Evaluation of Acute Mountain Sickness by Unsedated Transnasal Esophagogastroduodenoscopy at High Altitude.

BACKGROUND & AIMS: It is not clear how rapid ascent to a high altitude causes the gastrointestinal symptoms of acute mountain sickness (AMS). We assessed the incidence of endoscopic lesions in the upper gastrointestinal tract in healthy mountaineers after a rapid ascent to high altitude, their association with symptoms, and their pathogenic mechanisms. METHODS: In a prospective study, 25 mountaineers (10 women; mean age, 43.8 ± 9.5 y) underwent unsedated, transnasal esophagogastroduodenoscopy in Zurich (490 m) and then on 2 test days (days 2 and 4) at a high altitude laboratory in the Alps (Capanna Regina Margherita, 4559 m). Symptoms were assessed using validated instruments for AMS (the acute mountain sickness score and the Lake Louise scoring system) and visual analogue scales (scale, 0-100). Levels of messenger RNAs (mRNAs) in duodenal biopsy specimens were measured by quantitative polymerase chain rection. RESULTS: The follow-up endoscopy at high altitude was performed in 19 of 25 patients on day 2 and in 23 of 25 patients on day 4. The frequency of endoscopic lesions increased from 12% at baseline to 26.3% on day 2 and to 60.9% on day 4 (P < .001). The incidence of ulcer disease increased from 0 at baseline to 10.5% on day 2 and to 21.7% on day 4 (P = .014). Mucosal lesions were associated with lower hunger scores (37.3 vs 67.4 in patients without lesions; P = .012). Subjects with peptic lesions had higher levels of HIF2A mRNA, which encodes a hypoxia-induced transcription factor, and ICAM1 mRNA, which encodes an adhesion molecule, compared with subjects without lesions (fold changes, 1.38 vs 0.63; P = .001; and 1.37 vs 0.66; P = .011, respectively). CONCLUSIONS: In a prospective study of 25 mountaineers, fast ascent to a high altitude resulted in rapid onset of clinically meaningful mucosal lesions and ulcer disease. Duodenal biopsy specimens from these subjects had increased levels of HIF2A mRNA and ICAM1 mRNA, which might contribute to the formation of hypoxia-induced peptic lesions. Further studies are needed of the mechanisms of this process.

The Dynamics of Gastric Emptying and Self-Reported Feelings of Satiation Are Better Predictors Than Gastrointestinal Hormones of the Effects of Lipid Emulsion Structure on Fat Digestion in Healthy Adults-A Bayesian Inference Approach.

Background: Limited information exists on the relation between fat emulsion structure and its effect on the release of gastrointestinal hormones and feelings of satiation.Objective: We investigated the impact of fat emulsion droplet size, gravitational and acid stability, and redispersibility on gastrointestinal responses and sought to deduce the relative importance of the hormones ghrelin, cholecystokinin, glucagon-like peptide-1, and peptide YY (PYY) in controlling fat emptying and related satiation.Methods: Within a randomized, double-blind, 4-armed crossover study, an extensive data set was generated by MRI of gastric function, analysis of hormone profiles, and ratings of satiation in healthy participants [10 women and 7 men with a mean ± SD age of 25 ± 7 y and body mass index (in kg/m2) of 22 ± 1] after intake of 4 different fat emulsions. Iterative Bayesian model averaging variable selection was used to investigate the influence of hormone profiles in controlling fat emulsion emptying and satiation.Results: The emulsion structure had a distinct effect on the gastric emptying (primary outcome), gastrointestinal hormone profiles, and ratings of satiation (secondary outcomes). Gravitational and acid stability were stronger modulators of fat emptying and hormone profiles than were emulsion droplet size or redispersibility. Cholecystokinin and PYY were most strongly affected by fat emulsion instability and droplet size. Although both hormones were relevant predictors of gastric emptying, only PYY was identified as a relevant predictor of satiation.Conclusions: This work indicates that evenly dispersed, stable, small-emulsion droplets within the stomach lead to prolonged gastric distension, longer ghrelin suppression, and accelerated fat sensing (cholecystokinin and PPY), triggering prolonged feelings of satiation. It suggests that the effects of emulsion instability and droplet size on energy consumption are best studied by assessing changes in gastric emptying and ratings of satiation rather than changes in venous hormone profiles. This trial was registered at clinicaltrials.gov as NCT01253005.

