Rosario Cuomo

Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia

Aims: Impaired gastric accommodation is a major pathophysiological mechanism in functional dyspepsia. The aim of the present work was to assess a satiety drinking test in the evaluation of accommodation in health and dyspepsia. Methods: Twenty five controls and 37 severely dyspeptic patients seen at a tertiary care centre completed a dyspepsia questionnaire, and gastric emptying and gastric barostat studies. The amount of liquid meal ingested at maximum satiety during a slow satiety drinking test was determined. In controls, we studied the influence of caloric density and of pharmacological agents that influence accommodation. Results: In patients, satiety scores were higher and maximum satiety occurred at lower calories (542 (50) v 1508 (53) kcal; p<0.0001). Six patients had required nutritional support, but excluding these did not alter the correlations. With increasing severity of early satiety, less calories were ingested at maximum satiety. In multivariate analysis, the amount of calories was significantly correlated to accommodation but not to gastric emptying or sensitivity. Sensitivity and specificity of the satiety test in predicting impaired accommodation reached 92% and 86%, respectively. At different caloric densities, ingested volume rather than caloric load determined maximum satiety. Pharmacological agents (sumatriptan, cisapride, erythromycin) affected the satiety test according to their effect on accommodation. Conclusion: A slow caloric drinking test can be used to evaluate accommodation and early satiety. It provides a non-invasive method of predicting impaired accommodation and quantifying pharmacological influences on accommodation.

Influence of Motilin on Gastric Fundus Tone and on Meal-Induced Satiety in Man: Role of Cholinergic Pathways

BACKGROUND:Motilin agonists are strong gastroprokinetics, but their impact on symptoms in delayed gastric emptying has been disappointing. It has been speculated that it is due to the contractile effect of motilin agonists on the proximal stomach, but the pathway involved and the symptomatic consequences have been incompletely elucidated.AIMS:To study whether motilin enhances proximal stomach tone and enhances meal-induced satiety and to evaluate whether this effect involves a cholinergic pathway.METHODS:A gastric barostat was used to study, in healthy subjects, the effect of motilin (300 ng/kg/30 min IV) or saline on fasting gastric fundus tone and on post-prandial relaxation. To evaluate the involvement of a cholinergic pathway, atropine (12 μg/kg/h) was administered intravenously simultaneously with or before and during motilin infusion in the fasting state. Finally, a satiety drinking test was performed in 21 subjects twice after pretreatment with placebo or motilin and with placebo or atropine.RESULTS:Administration of motilin caused a significant increase of fasting fundus tone expressed as decrease of the mean balloon volume (324 ± 60 mL vs 213 ± 62 mL, p < 0.05). Simultaneous administration of atropine and motilin did not generate a significant volume change (192 ± 60 mL vs 181 ± 83 mL, NS), but pretreatment with atropine alone induced a relaxation, and when motilin was added this revealed an ongoing contraction (192 ± 24 mL vs 136 ± 21 mL, p≤ 0.05). Motilin infusion also inhibited gastric accommodation (p≤ 0.05 vs placebo) and increased satiety during a satiety drinking test (p≤ 0.05 vs placebo).CONCLUSIONS:Administration of motilin causes a contraction of the proximal stomach in humans and increases meal-induced satiety. The effect of motilin is atropine-resistant and involves a direct muscular pathway or a non-cholinergic neural pathway.

Reproducibility of gastric barostat studies in healthy controls and in dyspeptic patients.

Objectives:Gastric barostat studies are increasingly being performed, but their reproducibility and the most suitable study protocol have not been determined. The aim of this study was to verify the reproducibility of gastric sensitivity and accommodation testing in healthy and in dyspeptic subjects, and to compare stepwise and double random staircase distensions.METHODS:A total of 13 dyspeptic patients and 25 healthy control subjects underwent two successive studies. Sensory thresholds were assessed on a same-day/different-days protocol, using a stepwise (11/14 healthy subjects and 11/13 patients) or a double random staircase inflation (11/21 healthy subjects). In 10 healthy subjects, both methods were compared. Gastric accommodation was measured on different days in 13 patients and nine healthy subjects. Data (mean ± SEM) were compared using the paired t test, and individual variability was expressed as the percent coefficient of variation.RESULTS:In healthy subjects, the thresholds for first perception and for discomfort were highly reproducible (p > 0.05) and the pressure thresholds showed a lower degree of variability than the volumes. Pressure thresholds quantified by stepwise showed lower variability than double random staircase inflation. In the patients, the sensory thresholds were unchanged between the sessions on the same and on different days (p > 0.05). Gastric accommodation also showed excellent reproducibility for both dyspeptic patients and healthy control subjects (p > 0.05).CONCLUSIONS:Both in dyspeptic patients and in healthy control subjects, gastric sensitivity and accommodation quantified by isobaric distensions show excellent reproducibility. Pressure and volume thresholds both are well reproducible, but the former shows less variability. Finally, the simplest stepwise protocol is better than the double random staircase to assess the gastric sensitivity to distension.

Symptom patterns and pathophysiological mechanisms in dyspeptic patients with and without Helicobacter pylori.

