Stefania Carmagnola

Relationship between motor function of the proximal stomach and transient lower oesophageal sphincter relaxation after morphine

Background: Morphine reduces the rate of transient lower oesophageal sphincter (LOS) relaxations but its site of action is presently unknown. There are no data available concerning its motor effects on the proximal stomach, an important site for triggering transient LOS relaxations. Aim: To evaluate the effect of morphine on the rate of transient LOS relaxations and motor function of the proximal stomach. Subjects and methods: In 19 healthy subjects, concurrent transient LOS relaxations with a sleeve sensor and motor function of the proximal stomach with a bag connected to an electronic barostat were recorded during pressure controlled (n = 9) and volume controlled (n = 10) gastric distensions after intravenous administration of placebo and morphine 100 μg/kg. Results: During pressure controlled distensions, intrabag volume was markedly decreased by morphine (median 189 ml (interquartile range 101–448) v 404 (265–868) after placebo; p<0.01) as was the rate of transient LOS relaxations (0.5/30 minutes (0.4–2) v 2.5 (2–4); p<0.01). When intrabag volume was kept constant (525 ml (490–600)) (that is, in volume controlled distensions), the rate of transient LOS relaxations was not affected by morphine (2/30 minutes (2–3) v 2.5 (2–3)). Gastric contractions decreased after morphine similarly during pressure controlled and volume controlled distensions (8.5/30 minutes (4–10) v 15.5 (9.5–20.5), p<0.02; and 6.5 (0–24) v 19.5 (12–22), p<0.05). Conclusions: The effect of morphine on transient LOS relaxations is dependent on the decrease in volume of the proximal stomach. Our data suggest that pharmacological interventions which decrease fundal volume should result in control of transient LOS relaxation mediated gastro-oesophageal reflux.

Gastro‐oesophageal reflux disease – pathophysiological issues of clinical relevance

Gastro‐oesophageal reflux disease is a multifactorial disorder in which the pathophysiological mechanisms are variably combined in different patients. Motor dysfunction of the lower oesophageal sphincter (LOS) and, possibly, the proximal stomach is a major cause of the increase in the number of reflux episodes. Transient LOS relaxation is the main mechanism of reflux in many patients with endoscopically negative disease, whereas a hypotensive LOS becomes relevant only in patients with oesophagitis. Alterations in primary and secondary peristalsis contribute to the increased oesophageal acid exposure by delaying clearance. The presence of a hiatus hernia, especially when voluminous and/or non‐reducible, increases the number of reflux episodes by mechanically weakening the oesophago‐gastric junction, and impairs oesophageal clearance. Hypersensitivity to acid is often present and contributes to the clinical manifestations of the disease, whereas oesophageal hypersensitivity, both to chemical and mechanical stimuli, plays a predominant role in a subset of patients. Increased concentrations of noxious compounds in the oesophageal refluxate may contribute to the development of anatomical lesions, but this is still a matter for debate. The clinical relevance of Helicobacter pylori infection and of mucosal defensive factors still needs to be fully elucidated.

Mechanoreceptors of the proximal stomach and perception of gastric distension

OBJECTIVES:To assess the role of tension receptors in gastric perception by pharmacologically modifying gastric contractile activity during isovolumetric distensions of the proximal stomach with the hypothesis that relaxation decreased perception and contraction increased it.METHODS:Fourteen healthy subjects underwent two 30-min isovolumetric (75% of the threshold volume for discomfort) distensions using a barostat. During the second distension, either gastric relaxation was induced by intravenous (i.v.) glucagon 4.8 μg/kg bolus plus 9.6 μg/kg per h or contraction by i.v. erythromycin 3 mg/kg. Hunger and fullness were assessed with a 100-mm analog scale before and at 15 and 30 min during each distension.RESULTS:Glucagon decreased baseline intrabag pressure (8.4 ± 1.0 vs 10.7 ± 1.3 mmHg; p < 0.05) and abolished the pressure waves (0 vs 16.7 ± 2.3) when compared with placebo, whereas erythromycin increased baseline pressure (13.2 ± 1.0 vs 11.9 ± 0.9 mmHg; p < 0.05) and the rate of pressure waves (31.7 ± 5.4 vs 20.5 ± 3.1; p < 0.05). Fullness increased (p < 0.05) during distension, but it was unaffected by either of the drugs: Δ score (i.e., score during distension− baseline score) of 38 ± 10 mm (glucagon) versus 22 ± 10 (placebo) and 24 ± 17 mm (erythromycin) versus 36 ± 14 (placebo) at 15 min. Similar observation were made at 30 min. Hunger was influenced neither by distension nor by any of the two drugs consistently.CONCLUSIONS:Our data do not support a prominent role of tension receptors of the proximal stomach on perception of fullness, suggesting that stretch, that is, volume, is the more relevant stimulus.