Gastric and Postgastric Processing of 13C Markers Renders the 13C Breath Test an Inappropriate Measurement Method for the Gastric Emptying of Lipid Emulsions in Healthy Adults.

Background: Breath tests (BTs) present an alternative gastric-emptying (GE) measure. However, their efficacy in the measurement of the GE rate of lipid emulsions (LEs) is unknown.Objective: The objective of this work was to investigate the validity of 13C BTs as a measure of fat GE rate in LEs.Methods: The lipophilic 13C octanoate (OCC) BT marker was investigated for fat GE with the hydrophilic 13C sodium acetate (ACC) and the triglyceride 13C trioctanoin (TCC) markers as comparators. Data from 2 randomized studies were combined [50 healthy participants; 25 men, mean ± SD age: 23 ± 2.8 y; mean ± SD body mass index (in kg/m2): 22.4 ± 1.7]. Each participant was given either an acid-stable LE (LE1) or an acid-unstable LE (LE4) at each visit. Twenty-three participants underwent simultaneous MRI. The effect of LEs on 13CO2 excretion profiles was determined. The BT half-emptying times (BT T50) were validated with the MRI half-emptying time of the ingested fat volume (MRI T50).Results: The effect of LEs on 13CO2 excretion depended on the properties of the 13C marker. T50 for OCC was shorter by 98 min for LE1 than for LE4 (P < 0.001). Other markers showed either no LE dependency or a longer T50 for LE1 than for LE4. No difference in T50 between OCC and ACC was detected in LE1. In LE4, the T50 was longer by 154 min (P < 0.0001). There was some concordance between MRI T50 and OCC BT T50 for LE1 (rc = 0.7). No other marker showed any concordance with fat GE. 13C-Nuclear magnetic resonance in vitro findings were compatible with changes in the kinetics of phase transfer of OCC dependent on its protonation state.Conclusions: The structure of fat present in the stomach affects 13CO2 excretion. The chemical properties of the 13C marker and their gastric and postgastric interaction with fat renders 13CO2 excretion an inappropriate measure of LE emptying in healthy adults. This trial was registered at clinicaltrials.gov as NCT02226029 and NCT02602158.

Relationship of body weight with gastrointestinal motor and sensory function: studies in anorexia nervosa and obesity.

BACKGROUND: Whether gastrointestinal motor and sensory function is primary cause or secondary effect of abnormal body weight is uncertain. Moreover, studies relating continuous postprandial sensations of satiation to measurable pathology are scarce. This work assessed postprandial gastrointestinal function and concurrent sensations of satiation across a wide range of body weight and after weight change. METHODS: Patients with anorexia nervosa (AN) and obesity (OB) were investigated in reference to normal weight controls (HC). AN were additionally investigated longitudinally. Gastric emptying, antral contractions and oro-cecal transit after ingestion of a solid meal were investigated by MRI and 13C-lactose-ureide breath test. The dependency of self-reported sensations of satiation on the varying degree of stomach filling during gastric emptying was compared between groups. RESULTS: 24 AN (BMI 14.4 (11.9-16.0) kg/m2), 16 OB (34.9 (29.6-41.5) kg/m2) and 20 HC (21.9 (18.9-24.9) kg/m2) were studied. Gastric half-emptying time (t50) was slower in AN than HC (p = 0.016) and OB (p = 0.007), and a negative association between t50 and BMI was observed between BMI 12 and 25 kg/m2 (p = 0.007). Antral contractions and oro-cecal transit were not different. For any given gastric content volume, self-reported postprandial fullness was greater in AN than in HC or OB (p < 0.001). After weight rehabilitation, t50 in AN tended to become shorter (p = 0.09) and postprandial fullness was less marked (p < 0.01). CONCLUSIONS: A relationship between body weight and gastric emptying as well as self-reported feelings of satiation is present. AN have slower gastric emptying and heightened visceral perception compared to HC and OB. Longitudinal follow-up after weight rehabilitation in AN suggests these abnormalities are not a primary feature, but secondary to other factors that determine abnormal body weight. TRIAL REGISTRATION: Registered July 20, 2009 at ClinicalTrials.gov ( NCT00946816 ).

The visualisation and quantification of human gastrointestinal fat distribution with MRI: a randomised study in healthy subjects.

