[Malabsorption of fermentable oligo-, di-, or monosaccharides and polyols (FODMAP) as a common cause of unclear abdominal discomfort]. / Kohlenhydratmalabsorption: Unverträglichkeit fermentierbarer Oligo-, Di-, Monosaccharide und Polyole (FODMAP) als häufige Ursache unklarer abdomineller Beschwerden.

Carbohydrate malabsorption is a frequent but underestimated cause of unexplained gastrointestinal symptoms like meteorism, flatulence, pain and diarrhea. By means of hydrogen and/or methane breath test after ingestion of the respective carbohydrate it can be identified and diagnosed easily, fast and reliably by successful nutritional therapy. Besides the well known complaints caused by lactose and fructose malabsorption, other fermentable oligo-, di-, or monosaccharides and polyols (akronym: FODMAP) can cause abdominal discomfort and IBS-like symptoms. In addition to lactose (dairy products) and fructose (apples, pears, mango, watermelon), FODMAPs comprise galactans (legumes), fructans (wheat, onions, garlic, artichoke) and the artificial sweeteners sorbitol, mannitol, maltitol and xylitol (sugar free candy, light products). A general restriction of all FODMAP components can be beneficial in relieving symptoms and improving quality of life in patients with functional gastrointestinal complaints.

[Diagnosis of oesophageal reflux by PH, impedance, and bilirubin measurement: recommendations of the German Society of Neurogastroenterology and of the working group for neurogastroenterology of the German Society for Digestive and Metabolic Diseases]. / Ösophageale Refluxdiagnostik - pH-Metrie, Impedanzmessung, Bilirubin-Messung: Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität und der Arbeitsgruppe Neurogastroenterologie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten.

The current recommendations on indications, technical performance, and interpretation of diagnostic techniques for oesophageal reflux update the German recommandations about 24 hour pH measurement of 2003. The recommendations encompass conventional pH measurement, wireless pH measurement, pH and impedance measurements, and bilirubin measurement (duodenogastro-oesophageal reflux).

Randomised clinical trial: sustained response to PPI treatment of symptoms resembling functional dyspepsia and irritable bowel syndrome in patients suffering from an overlap with erosive gastro-oesophageal reflux disease.

BACKGROUND: Gastro-oesophageal reflux disease (GERD), functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent gastrointestinal conditions with accumulating evidence of overlap in patients. Despite availability of a vast body of research related to individual disorders, major pharmacological breakthrough in treatment of the overlap condition is still lacking. AIM: To assess sustainability of GERD healing and whether known beneficial effects of proton pump inhibitor treatment on GERD also extend to symptoms suggestive of FD and IBS. METHODS: A total of 626 patients with reflux oesophagitis were treated with pantoprazole for up to 16 weeks depending on healing of GERD, followed by an observational phase of up to 6 months without treatment. Rates of patients suffering from GERD, FD or IBS were assessed at baseline, and at last visits of treatment and observational phase. RESULTS: Rates of patients with reflux oesophagitis and concomitantly with reflux symptoms, FD or IBS were each significantly lower after pantoprazole treatment (P < 0.0001). While rates of patients with reflux signs or symptoms increased again during observational phase, rates of FD and IBS were maintained at the low level after cessation of medication (P < 0.0001). CONCLUSIONS: Pantoprazole is efficacious in the treatment of patients suffering from signs and symptoms suggesting an overlap of GERD, FD and/or IBS, providing a sustained response post-treatment in FD and IBS symptom categories. Mechanisms underlying the beneficial effects of improvement in reflux oesophagitis on symptoms suggestive of FD or IBS still need to be determined.

Selective central activation of somatostatin receptor 2 increases food intake, grooming behavior and rectal temperature in rats.

The consequences of selective activation of brain somatostatin receptor-2 (sst2) were assessed using the sst2 agonist, des-AA(1,4-6,11-13)-[DPhe(2),Aph7(Cbm),DTrp(8)]-Cbm-SST-Thr-NH2. Food intake (FI) was monitored in ad libitum fed rats chronically implanted with an intracerebroventricular (i.c.v.) cannula. The sst(2) agonist injected i.c.v. at 0.1 and 1 microg/rat dose-dependently increased light phase FI from 2 to 6 hours post injection (2.3+/-0.5 and 7.5+/-1.2 respectively vs. vehicle: 0.2+/-0.2 g/300 g bw, P<0.001). Peptide action was reversed by i.c.v. injection of the sst2 antagonist, des-AA(1,4-6,11-13)-[pNO(2)-Phe(2),DCys(3),Tyr(7),DAph(Cbm)8]-SST-2Nal-NH(2) and not reproduced by intraperitoneal injection (30 microg/rat). The sst(2) antagonist alone i.c.v. significantly decreased the cumulative 14-hours dark phase FI by 29.5%. Other behaviors, namely grooming, drinking and locomotor activity were also increased by the sst(2) agonist (1 microg/rat, i.c.v.) as monitored during the 2(nd) hour post injection while gastric emptying of solid food was unaltered. Rectal temperature rose 1 hour after the sst(2) agonist (1 microg/rat, i.c.v.) with a maximal response maintained from 1 to 4 hours post injection. These data show that selective activation of the brain sst(2) receptor induces a feeding response in the light phase not associated with changes in gastric emptying. The food intake reduction following sst(2) receptor blockade suggests a role of this receptor in the orexigenic drive during the dark phase.

