On the validity of the (13) C-acetate breath test for comparing gastric emptying of different liquid test meals: a validation study using magnetic resonance imaging.

BACKGROUND: (13) C-acetate breath testing (BT) is applied to assess and compare gastric emptying of liquid meals. Gastric half-emptying times (t50 ) from BT show offsets compared to t50 values from γ-scintigraphy and ultrasonography. Linear transformations have been proposed to correct these offsets. This investigation critically validates the BT for the assessment of liquid gastric emptying by using simultaneously recorded meal and total gastric content volume emptying data from magnetic resonance imaging (MRI). METHODS: Data were collected during a recently published double-blind, randomized, cross-over MRI gastric emptying study of three (13) C-labeled enteral formulas differing in protein sources (PMID: 24699556). Breath testing-derived t50 was computed with the analysis methods commonly applied in gastric emptying research, i.e., the exponential-beta function and the Wagner-Nelson (WN) method, respectively. KEY RESULTS: Breath testing t50 values from exponential-beta function and WN method showed a positive and negative offset to MRI data, respectively. Linear regression detected low concordance between MRI and both BT methods revealing meal specific and emptying rate-dependent offsets. The WN method showed worse agreement and correlation with MRI emptying data. Breath testing rather reflected meal volume than total gastric content volume emptying. CONCLUSIONS & INFERENCES: This validation study indicates that the (13) C-acetate breath test may not be applied to compare gastric emptying of arbitrary liquid meals without prior validation by imaging methods. t50 values from BT are biased by (i) the properties of the meal and (ii) the selected method used for (13) CO2 exhalation analysis. No linear transformation common for all meals was applicable to correct the offsets between BT and MRI.

Effects of baclofen on the functional anatomy of the oesophago-gastric junction and proximal stomach in healthy volunteers and patients with GERD assessed by magnetic resonance imaging and high-resolution manometry: a randomised controlled double-blind study.

BACKGROUND: The mechanism of reflux protection may involve a 'flap valve' at the oesophago-gastric junction (OGJ). AIM: To assess the effects of baclofen, a gamma-aminobutyric acid receptor type-B (GABA-B) agonist known to suppress reflux events, on the 'functional anatomy' of the OGJ and proximal stomach after a large test meal. METHODS: Twelve healthy volunteers (HVs) and 12 patients with gastro-oesophageal reflux disease (GERD); with erosive oesophagitis or pathological oesophageal acid exposure completed a randomised, double-blind, cross-over study. On 2 test days participants received 40-mg baclofen or placebo before ingestion of a large test meal. OGJ structure and function were assessed by high-resolution manometry (HRM) and magnetic resonance imaging (MRI) using validated methods. Measurements of the oesophago-gastric angle were derived from three-dimensional models reconstructed from anatomic MRI images. Cine-MRI and HRM identified postprandial reflux events. Mixed model analysis and Wilcoxon rank signed tests assessed differences between participant groups and treatment conditions. RESULTS: In both HVs and GERD patients, baclofen reduced the frequency of postprandial reflux events. The oesophago-gastric insertion angle in GERD patients was reduced (-4.1 ± 1.8, P = 0.025), but was unchanged in healthy controls. In both study groups, baclofen augmented lower oesophageal sphincter (LES) pressure (HVs: +7.3 ± 1.8 mmHg, P < 0.0001, GERD: +4.50 ± 1.49 mmHg, P < 0.003) and increased LES length (HVs: +0.48 ± 0.11 cm, P < 0.0003, GERD: +0.35 ± 0.06 cm, P < 0.0001). CONCLUSIONS: Baclofen inhibits transient LES relaxations and augments LES pressure and length. Additionally, baclofen has effects on the 'functional anatomy' of the OGJ and proximal stomach in GERD patients, which may suppress reflux by means of a 'flap valve' mechanism.

L-lysine dose dependently delays gastric emptying and increases intestinal fluid volume in humans and rats.