We aimed to study the fate of fat during digestion. For this purpose, we validated and investigated the non-invasive quantification of gastric and duodenal fat emptying and emulsion processing (creaming and phase separation) using the MRI method iterative decomposition with echo asymmetry and least squares estimation (IDEAL). In total, twelve healthy subjects were studied on two separate visits in a single-blind, randomised, cross-over design study. IDEAL was utilised to repeatedly acquire quantitative fat fraction maps of the gastrointestinal tract after infusion of one of two fat emulsions: E1 (acid stable, droplet size 0·33 mm) and E4 (acid unstable, 0·38 mm). In vitro and in vivo validation was carried out using diluted emulsion and gastric content samples, respectively, and resulted in Lin's concordance correlation coefficients of 1·00 (95% CI 0·98, 1·00) and 0·91 (95% CI 0·87, 0·94), respectively. Fat fraction maps and intragastric emulsion profiles enabled the identification of features of intraluminal phase separation and creaming that were not visible in conventional MRI. Gastric fat emptying was faster for E4 compared with E1 with a difference of 2·5 (95% CI 1·9, 3·1) ml/h. Duodenal content volumes were larger for E1 than for E4 with a difference of 4·9 (95% CI 3·9, 8·5) ml. This study demonstrated that with IDEAL it was possible (1) to visualise the intragastric and duodenal fat distribution and (2) to quantify the differences in emptying, phase separation and creaming of an acid-stable and an acid-unstable emulsion. This method has potential to bridge the gap between current in vitro digestive models and in vivo behaviour and to be applied in the development of effective functional foods.

Assessment of Obstructive Defecation by High-Resolution Anorectal Manometry Compared With Magnetic Resonance Defecography.

BACKGROUND & AIMS: Patients with obstructive defecation have abnormalities of anorectal function and/or structure. Conventional anorectal manometry (ARM) can identify abnormal function and behavior (dyssynergia); however, agreement between manometry and defecography is only fair. High-resolution (HR)-ARM may improve diagnostic agreement by differentiating pressure effects caused by dyssynergia and obstruction. We compared HR-ARM findings with magnetic resonance (MR) defecography in the clinical assessment of patients with symptoms of obstructive defecation defined by Rome III criteria. METHODS: HR-ARM (Manoscan AR 360; Given Imaging, Yoqeam, Israel) assessed anal sphincter function and pressure during simulated defecation. Abnormal manometric findings were classified according to the Rao system and compared with MR defecography as the reference standard. RESULTS: A total of 188 consecutive patients (155 women; age, 19-93 y) with obstructive defecation underwent a full investigation. Compared with patients with dyssynergia on MR imaging (n = 66), patients with structural pathology (n = 87) had lower resting (P < .003) and squeeze pressures (P < .011), but a higher rectoanal pressure gradient (P < .0001) on HR-ARM. High intrarectal pressure with a steep, positive pressure gradient consistent with outlet obstruction on HR-ARM was present in 24 patients with intra-anal intussusception on MR imaging. This pattern was not observed in other patients. Interobserver agreement was substantial for HR-ARM diagnoses (κ = 0.67; 95% confidence interval, 0.559-0.779). Diagnostic accuracy for dyssynergia was 82% compared with MR imaging (sensitivity, 77% [51 of 66]; specificity, 85% [104 of 122]). CONCLUSIONS: The diagnostic agreement between anorectal HR-ARM and MR defecography is high and pressure measurements accurately identify recto-anal dyssynergia and intra-anal outlet obstruction by structural pathology as causes of obstructive defecation.

Validation of a golden angle radial sequence (GOLD) for abdominal T1 mapping during free breathing: demonstrating clinical feasibility for quantifying gastric secretion and emptying.

