Blueberries Improve Abdominal Symptoms, Well-Being and Functioning in Patients with Functional Gastrointestinal Disorders.

Blueberries beneficially modulate physiologic mechanisms relevant to the pathogenesis of functional gastrointestinal disorders (FGID). Forty-three patients with FGID received freeze-dried blueberries (equivalent to 180 g fresh blueberries) or sugar and energy-matched placebo in a double-blind, randomized, cross-over study. After 6 weeks of treatment, the differences in Gastrointestinal Clinical Rating Scale (GSRS) scores and abdominal symptom relief were compared as primary outcome measures. The quality of life and life functioning ratings (OQ45.2 questionnaire), Bristol stool scales, and fructose breath test results constituted secondary outcome measures. Blueberry treatment resulted in more patients with relevant abdominal symptom relief compared to placebo (53% vs. 30%, p = 0.03). Total and pain GSRS scores improved insignificantly (mean treatment differences [95% CI]: -3.4 [-7.4 to 0.6] (p = 0.09) and -1.0 [-2.2 to 0.1] (p = 0.08), respectively). OQ45.2 scores improved during blueberry treatment compared to placebo (treatment difference -3.2 [95% CI: -5.6 to -0], p = 0.01). Treatment effect differences for the further measures did not reach statistical significance. Blueberries relieved abdominal symptoms and improved general markers of well-being, quality of life, and life functioning more than placebo in patients with FGID. Consequently, the polyphenol and fiber components of blueberries exert broad beneficial effects separate from the sugars present in both treatments.

Fructose intolerance is not associated with malabsorption in patients with functional gastrointestinal disorders.

BACKGROUND: Symptoms following fructose ingestion, or fructose intolerance, are common in patients with functional gastrointestinal disorders (FGID) and are generally attributed to intestinal malabsorption. The relationships between absorption, symptoms, and intestinal gas production following fructose ingestion were studied in patients with FGID. METHODS: Thirty FGID patients ingested a single dose of fructose 35 g or water in a randomized, double-blind, crossover study. Blood and breath gas samples were collected, and gastrointestinal symptoms rated. Plasma fructose metabolites and short-chain fatty acids were quantified by targeted liquid chromatography-tandem mass spectrometry. Patients were classified as fructose intolerant or tolerant based on symptoms following fructose ingestion. KEY RESULTS: The median (IQR) areas under the curve of fructose plasma concentrations within the first 2 h (AUC0-2 h ) after fructose ingestion were similar for patients with and without fructose intolerance (578 (70) µM·h vs. 564 (240) µM·h, respectively, p = 0.39), as well as for the main fructose metabolites. There were no statistically significant correlations between the AUC0-2 h of fructose or its metabolites concentrations and the AUCs of symptoms, breath hydrogen, and breath methane. However, the AUCs of symptoms correlated significantly and positively with the AUC0-2 h of hydrogen and methane breath concentrations (r = 0.73, r = 0.62, respectively), and the AUCs of hydrogen and methane concentrations were greater in the fructose-intolerant than in the fructose-tolerant patients after fructose ingestion (p ≤ 0.02). CONCLUSIONS & INFERENCES: Fructose intolerance in FGID is not related to post-ingestion plasma concentrations of fructose and its metabolites. Factors other than malabsorption, such as altered gut microbiota or sensory function, may be important mechanisms.

Extragastrointestinal Symptoms and Sensory Responses During Breath Tests Distinguish Patients With Functional Gastrointestinal Disorders.