BACKGROUND: Novel sensory inputs for the control of food intake and gastrointestinal (GI) function are of increasing interest due to the rapid increase in nutrition-related diseases. The essential amino acid L-lysine was demonstrated to have a selective impact on food intake, gastric emptying, and intestinal transit in rats, thus indicating a potential novel direct sensory input to assess dietary protein content and quality. The aim of this study was to assess translational aspects of this finding and to investigate the dose-dependent effect of L-lysine on human and rat GI function. METHODS: L-lysine doses from 0-800 mg in rats and 0.5-7.5 g in humans were analyzed for their effect on gastric emptying and GI secretion. Human GI function was assessed non-invasively using magnetic resonance imaging (MRI), rat data were acquired using standard lethal measurement methods. L-lysine dose dependently delayed gastric emptying and stimulated GI secretion in rats as reflected by residual phenol red content and increased gastric wet weight. KEY RESULTS: The dose-dependent delay in gastric emptying observed in rats was confirmed in humans with an increase in halftime of gastric emptying of 4 min/g L-lysine, p < 0.01. Moreover, a dose-dependent increase in intestinal fluid accumulation was observed (0.4 mL/min/g L-lysine, p < 0.0001). No effect on alkaline tide, glucose concentration, hematocrit, or visceral sensations was detected. CONCLUSIONS & INFERENCES: This translational study demonstrates comparable dose-dependent effects of intragastric L-lysine on GI function in humans and rats and suggests a broader role for individual amino acids in the control of GI motility and secretion in vivo.

Toward more accurate measurements of anorectal motor and sensory function in routine clinical practice: validation of high-resolution anorectal manometry and Rapid Barostat Bag measurements of rectal function.

BACKGROUND: Measurements of anorectal function using high-resolution anorectal manometry (HR-ARM) and rectal barostat technology provide more reliable results than standard ARM with an elastic balloon; however, HR-ARM results have not been compared to ARM and standard barostat protocols are impractical in routine clinical practice. The aim of this study was to validate HR-ARM against standard ARM and standard barostat against a novel Rapid Barostat Bag (RBB) measurement and elastic balloon measurements of rectal function. METHODS: Twenty-six healthy volunteers (15 female, 11 male, 19-52 years) were studied. Measurements of anal function and simulated defecation were compared for 12-sensor HR-ARM and 6-sensor standard ARM using line plots from the same recording. Rectal capacity, compliance, and sensation (volume threshold) were measured by elastic balloon, standard barostat, and RBB methods using stepwise inflation of a 700-mL polyethylene bag to 40 mmHg distension by electronic barostat and handheld syringe monitored by sphygmo-manometer, respectively. Results are reported as mean ± SD. Bland-Altman plots and correlation coefficients (r) for measurements were calculated. KEY RESULTS: There was excellent agreement between HR- and standard ARM measurements (r > 0.86, <25 mmHg difference) and between standard barostat and RBB measurements of rectal capacity (r = 0.97, <25 mL difference). Correlation coefficients of threshold volumes for initial perception, urgency and discomfort were 0.37, 0.71, and 0.95, respectively. No significant correlation was present with elastic balloon measurements. Time to complete studies was shorter for HR-ARM than standard ARM and for RBB than standard barostat in historical controls. CONCLUSIONS & INFERENCES: HR-ARM with RBB measurements of anorectal function provides quick and reasonably accurate measurements of continence function suitable for use in routine clinical practice (ClinicalTrial.gov NCT01456442).

Post-prandial reflux suppression by a raft-forming alginate (Gaviscon Advance) compared to a simple antacid documented by magnetic resonance imaging and pH-impedance monitoring: mechanistic assessment in healthy volunteers and randomised, controlled, double-blind study in reflux patients.

