Further validation of the visual analogue scale for irritable bowel syndrome after use in clinical practice.

The Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS), a self-rating questionnaire, was designed to measure symptoms and the effect of treatment in patients suffering from irritable bowel syndrome. The aim of this descriptive correlational study was to conduct further psychometric validation after the VAS-IBS had been used in clinical practice, translate it into English, and compare the results with controls. Forty-nine patients with irritable bowel syndrome (median age = 38 years old [range, 18-69 years]) were compared with 90 healthy persons (median age = 44 years old [range, 21-77 years]) who served as controls. The patients with irritable bowel syndrome completed 3 questionnaires: the VAS-IBS, the Gastrointestinal Symptom Rating Scale, and the Perception of Change of Symptoms. Controls completed only the VAS-IBS. Results showed that the VAS-IBS is a valid questionnaire that measures the degree of change of symptoms and discriminates between patients who have irritable bowel syndrome from those who do not. It is important to compare the VAS-IBS among different cultural populations so we suggest that the English version of the VAS-IBS should now be used in English-speaking countries and be further tested for validity and reliability with English-speaking patients.

Covariation of plasma ghrelin and motilin in irritable bowel syndrome.

We have previously shown that ghrelin is mainly localized to the stomach but also occurs, together with the prokinetic hormone motilin, in endocrine cells in the proximal small intestine. This study explored ghrelin and motilin concentrations in plasma in relation to gastrointestinal motility and whether plasma ghrelin is changed in patients with irritable bowel syndrome (IBS). Nine patients with severe IBS and 10 healthy subjects underwent stationary antro-duodeni-jejunal manometry; blood was sampled during similar motility phases in the two groups. The motility phases were monitored and blood samples were collected during fasting and after food intake. Plasma was analyzed for two forms of ghrelin (octanylated and desoctanylated) as well as for motilin. In IBS patients circulating motilin levels covaried with total ghrelin levels (r=0.90; p<0.004), octanylated ghrelin (r=0.77; p<0.02) and desoctanylated ghrelin (r=0.69; p<0.04). No such correlations were seen in the control group. Octanylated ghrelin comprised 35.3+/-3.9% (mean+/-SEM) of the total circulating ghrelin in the IBS patients compared to 40.4+/-4.5% (mean+/-SEM) in the control group (NS). Ghrelin covaried with motilin in plasma in IBS but not in plasma from healthy subjects. This suggests the two peptides act together in IBS.

Function and dysfunction of the colon and anorectum in adults: working team report of the Swedish Motility Group (SMoG).

Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.

Effects of anti-secretory factor (ASF) on irritable bowel syndrome (IBS). A double-blind, randomized study.

OBJECTIVE: To evaluate the role of the endogenous protein anti-secretory factor (ASF) on the symptoms, especially loose stools, in irritable bowel ayndrome (IBS). DESIGN: A diet with specially processed cereals (SPC) known to induce ASF production was used in patients with IBS, in an eight-week randomized, placebo-controlled study. SUBJECTS: Eighty-two patients with IBS were randomized to a diet with either SPC or placebo. MAIN OUTCOME MEASURES: The overall clinical condition and the quality of life were measured by VAS and SF-36 questionnaire, respectively. The plasma levels of ASF were determined in 14 patients with dominating loose stools before and after diet. RESULTS: All patients significantly (p<0.001) improved in IBS-related symptoms irrespective of active or placebo diet. In an active-diet sub-group with diarrhoea (n=11) there was a significant (p<0.05) correlation between the increase of plasma ASF level and the improvement on the VAS. CONCLUSION: Both study groups improved significantly on the VAS but no additive effect was seen for the active treatment. In the sub-group with loose stools, the SPC diet induced ASF plasma levels in IBS patients and was correlated to significant symptom improvement in the individual patient.

Ghrelin and motilin are cosecreted from a prominent endocrine cell population in the small intestine.

CONTEXT: Ghrelin is a novel hormone produced mainly in the gastric body. Hitherto, mapping studies of ghrelin cells covering the entire gastrointestinal (GI) tract in humans have been lacking. Furthermore, the phenotype of extragastric ghrelin cells is not known. OBJECTIVE: The objective of the study was to perform a detailed mapping with specimens from all parts of the GI tract, and colocalization studies to phenotype ghrelin cells along the tract. In addition, mapping of ghrelin cells was performed in porcine GI tract, and the plasma profiles of ghrelin and motilin in blood from the porcine intestine were measured. DESIGN: Biopsies from patients were obtained during gastroscopy or surgery. Ghrelin cell density and phenotyping was assessed with immunocytochemistry, in situ hybridization, and immunogold electron microscopy. Plasma ghrelin and motilin levels were measured in pigs, fitted with cannulas in the mesenteric vein. RESULTS: The upper small intestine is unexpectedly rich in ghrelin cells, and these cells contribute to circulating ghrelin. Ghrelin and motilin are coproduced in the same cells in the duodenum and jejunum of both species, and ghrelin and motilin are stored in all secretory granules of such cells in humans, indicating cosecretion. The plasma profiles of ghrelin and motilin in pig were parallel, and a correlation between ghrelin and motilin (r(2) = 0.22; P < 0.001) was evident in intestinal blood. CONCLUSIONS: The upper small intestine is an important source of ghrelin. The likely cosecretion of intestinal ghrelin and motilin suggests concerted actions of the two hormones. These data may have implications for understanding gut motility and clinical implications for dysmotility and bariatric surgery.