Helicobacter pylori (HP) has been proposed as a mechanism of functional dyspepsia, but its role is still unclear. Our aim was to investigate the association between HP infection and dyspeptic symptoms and to verify whether the infection affects the pathophysiological mechanism of functional dyspepsia. The presence of HP and its association with dyspeptic symptoms were studied in 326 patients. Also, the effect of HP infection on solid/liquid gastric emptying rates, gastric sensitivity, and accommodation to meal was studied. HP was present in 17% of the patients, who showed symptom prevalence similar to that of HP-negative patients. Presence of HP did not significantly affect gastric emptying rates for solids and liquids, discomfort sensitivity thresholds (8.7 ± 0.3 vs 9.8 ± 0.9 mm Hg), or meal-induced gastric relaxation (133 ± 12 vs 125 ± 29 ml; all Ps NS). In conclusion, in patients with functional dyspepsia the presence of HP infection does not seem to affect significantly the overall prevalence of symptoms or the gastric sensory–motor functions.

Analysis of ambulatory duodenogastroesophageal reflux monitoring.

Some methodological in vitro observations concerning bile reflux monitoring (Bilitec) suggested that Bilitec monitoring is underestimating reflux in an acid environment. Moreover, other studies showed that the area above the cutoff level of bilirubin absorbance would provide an adequate quantitative marker for reflux of duodenal contents. Our aim was to study whether correction for intraesophageal acidity and the area above cutoff during Bilitec monitoring affects the results and the correlation with pH measurement and esophageal lesions. In 84 patients (46 men; mean age 46 ± 2.7 years) evaluated for suspected gastroesophageal reflux disease, we performed ambulatory 24-hr esophageal pH and Bilitec monitoring after an upper gastrointestinal endoscopy. We obtained total area, percent total time, and correction by computer software. The correction factor for bilirubin absorbance was based on literature data for acidified bile (0.06 for pH < 3.6; 0.21 for pH < 2.6). Endoscopy revealed esophagitis grade 1–2 (E1–2) and 3–4 (E3–4) in 23 and 16 patients, respectively. A progressive increase of mixed (acid + bile) reflux occurred with increasing severity of endoscopic lesions (E3–4 vs no esophagitis, P < 0.05). A pathologic Bilitec monitoring result was present in the same 35 patients before and after correction and the correlation between the pH measurement and percent time of bile reflux was not improved by correction for intraesophageal pH (r = 0.386 and r = 0.391; P < 0.05). The total area of bilirubin absorbance above 0.14 (abs × min) was 7.8 ± 2.2 in patients without esophagitis, and 11.7 ± 4.4 and 17.0 ± 4.2 in the E1–2 and E3–4 groups, respectively (E3–4 vs no esophagitis, P < 0.05). The correlation between the Bilitec monitoring and pH measurement regarding percent (r = 0.427, P < 0.01) or area of time below 4 (r = 0.280, P < 0.05) was not improved by considering the area of bilirubin absorbance above the cutoff level. Correction for intraesophageal pH has only a minor effect on the results of ambulatory Bilitec monitoring. Taking into account the surface rather than the percent of time above the cutoff level for bilirubin absorbance does not improve the correlation of Bilitec with acid reflux and with esophageal lesions.

Mechanisms underlying duodeno-gastric reflux in man

Abstractu2002 Background:u2002 Recent studies suggest that duodeno‐gastro‐oesophageal reflux (DGER) contributes to the occurrence of reflux oesophagitis and Barretts oesophagus. The mechanisms underlying duodeno‐gastric reflux (DGR), a prerequisite for DGER, are poorly understood.

Enteric Nervous System Abnormalities in Ulcerative Colitis

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease affecting the mucosa and the submucosa of the colon, and is characterized by alterations of gut functions which influence the clinical symptoms (Fiocchi, 1998; Reddy et al., 1991; Spriggs et al., 1951). Although reports showed morpho-functional abnormalities of the enteric nervous system in UC patients, the available literature is still heterogeneous and confusing. UC-related intestinal inflammation causes structural and functional changes to the enteric nervous system and its cellular components (neurons and glial cells), which could be directly related to the development of the disease and its associated symptoms (Geboes & Collins, 1998; Lakhan & Kirchgessner, 2010; Lomax et al., 2005; Villanacci et al., 2008). UC-related alteration in the enteric nervous system can be categorised into two groups: a) the alterations that occur in the structural morphology of the system, and b) those that occur in the level of enteric transmitters released by neurons and glial cells (Lakhan & Kirchgessner, 2010). Routine pathology of UC reports describe: 1) hypertrophy, hyperplasia and axonal damage of nerve fibres (Cook & Dixon, 1973; Geboes, 1993); 2) a normal aspect, hypertrophy, hyperplasia or damage of neuronal cell bodies (Belai et al., 1997; Siemers & Dobbins, 1974; Strobach et al., 1990); 3) glial cells hyperplasia (Antonius et al., 1960); 4) a variable increase of glial cells number (Geboes et al., 1992; Koretz et al., 1987); and 5) ganglioneuritis (Ohlsson et al., 2007). Besides structural changes, disruption in the function of neurons and glial cells is reported in patients with UC: defective neuronal control of epithelial secretion, increased excitability of enteric neurons, alteration in synaptic transmission, and variablility in the expression of neuronal and glial-derived factors (vasoactive intestinal peptide, inducible nitric oxide synthase and other mediators in neuronal cell bodies; S100B protein, glial fibrillary acidic protein and other factors in glial cells) (Lomax et al., 2005). The aim of this chapter is to illustrate the new insights into the pathophysiology of UC, providing an exhaustive overview of the current knowledge of the role of the enteric nervous system during gut inflammation. Initially, we describe the morphology and the basic physiological functions of the enteric nervous system and its cellular components, neurons and glial cells, respectively. Then, a more extensive part is dedicated to the modifications of the enteric nervous system in UC. Besides the well documented role of enteric neurons, attention is also focused on the