Do we need gastric acid?

Evidence from comparative anatomy and physiology studies indicates that gastric acid secretion developed during the evolution of vertebrates approximately 350 million years ago. The cellular mechanisms that produce gastric acid have been conserved over the millennia and therefore proton pump inhibitors have pharmacological effects in almost all relevant species. These observations suggest that gastric acid provides an important selective advantage; however, in modern-day humans the need for gastric acid can be questioned in light of the widespread use of safe and effective pharmacologic acid suppression. The Kandahar Working Group addressed questions concerning the need, production and effects of gastric acid, specifically: (1) motility in the upper gastrointestinal (GI) tract; (2) neuroendocrine factors; (3) digestive and mucosal processes; (4) microbiology, and (5) central processes and psychological involvement. We addressed each topic with the individual models available to answer our questions including animal versus human studies, pharmacologic, surgical as well as pathophysiologic states of acid suppression.

Bioavailability of amoxicillin and clavulanic acid from extended release tablets depends on intragastric tablet deposition and gastric emptying.

The rate and extent of amoxicillin and clavulanic acid absorption from pharmacokinetically enhanced extended release (ER) tablets is strongly influenced by the intake conditions. In order to investigate the cause of the food effects, a pharmacokinetic study with simultaneous imaging of the in vivo behaviour of the ER tablets by magnetic marker monitoring (MMM) was performed. Under fasting conditions the amoxicillin AUC (1854+/-280microg min ml(-1)) was significantly lower than after intake at the beginning of the breakfast (2452+/-354microg min ml(-1)) or after the breakfast (2605+/-446microg min ml(-1)). In contrast, clavulanic acid AUC was well comparable after tablet intake under fasting conditions and intake at the beginning of a breakfast (191+/-46 and 189+/-44microg min ml(-1), respectively) but significantly lower following a breakfast (126+/-71microg min ml(-1)). The localization data showed that the reduced bioavailability of amoxicillin under fasting conditions is due to early gastric emptying in combination with poor absorption from deeper parts of the small intestine. Prolonged gastric residence of clavulanic acid caused by intragastric tablet deposition in the proximal stomach was identified as the reason for the decreased bioavailability of clavulanic acid after tablet intake following the meal.

[Anorectal manometry]. / Empfehlungen zur Anorektalen Manometrie im Erwachsenenalter.

This document contains the guidelines of the German Societies of Neurogastroenterology and Motility, Gastroenterology (committee for proctology), Abdominal Surgery (coloproctology working group), and Coloproctology for anorectal manometry in adults. Recommendations are given about technical notes, study preparation (equipment; patient), technique for performing manometry and data analysis, reproducibility, and indications. Minimum standards for anorectal manometry are measurement of resting and squeeze pressure, testing of rectoanal inhibitory reflex, determination of rectal sensation (first perception and urge), and calculation of rectal compliance. Anorectal manometry is indicated in patients with fecal incontinence and constipation in the context of a structured programme.

Systematic review: do we need a new gastro-oesophageal reflux disease questionnaire?

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinical trials. AIM: To evaluate the validity of available GERD measurement tools. METHODS: An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use 'word pictures' which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use. RESULTS: A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria. CONCLUSION: There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.

Evaluation of GERD symptoms during therapy. Part I. Development of the new GERD questionnaire ReQuest.

BACKGROUND/AIMS: The changes in gastroesophageal reflux disease (GERD)-related symptoms on treatment are variously described, but currently available questionnaires have shortcomings. We therefore developed a self-assessment reflux questionnaire (ReQuest). This article describes the process of development and testing. MATERIALS AND METHODS: For the first version of ReQuest the symptom spectrum of GERD and the various symptom descriptions were investigated. The 67 identified symptom descriptions were condensed empirically into 6 dimensions, to which a 7th dimension on general well-being was added. The symptom burden of the dimensions was measured by frequency and/or intensity. ReQuest was translated into different languages and then tested in focus groups. The initial validation was based on data from a clinical trial of patients with erosive GERD, treated with pantoprazole 20 or 40 mg daily for 28 days. Factor analyses determined the contribution of each symptom to the different dimensions. Additionally, correlation analyses between the identified factors and the dimensions were performed. RESULTS: On the basis of factor analyses, ReQuest was reduced to a 60-item scale. The factors generated correlated strongly with the dimensions and confirmed the empirical process mathematically. CONCLUSION: ReQuest provides a valuable, self-assessment tool for evaluating the daily treatment response in patients with erosive GERD.