INTRODUCTION: Patients with functional gastrointestinal disorders (FGIDs) are classified based on their gastrointestinal (GI) symptoms, without considering their frequent extra-GI symptoms. This study defined subgroups of patients using both GI and extra-GI symptoms and examined underlying mechanisms with fructose and lactose breath tests. METHODS: Latent class analysis defined distinct clusters of patients with FGID based on their long-term GI and extra-GI symptoms. Sensory and breath gas responses after fructose and lactose ingestion were compared across symptom clusters to investigate differences in sensory function and fermentation by intestinal microbiota. RESULTS: Six symptom clusters were identified in 2,083 patients with FGID. Clusters were characterized mainly by GI fermentation-type (cluster 1), allergy-like (cluster 2), intense pain-accentuated GI symptoms (cluster 3), central nervous system (cluster 4), musculoskeletal (cluster 5), and generalized extra-GI (cluster 6) symptoms. In the 68% of patients with complete breath tests, the areas under the curve of GI and central nervous system symptoms after fructose and lactose ingestion differed across the clusters (P < 0.001). The clusters with extensive long-term extra-GI symptoms had greater symptoms after the sugars and were predominantly women, with family or childhood allergy histories. Importantly, the areas under the curves of hydrogen and methane breath concentrations were similar (P > 0.05) across all symptom clusters. Rome III criteria did not distinguish between the symptom clusters. DISCUSSION: Patients with FGID fall into clusters defined extensively by extra-GI symptoms. Greater extra-GI symptoms are associated with evidence of generalized sensory hypersensitivity to sugar ingestion, unrelated to intestinal gas production. Possible underlying mechanisms include metabolites originating from the intestinal microbiota and somatization.

Symptoms of mast cell activation syndrome in functional gastrointestinal disorders.

Objectives: Mast cell involvement is evident in functional gastrointestinal disorders (FGID). FGID and mast cell activation syndrome (MCAS) are associated with multi-organ symptoms. An overlap has not been assessed.Methods: MCAS symptoms were determined by questionnaires in 2083 FGID patients.Results: The median number of MCAS symptoms ([IQR] (range 0-16)) was 6 [4-8] in all FGID, and in functional dyspepsia (FD) patients, 7 [5-9] in overlapping irritable bowel syndrome and FD (IBS+FD), 5 [3-8] in IBS and 5 [3-6] in non-IBS/non-FD (p < .001 vs. FD and IBS + FD) patients. MCAS symptoms in ≥2 organ-systems existed in 1773 (85%) of all patients.Conclusions: MCAS symptoms are common in FGID warranting further mechanistic investigation.

Repeatability and effect of blinding of fructose breath tests in patients with functional gastrointestinal disorders.

BACKGROUND: Breath tests are used as measures of sugar intolerance or malabsorption in patients with functional gastrointestinal disorders (FGID), although the repeatability or anticipatory bias have not been adequately studied. We examined the repeatability and anticipatory bias during fructose breath testing using a nocebo-controlled, randomized, cross-over, and double-blind study design. METHODS: Gastrointestinal symptoms and breath concentrations of hydrogen and methane were documented during breath tests with fructose (given open twice and blinded once), water (blind neutral nocebo) and a cyclamate/saccharine sweetener (blind sweet nocebo) on 5 days in patients with FGID. Repeatability of fructose breath tests (16 patients) and differences between open and blinded substrate groups (31 patients) was assessed using thresholds for intolerance and malabsorption, and areas-under-the-curve (AUC) of symptoms and breath gas concentrations. KEY RESULTS: Fructose breath tests showed moderate repeatability for intolerance status (absolute agreement 87%, kappa 0.72), but limited repeatability for malabsorber status (absolute agreement 53%, kappa 0.05). Repeatability of AUCs of GI symptoms, hydrogen and methane breath concentrations was moderate (intraclass correlation coefficients 0.70, 0.57, and 0.57, respectively). There were no significant differences between open and blinded fructose breath tests in intolerance or malabsorber status, or in AUCs of GI symptoms, hydrogen and methane concentrations. CONCLUSIONS & INFERENCES: Fructose breath tests showed moderate repeatability for intolerance status and for AUCs of symptoms and gas concentrations, lying within the range of accepted gastrointestinal sensory and transit tests. Repeatability for malabsorption status was inadequate and requires revisiting. The fructose breath test can be used unblinded in FGID.

Fermentable Sugar Ingestion, Gas Production, and Gastrointestinal and Central Nervous System Symptoms in Patients With Functional Disorders.