PURPOSE: To validate a magnetic resonance imaging sequence suitable for quantitative assessment of acid suppression by a proton pump inhibitor (PPI) on gastric secretion and emptying in clinical practice. METHODS: A golden angle radial sequence (GOLD) was validated in a series of in vitro and in vivo experiments and clinical feasibility was shown in two studies. The impact of free breathing and image plane orientation on T1 values was evaluated in a controlled in vivo experiment. The free-breathing GOLD sequence was compared against a standard breath-hold gradient echo sequence for gastric half emptying time in 23 subjects during a gastric emptying study. Pilot data from five subjects assessed the sensitivity of the GOLD sequence to detect changes in acid secretion volume produced by PPI treatment. RESULTS: The coronal free-breathing GOLD sequence and the axial breath-hold standard gradient echo sequence showed good agreement of the gastric half emptying time (6 ± 3 min, P = 0.053). The GOLD sequence demonstrated sensitivity to reduction of gastric secretion volumes induced by PPI treatment (55 ± 5 mL, P < 0.001). CONCLUSION: The GOLD sequence allowed for free breathing, multislice, combined imaging and T1 mapping of the stomach content. GOLD presents a promising multipurpose, noninvasive imaging tool for monitoring gastric function in clinical studies.

Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.

Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

Volume, distribution and acidity of gastric secretion on and off proton pump inhibitor treatment: a randomized double-blind controlled study in patients with gastro-esophageal reflux disease (GERD) and healthy subjects.

BACKGROUND: Postprandial accumulation of gastric secretions in the proximal stomach above the meal adjacent to the esophagogastric junction (EGJ), referred to as the 'acid pocket', has been proposed as a pathophysiological factor in gastro-esophageal reflux disease (GERD) and as a target for GERD treatment. This study assessed the effect of proton pump inhibitor (PPI) therapy on the volume, distribution and acidity of gastric secretions in GERD and healthy subjects (HS). METHODS: A randomized, double blind, cross-over study in 12 HS and 12 GERD patients pre-treated with 40 mg pantoprazole (PPI) or placebo b.i.d. was performed. Postprandial secretion volume (SV), formation of a secretion layer and contact between the layer and the EGJ were quantified by Magnetic Resonance Imaging (MRI). Multi-channel pH-monitoring assessed intragastric pH. RESULTS: A distinct layer of undiluted acid secretion was present on top of gastric contents in almost all participants on and off high-dose acid suppression. PPI reduced SV (193 ml to 100 ml, in HS, 227 ml to 94 ml in GERD; p < 0.01) and thickness of the acid layer (26 mm to 7 mm, 36 mm to 9 mm respectively, p < 0.01). No differences in secretion volume or layer thickness were observed between groups; however, off treatment, contact time between the secretion layer and EGJ was 2.6 times longer in GERD compared to HS (p = 0.012). This was not the case on PPI. CONCLUSIONS: MRI can visualize and quantify the volume and distribution dynamics of gastric secretions that form a layer in the proximal stomach after ingestion of a liquid meal. The secretion volume and the secretion layer on top of gastric contents is similar in GERD patients and HS; however contact between the layer of undiluted secretion and the EGJ is prolonged in patients. High dose PPI reduced secretion volume by about 50% and reduced contact time between secretion and EGJ towards normal levels. TRIAL REGISTRATION: NCT01212614.

Microgravity Simulated by the 6° Head-Down Tilt Bed Rest Test Increases Intestinal Motility but Fails to Induce Gastrointestinal Symptoms of Space Motion Sickness.

BACKGROUND: Space motion sickness (SMS) is the most relevant medical problem during the first days in microgravity. Studies addressing pathophysiology in space face severe technical challenges and microgravity is frequently simulated using the 6° head-down tilt bed rest test (HDT). AIM: We were aiming to test whether SMS could be simulated by HDT, identify related changes in gastrointestinal physiology and test for beneficial effects of exercise interventions. METHODS: HDT was performed in ten healthy individuals. Each individual was tested in three study campaigns varying by a 30-min daily exercise intervention of either standing, an upright exercise regimen, or no intervention. Gastrointestinal symptoms, stool characteristics, gastric emptying time, and small intestinal transit were assessed using standardized questionnaires, (13)C octanoate breath test, and H2 lactulose breath test, respectively, before and at day 2 and 5 of HDT. RESULTS: Individuals described no or minimal gastrointestinal symptoms during HDT. Gastric emptying remained unchanged relative to baseline data collection (BDC). At day 2 of HDT the H2 peak of the lactulose test appeared earlier (mean ± standard error for BDC-1, HDT2, HDT5: 198 ± 7, 139 ± 18, 183 ± 10 min; p: 0.040), indicating accelerated small intestinal transit. Furthermore, during HDT, stool was softer and stool mass increased (BDC: 47 ± 6, HDT: 91 ± 12, recovery: 53 ± 8 g/day; p: 0.014), indicating accelerated colonic transit. Exercise interventions had no effect. CONCLUSION: HDT did not induce symptoms of SMS. During HDT, gastric emptying remained unchanged, but small and large intestinal transit was accelerated.

