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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

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 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.

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.

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.

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—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

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

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

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.

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.

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.

Scarce data suggest that cholecystectomy may alter bowel habit. The aim of this study was to determine whether cholecystectomy modifies gut transit.Five experimental groups were studied: 29 patients with uncomplicated gallstones before and 1 month after elective cholecystectomy, 22 patients 4 years after elective cholecystectomy, 14 patients with postcholecystectomy diarrhea, 5 patients with acute infectious diarrhea (disease controls), and 13 patients before and 1 month after other elective surgery (surgical controls). All participants underwent measurement of colonic transit by a modified radiopaque pellet method and orocecal transit by the standard lactulose breath H2 test.One month postoperatively, cholecystectomy had substantially accelerated total colonic transit (51 +/- 5 hours before vs. 38 +/- 5 hours after; P0.05) and delayed slightly orocecal transit (80 +/- 4 minutes before vs. 103 +/- 8 minutes after; P = 0.05). Similar colonic and orocecal transit times were measured 4 years after cholecystectomy (40 +/- 4 hours and 105 +/- 8 minutes, respectively). Colonic transit times in patients with the postcholecystectomy diarrhea syndrome were accelerated as much as in patients with infectious diarrhea, who served as controls (19 +/- 3 hours and 15 +/- 4 hours, respectively). Surgery per se had no effect on gut transit.Cholecystectomy shortens gut transit by accelerating colonic passage. These sequelae develop early and persist at least 4 years after cholecystectomy. The postcholecystectomy diarrhea syndrome probably represents a magnification of the above colonic sequelae.

AIM--To measure the intracolonic release of nitric oxide end products (nitrates plus nitrites) and eicosanoids in response to intraluminal irritation with deoxycholic acid (DCA). PATIENTS--Seven patients with irritable bowel syndrome. METHODS--The left colon was perfused with a solution with or without 3 mM deoxycholic acid. Aspirates were assayed for eicosanoids by specific radioimmuno-assay, and for nitrates plus nitrites by the Griess reaction. To confirm that stimulated colonic mucosa can produce nitric oxide (NO), ancillary studies were performed in vitro using samples of normal mucosa obtained from five surgically resected colons. Samples were incubated for 30 minutes in Kreb's solution, 3 mM DCA or DCA with 1 mM L-nitro-arginine-methyl-ester (L-NAME) to inhibit the NO synthase. Finally, NO synthase activity was measured in five samples of human colonic mucosa. RESULTS--Intracolonic release of nitrates plus nitrites was basally undetectable in six of seven patients. Bile acid considerably increased the release of prostaglandin E2 and nitrates plus nitrites (p < 0.01). By contrast, no increase in thromboxane and leukotriene was seen. In vitro mucosal incubation with DCA increased the production of NO synthase products, which was blocked by L-NAME. Activity of Ca+2 independent NO synthase was detectable in four of five samples of human colonic mucosa. CONCLUSION--The human colonic mucosa responds to bile acid induced irritation by a surge in NO generation via NO synthase.

BACKGROUND/OBJECTIVES: The vitamin E derivative, alpha-tocopheryl acetate, is often included in formulations used in enteral nutrition. In this respect, we compared alpha-tocopherol and alpha-tocopheryl acetate absorption under 'maldigestion' conditions, such as occurring during enteral tube feeding, using differentially labeled RRR-[5,7-methyl-(21-16)]-alpha-tocopherol and RRR-[5-methyl-H-2(3)]-alpha-tocopheryl acetate allowing direct comparison between free and esterified forms. SUBJECTS/METHODS: The two derivatives were given together in a single dose to six volunteers directly into the jejunum using a double-balloon perfusion system. Perfusion lasted for 1 h, and the collected blood and effluent samples were analyzed by liquid chromatography-mass spectrometry. RESULTS: In the isolated 20-cm length of exposed jejunum, on average similar to 6% of the two vitamin E forms were absorbed >1 h based on subtraction of effluent from influent. There was substantial difference in the absolute absorbed quantity between individuals, but no significant differences were observed in the absorption between the two labeled forms as assessed in the plasma. H-2(3)-alpha-tocopherol was not present in the influent, but appeared in the effluent, indicating that the acetylated form of vitamin E is cleaved by brush border enzymes in the small intestine. CONCLUSIONS: This study shows that even in the absence of digestive enzymes and bile salts, the appropriately solubilized acetylated form of alpha-tocopherol exhibits the same bioavailability as free alpha-tocopherol. This suggests that both forms can be absorbed equally under maldigestion conditions such as present clinically during enteral tube feeding. European Journal of Clinical Nutrition (2013) 67, 202-206; doi:10.1038/ejcn.2012.183; published online 5 December 2012

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.