BACKGROUND & AIMS: Functional gastrointestinal disorders (FGID) are defined by broad phenotypic descriptions and exclusion of recognizable disease. FGIDs cause multi-organ symptoms and abnormal results in a wide range of laboratory tests, indicating broad mechanisms of pathogenesis. Many patients with FGID develop symptoms following ingestion of fermentable sugars; we investigated the associations between symptoms and intestinal gas production following sugar provocation tests to elucidate mechanisms of FGID. METHODS: We performed fructose and lactose breath tests in 2042 patients with a diagnosis of FGID (based on Rome III criteria), referred to a gastroenterology practice from January 2008 through December 2011. Medical and diet histories were collected from all subjects. Breath samples were collected before and each hour after, for 5 hours, subjects ingested fructose (35 g) and lactose (50 g) dissolved in 300 mL water. Hydrogen and methane gas concentrations were measured and GI and non-GI symptoms were registered for 5 hours following sugar ingestion. Symptom and gas time profiles were compared, treelet transforms were used to derive data-related symptom clusters, and the symptom severity of the clusters were analyzed for their association with breath gas characteristics. RESULTS: We identified 11 GI and central nervous system (CNS) symptom profiles and hydrogen and methane breath concentrations that changed significantly with time following sugar ingestion. Treelet transform analysis identified 2 distinct clusters, based on GI and CNS symptoms. The severity scores for the GI and CNS symptoms correlated following ingestion of sugars (all, P < .0001). However, only the GI symptoms associated with hydrogen and methane gas production (all, P < .0001). CONCLUSIONS: In an analysis of breath test results from more than 2000 patients with FGIDs, we identified clusters of GI and CNS symptoms in response to fructose of lactose ingestion. The association between specific symptoms and breath gas concentrations indicate distinct mechanisms of FGID pathogenesis, such as changes in the microbiome or mechanical and chemical sensitization. ClinicalTrials.gov ID: NCT02085889.

Breath methane concentrations and markers of obesity in patients with functional gastrointestinal disorders.

BACKGROUND: Obesity is associated with changes in the intestinal microbiome and methane-producing archaea may be involved in energy homeostasis. OBJECTIVE: The objective of this article is to investigate the associations between intestinal methane production, waist circumference and body mass index (BMI) as biomarkers for obesity. METHODS: Breath methane and hydrogen concentrations were measured over five hours following fructose or lactose ingestion in 1647 patients with functional gastrointestinal disorders. The relationships between gas concentrations and measures of obesity were investigated by stratifying gas concentration-time profiles by BMI and waist circumference, and, conversely, BMI and waist circumference by peak breath hydrogen and methane concentrations. RESULTS: Following fructose ingestion, patients with lower BMI and lesser waist circumference had greater breath methane concentrations (all p < 0.003). Conversely, patients with increased methane concentrations had lower BMI (p < 0.001) and waist circumference (p = 0.02). After lactose ingestion, BMI and waist circumference were not associated with significant differences in methane. However, greater methane concentrations were associated with a lower BMI (p < 0.002), but not with waist circumference. CONCLUSION: In this large group of patients mainly negative associations between breath methane concentrations and anthropometric biomarkers of obesity were evident. Studies investigating microbial methane production and energy homoeostasis in different populations are of substantial interest to distinguish epiphenomena from true causality.A follow-up study was registered at Clinical trials.gov NCT02085889.

Longitudinal study of gastroesophageal reflux and erosive tooth wear.

