Giovanni Sarnelli

Symptoms Associated With Impaired Gastric Emptying of Solids and Liquids in Functional Dyspepsia

OBJECTIVES:The relationship between functional dyspepsia and delayed gastric emptying of solids or liquids is still unclear. The aim of the present study was to investigate in dyspeptic patients the prevalence of delayed gastric emptying for solids or for liquids and to investigate the relationship to the dyspepsia symptom pattern.METHODS:In 392 and 330 patients with functional dyspepsia, the solid and liquid gastric emptying, respectively, was measured using breath tests, and the severity of eight dyspeptic symptoms was scored.RESULTS:Gastric emptying of solids and liquids were delayed in 23% and 35% of the patients. Multivariate analysis showed that the presence of vomiting and postprandial fullness was associated with delayed solid emptying (OR 2.65, 95% CI = 1.62–4.35 and OR 3.08, 95% CI = 1.28–9.16, respectively). Postprandial fullness was also associated with the risk of delayed liquid emptying when symptom was present (OR 3.5, 95% CI = 1.57–8.68), relevant or severe (OR 2.504, 95% CI = 1.41–4.65), and severe (OR 2.214, 95% CI = 1.34–3.67). Severe early satiety was associated with the risk of delayed liquid emptying (OR 1.902, 95% CI = 1.90–3.30).CONCLUSIONS:A subset of dyspeptic patients has delayed gastric emptying of solids or of liquids. Delayed gastric emptying of solids was constantly associated with postprandial fullness and with vomiting. Delayed emptying for liquids was also associated with postprandial fullness and with severe early satiety.

Serotonergic modulation of visceral sensation: upper gastrointestinal tract

Agents that modify serotonergic function have therapeutic potential for the treatment of visceral hypersensitivity, either through a direct effect on perception or through modulation of visceral tone or motility. Administration of selective serotonin reuptake inhibitors reduces oesophageal sensitivity to distension but not gastric sensitivity to distension. 5-HT ligands may also influence gastric mechanosensitivity by altering tone. Although the exact role of 5-HT receptors in the control of gastrointestinal functions remains unknown, 5-HT is generally considered to be the main candidate involved in the modulation of motor and sensory function from the gastrointestinal tract. Hence serotonergic modulation of upper gut sensitivity appears to be promising for the development of novel approaches to the treatment of functional disorders of the upper gastrointestinal tract.

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.

Effect of intranasal sumatriptan on gastric tone and sensitivity to distension.

Sumatriptan is able to improve symptoms of early satiety in dyspeptic patients by relaxing the gastric fundus. The aim of this study was to verify the efficacy of intranasal administration of sumatriptan on gastric sensory motor function, in order to provide a new pharmacotherapeutic approach to functional dyspepsia. Thirteen healthy subjects were investigated twice on separate days. A gastric barostat was used to study the effect of placebo and sumatriptan, 20 mg intranasally, on basal fundic tone. In addition, stepwise isobaric distensions were performed and perception was measured before and after administration of drugs. Placebo had no effect on gastric tone and on perception. Sumatriptan caused a small, but short-lasting gastric relaxation and had no significant effect on sensitivity to distension and gastric compliance. Unlike the subcutaneous formulation, the intranasal administration of sumatriptan had no effect on gastric sensory motor functions, and this probably reflects a low biovailability of intranasally administered sumatriptan.

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