BACKGROUND: Alginates form a raft above the gastric contents, which may suppress gastro-oesophageal reflux; however, inconsistent effects have been reported in mechanistic and clinical studies. AIMS: To visualise reflux suppression by an alginate-antacid [Gaviscon Advance (GA), Reckitt Benckiser, UK] compared with a nonraft-forming antacid using magnetic resonance imaging (MRI), and to determine the feasibility of pH-impedance monitoring for assessment of reflux suppression by alginates. METHODS: Two studies were performed: (i) GA and antacid (Alucol, Wander Ltd, Switzerland) were visualised in the stomach after ingestion in 12 healthy volunteers over 30 min after a meal by MRI, with reflux events documented by manometry. (ii) A randomised controlled, double-blind cross-over trial of post-prandial reflux suppression documented by pH-impedance in 20 patients randomised to GA or antacid (Milk of Magnesia; Boots, UK) after two meals taken 24 h apart. RESULTS: MRI visualized a "mass" of GA form at the oesophago-gastric junction (OGJ); simple antacid sank to the distal stomach. The number of post-prandial common cavity reflux events was less with GA than antacid [median 2 (0-5) vs. 5 (1-11); P < 0.035]. Distal reflux events and acid exposure measured by pH-impedance were similar after GA and antacid. There was a trend to reduced proximal reflux events with GA compared with antacid [10.5 (8.9) vs. 13.9 (8.3); P = 0.070]. CONCLUSIONS: Gaviscon Advance forms a 'mass' close to the OGJ and significantly suppresses reflux compared with a nonraft-forming antacid. Standard pH-impedance monitoring is suitable for clinical studies of GA in gastro-oesophageal reflux disease patients where proximal reflux is the primary outcome.

[Gastro-highlights 2012]. / Gastro-Highlights 2012.

The annual Gastro Highlights training event, held at the university Hospital Zurich last autumn, also celebrated the 60th birthday of prof.Dr.med. Michael Fried, who initiated this widely recognized event 17 years ago. Featured at the symposium was a round up of the most important new discoveries in the field of gastroenterology and hepatology to be published during the course of the previous year or represented at the Digestive Disease Week (DDW). To mark the birthday of Prf. Dr. med. Michael Fried, two international experts made a special report on the key developments in the gastroenterology to emerge over the past decades.

Gastric secretion does not affect the reliability of the 13C-acetate breath test: A validation of the 13C-acetate breath test by magnetic resonance imaging.

BACKGROUND: (13)C-Acetate labeled meals are widely used to determine meal emptying by means of analyzing resulting (13)CO(2) exhalation dynamics. In contrast to the underlying metabolic processes, only few (13)C breath test meal emptying studies have focused on intragastric processes that may alter (13)CO(2) exhalation. This work assessed the effect of enhanced gastric secretion on the reliability of half emptying time (t50) measurements by (13)C-acetate breath test. METHODS: (13)CO(2) exhalation data were acquired in a double-blind, randomized, cross-over gastric emptying study in 12 healthy volunteers receiving either pentagastrin or placebo intravenously. The standard method proposed by Ghoos et al. was applied to calculate t50 (t50_Ghoos) from (13)CO(2) exhalation data, which were compared and tested for agreement to meal half emptying times (t50_MV) from concurrent recorded MRI (magnetic resonance imaging) volume data. In addition, the accumulated gastric secretion volumes during infusion as detected by MRI (AUC_SV(60)) were correlated with the corresponding cumulative percent (13)C doses recovered (cPDR(60)). KEY RESULTS: t50_Ghoos and t50_MV showed a linear correlation with a slope of 1.1 ± 0.3 (r(2) = 0.67), however, a positive offset of 136 min for t50_Ghoos. No correlation was detected between AUC_SV(60) and cPDR(60) (r(2) = 0.11). Both, breath test and MRI, revealed a prolonged t50 under pentagastrin infusion with median differences in t50_Ghoos of 45[28-84] min (P = 0.002) and t50_MV of 39[28-52] min (P = 0.002). CONCLUSIONS & INFERENCES: This study suggests that (13)CO(2) exhalation after ingestion of a (13) C-labeled liquid test meal is not affected by stimulated gastric secretion, but is rather reflecting the dynamics of meal or caloric emptying from the stomach.