1. Tumour necrosis factor is a proinflammatory macrophage-derived polypeptide cytokine. Its participation in disease processes has been usually inferred from data obtained from experiments in vitro or from measurements of its plasma circulating levels. To investigate its role in chronic ulcerative colitis, we have quantified in vivo the steady-state release of tumour necrosis factor into the colonic lumen. 2. We studied 19 patients with untreated active ulcerative colitis and seven patients with irritable bowel syndrome as controls. A group of seven patients with active ulcerative colitis were studied before and after 4 weeks on treatment with oral 5-aminosalicylic acid. By means of an intracolonic double-lumen perfusion tube, an isotonic solution was continuously infused 50 cm from the anal verge at a rate of 5 ml/min, and was recovered 30 cm distally by siphonage. Effluents were assayed for tumour necrosis factor by a specific e.l.i.s.a. and for prostaglandin E2 and leukotriene B4 by specific r.i.a.s. 3. The intracolonic release of tumour necrosis factor was undetectable in patients with irritable bowel syndrome, whereas measurable release occurred in 15 out of 19 patients with active ulcerative colitis (P < 0.01). Prostaglandin E2 and leukotriene B4 release were also increased in active ulcerative colitis by comparison with irritable bowel syndrome (P < 0.01). Five out of seven patients with colitis improved with 5-aminosalicylic acid treatment, and tumour necrosis factor release became undetectable or decreased markedly (P < 0.05 compared with before treatment). However, tumour necrosis factor release remained high in the non-responder patients. 4. These findings indicate that intracolonic immunoreactive tumour necrosis factor release is enhanced in active chronic ulcerative colitis, becoming undetectable when mucosal lesions are healed. These results suggest that the luminal release of tumour necrosis factor may serve as an objective index of inflammatory activity in patients with chronic ulcerative colitis.

OBJECTIVES Some patients with chronic pancreatitis present recurrent flare-ups of pancreatitis and/or unrelenting pain. Current management is mostly limited to analgesics and surgery. We reasoned that anti-inflammatory radiotherapy, which has proven useful to alleviate other painful inflammatory painful disorders, might prove valuable for severely symptomatic patients with chronic pancreatitis. METHODS We prospectively studied the efficacy of single-dose anti-inflammatory radiotherapy in 15 consecutive patients with chronic pancreatitis who fulfilled the following criteria: either two flare-ups of pancreatitis in the previous 6 months and/or continuous pain for more than 3 months. Treatment consisted of a single radiation dose of 8 Gy to the pancreas. Exocrine function (fecal elastase), endocrine function (c peptide), quality of life (EuroQol questionnaire), and clinical outcome were assessed before and after radiation. Response was defined as no further pain or flare-ups of pancreatitis. RESULTS During follow-up (median: 39 months; range: 4-72 months), 12 patients had no further pain or flare-ups. One patient required a second radiation dose 1 year after the initial treatment, but he has remained well ever since (50 months). Two other patients did not respond to radiotherapy. After radiotherapy either exocrine or endocrine pancreatic function, or both, deteriorated in three patients. Patients who responded to treatment (13/15) gained 4-20 kg in body weight during follow-up (median 4 kg) and EuroQol improved significantly from 0.58 to 0.86 (P

Summary Background Although erosive gastro-oesophageal reflux disease (GERD) is a highly prevalent condition, there is no specific, valid, reliable and sensitive questionnaire that allows evaluating treatment-induced changes in health-related quality of life (HRQoL). Aim To design a self-administered questionnaire, the GERD Analyzer (GERDyzer), for use in clinical studies. Methods The GERDyzer comprises 10 dimensions each illustrated by pictogram-like drawings, simplifying communication with the patients. Self-assessment is performed by 100 mm Visual Analogue Scales. For validation, a 5-week clinical trial involving 395 patients (per-protocol) with oesophagitis was conducted. Patients were treated with pantoprazole (40 mg o.d.) for 28 days. Psychometric analyses included internal consistency, test–retest reliability, responsiveness and construct validity. Results Factor analysis showed consistency of the dimensions and no reduction was necessary. Validation of GERDyzer indicated high internal consistency (Cronbach’s α = 0.95) and test–retest reliability (intraclass correlation coefficient =0.91). Responsiveness of the total score expressed by nonparametric effect size was 1.38. Comparison of scores with other questionnaires resulted in logical correlation levels depending on the respected concepts measured. Conclusions GERDyzer proved to be highly valid, reproducible and responsive. It allows reliably assessing treatment-induced changes in HRQoL in erosive GERD.