BACKGROUND: Approximately 60% of patients presenting to dentists with erosive tooth wear have significant gastroesophageal reflux (GERD), despite minor reflux symptoms. No longitudinal studies of reflux-associated erosive tooth wear and of reflux characteristics have been reported to date. The aim of this study was to characterize the longitudinal course of GERD and of associated erosive tooth wear, as well as factors predictive of its progression, in a large group of patients. METHODS: Seventy-two patients presenting to dentists with clinically significant erosive tooth wear and increased esophageal acid exposure by 24-h multichannel intraluminal pH-impedance measurement (MII-pH) were re-assessed clinically and by MII-pH after 1 year treatment with esomeprazole 20 mg twice-daily. Predictive factors for erosive tooth wear were assessed by logistic regression. RESULTS: At follow-up, no further progression in erosive tooth wear was observed in 53 (74%) of patients. The percentage of time with a pH < 4, the number of acid reflux episodes and the percentage of proximal esophageal reflux off-PPI did not change significantly after one year, but the number of weakly acidic reflux episodes decreased significantly in the large subgroup without progression. None of the baseline demographic, clinical, endoscopic or esophageal acid exposure characteristics were significantly associated with progression of erosive tooth wear at follow-up. CONCLUSIONS: In this longitudinal study in patients with erosive tooth wear and oligosymptomatic GERD receiving esomeprazole for one year, erosive tooth wear did not progress further in the majority of patients. Background acidic esophageal reflux exposure appeared stable over time, whereas weakly acidic exposure decreased significantly in patients without erosion progression. MII-pH measurements on-PPI and with healthy controls will be useful in the further elucidation of the causal role of reflux in erosive tooth wear. TRIAL REGISTRATION: ClinicalTrials.gov , retrospectively registered: NCT02087345 .

Visceral pain perception in patients with irritable bowel syndrome and healthy volunteers is affected by the MRI scanner environment.

BACKGROUND: The MRI scanner environment induces marked psychological effects, but specific effects on pain perception and processing are unknown and relevant to all brain imaging studies. OBJECTIVES AND METHODS: We performed visceral and somatic quantitative sensory and pain testing and studied endogenous pain modulation by heterotopic stimulation outside and inside the functional MRI scanner in 11 healthy controls and 13 patients with irritable bowel syndrome. RESULTS: Rectal pain intensity (VAS 0-100) during identical distension pressures increased from 39 (95% confidence interval: 35-42) outside the scanner to 53 (43-63) inside the scanner in irritable bowel syndrome, and from 42 (31-52) to 49 (39-58), respectively, in controls (ANOVA for scanner effect: p = 0.006, group effect: p = 0.92). The difference in rectal pain outside versus inside correlated significantly with stress (r = -0.76, p = 0.006), anxiety (r = -0.68, p = 0.02) and depression scores (r = -0.67, p = 0.02) in controls, but not in irritable bowel syndrome patients, who a priori had significantly higher stress and anxiety scores. ANOVA analysis showed trends for effect of the scanner environment and subject group on endogenous pain modulation (p = 0.09 and p = 0.1, respectively), but not on somatic pain (p > 0.3). CONCLUSION: The scanner environment significantly increased visceral, but not somatic, pain perception in irritable bowel syndrome patients and healthy controls in a protocol specifically aimed at investigating visceral pain. Psychological factors, including anxiety and stress, are the likely underlying causes, whereas classic endogenous pain modulation pathways activated by heterotopic stimulation play a lesser role. These results are highly relevant to a wide range of imaging applications and need to be taken into account in future pain research. Further controlled studies are indicated to clarify these findings.

Gastrointestinal Symptoms and Altered Intestinal Permeability Induced by Combat Training Are Associated with Distinct Metabotypic Changes.

Physical and psychological stress have been shown to modulate multiple aspects of gastrointestinal (GI) physiology, but its molecular basis remains elusive. We therefore characterized the stress-induced metabolic phenotype (metabotype) in soldiers during high-intensity combat training and correlated the metabotype with changes in GI symptoms and permeability. In a prospective, longitudinal study, urinary metabotyping was conducted on 38 male healthy soldiers during combat training and a rest period using gas chromatography-mass spectrometry. The urinary metabotype during combat training was clearly distinct from the rest period (partial least-squares discriminant analysis (PLSDA) Q(2) = 0.581), confirming the presence of a unique stress-induced metabotype. Differential metabolites related to combat stress were further uncovered, including elevated pyroglutamate and fructose, and reduced gut microbial metabolites, namely, hippurate and m-hydroxyphenylacetate (p < 0.05). The extent of pyroglutamate upregulation exhibited a positive correlation with an increase in IBS-SSS in soldiers during combat training (r = 0.5, p < 0.05). Additionally, the rise in fructose levels was positively correlated with an increase in intestinal permeability (r = 0.6, p < 0.005). In summary, protracted and mixed psychological and physical combat-training stress yielded unique metabolic changes that corresponded with the incidence and severity of GI symptoms and alteration in intestinal permeability. Our study provided novel molecular insights into stress-induced GI perturbations, which could be exploited for future biomarker research or development of therapeutic strategies.