The effect of standard compared to enhanced instruction and verbal feedback on anorectal manometry measurements.

BACKGROUND: Guidelines recommend instruction and motivation during anorectal manometry; however, its impact on findings has not been reported. This study assessed the effects of standard versus enhanced instruction and verbal feedback on the results of anorectal manometry. METHODS: High-resolution manometry was performed by a solid-state catheter with 10 circumferential sensors at 6 mm separation across the anal canal and two rectal sensors. Measurements were acquired first with standard instruction and then with enhanced instruction and verbal feedback. On both occasions, squeeze pressure and duration during three voluntary contractions and intra-rectal pressure and recto-anal pressure gradient (RAPG) during three attempts at simulated defecation were assessed. KEY RESULTS: A total of 70 consecutive patients (54 female; age 25-82 years) referred for investigation of fecal incontinence (n = 31), constipation, and related disorders of defecation (n = 39) were studied. Enhanced instruction and verbal feedback increased maximum squeeze pressure (Δ10 ± 28.5 mmHg; P < 0.0038) and duration of contraction (Δ3 ± 4 s; P < 0.0001). During simulated defecation, it increased intra-rectal pressure (Δ12 ± 14 mmHg; P < 0.003) and RAPG (Δ11 ± 20 mmHg; P < 0.0001). Using standard diagnostic criteria, the intervention changed manometric findings from locally validated 'pathologic' to 'normal' values in 14/31 patients with incontinence and 12/39 with disorders of defecation. CONCLUSIONS & INFERENCES: Enhanced instruction and verbal feedback significantly improved voluntary anorectal functions and resulted in a clinically relevant change of manometric diagnosis in some patients. Effective explanation of procedures and motivation during manometry is required to ensure consistent results and to provide an accurate representation of patient ability to retain continence and evacuate stool.

The gastro-esophageal reflux barrier: biophysical analysis on 3D models of anatomy from magnetic resonance imaging.

BACKGROUND: The function and structure of the gastro-esophageal junction (GEJ) determine its efficacy as a reflux barrier. This study presents a novel methodology for the quantitative assessment of GEJ and proximal gastric morphology from magnetic resonance (MR) imaging. Based on this data we propose a new conceptualization of the hypothesis that a flap valve mechanism contributes to reflux protection. METHODS: 3D models of the GEJ and proximal stomach were reconstructed from MR images in 12 healthy volunteers during respiration and on eating a test meal to maximum satiation. A rotating plane analysis measured the gastro-esophageal insertion angle and span of contact. An ellipsoid fit provided quantitative assessment of gastric shape and orientation relative to a fixed anatomical reference point. Position of the esophageal insertion on the 'gastric ellipse' was noted. An ellipsoid-cylinder model was designed to analyze the relationships among parameters describing the GEJ morphology. KEY RESULTS: The insertion angle became more acute on expiration, but did not change with meal ingestion. In contrast the span of contact did not vary with respiration, but increased with gastric filling. Changes in gastric morphology with distension further augmented the span of gastro-esophageal contact in almost 70% of the studies. CONCLUSIONS & INFERENCES: Novel MR imaging and biophysical analysis of the GEJ and proximal stomach provide a quantitative description of structures contributing to the reflux barrier. Changes in these parameters during respiration and on eating support the hypothesis that structural components of a functional 'flap valve' like mechanism contribute to reflux protection.

Measuring the interaction of meal and gastric secretion: a combined quantitative magnetic resonance imaging and pharmacokinetic modeling approach.