Chronic (obesity) and acute intraabdominal pressure increases appear to favor gastroesophageal reflux, but the mechanism is not completely understood. We hypothesized that it could be due to an alteration in the resistance gradient between the stomach and the gastroesophageal junction, even increasing intragastric resistance above resistance at the gastroesophageal junction. Hence, we used a pneumatic resistometer to measure gastric and gastroesophageal resistance to flow in 11 lean healthy controls and eight morbidly obese individuals without gastroesophageal reflux disease. Resistance was quantified at rest and during acute intraabdominal pressure increases, both in the recumbent and sitting positions. We found that gastroesophageal junction resistance was higher than gastric resistance in lean as well as in obese subjects (P less than 0.001). In obese individuals both gastric and gastroesophageal junction resistance were increased (P less than 0.001), thus a normal gastric-gastroesophageal junction resistance gradient was maintained. Body position did not modify resistance. Acute increases in intraabdominal pressure decreased the gastric-gastroesophageal junction resistance gradient similarly in obese and lean subjects. We conclude that obesity by itself does not appear to predispose to gastroesophageal reflux, but it creates intraabdominal conditions that may favor reflux whenever the gastroesophageal barrier becomes weakened.

Using an original technique, we demonstrated a modulation of intestinal tonic muscular activity (intestinal tone) by intestino-intestinal reflexes. In 11 healthy volunteers we quantitated intestinal tone variations as changes in the air volume within a flaccid bag (12 cm long) located in the proximal jejunum and maintained at a constant pressure by an electronic barostat. Validation studies with glucagon showed significant intestinal relaxation (117 +/- 10% delta vol; P less than 0.05). In six healthy volunteers, graded balloon distensions (1 min duration at 10-min intervals in 8-ml stepwise increments) were randomly performed 8 cm orad, 8 cm caudad, and 20 cm caudad to the bag of the barostat. Perception was scored (0-6) by a questionnaire. Distensions at the three sites induced similar perception; at the threshold for discomfort (score greater than or equal to 5) distension also induced intestinal relaxatory responses (43 +/- 10%, 34 +/- 5%, and 32 +/- 4% delta vol from orad to caudad, respectively; P less than 0.05 for all). However, while unperceived orad distensions (13 +/- 2 ml) induced reflex relaxation (21 +/- 6% delta vol; P less than 0.05), 20-cm-caudad distensions at higher levels (16 +/- 2 ml, 2.7 +/- 0.5 perception score; P less than 0.05) did not (1 +/- 7% delta vol). This dissociation between perception and intestinal tone reflexes suggests that both responses to intestinal distension are mediated by specific mechanisms.

AIM: To evaluate the factors involved in the impairment of health-related quality of life (HRQOL) in patients with celiac disease. METHODS: A multicenter, cross-sectional prospective study was performed in patients with celiac disease who completed two HRQOL questionnaires: the gastrointestinal quality of life index (GIQLI) and the EuroQol-5D (EQ). RESULTS: Three hundred and forty patients (163 controlled with a gluten-free diet, and 177 newly diagnosed with a normal diet) were included. The GIQLI score was significantly better in patients on a gluten-free diet (GFD) than in non-treated patients on their usual diet, both in terms of the overall score (3.3 vs 2.7, respectively; P < 0.001), as well as on the individual questionnaire dimensions. Both the preference value of the EQ as the visual analogue scale were significantly better in treated than in non-treated patients (0.93 vs 0.72, P < 0.001 and 80 vs 70, P < 0.001, respectively). Variables significantly associated with a worse HRQOL score were female gender, failure to adhere to a GFD, and symptomatic status. CONCLUSION: In untreated celiac disease, the most important factors that influence patient perception of health are the presence of symptoms and a normal diet. HRQOL improves to levels similar to those described in the general population in celiac disease patients well controlled with a GFD.