Gastro-oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH-impedance and endoscopic study.

BACKGROUND: Dental erosion is a complication of gastro-oesophageal reflux disease (GORD) according to the Montreal consensus statement. However, GORD has not been comprehensively characterized in patients with dental erosions and pH-impedance measures have not been reported. OBJECTIVES: Characterize GORD in patients with dental erosions using 24-h multichannel intraluminal pH-impedance measurements (pH-MII) and endoscopy. METHODS: This single-centre study investigated reflux in successive patients presenting to dentists with dental erosion using pH-MII and endoscopy. RESULTS: Of the 374 patients, 298 (80%) reported GORD symptoms <2 per week, 72 (19%) had oesophagitis and 59 (16%) had a hiatal hernia. In the 349 with pH-MII the mean percentage time with a pH <4 (95% CI) was 11.0 (9.3-12.7), and 34.4% (31.9-36.9) for a pH <5.5, a critical threshold for dental tissue. The mean numbers of total, acidic and weakly acidic reflux episodes were 71 (63-79), 43 (38-49) and 31 (26-35), respectively. Of the reflux episodes, 19% (17-21) reached the proximal oesophagus. In 241 (69%) patients reflux was abnormal using published normal values for acid exposure time and reflux episodes. No significant associations between the severity of dental erosions and any reflux variables were found. The presence of GORD symptoms and of oesophagitis or a hiatal hernia was associated with greater reflux, but not with increased dental erosion scores. CONCLUSIONS: Significant oligosymptomatic gastro-oesophageal reflux occurs in the majority of patients with dental erosion. The degree of dental erosion did not correlate with any of the accepted quantitative reflux indicators. Definition of clinically relevant reflux parameters by pH-MII for dental erosion and of treatment guidelines are outstanding. Gastroenterologists and dentists need to be aware of the widely prevalent association between dental erosion and atypical GORD.

Fructose transporters GLUT5 and GLUT2 expression in adult patients with fructose intolerance.

BACKGROUND: Gastrointestinal symptoms and malabsorption following fructose ingestion (fructose intolerance) are common in functional gastrointestinal disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be related an abnormality of intestinal fructose transporter proteins. OBJECTIVE: To assess the expression of the main intestinal fructose transporter proteins, glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID. METHODS: The expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue was investigated using real-time reverse-transcription PCR and Western immunoblotting in 11 adults with FGID and fructose intolerance ascertained by breath testing and in 15 controls. RESULTS: Median expression levels of GLUT5 mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13-0.21) in patients and 0.17 (IQR 0.12-0.19) in controls (p > 0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.20-0.31) and 0.26 (IQR 0.19-0.31) (p > 0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.52-1.68) in patients and 0.95 (IQR 0.59-1.15) in controls (p > 0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06-2.14) and 1.35 (IQR 0.96-1.79) (p > 0.05). CONCLUSIONS: Human fructose intolerance may not be associated with marked changes in GLUT5 and GLUT2 expression. Replication of these results in a larger subject group, including measures of transporter activation and membrane and subcellular localization, is warranted.

Combat-training stress in soldiers increases S100B, a marker of increased blood-brain-barrier permeability, and induces immune activation.

BACKGROUND: Experimental data suggest stress-related cognitive dysfunction may be associated with increased blood-brain-barrier (BBB) permeability secondary to immune activation. METHODS: We investigated the relationship between prolonged and intense physical and psychological combat-training stress, immune activation and blood-brain-barrier permeability in 37 healthy male army medical rapid response troops. RESULTS: Soldiers during intense combat training showed greater self-reported stress, anxiety and depression levels than at rest, as assessed by specific questionnaires. S100B, a marker of BBB permeability, as well as serum cortisol, IL-6 and TNF-α concentrations, were significantly increased in soldiers during combat training compared to rest (all p<0.05). Serum S100B correlated negatively with morning serum cortisol in soldiers during combat training, but not during the rest period (r=-0.387, p<0.05). CONCLUSION: We conclude that combat training inducing significant levels of stress, depression and anxiety is accompanied by evidence of increased blood-brain barrier permeability and by increases in systemic pro-inflammatory mediators.