BACKGROUND: The stimulation and intragastric accumulation of gastric secretion has been recognized as an important factor in gastroesophageal reflux disease. However, the interaction of gastric secretion and meal emptying has not been fully understood. Current methods to assess gastric secretion are either invasive or unable to provide information on its volume, distribution and dynamics. The aim of this study was to quantify the interaction between meal emptying and meal induced gastric secretion by using quantitative magnetic resonance imaging (MRI) and pharmacokinetic analysis. METHODS: A chocolate test meal was developed which is secretion stimulating and MRI compatible. Meal emptying and gastric secretion were assessed in fourteen healthy volunteers using a validated quantitative MRI technique. A population based pharmacokinetic model was developed and applied to the extracted volume data, assessing the meal emptying rate, rate of secretion and their interaction. KEY RESULTS: The test meal continuously induced gastric secretion in all subjects, which partly accumulated at the meal-air interface, forming a 'secretion layer' in the proximal stomach. Traditional fitting detected a significant correlation between meal emptying rate and rate of secretion. The pharmacokinetic model quantified this interaction and estimated a 2.3 ± 1 fold higher effect of meal on secretion than vice versa. The efficacy of the emptied meal to produce gastric secretion was 61%. CONCLUSIONS & INFERENCES: The combined quantitative MRI and pharmacokinetic model approach allows for the quantification of gastric secretion volume and its interaction on meal emptying. The observed secretion layer might explain previous findings postulating the presence of an intragastric 'acid pocket'.

Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography.

BACKGROUND: The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking. PURPOSE: This publication summarizes the state of our knowledge as of the most recent meeting of the International High Resolution Manometry Working Group in Ascona, Switzerland in April 2011. The prior iteration of the Chicago Classification was updated through a process of literature analysis and discussion. The major changes in this document from the prior iteration are largely attributable to research studies published since the prior iteration, in many cases research conducted in response to prior deliberations of the International High Resolution Manometry Working Group. The classification now includes criteria for subtyping achalasia, EGJ outflow obstruction, motility disorders not observed in normal subjects (Distal esophageal spasm, Hypercontractile esophagus, and Absent peristalsis), and statistically defined peristaltic abnormalities (Weak peristalsis, Frequent failed peristalsis, Rapid contractions with normal latency, and Hypertensive peristalsis). The Chicago Classification is an algorithmic scheme for diagnosis of esophageal motility disorders from clinical EPT studies. Moving forward, we anticipate continuing this process with increased emphasis placed on natural history studies and outcome data based on the classification.

[Highlights in gastroenterology 2011]. / Gastro-Highlights 2011. Zusammenfassung der Referate anlässlich des gastroenterologischen Symposiums am Universitätsspital Zürich vom 10. September 2011 unter der Leitung von Professor Michael Fried.

«Gastro-Highlights¼, an annual symposium dedicated to continuing education, took place at the University Hospital Zürich for the sixteenth time this autumn. In this well-attended event, major new findings in the fields of gastroenterology and hepatology that were published in the past year or recently presented at the «Digestive Disease Week (DDW)¼ were summarized for practising gastroenterologists and internists.

Inter-observer reproducibility and analysis of gastric volume measurements and gastric emptying assessed with magnetic resonance imaging.

BACKGROUND: Magnetic resonance (MR) imaging provides direct, non-invasive measurements of gastric function and emptying. The inter-observer variability (IOV) of MR volume measurements and the most appropriate analysis of MR data have not been established. To assess IOV of total gastric volume (TGV) and gastric content volume (GCV) measurements from MR images and the ability of standard power exponential (PowExp), and a novel linear exponential (LinExp) model to describe MR data. METHODS: Ten healthy volunteers received three different volumes of a liquid nutrient test meal (200-800 mL) on 3 days in a randomized order. Magnetic resonance scans were acquired using a 1.5T system every 1-5 min for 60 min. Total gastric volume and GCV were measured independently by three observers. Volume data were fitted by PowExp and LinExp models to assess postprandial volume change and gastric emptying half time (T(50) ). KEY RESULTS: An initial rise in GCV and TGV was often observed after meal ingestion, thereafter GCV and TGV decreased in an approximately linear fashion. Inter-observer variability decreased with greater volumes from 12% at 200 mL to 6% at 600 and 800 mL. Inter-observer variability for T(50) was <5%. PowExp and LinExp models provided comparable estimates of T(50) ; however, only LinExp described dynamic volume change in the early postprandial period. CONCLUSIONS & INFERENCES: Gastric MR provides quantitative measurements of postprandial volume change with low IOV, unless the stomach is nearly empty. The novel LinExp model describes the dynamic volume changes in the early postprandial period more accurately than the PowExp model used in existing gastric emptying studies.