Intestinal sensitivity can be tested using transmucosal electrical nerve stimulation. The aim of this study was to establish the stimulus characteristics that determine perception. In six healthy subjects constant current electrical stimuli were applied via an intrajejunal bipolar electrode while measuring perception. Intensity–response tests with stimuli trains of various frequencies (5 and 100 Hz) and pulse durations (50 and 1000 μs) were performed. All stimuli within the broad range tested induced similar-type abdominal sensations, but the intensity of the stimuli to produce perception differed depending on both pulse duration and frequency. A 20-fold increase in pulse duration decreased the intensity of perceived stimuli by a factor of 0.34 ± 0.04 (P

Crohn's disease (CD) has a negative impact on patients' perception of health. Several factors, such as disease activity, influence HRQOL impairment. However, the effect of the phenotypic CD characteristics recognized in the Vienna classification on health-related quality of life (HRQoL) remains unknown.HRQOL was measured in CD patients using three questionnaires: the Spanish version of the Inflammatory Bowel Disease Questionnaire (IBDQ-36), the Psychological General Well-Being Index (PGWBI), and the EuroQol.One hundred ninety-eight CD patients were included. Scores for the IBDQ-36, PGWBI, and EuroQol dimensions did not differ according to age at diagnosis (177 patients under 40 yr and 21 over 40 yr), disease location (53 in terminal ileum, 62 in colon, 72 in ileocolon, and 11 in upper gastrointestinal tract) or disease behavior (99 nonstricturing-nonpenetrating, 32 stricturing, and 67 penetrating). Multivariate analysis identified as significant independent variables for worse HRQoL: female sex (t: -3.70), higher number of relapses per year (t: -2.71), and worse clinical disease activity (t: -7.82). None of the three Vienna variables reached statistical significance.HRQoL impairment in CD patients is independent of the clinical variables established in the Vienna classification for phenotypic type of disease.

Background: the widespread of serologic diagnosis for celiac disease has brought about an epidemiologic shift. Little up-to-date information is available on relevant epidemiologic issues regarding diagnosis, information, and therapy. Objective: to examine forms of presentation, diagnostic difficulties, follow-up, information sources, and treatment-related issues regarding celiac disease. Method: a cross-sectional observational study using a self-completed questionnaire. Results: seventy-three adult patients were included; 15.0% of cases were diagnosed over 60 years of age. Most were non-smokers (91.8%). The rate of first-degree relatives with celiac sprue was 10.9%. The disease had a classic presentation in only 54.7% of cases. A functional gastrointestinal disorder was initially suspected in 42.4% of patients. Diet adherence is adequate, with unintentional lack of compliance in 15.5% of patients. Diet results in absent or improved symptoms in virtually all patients, but most of them consider compliance a challenge. Forty percent had difficulty finding gluten-free food, and 50.8% had problems in labelling recognition. Conclusions: celiac disease presents at any age, has a great variety of manifestations, and responds very well to gluten-free diet. It is crucial that patients be highly motivated and informed, and that they know for certain which foods and manufactured products are to be to used. Therefore, adequate control will result from coordination and cooperation regarding all resources involved, including medical care, and information provided by associations and other sources such as the Web.

Background: Patients with abdominal bloating and distension exhibit impaired transit of intestinal gas which may lead to excessive gas retention and symptoms. Furthermore, we have previously shown that intestinal gas transit is normally accelerated by rectal distension. We hypothesise that in patients with functional bloating this modulatory mechanism fails and impairs gas transit. Methods: In 12 healthy subjects and eight patients with abdominal bloating we compared, by paired studies, the effect of rectal versus sham distension on intestinal gas transit. Gas was infused into the jejunum (12 ml/min) for three hours with simultaneous perfusion of lipids into the duodenum (Intralipid 1 kcal/min) while measuring evacuation of gas per rectum. Results: In healthy subjects, duodenal lipid infusion produced gas retention (409 (68) ml) which was prevented by rectal distension (90 (90) ml; p v sham distension). In contrast, rectal distension in patients with abdominal bloating failed to reduce lipid induced gas retention (771 (217) ml retention during rectal distension v 730 (183) ml during sham distension; NS; p v healthy controls for both). Conclusion: Failure of distension related reflexes impairs intestinal gas propulsion and clearance in patients with abdominal bloating.

