air maintained by the barostat (51 +/- 13 ml with 100 ml of liquid filling, P < 0.05), but this effect became inconsistent with further filling. An accommodation-like reflex was best evidenced by warm stimulation below the discomfort threshold (58 +/- 13 ml relaxation at 47 +/- 1 degrees C, P < 0.05). By contrast, cooling below discomfort induced a reflex contraction (-62 +/- 22 ml change at 18 +/- 2 degrees C, P < 0.05). In conclusion, gastric tone, i.e., accommodation and contraction, is modulated by a net of reflexes that arise from the proper wall of the stomach below the discomfort threshold.

OBJECTIVE To evaluate the influence of regular smoking on the presentation and clinical course of inflammatory bowel disease. METHODS We performed a case-control study interviewing 160 inflammatory bowel disease patients (63 with Crohn's disease (CD) and 97 with ulcerative colitis (UC)) and 140 first-degree relatives as controls. The risk of developing the disease relative to a smoking habit was calculated as the odds ratio. Furthermore, to evaluate the influence of smoking on the subsequent course of inflammatory bowel disease, we performed a multivariate analysis that included pertinent variables such as the need for surgery, number of hospitalizations and relapses. RESULTS The pattern of smoking in UC patients was different from that in CD patients. In UC there was a significant predominance of non-smokers and ex-smokers (P = 0.02), whereas smoking habits in CD were not different from those in controls. Giving up smoking was a risk factor to develop UC (odds ratio: 3.2, P = 0.02). In UC, non-smokers and specially ex-smokers need surgery more frequently than smokers (P < 0.01). Otherwise the relapse/year index was not influenced by smoking. In CD there was a non-significant association between smoking habits and the various clinical parameters analysed. UC patients who begin smoking after diagnosis of the disease present a significant reduction in the number of recurrences. CONCLUSION Smoking habit significantly affects the presentation and clinical course of UC, whereas in CD, a smoking habit does not have any apparent influence on the disease.

Background Diets rich in fermentable residues increase intestinal gas production. Our aim was to demonstrate the potential effects of diet on gas-related symptoms. Methods The effect of a low-flatulogenic test diet (restricted to foodstuffs low in fermentable residues; n = 15) was compared to that of a balanced control diet (Mediterranean type; n = 15) in 30 patients complaining of flatulence and other abdominal symptoms using a randomized parallel design. The following outcomes were measured daily: number of anal gas evacuations by an event marker, severity of gas-related symptoms by 0–10 scales, and sensation of digestive comfort by a −5 (unpleasant) to +5 (pleasant) scale. Measurements were taken pretreatment for 3 days on their habitual diet and for 7 days during the treatment phase. Key Results No pretreatment differences were detected between patients allocated to the control or test diets. The test diet significantly reduced the number of gas evacuations (by 54 ± 10%; p = 0.002 vs basal diet) whereas the control diet had a lesser effect (reduction by 28 ± 9%; p = 0.059 vs basal diet; p = 0.089 vs test diet). Compared to the control diet, the test diet significantly reduced flatulence (by 48 ± 7% vs 27 ± 8%, respectively; p = 0.018), abdominal distension (by 48 ± 4% vs 22 ± 12%, respectively; p = 0.038), and enhanced digestive well-being (by 149 ± 18% vs 58 ± 22%, respectively; p = 0.006). Conclusions & Inferences In patients with gas-related symptoms, a low-flatulogenic diet produces immediate beneficial effects with digestive, cognitive, and emotive dimensions. The number of gas evacuations is an objective biological marker of response to dietary treatment.

Hydrogen breath tests (H2-BT) are commonly used to diagnose carbohydrate malabsorption. Specifically, the H2-BT with D-xylose has been shown to be as valid as the traditional urinary test for the recognition of intestinal malabsorption. We have now investigated the H2-BT with D-xylose in the follow-up of patients with celiac disease. Seventeen patients with celiac disease established clinically and confirmed by jejunal biopsy were studied. H2-BT was performed before and after treatment with a gluten-free diet for at least five months. Alveolar breath samples were obtained before administering orally 25 g of D-xylose and thereafter at 30 min intervals for 5 hr. Samples were analyzed for H2 by chromatography. Simultaneously, the 5-hr urinary excretion of D-xylose was determined by colorimetry. Gluten removal significantly decreased the H2 delta change (from 56.5 +/- 5.9 ppm to 32.2 +/- 8.8, P < 0.05). A similar decrease was observed in the area under the curve (P < 0.05). Conversely, urinary D-xylose excretion increased significantly (P < 0.05). Eleven of the 17 celiacs clinically improved after treatment. The H2-BT normalized in every patient who entered remission on the gluten-free diet, whereas the urinary D-xylose excretion remained abnormal in six of them. In the six nonresponder patients the H2-BT remained high in five, whereas urinary D-xylose excretion paradoxically normalized in 2. We conclude that H2-BT with D-xylose is a useful and practical test for the follow-up of celiac disease and is simpler and more reliable than the urinary D-xylose test.