Halitosis and tongue coating in patients with erosive gastroesophageal reflux disease versus nonerosive gastroesophageal reflux disease.

OBJECTIVE: The aim of this study was to investigate whether patients with diagnosed erosive gastroesophageal reflux disease (ERD) have an increased probability of halitosis and tongue coating compared to patients with nonerosive gastroesophageal reflux disease (NERD). MATERIALS AND METHODS: Sixty-six patients (33 males and 33 females) were recruited for the study and received an upper gastrointestinal endoscopy. The presence of ERD (n = 31) and NERD (n = 35) was classified based on the Los Angeles classification for erosive changes in the esophagus. Additionally, the patients filled in a questionnaire regarding their subjective assessment of halitosis, and an organoleptic assessment of halitosis, a measurement of oral volatile sulfur compounds (VSC) with the Halimeter, and a tongue coating index were performed. ERD and NERD subjects were compared with regard to Halitosis-related clinical and anamnestic findings. RESULTS: No statistically significant difference could be found between ERD and NERD patients regarding tongue coating index, organoleptic scores, and VSC values as well as self-perceived bad taste, tongue coating, and bad breath. CONCLUSIONS: These data suggest that halitosis is not typically associated with erosive gastroesophageal reflux disease and the presence of esophageal mucosal damage (ERD patients). CLINICAL RELEVANCE: The data of this investigation support the findings of interdisciplinary bad breath clinics that gastroesophageal reflux disease is not a leading cause for halitosis.

The balancing act: endogenous modulation of pain in functional gastrointestinal disorders.

Functional gastrointestinal disorders (FGIDs) are characterised by visceral pain or discomfort with an unknown cause. There is increasing evidence for abnormal processing of sensory input in FGIDs. Modulation of sensory input occurs at all levels of the nervous system, with a dynamic balance between facilitation and inhibition and close integration with the body's wider homoeostatic control. Cognitive, emotional, autonomic and spinal reflex pathways effectively orchestrate supraspinal and spinal pain modulation, as demonstrated in neurophysiological and brain imaging studies. Endogenous pain modulation has been studied in visceral pain conditions and abnormal regulation has been shown in irritable bowel syndrome (IBS) and functional dyspepsia, as well as other chronic pain syndromes. A majority of patients with IBS have diminished pain inhibition or even pain facilitation compared with healthy controls. Brain imaging during specific activation of endogenous pain modulation demonstrates a fairly consistent functional hub of mainly frontal, limbic and brainstem modulatory regions in healthy humans. Patients with IBS have a different pattern of activation and a correlation between the imaging and sensory changes. Because the modulatory balance of inhibition and facilitation appears to be distributed within the same functional network, future imaging studies of modulation mechanisms should include conditions allowing quantification of inhibitory and facilitatory components. An altered modulatory balance may well be a unifying pathophysiological mechanism in FGID as it can be driven by both top-down (ie, CNS pathology) and bottom-up (ie, peripheral immune activation) influences, but further validation in diverse FGID groups over time is required. Therapeutic manipulation of the modulatory system is possible by both pharmacological and non-pharmacological means.

Acid control cannot be improved with a modified-release formulation of a proton pump inhibitor compared with twice-daily dosing of the conventional formulation.

AIM: The aim of this study was to compare acid control with a once-daily (od) modified-release (MR) formulation of esomeprazole vs. the conventional formulation (CF) dosed twice-daily (bid). METHODS: In a randomized, five-way crossover study, 55 healthy volunteers underwent 24-h intragastric pH monitoring after 5-day treatment with MR esomeprazole (40, 60 or 80 mg od) and CF esomeprazole (20 or 40 mg bid). RESULTS: Modified-release 60 and 80 mg od resulted in a significantly longer time with intragastric pH > 4 than MR 40 mg od (77.1 and 79.0% vs. 66.4%, respectively; both p < 0.05). At equivalent total daily doses, CF 20 mg bid led to a significantly longer time with intragastric pH > 4 than MR 40 mg od (72.3 vs. 66.4%; p < 0.05), and CF 40 mg bid led to a significantly longer time with pH > 4 than MR 80 mg od (85.5 vs. 79.0%; p < 0.05). CONCLUSIONS: At equivalent total daily doses, the MR formulation of esomeprazole provides less 24-h acid control than the conventional formulation dosed twice-daily.