Chronic Helicobacter pylori infection in a population in southern Sweden analysed by histopathology, immunoblot and ELISA serology.

BACKGROUND: Many individuals are infected with the bacterium Helicobacter pylori. Some develop ulcers or mucosal atrophy. AIMS: To correlate the histological characteristics of the H. pylori -induced gastritis to the immunoblot pattern of the H. pylori infection and to compare the presence of H. pylori bacteria in tissue specimens with ELISA serology and immunoblot analysis. METHODS: One hundred and sixty-six consecutive patients were referred to gastroscopy. Forty patients were excluded for various reasons and 126 were included in the study. RESULTS: Twenty-three patients had ulcerations and 25 erosions. Ninety-two (73%) had a chronic gastritis and in 90 (71%) it involved both the antrum and corpus. Ninety-one (72%), of whom 96% had a chronic gastritis, had visible bacteria in the tissue specimens, used as the 'gold standard' for the detection of infection. In patients with chronic gastritis 65 (70%) had positive H. pylori ELISA serology, 27 (30%) had negative H. pylori ELISA, while 76 (83%) had a positive immunoblot pattern. The ELISA positive patients had more advanced chronic gastritis but a lower frequency of metaplasia and atrophy. Acute inflammatory activity in the chronic gastritis had a high immunoreactivity to 120 kDa (CagA) protein and was significantly correlated to antibody reactivity to proteins in the 53-65 kDa range (heat shock proteins) and to a 43 kDa subunit. Metaplasia and atrophy in antrum was associated with a 62 kDa protein band. CONCLUSION: Almost all H. pylori-infected patients had a pangastritis, visible in both antrum and corpus. Acute inflammatory activity in the chronic gastritis and the presence of metaplasia and atrophy in antrum were associated with a specific immunoblot pattern, indicating infection with more virulent strains. Immunoblot analysis had a better sensitivity than ELISA H. pylori serology.

Small intestinal manometry in patients with systemic sclerosis.

OBJECTIVES: The study explores, by the use of manometry, the frequency and severity of small intestinal involvement in patients with systemic sclerosis, and relates the manometric findings to clinical symptoms, radiology, and some intestinal regulatory peptides. METHODS: Stationary antroduodeno-jejunal manometry was used to study small bowel involvement in 10 patients with systemic sclerosis and dysmotility of the oesophagus or signs of malabsorption. Measurements were made during fasting, after a meal, and after octreotide administration and were then compared with a sex-matched control group of healthy individuals. Plasma samples were taken in order to analyse levels of motilin, peptide YY, cholecystokinin, and somatostatin. RESULTS: Manometry was abnormal, with signs of intestinal pseudo-obstruction in eight out of 10 patients. In the control group, one individual had an abnormal manometry, as a result of burst activity. The mean contractile amplitudes during fasting and periods after food, spontaneous phase III periods, and octreotide-induced activity complexes were significantly reduced in the systemic sclerosis group when compared with controls. None of the patients, including two with advanced manometric intestinal disturbances, had small intestinal dilatation when examined by radiography. The plasma peptide levels did not differ significantly between the two groups. CONCLUSIONS: In eight out of 10 patients the manometric criteria for intestinal pseudo-obstruction were fulfilled, with a motility pattern consistent with both neuropathy and myopathy. The release of motility-regulating peptides was unaffected.

Jejunoileal bypass changes the duodenal cholecystokinin and somatostatin cell density.

BACKGROUND: In obese patients, jejunoileal bypass (JIB) has been used to induce weight reduction. Changes in the neuroendocrine system may be affected by the JIB-operation, because the proximal small intestinal mucosa has a rich supply of endocrine cells and peptidergic nerves. MATERIALS AND METHODS: In 37 obese patients operated with JIB 1-30 years ago, small intestinal biopsies were taken at the duodeno-jejunal flexure, proximal to the anastomosis and from 5 unoperated obese persons and 20 normal weight patients. The tissue specimens were processed for immunocytochemical demonstration of cells/nerves containing: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), motilin, somatostatin, serotonin, glicentine, peptide YY (PYY), neurotensin, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and galanin. The number of different endocrine cell-types were counted per unit length of mucosa, and the density of the peptidergic nerves was assessed semiquantitatively according to a schematic scale. RESULTS: JIB-patients had an increased density of CCK and somatostatin cells in the duodenal mucosa. The CCK cells displayed a changed reaction pattern, with a greater cell number reacting with an antiserum directed towards a non-amidated mid-sequence of procholecystokinin compared with the other groups. In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups. CONCLUSION: JIB induces an up-regulation of somatostatin and CCK precursor-containing cells in the duodenal mucosa. The time duration after the JIB did not seem to influence the results.