Introduction: chronic conditions modify perceived health in affected individuals. For this reason celiac disease, being a chronic condition, may impair health-related quality of life (HRQOL). Objective: to analyze the impact of celiac disease in affected individuals. Method: observational, cross-sectional, prospective study in patients with celiac disease by administering two HRQOL questionnaires: EuroQol-5D and GastroIntestinal Quality of Life (GIQLI). Results: 54 stable patients on a gluten-free diet for a median 60 months, and 9 newly diagnosed individuals still on their usual diet were included. Overall GIQLI score was significantly higher, meaning a better HRQOL, in treated celiac patients versus pre-treated celiac patients (3.1 [2.7-3.5] vs. 2.4 [2.1-2.6], p < 0.01). Similarly, EuroQol's health status preference value was also significantly better in treated patients (0.87[0.8-1.0] vs. 0.7 [0.5-0.8], p < 0.01). EuroQol's visual analogic scale had also better scores, representing a better perceived health, among treated patients (80.0 [70.0-90.0] vs. 65.0 [40.0-71.0], p < 0.05). In comparison to EuroQol-5D scores among the healthy Spanish population, values obtained for celiac patients under treatment are similar to those seen in the general population. Conclusions: celiac disease impairs perceived health in affected individuals, which improves and reaches results similar to those in the general population when on a gluten-free diet.

OBJECTIVES The hydrogen (H2) breath test is widely used in the assessment of carbohydrate malabsorption. Severe exocrine pancreatic insufficiency markedly diminishes pancreatic amylase production and results in malabsorption of complex carbohydrates. Thus, the H2 breath test with low-dose rice flour starch was tested to determine its value in detecting exocrine pancreatic insufficiency by comparison with a direct measurement of pancreatic function. METHODS Ten patients with clinically suspected pancreatic insufficiency confirmed with a duodenal perfusion technique and measurement of trypsin and lipase output after cerulein stimulation were included. An H2-rice flour breath test was performed by orally administering 30 g of rice flour. End-alveolar breath samples were obtained before rice load and at 30-minute intervals thereafter for the next 5 hours. RESULTS The results are expressed as median (percentile 25-75). Patients included 8 men and 2 women with moderate to severe exocrine pancreatic insufficiency due to chronic pancreatitis, pancreatectomy, or cystic fibrosis. Stimulated duodenal output of lipase and trypsin was abnormally low in all patients (median release, 1.7; range, 0.5-4.5 and 0.8, range, 0.1-11.3 KU/h, respectively). Basal H2 excretion was 9 ppm (range, 7-17) and delta increase over basal H2 excretion was 4 ppm (range, 1-6). Correlation between H2-rice breath test and basal or stimulated duodenal output of lipase and trypsin was not significant. CONCLUSION In exocrine pancreatic insufficiency, an oral load of 30 g rice flour slightly raises H2 excretion in breath. This increase is not useful for detecting pancreatic insufficiency due to poor sensitivity and because it is influenced by extrapancreatic factors such as small bowel bacterial overgrowth.

Questionnaires for measuring quality of life in patients with inflammatory bowel disease usually include a large number of items and are time-consuming for both administration and interpretation. Our aim was to elaborate and validate a short quality-of-life questionnaire with the most representative items from the Spanish version of the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ-36) using the Rasch analysis. The responses to 311 IBDQ-36 questionnaires from 167 patients with ulcerative colitis (UC) and 144 with Crohn's disease (CD) were analyzed. IBDQ-36 was shortened with successive Rasch analyses until all the remaining items showed acceptable separation and goodness-of-fit properties. Validation of the short questionnaire was studied in a new group of 125 patients by determining its validity and reliability. A 9-item short questionnaire was obtained (IBDQ-9). Its correlation with IBDQ-36 was excellent (r = 0.91). Correlation between IBDQ-9 and clinical indices of activity was statistically significant in UC (r = 0.70) and CD (r= 0.70). IBDQ-9 score discriminates adequately between patients in clinical remission or relapse (P < 0.01). Sensitivity to change was determined in 14 patients who improved clinically, showing significant IBDQ-9 changes between both determinations (P < 0.01), with an effect size of -2.67 in UC and -5.29 in CD. IBDQ-9 was also homogeneous, with a Cronbach's alpha of 0.95 in UC and 0.91 in CD. In 35-clinically stable patients, test-retest reliability was good, with a statistically-significant correlation between both questionnaires (r = 0.76 in UC and 0.86 in CD, P < 0.01) and an intraclass correlation coefficient of 0.82 in UC and 0.84 in CD. In conclusion, a short and valid questionnaire to measure quality of life in patients with inflammatory bowel disease was obtained using a new measurement model. Its use should facilitate comprehension of the impact of inflammatory bowel disease.