Quantification of dental erosions in patients with GERD using optical coherence tomography before and after double-blind, randomized treatment with esomeprazole or placebo.

OBJECTIVES: Dental erosion, the chemical dissolution of enamel without bacterial involvement, is a rarely reported manifestation of gastroesophageal reflux disease (GERD), as well as of recurrent vomiting and dietary habits. It leads to loss of tooth substance, hypersensitivity, functional impairment, and even tooth fracture. To date, dental erosions have been assessed using only very basic visual methods, and no evidence-based guidelines or studies exist regarding the prevention or treatment of GERD-related dental erosions. METHODS: In this randomized, double-blind study, we used optical coherence tomography (OCT) to quantify dental tissue demineralization and enamel loss before and after 3 weeks of acid-suppressive treatment with esomeprazole 20 mg b.i.d. or placebo in 30 patients presenting to the Berne University Dental Clinic with advanced dental erosions and abnormal acid exposure by 24-h esophageal pH manometry (defined as >4% of the 24-h period with pH<4). Enamel thickness, reflectivity, and absorbance as measures of demineralization were quantified by OCT before and after therapy at identical localizations on teeth with most severe visible erosions as well as several other predefined changes in teeth. RESULTS: The mean+/-s.e.m. decrease of enamel thickness of all teeth before and after treatment at the site of maximum exposure was 7.2+/-0.16 black trianglem with esomeprazole and 15.25+/-0.17black trianglem with placebo (P=0.013), representing a loss of 0.3% and 0.8% of the total enamel thickness, respectively. The change in optical reflectivity to a depth of 25 black trianglem after treatment was-1.122 +/-0.769 dB with esomeprazole and +2.059+/-0.534 dB with placebo (P 0.012), with increased reflectivity signifying demineralization. CONCLUSIONS: OCT non-invasively detected and quantified significantly diminished progression of dental tissue demineralization and enamel loss after only 3 weeks of treatment with esomeprazole 20 mg b.i.d. vs. placebo. This suggests that esomeprazole may be useful in counteracting progression of GERD-related dental erosions. Further validation of preventative treatment regimens using this sensitive detection method is required, including longer follow-up and correlation with quantitative reflux measures.

Activating endogenous visceral pain modulation: a comparison of heterotopic stimulation methods in healthy controls.

All sensory input underlies modulation by endogenous central nervous system pathways. Dysfunctional endogenous pain modulation has been demonstrated in central sensitization and in several pain syndromes, including Irritable Bowel Syndrome (IBS) Activation of endogenous visceral pain modulation by heterotopic stimulation was compared using different methods. Rectal electrical or distension pain alone or with simultaneous (i.e. heterotopic) noxious hand or foot cold stimulation were investigated in randomized sequence in 14 male and 1 female healthy subjects. Mean pain intensities on a visual analogue scale of 0-100 (95% CI) during tonic rectal electrical and distension stimulation alone were 64 (52-76) and 55 (39-71), respectively. Rectal distension pain decreased by 36% (18-55) with simultaneous hand and by 45% (24-66) with simultaneous foot cold pain. Rectal electrical pain decreased by 45% (29-61) during hand and by 46% (28-64) during foot cold pain. Facilitation, i.e. increased rectal pain during heterotopic stimulation was observed in only 1 of 60 stimulation runs. Potent and consistent activation of endogenous visceral pain inhibition was achieved with heterotopic cold pain limb stimulation. Somato-visceral convergence did not affect the effectiveness of induction of endogenous visceral pain inhibition in healthy subjects, as hand and foot heterotopic stimulation resulted in similar pain inhibition. Pain facilitation, as shown earlier in IBS patients, was not evident in healthy controls.