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Objective: At high altitude (HA), acute mountain sickness (AMS) is accompanied by neurologic and upper gastrointestinal symptoms (UGS). The primary aim of this study was to test the hypothesis that delayed gastric emptying (GE), assessed by 13 C-octanoate breath testing (OBT), causes UGS in AMS. The secondary aim was to assess post-gastric mechanisms of OBT, which could confound results under these conditions, by determination of intermediary metabolites, gastrointestinal peptides, and basal metabolic rate., Methods: A prospective trial was performed in 25 healthy participants (15 male) at 4559 m (HA) and at 490 m (Zurich). GE was assessed by OBT (428 kcal solid meal) and UGS by visual analogue scales (VAS). Blood sampling of metabolites (glucose, free fatty acids (FFA), triglycerides (TG), beta-hydroxyl butyrate (BHB), L-lactate) and gastrointestinal peptides (insulin, amylin, PYY, etc.) was performed as well as blood gas analysis and spirometry., Statistical Analysis: variance analyses, bivariate correlation, and multilinear regression analysis., Results: After 24 h under hypoxic conditions at HA, participants developed AMS (p < 0.001). 13 CO 2 exhalation kinetics increased (p < 0.05) resulting in reduced estimates of gastric half-emptying times (p < 0.01). However, median resting respiratory quotients and plasma profiles of TG indicated that augmented beta-oxidation was the main predictor of accelerated 13 CO 2 -generation under these conditions., Conclusion: Quantification of 13 C-octanoate oxidation by a breath test is sensitive to variation in metabolic (liver) function under hypoxic conditions. 13 C-breath testing using short-chain fatty acids is not reliable for measurement of gastric function at HA and should be considered critically in other severe hypoxic conditions, like sepsis or chronic lung disease., (© 2021 The Authors. Neurogastroenterology && Motility published by John Wiley & Sons Ltd.)

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)., (© 2014 John Wiley & Sons Ltd.)

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., (© 2012 Blackwell Publishing Ltd.)

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., (© 2011 Blackwell Publishing Ltd.)

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.

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 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.

Gastric emptying (GE) has a considerable variability, but data on reproducibility of gastric volume measurements are sparse. We aimed to study the reproducibility of postprandial gastric volume responses and GE using magnetic resonance imaging (MRI) in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent a MRI study on two occasions. MR images were acquired in seated position before and up to 120 min after liquid meal administration (200 mL, 300 kcal). Fasting (V0), initial postprandial stomach volumes (V1), volume changes (V1 - V0) and meal emptying half-times (T 1/2) were determined. Intersubject and intrasubject coefficients of variation (CV(inter), CV(intra)) and Pearson's correlation coefficients (r) were calculated. T 1/2 on both occasions were (mean +/- SD) 113 +/- 28 and 121 +/- 30 min in HC (ns) and 127 +/- 31 and 128 +/- 37 min in FD (ns), respectively. In HC, CV(inter), CV(intra), r were 31%, 23%, 0.49 for V0; 13%, 7%, 0.68 for V1; 10%, 4%, 0.71 for V1 - V0 and 25%, 7%, 0.90 for T 1/2. In FD these parameters were for V0: 42%, 41%, -0.06; for V1: 18%, 10%, 0.40; for V1 - V0: 20%, 14%, 0.74 and for T 1/2: 26%, 10%, 0.84. The stomach accommodates to a given meal volume, resulting in similar and reproducible postprandial volumes within- and between-subjects. MRI provides reproducible measurements of gastric volume responses in health and disease.