Several indices evaluate disease activity in ulcerative colitis, but most have drawbacks to their application (invasiveness, complexity, or lack of specificity), and discrepancies between them are frequent. Assuming that desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa, we hypothesized that fecal excretion of human DNA is an index of mucosal inflammation and damage. The aim of our study was to determine whether excretion of human DNA is useful in the evaluation of disease activity in ulcerative colitis.Thirty-one controls and 36 ulcerative colitis patients were included. Ulcerative colitis patients and controls underwent colonoscopic examination after preparation by gut lavage with polyethylene-glycol electrolyte solution. In patients, disease activity was established using the clinical index of Rachmilewitz and an endoscopic score. Feces and gut lavage fluid were obtained and DNA levels were measured by quantitative polymerase chain reaction of the human beta-globin gene.Fecal DNA excretion correlated with the clinical index (r = 0.59, P0.05) and the endoscopic score (r = 0.76, P0.01). Gut lavage fluid DNA levels also correlated with clinical and endoscopic activity scores (r = 0.41 and 0.51, respectively, P0.05). Fecal DNA excretion was significantly higher in patients with endoscopically or clinically active disease than in controls or patients in remission. Fecal DNA excretion discriminates between endoscopically active disease and remission (sensitivity 0.67, specificity 1.00, P0.01).Excretion of human DNA in feces, as an expression of cellular desquamation, is a novel noninvasive technique to objectively assess disease activity in ulcerative colitis.

Introduction: corticoid administration is the usual treatment of Crohn' disease (CD) and ulcerative colitis (UC) attacks. How-ever, information available on response rates and their predictive factors is scarce. Objective: to establish response to steroidal treatment in an homogeneous group of patients with CD or UC during their first admission to hospital. Methods: restrospective analysis of 86 patients who received systemic steroidal treatment for a severe flare-up during their first hospital admission between 1995 and 2000. Patients were treated per protocol with fluid therapy, absolute diet, IV 6-methyl-prednisolone 1 mg/kg/day, and enoxaparin at prophylactic doses. Clinical response at 30 days was considered good in case of complete remission, and poor in case of partial or absent remission. Univariate and multivariate analyses according to non-parametric statistics were performed for sociodemographic and biologic variables. Results: 45 patients with CD and 41 with UC were included. Good response rates were 64.4% for CD and 60.9% for UC. The univariate analysis showed that patients with good response have shorter evolution times and fewer previous flare-ups (p < 0.05) regarding CD. However, the multivariate analysis showed that none of the analyzed variables had predictive value. Conclusion: the response rate of severe inflammatory bowel disease attacks to corticoids is around 60% in CD and UC. Data resulting from the current study cannot predict which patients will ultimately respond to therapy.

Inflammatory bowel disease impairs health-related quality of life. Therefore, it is very important to develop adequate instruments to measure the disease impact, but these instruments need to be practical as well as accurate. Our aim was to determine whether a short questionnaire obtained from the reduction of the 36-item version of the inflammatory bowel disease questionnaire (IBDQ-36) accurately reflects the impact of clinical and endoscopic activity on health-related quality of life.To this purpose the original IBDQ-36 and a reduced version, composed of only 9 items (IBDQ-9), were administered to 68 patients with inflammatory bowel disease. Disease activity was established by standard clinical activity indices (Rachmilewitz for ulcerative colitis (UC) and Harvey-Bradshaw for Crohn's disease (CD)) and by information gathered at colonoscopy.In UC patients the Spearman's correlation coefficients between IBDQ-9 and clinical and colonoscopic indices were statistically significant (-0.67 and -0.70, respectively, p0.01) and similar to those obtained with IBDQ-36 (-0.61 and -0.67). In CD patients IBDQ-9 also correlated well with the clinical index (-0.59, p0.05) but less with the colonoscopic index (-0.30, p= 0.1). In CD patients, the correlation of the IBDQ-36 with clinical and colonoscopic indices gave similar results to the IBDQ-9 (-0.58 and -0.21, respectively). The IBDQ-9 power to discriminate between clinical relapse and remission was statistically significant (p0.01) both for UC (55 (48-57) vs 69 (63-75) and CD (58 (51-63) vs 69 (64-83)) patients. Similar results were obtained for conoloscopic indices of endoscopic relapse and remission (56 (52-65) vs 70 (66-77) in UC and 58 (52-63) vs 68 (62-73) in CD).Quality of life impairment produced by relapses of inflammatory bowel disease can be reliably assessed with a short questionnaire, with considerable savings in time and expense.