Abnormal structure and function of the esophagogastric junction and proximal stomach in gastroesophageal reflux disease.

OBJECTIVES: This study applies concurrent magnetic resonance imaging (MRI) and high-resolution manometry (HRM) to test the hypothesis that structural factors involved in reflux protection, in particular, the acute insertion angle of the esophagus into the stomach, are impaired in gastroesophageal reflux disease (GERD) patients. METHODS: A total of 24 healthy volunteers and 24 patients with mild-moderate GERD ingested a test meal. Three-dimensional models of the esophagogastric junction (EGJ) were reconstructed from MRI images. Measurements of the esophagogastric insertion angle, gastric orientation, and volume change were obtained. Esophageal function was assessed by HRM. Number of reflux events and EGJ opening during reflux events were assessed by HRM and cine-MRI. Statistical analysis applied mixed-effects modeling. RESULTS: The esophagogastric insertion angle was wider in GERD patients than in healthy subjects (+7° ± 3°; P=0.03). EGJ opening during reflux events was greater in GERD patients than in healthy subjects (19.3 mm vs. 16.8 mm; P=0.04). The position of insertion and gastric orientation within the abdomen were also altered (both P<0.05). Median number of reflux events was 3 (95% CI: 2.5-4.6) in GERD and 2 (95% CI: 1.8-3.3) in healthy subjects (P=0.09). Lower esophageal sphincter (LES) pressure was lower (-11 ± 2 mm Hg; P<0.0001) and intra-abdominal LES length was shorter (-1.0 ± 0.3 cm, P<0.0006) in GERD patients. CONCLUSIONS: GERD patients have a wider esophagogastric insertion angle and have altered gastric morphology; structural changes that could compromise reflux protection by the "flap valve" mechanism. In addition, the EGJ opens wider during reflux in GERD patients than in healthy volunteers: an effect that facilitates volume reflux of gastric contents.

Real-time multipoint gastrointestinal 19-fluorine catheter tracking.

PURPOSE: To develop MR based real-time gastrointestinal 19-Fluorine (19F) catheter tracking and visualization allowing for real-time detection and feedback of 3D catheter shape and movement as well as catheter-driven adjustments of 1H imaging geometry parameters. METHODS: Data were acquired on a 3T clinical system using 3D Golden Angle radial sampling. Two gastrointestinal catheters incorporating four fiducial 19F markers (65 or 50 µL marker volume) were tracked while being pulled through a gel phantom by an operator inside the MR room with velocities of 2-18 mm/s. During continuous acquisition, k-space profiles were transferred in real-time to an external computer for concurrent reconstruction of 3D 19F images and detection and visualization of marker positions. Based on αthe marker positions, automatic adjustments of 1H imaging planes to facilitate targeted anatomical scanning was implemented. RESULTS: Mean tracking reliabilities were 94.5 and 83.6% (catheters 1 and 2) for temporal resolutions 185-740 ms. Reconstruction times of 196 ms were achieved. Real-time visual feedback allowed the operator to accurately control the catheter movement. Catheter-guidance for 1H imaging was reliable. CONCLUSION: The presented real-time 19F MR based framework for the tracking of 19F labeled devices is applicable to combined 19F and 1H MRI guidance of gastrointestinal devices in vivo.

19F MR imaging golden angle-based capsule tracking for intestinal transit and catheter tracking: initial in vivo experience.