Chromoendoscopic evaluation of gastric mucosa after partial gastrectomy by use of modified endoscopic Congo red test.

The need for partial gastrectomy has decreased as a result of reduced incidence and improved endoscopic and medical treatment of peptic ulcer disease. Nonetheless, several patients with resected stomach remain in the population, and it is well known that important pathological changes can occur in the gastric remnant. We evaluated the morphological and functional status of the gastric stump by use of modified endoscopic Congo red test (MCRT). For this purpose, 87 partially gastrectomized (Billroth I and II) patients referred for elective gastroscopy were consecutively enrolled. We found a high prevalence of severe chronic atrophic fundal gastritis (CAFG) (67%) in the gastric remnant. We also observed, however, that one-third of the patients had almost unaffected gastric acid production even as long as 26 years after partial gastrectomy. Moreover, the accuracy, sensitivity, and specificity of routine gastroscopy in diagnosing CAFG in the gastric stump were found to be 55%, 50%, and 84%, respectively. The presence of bile reflux correlated well with the degree of CAFG. Importantly, we observed that more than 71% of the patients receiving acid-suppressing therapy had no or very little capacity to produce gastric acid. Taken together, our study has demonstrated that MCRT is a simple and well-tolerated method providing important morphological and functional information about the mucosa of the resected stomach. Furthermore, MCRT was superior to routine gastroscopy in diagnosing CAFG in the gastric stump. Outcome studies should define the clinical benefit of MCRT in the management of patients with resected stomach.

Evaluation of gastric acid secretion at endoscopy with a modified Congo red test.

BACKGROUND: Markedly decreased or absent gastric acid production is associated with a number of clinically significant conditions, and identification of patients with hypo/achlorhydria may be important. However, current methods of assessing impaired acid secretion are unreliable, time-consuming, and/or complex. The aim of this prospective study was to evaluate a modified endoscopic Congo red test for the diagnosis of hypo/achlorhydria by correlation with a standard gastric acid secretory test. METHODS: One hundred six consecutive outpatients with or without dyspeptic symptoms referred for endoscopy were evaluated by using a modified endoscopic Congo red test and a standard test of gastric acid secretion. The modified endoscopic Congo red test suggested hypo/achlorhydria when there was no color shift or a shift of small extent (less than one third of fundic mucosa). Hypo/achlorhydria by the standard gastric acid secretory test was defined as a maximal acid output of less than 6.9 mmol/hour in men and 5.0 mmol/hour in women. RESULTS: The accuracy of the modified endoscopic Congo red test for the diagnosis of hypo/achlorhydria was 0.98 (95% CI [0.93, 0.99]). The sensitivity was 1.0 (95% CI [0.92, 1.00]) and specificity 0.96 (95% CI [0.88, 0.99]). All patients tolerated the modified endoscopic Congo red test well. CONCLUSION: The modified endoscopic Congo red is an accurate, simple, fast, inexpensive, and well-tolerated chromoendoscopic method for identification of patients with hypo/achlorhydria during routine upper endoscopy.

Cholecystokinin stimulation leads to increased oxytocin secretion in women.

OBJECTIVE: To find out if cholecystokinin (CCK) stimulates the secretion of oxytocin in humans, and if there are any differences in secretion between healthy women and those with normal-transit constipation. DESIGN: Prospective open study. SETTING: Teaching hospital, Sweden. SUBJECTS: 8 healthy female volunteers and 6 women with chronic refractory normal-transit constipation. INTERVENTIONS: Subjects were fasted before experiments. On one day they were given emulsified corn oil and another an intravenous injection of 1 Ivy dog unit (IDU) CCK/kg body weight. Blood samples were taken before each experiment at 10 minutes and at the time the experiments started. Blood samples were also taken after each experiment at 10, 20, 30, 45, 60, 90 and 120 minutes. MAIN OUTCOME MEASURES: Concentrations of CCK and oxytocin. RESULTS: Ingestion of corn oil significantly increased the plasma concentration of CCK in both groups (healthy women p = 0.03 and constipated women p = 0.008). Injection of CCK also led as expected to hypercholecystokininaemia in both groups (p = 0.008 and p = 0.03, respectively). The corn oil increased oxytocin secretion in both groups (p = 0.02 and 0.03, respectively) and exogenous CCK increased the secretion still further (p = 0.008 and 0.03, respectively). CONCLUSIONS: Both corn oil and injection of CCK led to an increased CCK concentration in plasma. Oxytocin was secreted in response to endogenous as well as exogenous CCK stimulation. There was no difference between healthy and constipated women in either parameter analysed.