Backgrounds and aim: an item to consider in analyzing a healthcare model for a population group suffering from chronic disease is necessary health-care resources, their use, and their rating by endusers. Regarding inflammatory bowel disease (IBD), healthcare resources used by patients are numerous and varied, and yet they have been never assessed. Design: an anonymous self-rated questionnaire has been developed with 24 basic questions on overall disease, who is monitoring the patient, how are visits scheduled, need for urgent care, patient view on how control may be improved, etc. This questionnaire was sent to 393 patients who were asked to fill it out and then return it by mail. Results: two hundred and thirty-seven patients returned a filled-out questionnaire. Most patients were followed up in a hospital, and only 8.8% were being monitored by a general practitioner or area specialist. Ninety-two percent of patients reported visits were routinely scheduled irrespective of clinical status, and 79.6% of patients reported having occasionally presented to an emergency department, because of not knowing what to do or due to having no other resources available in 25.2% of times. This entails that 38% of visits to an emergency unit may be prevented with a better understanding of disease or by means of a phone call. Thirty percent of patients reported that current healthcare is inadequate in terms of contents, form, or waiting time. In all, 97.8% of patients feel that information and knowledge on their disease would help in its control, and 69.6% consider that adequate information would allow them to initiate a proper treatment before visiting their doctor. Family care is another poorly lookedafter aspect that 74.6% of subjects believe would be of help in controlling their disease. Conclusions: overall, the opinion of patients with IBD on healthcare received is good; however, a number of deficiencies were detected, as is the case with insufficient information, care of family members, and healthcare resources accessibility/agility.

OBJECTIVE: Household members of patients with inflammatory bowel disease (IBD) are impacted in their daily lives by close interaction with chronic illness. However, the effect of IBD on the quality of life of household members has not been evaluated because appropriate instruments to measure it are lacking. The aim of this study was to develop and validate a specific instrument to measure the quality of life of household members of patients with IBD. METHODS: Household members were interviewed to generate an initial pool of items. A group of investigators excluded redundant and incomprehensible items, and the resulting preliminary questionnaire was completed by 81 subjects. Further item reduction was performed using the psychometric method. The psychometric properties of the final questionnaire were determined in a group of 106 subjects. RESULTS: Of the initial 67 items, 19 were excluded by investigators. The remaining 48 items were answered by 81 household members, and 32 items were excluded by factor analysis. Two others were excluded because of poor comprehension. The definitive questionnaire consisted of 14 items. CONCLUSIONS: We have developed and validated a questionnaire to measure the quality of life of household members of IBD patients. It will greatly enhance the possibilities of quantifying the effects of IBD on home life and should become a useful tool in health care planning.

Both total parenteral nutrition and long-term octreotide treatment (2 months) may induce biliary sludge and lithiasis. However, the lithogenic capacity of the combination of the two treatments in the short-term is unknown. This study was undertaken to evaluate the lithogenic capacity of short-term octreotide treatment (1 month) in patients with acute pancreatitis who are also receiving total parenteral nutrition, and to determine the evolution of patients who develop biliary sludge and/or lithiasis.Thirty patients with acute pancreatitis were studied (21 males, 9 females; average age: 38). All patients received total parenteral nutrition and analgesics. In a double-blind random manner, 15 patients were treated with a continuous subcutaneous administration of octreotide (200 micrograms/8 h) and a further 15 patients received placebo. Biliary sludge and/or lithiasis were examined by ultrasonography. An echographic examination of the gallbladder was performed every seven days while the patients were in hospital. They were followed up every month, when another ultrasound of the gallbladder was carried out.Sixteen patients (53%) developed sludge: ten (67%) from the octreotide group and six (33%) from the placebo group (P = 0.29). Two of the patients from the octreotide group had microlithiasis (P = 0.34) and a cholecystectomy was required. In the other 14 patients, sludge had disappeared by the time of the check-up performed one month after discharge.Short-term octreotide treatment does not increase the risk of developing biliary sludge and/or lithiasis in patients also receiving total parenteral nutrition. Biliary sludge formed during total parenteral nutrition and short-term octreotide therapy may disappear when patients begin oral intake. Therefore, preventive measures are not required.