PURPOSE: To combine fluorine 19 ((19)F) magnetic resonance (MR) imaging and golden angle radial acquisition and to assess the feasibility of (19)F MR imaging golden angle-based tracking for catheter tracking applications and simultaneous three-dimensional (3D) intestinal tracking of ingested (19)F-labeled capsules in vivo. MATERIALS AND METHODS: Approval from the local ethical committee and informed consent from the subject were obtained. In vitro studies were performed to assess (19)F MR imaging golden angle-based tracking reliability with regard to temporal resolution and different tracking strategies (boundary condition-free tracking, composite image-based tracking, and model-based tracking). In vivo performance of the method was investigated in one healthy volunteer on 2 days. On study day 1, a duodenal catheter incorporating five (19)F-labeled capsules was administered nasally, and its 3D movement was tracked inside the stomach and esophagus. On study day 2, three (19)F-labeled capsules were swallowed, and intestinal movement was tracked. RESULTS: Simultaneous in vivo 3D tracking of multiple (19)F-labeled capsules was successfully performed without incorporation of boundary conditions at a temporal resolution of 252 msec. Incorporation of boundary conditions with composite image-based tracking and model-based tracking increased tracking reliability and enabled temporal resolution as high as 108 msec. CONCLUSION: Use of (19)F MR imaging golden angle-based capsule tracking enables in vivo tracking of (19)F-labeled capsules and catheters at high temporal resolution. The presented method is applicable to physioanatomic studies of the gastrointestinal tract and shows potential for real-time tracking in interventional radiology.

Altered psychobiological responsiveness in women with irritable bowel syndrome.

OBJECTIVE: Although stress has been considered an important pathophysiological factor in irritable bowel syndrome (IBS), there is incomplete understanding of its physiological mechanisms. The current study was designed to compare diurnal hypothalamic-pituitary-adrenal (HPA) axis activity in IBS patients and controls and their psychobiological response to a psychosocial stressor. METHODS: Basal and stimulated HPA axis activity was assessed in 57 women with IBS and 20 matched controls. Psychiatric comorbidity was assessed using a standardized clinical interview. Salivary morning cortisol and diurnal profile were obtained, and the Trier Social Stress Test (TSST) was administered. Levels of cortisol and adrenocorticotropic hormone (ACTH) were measured before and within 1 hour after the stressor. Overall stress experience and stress related to the TSST were assessed using standardized questionnaires. RESULTS: All subjects showed intact circadian variation of cortisol. However, IBS patients with predominant diarrhea exhibited substantially heightened cortisol levels at awakening (p < .03) and a blunted cortisol awakening response. In response to the TSST, patients exhibited significantly blunted cortisol (p < .05) and slightly attenuated ACTH secretion compared with controls. During the recovery period, ACTH levels were significantly lower (p < .04) in patients than those in healthy subjects. Women with IBS perceived higher stress susceptibility than control subjects did (p < .01). CONCLUSIONS: The enhanced morning cortisol levels in one subgroup of IBS patients may indicate an association between basal HPA axis activity and predominant bowel habit. The downregulated HPA axis reactivity in IBS after the TSST suggests a downregulated sensitivity of the endocrine system. On the contrary, all subjective stress ratings were increased in the IBS group, which may indicate increased stress susceptibility.

Visualization and quantification of intestinal transit and motor function by real-time tracking of 19F labeled capsules in humans.

A combined (19)F and (1)H MRI framework for the assessment of human intestinal transit and motor function is presented. This framework consists of silicone coated polychlorotrifluoroethylene capsules filled with perfluoro-[15]-crown-5-ether as (19)F marker, a flexible (19)F surface coil and a (19)F projection imaging sequence, allowing for real-time tracking of a single or multiple capsules. The capsules (length 11.5 mm, Ø 7.2 mm) contain 140 µL perfluoro-[15]-crown-5-ether and were tested for cytotoxicity and leakage prior to oral administration. A balanced SSFP projection sequence was implemented, yielding a temporal resolution of 133 ms. Optional multi-frequency excitation, allowing for interleaved tracking of differently labeled (19)F capsules, was incorporated. The passage of the (19)F capsules through intestinal sections was monitored in two healthy volunteers. Capsule coordinates were successfully coregistered with anatomical reference scans. Intestinal motility, residence times, lengths and forward velocities were determined. Simultaneous tracking of two capsules allowed for the assessment of peristaltic patterns with correction for respiratory motion. By providing the means for real-time multiple capsule tracking and high resolution anatomical imaging, the presented multinuclear imaging framework has the potential to provide important supplemental information for physiological and pharmaceutical research.

Determinants of fecal continence in healthy, continent subjects: a comprehensive analysis by anal manometry, rectal barostat and a stool substitute retention test.