[Highlights in gastroenterology 2010]. / Gastro-Highlights 2010.

This summer saw the fifteenth edition of «Gastro-Highlights¼, a well-attended symposium dedicated to continuing education that takes place each year at the University Hospital in Zurich. Major new findings in the fields of gastroenterology and hepatology that were achieved in the past year and were recently presented at the «Digestive Disease Week (DDW)¼ were summarized here for practising gastroenterologists and internists.

Effects of postgastric 13C-acetate processing on measurement of gastric emptying: a systematic investigation in health.

Uniform postgastric processing of the gastric emptying (GE) marker 13C-acetate (Ac) is an unverified assumption behind its widespread application to measure GE. This study assessed the postgastric processing of Ac administered by intraduodenal (i.d.) infusion simulating different physiological conditions. 13CO2 in breath was assessed in three groups of six volunteers after i.d. administration of A: Different caloric densities (0.75/1.5/3 kcal min(-1) in a 200 mL meal at constant 1 mg Ac min(-1) simulating a physiological range of nutrient delivery rates; B: different tracer delivery rates (0.5/1.0/2.5 mg Ac min(-1) simulating delayed, normal and increased GE; C1: a 500 mL meal resulting in same marker and caloric delivery compared to protocol A; C2: 50 mL water bolus injections of 12.5/25/50/100 mg Ac and C3 bolus injections of 50 mg Ac in 50/100/200 mL water in randomized order. A: 13CO2 excretion was independent of caloric load (P = 0.59). B: The dynamic of 13CO2 excretion was modulated by tracer elimination which was in turn dependent on the speed of tracer delivery, i.e. with faster deliveries resulting in lower 13CO2 recovery during infusion (P < 0.001). C: Increasing Ac doses resulted in decreased 13CO2 recovery (P < 0.001) over the first hour. 13CO2 recovery kinetics was independent of the volume delivered. This study shows 13C-acetate absorption and metabolism is independent of the volume and caloric delivery of test meals. The 'lag' in estimates of GE derived from 13CO2 breath tests is due to a postgastric, dose-dependent delay to 13CO2 elimination. This can be corrected for in analytical derivations of GE parameters based on 13C-acetate breath test measurements.

Effects of clonidine and sumatriptan on postprandial gastric volume response, antral contraction waves and emptying: an MRI study.

Gastric emptying (GE) may be driven by tonic contraction of the stomach ('pressure pump') or antral contraction waves (ACW) ('peristaltic pump'). The mechanism underlying GE was studied by contrasting the effects of clonidine (alpha(2)-adrenergic agonist) and sumatriptan (5-HT(1) agonist) on gastric function. Magnetic resonance imaging provided non-invasive assessment of gastric volume responses, ACW and GE in nine healthy volunteers. Investigations were performed in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) under placebo [0.9% NaCl intravenous (IV) and subcutaneous (SC)], clonidine [0.01 mg min(-1) IV, max 0.1 mg (placebo SC)] or sumatriptan [6 mg SC (placebo IV)]. Total gastric volume (TGV) and gastric content volume (GCV) were assessed every 5 min for 90 min, interspersed with dynamic scan sequences to measure ACW activity. During gastric filling, TGV increased with GCV indicating that meal volume dictates initial relaxation. Gastric contents volume continued to increase over the early postprandial period due to gastric secretion surpassing initial gastric emptying. Clonidine diminished this early increase in GCV, reduced gastric relaxation, decreased ACW frequency compared with placebo. Gastric emptying (GE) rate increased. Sumatriptan had no effect on initial GCV, but prolonged gastric relaxation and disrupted ACW activity. Gastric emptying was delayed. There was a negative correlation between gastric relaxation and GE rate (r(2 )=49%, P < 0.001), whereas the association between ACW frequency and GE rate was inconsistent and weak (r2=15%, P = 0.05). These findings support the hypothesis that nutrient liquid emptying is primarily driven by the 'pressure pump' mechanism.

