Miriam Thumshirn

High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry

Background and aims:  High‐resolution manometry (HRM) is a recent development in oesophageal measurement; its value in the clinical setting remains a matter of controversy. (i) We compared the accuracy with which bolus transport could be predicted from conventional manometry and HRM. (ii) The clinical value of HRM was assessed in a series of patients with endoscopy‐negative dysphagia in whom conventional investigations had been non‐diagnostic.

Modulation of gastric sensory and motor functions by nitrergic and α2-adrenergic agents in humans

BACKGROUND & AIMS Disturbed gastric accommodation and sensation contribute to postprandial symptoms in dyspepsia, but the controlling mechanisms are unclear. Nitrergic and alpha2-adrenergic modulation of gastric sensory and motor function were assessed in this study. METHODS Using a factorial design, we assessed drug effects on gastric sensation during isobaric distentions and fasting and postprandial gastric motor function in 32 healthy volunteers. Each participant received one treatment: placebo; 0.3 or 0.5 microgram. kg-1. min-1 intravenous nitroglycerin; 0.0125, 0.025, or 0.1 mg clonidine orally; or combined nitroglycerin plus clonidine. In 16 other healthy subjects, the effects of clonidine and placebo on gastric emptying of solids were evaluated using the 13C-octanoic acid breath test. RESULTS Clonidine and nitroglycerin increased gastric compliance, but normal postprandial accommodation was still observed despite the induced relaxation. Clonidine but not nitroglycerin reduced aggregate and pain perception averaged over four distention levels. There were no significant drug interactions. No dose effect of clonidine was observed on gastric emptying. CONCLUSIONS Clonidine relaxes the stomach and reduces gastric sensation without inhibiting accommodation or emptying. Nitroglycerin relaxes the stomach without altering perception. Studies of the effects of clonidine on these gastric functions and symptoms in disease are warranted.

Non-invasive measurement of gastric accommodation in humans

Gastric accommodation describes the reduction in gastric tone and increase in compliance that follows ingestion of a meal and involves at least two responses: “receptive relaxation” which allows the stomach to accept a volume load without a significant rise in gastric pressure and “adaptive relaxation” which modulates gastric tone in response to the specific properties of the meal ingested. However, there are considerable technical difficulties in measuring the accommodation process. The current standard barostat studies, and other methods such as conventional and three dimensional ultrasound, or single photon emission computed tomography have significant disadvantages. Preliminary findings from the development and validation of a new magnetic resonance imaging technique that addresses many of the deficiencies of previous methods are presented.

Quantification of distal antral contractile motility in healthy human stomach with magnetic resonance imaging.

To quantify healthy postprandial: 1) propagation, periodicity, geometry, and percentage occlusion by distal antral contraction waves (ACWs); and 2) changes in ACW activity in relationship to gastric emptying (GE).

Gastric mechanosensory and lower esophageal sphincter function in rumination syndrome

Our hypothesis was that rumination syndrome is associated with gastric sensory and motor dysfunction. We studied gastric and somatic sensitivity, reflex relaxation of the lower esophageal sphincter (LES), and gastric compliance and accommodation postprandially and postglucagon. A barostatically controlled gastric bag and esophageal manometry were used to compare gastric sensorimotor functions and LES relaxation to gastric distension in 12 patients with rumination syndrome and 12 controls. During bag distensions, patients had greater nausea, bloating, and aggregate score, but not pain, compared with controls ( P < 0.05). At 4 and 8 mmHg gastric distension, LES tone reduction was greater in patients than in controls ( P < 0.05). Gastric compliance, accommodation to a standard meal, and response to glucagon were not different in patients and controls; however, 6 of 12 patients had no gastric accommodation; the latter patients had significantly greater pain perception during distension ( P < 0.05) but normal somatic sensitivity compared with healthy controls. Rumination syndrome is characterized by higher gastric sensitivity and LES relaxation during gastric distension. A subgroup of patients also had absent postprandial accommodation.

Magnetic Resonance Imaging for the in Vivo Evaluation of Gastric-Retentive Tablets

AbstractPurpose. To develop a magnetic resonance imaging (MRI) technique for assessing in vivo properties of orally ingested gastric-retentive tablets under physiologic conditions. Methods. Tablets with different floating characteristics (tablet A-C) were marked with superparamagnetic Fe3O4 particles to analyze intragastric tablet position and residence time in human volunteers. Optimal Fe3O4 concentration was determined in vitro. Intragastric release characteristic of one slow-release tablet (tablet D) was analyzed by embedding gadolinium chelates (Gd-DOTA) as a drug model into the tablet. All volunteers underwent MRI in the sitting position. Tablet performance was analyzed in terms of relative position of tablet to intragastric meal level (with 100% at meal surface), intragastric residence time (min) and Gd-DOTA distribution volume (% of meal volume). Results. Intragastric tablet floating performance and residence time of tablets (tablet A-D) as well as the intragastric Gd-DOTA distribution of tablet D could be monitored using MRI. Tablet floating performance was different between the tablets (A, 93%(95 − 9%); B, 80%(80 − 68%); C, 38%(63 − 32%); p < 0.05). The intragastric distribution volume of Gd-DOTA was 19.9% proximally and 35.5% distally. Conclusions. The use of MRI allows the assessment of galenic properties of orally ingested tablets in humans in seated position.

Intersubject and intrasubject variability of gastric volumes in response to isocaloric liquid meals in functional dyspepsia and health

Abstract  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 () were determined. Intersubject and intrasubject coefficients of variation (CVinter, CVintra) and Pearsons correlation coefficients (r) were calculated. 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, CVinter, CVintra, 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 . 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 : 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.

Efficacy and safety of botulinum toxin a injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure : A prospective randomized study

OBJECTIVES:To evaluate the efficacy and safety of botulinum toxin A injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure (CAF).METHODS:Fifty outpatients with CAF were randomized to receive either a single botulinum toxin injection (30 IU Botox®) or topical nitroglycerin ointment 0.2% b.i.d. for 2 wk. If the initial therapy failed, patients were assigned to the other treatment group for a further 2 wk. If CAF still showed no healing at wk 4, patients received combination therapy of botulinum toxin and nitroglycerin for 4 additional wk. Persisting CAF at wk 8 was treated according to the investigators decision. Healing rates, symptoms, and side effects of the therapy were recorded at wk 2, 4, 8, 12, and 24 after randomization.RESULTS:The group initially treated with nitroglycerin showed a higher healing rate of CAF (13 of 25, 52%) as compared with the botulinum toxin group (6 of 25, 24%) after the first 2 wk of therapy (p < 0.05). At the end of wk 4, CAF healed in three additional patients, all receiving nitroglycerin after initial botulinum toxin injection. Mild side effects occurred in 13 of 50 (26%) patients, all except one were on nitroglycerin.CONCLUSIONS:Nitroglycerin ointment was superior to the more expensive and invasive botulinum toxin injection for initial healing of CAF, but was associated with more but mild side effects.

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous 13C-acetate breath test

Abstract  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 13C‐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 (T½) 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. T½MRI 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, T½BT 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.

Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging

Background : Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric‐retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research.