International validation of ReQuest in patients with endoscopy-negative gastro-oesophageal reflux disease.

BACKGROUND: Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms. AIM: International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease. METHODS: In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test-retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients. RESULTS: Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test-retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale 0.6; Psychological General Well-being -0.4). CONCLUSION: ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.

Evaluation of GERD symptoms during therapy. Part II. Psychometric evaluation and validation of the new questionnaire ReQuest in erosive GERD.

BACKGROUND/AIMS: Evaluation of the response of gastroesophageal reflux disease (GERD) symptoms to treatment would be facilitated by a brief, valid, reliable and responsive, self-assessed GERD-sensitive scale. We therefore developed the Reflux Questionnaire (ReQuest). This publication describes the psychometric evaluation and validation of ReQuest. METHODS: This second phase of development was based on data from a clinical trial of patients with erosive GERD who received pantoprazole 20 or 40 mg daily for 28 days and completed weekly the long, and daily the short version of ReQuest. The psychometric analyses of ReQuest included internal consistency, test-retest reliability and responsiveness. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale (GSRS) and the Psychological General Well-Being (PGWB) scale. RESULTS: Validation of ReQuest indicated very high internal consistency (Cronbach's alpha = 0.90) and test-retest reliability (intraclass correlation coefficient 0.94 (long-long) and 0.86 (short-short)). This was also the case for the two subscales ReQuest-GI and ReQuest-WSO with Cronbach's alpha coefficients of 0.84 and 0.81. Responsiveness was high with a responsiveness index of >0.8 at day 28. Construct validity was good. CONCLUSION: ReQuest is a highly reliable, valid and responsive self-assessment tool for evaluating treatment response in patients with erosive GERD, and can be applied daily.

[Drug therapy for irritable bowel syndrome. What works, what doesn't work and for whom?]. / Arzneimitteltherapie des Reizdarmsyndroms. Was funktioniert, was nicht--und bei wem?

The therapy of patients with irritable bowel syndrome (IBS) is often challenging, especially if a broad spectrum of symptoms is present and trigger factors, such as the influence of diet or stress, are lacking. Current pathogenetic concepts propose central or peripheral alterations that cause disturbed gastrointestinal function (motility, visceral sensitivity) and subsequent symptoms. These alterations are possibly related to psychological (stress, depression, anxiety) and biological (post-infectious residuals, micro-inflammation) influences. Since no universally effective medical treatment is available to treat the causes of the disease, standard medical therapy is symptom directed (especially for pain, constipation and diarrhoea). In addition to well established drugs (like spasmolytics, opioids and laxatives), newly developed compounds including those with other primarily indications (e.g. antidepressants) are available for highly differentiated individualized therapies. New medical approaches which are currently undergoing evaluation, promise further progress in the treatment of IBS.

Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats.

BACKGROUND AND AIMS: Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity. Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal activation and food intake in non-fasted rats. METHODS: Animals received various doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin or vehicle was administered intraperitoneally 12 hours later and food intake was measured over four hours. Neuronal activation was assessed as c-Fos-like immunoreactivity in the arcuate nucleus. RESULTS: Treatment with NOX-B11 30 nmol suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and blocked the ghrelin induced increase in food intake within the first half hour after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX-B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10 nmol showed an intermediate effect on ghrelin induced food intake. CONCLUSIONS: Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an innovative new approach to inhibit the biological action of circulating ghrelin. This may be of particular relevance to conditions associated with elevated plasma ghrelin, such as the Prader-Willi syndrome.

Brain activation responses to subliminal or supraliminal rectal stimuli and to auditory stimuli in irritable bowel syndrome.

Visceral hypersensitivity in irritable bowel syndrome (IBS) has been associated with altered cerebral activations in response to visceral stimuli. It is unclear whether these processing alterations are specific for visceral sensation. In this study we aimed to determine by functional magnetic resonance imaging (fMRI) whether cerebral processing of supraliminal and subliminal rectal stimuli and of auditory stimuli is altered in IBS. In eight IBS patients and eight healthy controls, fMRI activations were recorded during auditory and rectal stimulation. Intensities of rectal balloon distension were adapted to the individual threshold of first perception (IPT): subliminal (IPT -10 mmHg), liminal (IPT), or supraliminal (IPT +10 mmHg). IBS patients relative to controls responded with lower activations of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) to both subliminal and supraliminal stimulation and with higher activation of the hippocampus (HC) to supraliminal stimulation. In IBS patients, not in controls, ACC and HC were also activated by auditory stimulation. In IBS patients, decreased ACC and PFC activation with subliminal and supraliminal rectal stimuli and increased HC activation with supraliminal stimuli suggest disturbances of the associative and emotional processing of visceral sensation. Hyperreactivity to auditory stimuli suggests that altered sensory processing in IBS may not be restricted to visceral sensation.