The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging.

Conventional measurement of gastric secretion is invasive and cannot assess the intra-gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T(1) mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium-DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double-blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T(1) mapping. Data was described by the kappa-coefficient (volume change after meal ingestion), by GE half time (T(50)) and maximal GE rate (GER(max)) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [kappa(GCV):1.6 +/- 0.1 vs 0.6 +/- 0.1; kappa(TGV): 1.6 +/- 0.1 vs 0.7 +/- 0.1; P < 0.001]. T(1) maps revealed a secretion layer above the meal, the volume of which was associated with kappa (R(2) = 83%, P < 0.001). TGV and GCV change were similar in both conditions (kappa; P = ns). T(50) was higher for pentagastrin than for placebo (84 +/- 7 vs 56 +/- 4min, P < 0.001); however, GER(max) was similar (5.9 +/- 0.6 vs 4.9 +/- 0.4 mL min(-1), P = ns). This study shows volume and distribution of gastric secretion can be quantified in-vivo by non-invasive MRI T(1) mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T(50); however, GE rate is unchanged.

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous C-acetate breath test.

The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and 13C-acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of (13)C-acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half-times (T(1/2)) for MRI and BT were calculated (mean +/- SD). We found: (i) Initial GCV was lower in FD than in HC (762 +/- 22 vs 810 +/- 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T(1/2)(MRI) was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 +/- 30 min vs FD 138 +/- 42 min, ns; 800 mL: HC 71 +/- 16 min vs FD 78 +/- 27 min, ns). In contrast, T(1/2)(BT) was similar between meals and groups (200 mL: HC 111 +/- 11 min vs FD 116 +/- 19 min; 800 mL: HC 114 +/- 14 min vs FD: 113 +/- 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non-invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high-volume compared to low-volume liquid nutrient meals in HC or FD.

Physiology of the oesophageal transition zone in the presence of chronic bolus retention: studies using concurrent high resolution manometry and digital fluoroscopy.

Distinct contraction waves (CWs) exist above and below the transition zone (TZ) between the striated and smooth muscle oesophagus. We hypothesize that bolus transport is impaired in patients with abnormal spatio-temporal coordination and/or contractile pressure in the TZ. Concurrent high resolution manometry and digital fluoroscopy were performed in healthy subjects and patients with reflux oesophagitis; a condition associated with ineffective oesophageal contractility and clearance. A detailed analysis of space-time variations in bolus movement, intra-bolus and intra-luminal pressure was performed on 17 normal studies and nine studies in oesophagitis patients with impaired bolus transit using an interactive computer based system. Compared with normal controls, oesophagitis patients had greater spatial separation between the upper and lower CW tails [median 5.2 cm (range 4.4-5.6) vs 3.1 cm (2.2-3.7)], the average relative pressure within the TZ region (TZ strength) was lower [30.8 mmHg (28.3-36.5) vs 45.8 mmHg (36.1-55.7), P < 0.001], and the risk of bolus retention was higher (90%vs 12%; P < 0.01). The presence of bolus retention was associated with a wider spatial separation of the upper and lower CWs (>3 cm, the upper limit of normal; P < 0.002), independent of the presence of oesophagitis. We conclude that bolus retention in the TZ is associated with excessively wide spatial separation between the upper and lower CWs and lower TZ muscle squeeze. These findings provide a physio-mechanical basis for the occurrence of bolus retention at the level of the aortic arch, and may underlie impaired clearance with reflux oesophagitis.

Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis--a randomized controlled, cross-over trial.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function. AIM: To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high-dose omeprazole. METHODS: Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross-over, placebo controlled study. At the end of each period a 24 h pH-study with intragastric and oesophageal pH measurement was performed. RESULTS: Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH-studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH-studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life. CONCLUSION: Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high-dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population.