Relationship between acceleration of gastric emptying and oesophageal acid exposure in patients with endoscopy-negative gastro-oesophageal reflux disease

Objective. A delay in gastric emptying has been reported in patients with gastro-oesophageal reflux disease (GORD), but its role in increasing the number of reflux episodes is still debated. The aim of this study was to assess the relationship between acceleration of gastric emptying and gastro-oesophageal reflux in patients with endoscopy-negative GORD and pathological oesophageal acid exposure. Material and methods. Twelve patients (7 M, age range 24–65 years) underwent 6-h postprandial (2.1 MJ meal) combined gastric emptying by real-time ultrasonography and intra-oesophageal pH monitoring after cisapride (20 mg b.i.d.) and placebo for 3 days, on two separate occasions at least 7 days apart in double-blind randomized order. Gastric emptying after placebo was also measured in 12 healthy volunteers (7 M, age range 25–54 years). Results. In the patients’ group, the area under the emptying time curve was greater (p<0.01), and half and total emptying times prolonged (p<0.01) compared to the healthy subjects, 115 min (mean)±6 (SEM) versus 86±6 and 232 min±16 versus 160±7, respectively. Cisapride accelerated both half- and total gastric emptying (p<0.02): −22 min (mean); −10 to −34 (95% CI) and −48 min; −10 to −85, respectively, decreased both percentage of time at pH < 4 (p<0.01) and number of reflux episodes (p<0.05). However, no relationship was found between changes in gastric emptying and in the reflux variables by linear regression analysis (R2<0.005). Conclusion. The emptying rate of the whole stomach is not a major determinant of gastro-oesophageal reflux.

Effect of non‐selective γ‐aminobutyric acid receptor stimulation on motor function of the lower oesophageal sphincter and gastro‐oesophageal reflux in healthy human subjects

Background : Transient lower oesophageal sphincter relaxation and low lower oesophageal sphincter pressure are the main mechanisms of reflux. It has recently been shown that the stimulation of γ‐aminobutyric acid type B (GABAB) receptors by baclofen decreases the rate of transient lower oesophageal sphincter relaxation and increases the lower oesophageal sphincter pressure in healthy humans. Valproic acid increases synaptosomal GABA concentrations, thus affecting all types of GABA receptors.

Narrow band imaging vs. high definition colonoscopy for detection of colorectal adenomas in patients with positive faecal occult blood test: A randomised trial

BACKGROUND The impact of narrow band imaging in improving the adenoma detection rate in a screening scenario is still unclear. AIM To evaluate whether narrow band imaging compared with high definition white light colonoscopy can enhance the adenoma detection rate during screening colonoscopy. METHODS Consecutive patients presenting for screening colonoscopy were included into this study and were randomly assigned to the narrow band imaging group (Group 1) or standard colonoscopy group (Group 2). Primary end point was the adenoma detection rate and secondary aim was the detection rate of advanced adenomas. RESULTS Overall, 117 patients were allocated to Group 1 and 120 to Group 2. Both the adenoma detection rate and the detection rate of advanced adenomas were not significantly different between the two groups (respectively, 52.1% vs. 55%, RR=0.95, 95% CI 0.75-1.20; 32.5% vs. 44.2%, RR=0.74, 95% CI 0.53-1.02). No significant difference between the proportions of polypoid and flat adenomas was found. Male gender, no prior history of screening, and endoscopists adenoma detection rate were independent predictive factors of higher advanced adenoma detection rate. CONCLUSIONS In a screening scenario, narrow band imaging did not improve the adenoma nor advanced adenoma detection rates compared to high definition white light colonoscopy.

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans

Abstract  A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30‐min distension periods separated by a 45‐min washout with the bag deflated. The studies lasted 145 ± 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2–4 vs 3;2.5–4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3–12.3 mmHg vs 10.8;9.3–12.5 mmHg and 16;13–28 mmHg vs 19;15–29 mmHg, respectively. Our model allows to perform 1‐day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.

Morphine and transient lower esophageal sphincter relaxation (TLESR): Relevance of fundic mechanoreceptors

Background and aim: TLESR is a major mechanism of gastroesophageal reflux. It has been previously shown that morphine decreases the rate of TLESRs, the volume of the proximal stomach and the number of its contractions (Gastroenterology 2000;118:A860). h is presently unknown if the effect on TLESRs depends on those exerted on the stomach, and in this case if it is due to a decrease in stimulation of stretch receptors (~, in gastric volume) or tension receptors (J. in the number of contractions). Our aim was to assess the effect of morphine on the rate of TLESRs and motor function of the proximal stomach in a lsovohimetric model of gastric distension (which does not modify stimulation of stretch receptors). Methods: 10 healthy subjects, 6 men, aged 21-30 yrs, were studied using a multihimen assembly recording pressures in the phaqmx, esophageal body, lower esophageal sphincter (Dentaleeve), stomach and a bag catheter positioned in the proximal stomach and connected to a harostat, lntrabag volume was set at 75% of the threshold volume for gastric discomfort and maintained for two 35-min distension periods separated by 45-min washout with the bag deflated. At the beginmng of the second distension morphine 100 p.g/kg iv as a bolus was administered, lntrabag fIB) baseline pressure and pressure waves (->3 mmHg) were evaluated as a measure of tone and phasic contractions in the proximal stomach respectively. Results (means -+ gEM): IB volume was 502 -+ 32 ml. See table. Conclusions: in a isovolumetnc model of gastric distension morphine decreases stimulation of tension receptors by inhibiting gasmc contractions, but it does not affect the rate of TLESRs, suggesting that a decrease in volume of the proximal stomach 0. in stretch receptor stimulation) is essential for its effect on TLESRs. Pharmacological interventions which decrease the volume of the proximal stomach should result in control of TLESR-mediated gastroesophageal reflux.