The aim of this study was to determine the prevalence and way of presentation of esophageal motor dysfunction in a nonselected population of subjects with Down's syndrome.The study was conducted in 58 Down's syndrome patients and 38 healthy controls. A global symptom score and individual scores for dysphagia for liquids and solids, heartburn, vomiting/regurgitation, and chest pain were obtained. Esophageal function was evaluated initially by scintigraphy using liquid and semisolid bolus. Time-activity curves based on the mean condensed images were used to calculate residual activity at 100 s after swallowing. According to both scintigraphy and clinical evaluation results, participants underwent a radiological and manometric study.The most frequent symptoms in Down's syndrome patients were: dysphagia for liquids (n = 9), dysphagia for solids (n = 10), vomiting/regurgitation (n = 8), and chest pain (n = 2). Liquid and semisolid retention of the tracer was significantly higher in Down's syndrome patients than in controls (p0.05). In 15 participants with Down's syndrome, tracer retention was higher than the 95 percentile of controls' retention. No correlation was found between the global or individual symptom score and esophageal retention quantified by scintigraphy. Hypothyroidism was unrelated to esophageal symptoms or retention. Five of the 15 esophagograms performed were abnormal, showing barium retention and/or esophageal dilation. Manometry showed achalasia in two subjects, total body aperistalsis in one, and nonspecific esophageal motor disorder in two.Esophageal motor disorders, particularly achalasia, are frequent in individuals with Down's syndrome. Awareness of esophageal dysmotility in this population is important, even though symptoms are not evident, to avoid potential complications.

OBJECTIVE: To establish the impairment of different dimensions of quality of life in inflammatory bowel disease (IBD). DESIGN: Prospective observational study. PARTICIPANTS: 289 patients [160 with ulcerative colitis (UC) and 129 with Crohn's disease (CD)]. MEASURES: Health-related quality of life was assessed by means of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Psychological General Well Being Index (PGWBI). RESULTS: In active IBD, all dimensions of the quality of life scored significantly lower than in inactive IBD, indicating a poor quality of life. Social impairment was the least impaired dimension of the IBDQ in active UC and CD, compared with digestive and systemic symptoms. In inactive IBD, the systemic symptoms domain received the lowest score (P < 0.01). In a subgroup of 22 patients studied before and after remission, emotional function was the most impaired dimension after achieving remission. The Psychological General Well Being Index was significantly impaired in active UC [78.5 (range 64-89)] and CD [76.5 (range 69-97)] relative inactive IBD [104 (range 93-111)] vs 106 (95-113), respectively; P < 0.05]. CONCLUSIONS: Quality of life is impaired in IBD. During relapse, clinicians should pay attention to digestive symptoms and psychological distress. In remission, they should be sensitive to systemic symptoms.

BACKGROUNDLipids may exacerbate symptoms induced by gut stimuli.AIMTo determine the mechanism whereby fat exerts this effect.SUBJECTSTwenty four healthy subjects were studied during fasting.METHODSWe measured perception (0–6 scale) in response to jejunal balloon distension and transmucosal electrical nerve stimulation; phasic stimuli (one minute) were randomly applied at five minute intervals during intestinal infusion (2 ml/min) of saline and then Intralipid 2 kcal/min (high fat; n=8 subjects), Intralipid 0.5 kcal/min (low fat; n=8), or saline (n=8).RESULTSIntestinal lipids increased the perception of jejunal distension regardless of concentration (by 53% with high fat, 49% with low fat, and 17% with saline; pCONCLUSIONPhysiological amounts of lipids heighten intestinal sensitivity by modulating intestinal mechanoreceptor response.