BACKGROUND/AIMS: This study aimed to identify anal sphincter and rectal factors that determine anorectal filling sensations and continence during rectal filling in health. METHODS: Measurements of anorectal physiology were collected from 42 continent healthy subjects participating in a prospective trial. Rectal function and capacity were assessed by barostat. Anal sphincter functions were assessed by manometry. A validated stool substitute retention test was performed in which a viscous suspension was infused into the rectum at 60 ml/min to 1,500 ml. Multivariate regression was applied to identify physiologic factors that determine anorectal sensation and continence during rectal filling. RESULTS: The volume at which first awareness of rectal filling occurred associated with age (p < 0.03), rectal capacity (p < 0.06) and anal resting pressure (p < 0.003); urgency associated with rectal capacity (p < 0.0007), anal resting (p < 0.04) and squeeze pressure (p < 0.02); volume at first incontinence with rectal capacity (p < 0.0001) and squeeze pressure (p < 0.04) and the maximum volume retained were closely correlated with rectal capacity only (p < 0.0001). CONCLUSION: Anorectal filling sensations and continence in health require a rectal reservoir of adequate capacity and effective voluntary anal sphincter function. Complementary associations between continence, motor and sensory function indicate the presence of an adaptive mechanism that enables timely, appropriate responses to events that threaten fecal continence.

Gastroesophageal junction: structure and function as assessed by using MR imaging.

PURPOSE: To develop and validate magnetic resonance (MR) imaging protocols for quantitative assessment of the structural and functional properties of the gastroesophageal junction (GEJ) and to compare MR imaging detection of reflux events against concurrent manometry as a reference method. MATERIALS AND METHODS: The local ethics committee approved this study, and written informed consent was obtained. Twelve healthy volunteers were examined. Three-dimensional models of the GEJ and proximal portion of the stomach were reconstructed from high-spatial-resolution anatomic MR images to assess the insertion angle of the esophagus into the stomach and proximal stomach distention before and after ingestion of a large test meal. A linear mixed-effects model was used to detect differences in the insertion angle and proximal stomach distention with respect to the respiratory cycle and gastric filling. Additionally, dynamic MR imaging at high temporal resolution was used to detect reflux events. RESULTS: The esophageal insertion angle, given in units of plane angle (radians), was more acute in expiration than in inspiration (0.57 vs 0.73 radian, P = .004) but was not affected by feeding. Progressive distention of the proximal stomach was observed from baseline compared with the postprandial period (0.95 vs 0.65 radian(-1), P < .05). Eighteen reflux events detected by using MR imaging were also detected by using manometry. CONCLUSION: MR imaging methods were developed and validated for the assessment of GEJ structure and function (a) to describe the effects of respiration and feeding on the reflux barrier and (b) to detect reflux events in real time. Anatomic and dynamic MR imaging may be useful techniques in the assessment of GEJ physiology and reflux.

Effect of meal volume and calorie load on postprandial gastric function and emptying: studies under physiological conditions by combined fiber-optic pressure measurement and MRI.

This study assessed the effects of meal volume (MV) and calorie load (CL) on gastric function. MRI and a minimally invasive fiber-optic recording system (FORS) provided simultaneous measurement of gastric volume and pressure changes during gastric filling and emptying of a liquid nutrient meal in physiological conditions. The gastric response to 12 iso-osmolar MV-CL combinations of a multinutrient drink (MV: 200, 400, 600, 800 ml; CL: 200, 300, 400 kcal) was tested in 16 healthy subjects according to a factorial design. Total gastric volume (TGV) and gastric content volume (GCV = MV + secretion) were measured by MRI during nasogastric meal infusion and gastric emptying over 60 min. Intragastric pressure was assessed at 1 Hz by FORS. The dynamic change in postprandial gastric volumes was described by a validated three-component linear exponential model. The stomach expanded with MV, but the ratio of GCV:MV at t(0) diminished with increasing MV (P < 0.01). Postprandial changes in TGV followed those of GCV. Intragastric pressure increased with MV, and this effect was augmented further by CL (P = 0.02); however, the absolute pressure rise was <4 mmHg. A further postprandial increase of gastric volumes was observed early on before any subsequent volume decrease. This "early" increase in GCV was greater for smaller than larger MV (P < 0.01), indicating faster initial gastric emptying of larger MV. In contrast, volume change during filling and in the early postprandial period were unaffected by CL. In the later postprandial period, gastric emptying rate continued to be more rapid with high MVs (P < 0.001); however, at any given volume, gastric emptying was slowed by higher CL (P < 0.001). GCV half-emptying time decreased with CL at 18 +/- 6 min for each additional 100-kcal load (P < 0.001). These findings indicate that gastric wall stress (passive strain and active tone) provides the driving force for gastric emptying, but distal resistance to gastric outflow regulates further passage of nutrients. The distinct early phase of gastric emptying with relatively rapid, uncontrolled passage of nutrients into the small bowel, modulated by meal volume but not nutrient composition, ensures that the delivery of nutrients in the later postprandial period is related to the overall calorie load of the meal.

Abnormal esophageal motility during a solid test meal in systemic sclerosis-detection even in very early disease and association with disease progression.

OBJECTIVE: This study assessed whether high-resolution manometry (HRM) with a test meal can detect clinically relevant, abnormal motility already in very early systemic sclerosis (SSc) and whether this finding is associated with subsequent disease progression. METHODS: This prospective, longitudinal cohort study recruited 68 consecutive SSc patients (group #1: 32 established disease (ACR, American College of Rheumatology /EULAR, The European League against Rheumatism 2013 and ACR 1980 criteria fulfilled); group #2: 24 early disease (only ACR/EULAR 2013 fulfilled); group #3: 12 very early disease (clinical expert diagnosis of SSc) and 72 healthy controls. HRM evaluated esophageal motility for water swallows and a solid test meal. RESULTS: Systemic sclerosis patients had less frequent effective esophageal contractions during the test meal compared to healthy controls even in very early disease (0.15, 1.0, 2.1 per minute for groups #1, #2, and #3, vs 2.5 per minute in health; P < 0.001, P < 0.001, and P < 0.0085, respectively). Ineffective motility at HRM was associated with a higher modified Rodnan skin score at baseline. Moreover, at mean 18 (10-31) months of follow-up, the presence of ineffective motility at baseline was associated with progression of skin disease (P = 0.01). Cox proportional hazard regression analysis identified hypotensive peristalsis in the test meal (<15% effective solid swallows) and low distal contractile integral (DCI; <400 mm Hg·cm·s) as predictors for skin aggravation, but not for new organ involvement. CONCLUSION: Ineffective motility during a test meal is present already in patients with very early SSc. Findings on HRM studies are associated with disease severity at baseline, and low percentage of effective swallows in test meal and low mean DCI are both predictors of skin progression during follow-up.

What to eat and drink in the festive season: a pan-European, observational, cross-sectional study.

BACKGROUND: Digestive discomfort after meals is common in the community, especially during the festive season. It is uncertain whether this is related to intake of either high-calorie or high-fat foods or, alternatively, intake of specific foods. This prospective, cross-sectional study tested the hypothesis that the risk of reflux or dyspepsia is associated with the fat content of the meal independent of caloric load in a 'real-life' setting. MATERIALS AND METHODS: Four festive meals were served to delegates attending a conference on four consecutive days. Test meals had the same volume, but varied in calorie and fat content. Study procedures and symptoms were monitored using a mobile application (SymTrack). The effect of alcoholic compared with nonalcoholic drinks was also assessed. Primary outcome was the occurrence of reflux or dyspeptic symptoms. Fullness was documented by a visual analogue scale. RESULTS: A total of 84/120 (70%) delegates aged 22-69 years consented to participate. At screening, 22 (31%) participants reported at least mild symptoms on the Leuven Dyspepsia Questionnaire. Specific ingredients did not appear to impact on postprandial symptoms. All high-calorie dinners [British, German, Italian (with alcohol)] induced more symptoms than the low-fat, low-calorie Czech dinner [odds ratio: 2.6, 95% confidence interval (CI): 0.97-6.9 (P=0.058), 1.5 (0.3-3.8), and 2.8 (0.7-10.5), respectively]. Self-reported fullness after the high-fat, high-calorie British dinner was higher by 23/100 (95% CI: 4-42, P=0.016) with respect to low-fat, low-calorie Czech and German dinners. CONCLUSION: Study participants tolerated a range of food and drink well. Reflux or dyspeptic symptoms were least likely after the low-fat, low-calorie meal. Fullness was increased after the high-fat, high-calorie dinner, but not low-fat meals. These results will help the public to make evidence-based dietary choices during the carnival season!