Cesare Tosetti

Fat-induced heal brake in humans: A dose-dependent phenomenon correlated to the plasma levels of peptide YY

BACKGROUND Upper gastrointestinal motility is regulated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric emptying (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release. METHODS Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured. RESULTS Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05). CONCLUSIONS This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent.

Helicobacter pylori infection and gastric function in patients with chronic idiopathic dyspepsia

Helicobacter pylori infection, histological features of the gastric mucosa, and gastric motor and secretory functions were evaluated in 45 consecutive patients with chronic idiopathic dyspepsia. H. pylori infection was found in 60% of dyspeptic patients, compared with 33% of 15 healthy controls (P = 0.1). No difference was detected in basal or stimulated gastric acid secretion between dyspeptic patients and healthy controls. Gastric emptying was significantly (P less than 0.01) delayed in dyspeptic patients compared with healthy controls when standardized for age and sex. Delayed gastric emptying was associated with a low frequency of H. pylori infection, female gender, and young age. Epigastric pain or burning and postprandial fullness were, respectively, more severe in patients with H. pylori infection (P less than 0.02) and in those with delayed gastric emptying (P less than 0.01). These findings support the existence of separate subsets of patients with chronic idiopathic dyspepsia. Despite the presence of overlaps, there appear to be partially different functional derangements and clinical features in different subgroups of dyspeptic patients.

Reversal of fundic atrophy after eradication of helicobacter pylori

Objectives:We sought to evaluate the effect of Helicobacter pylori eradication in patients with fundic atrophic gastritis.Methods:Acid secretion, gastric emptying, and histology were evaluated in 20 patients with fundic atrophic gastritis and H. pylori infection. After investigation, 10 patients (Group 1) received an eradicating treatment and 10 (Group 2) did not receive any treatment. One year later, the baseline investigations were repeated. Subsequently, patients in Group 2 received the same treatment given to patients in Group 1 and were reevaluated 12 months later. A further follow-up was performed in both groups 36 months after the treatment.Results:At 1-yr follow-up, all the patients in Group 1 were H. pylori negative whereas all the patients in Group 2 were still infected. In Group 1, there was a significant improvement of both fundic atrophy and acid secretion, compared with baseline (p < 0.01). In Group 2, no substantial modification of either histological or functional parameters was observed at the first follow-up; conversely, a significant (p < 0.01) improvement of fundic atrophy and acid secretion was detected in these patients 12 months after eradication of the bacterium. Histological pattern remained unchanged at 36 months of follow-up in both groups. Gastric emptying remained, on the average, unaffected by the treatment; however, three patients with delayed gastric emptying at entry had normal gastric emptying after eradication of H. pylori.Conclusions:Our data suggest that mucosal atrophy can be reduced or even reversed by the eradication of H. pylori, and this is associated with a recovery of gastric function.

Predominant symptoms identify different subgroups in functional dyspepsia.

OBJECTIVE:Dyspepsia is a common syndrome that often defies diagnosis. Whether the unexplained (or “functional”) dyspepsia represents a homogeneous syndrome or includes different subgroups with specific clinical features has not been clarified. The aim of this study was to investigate the relationship between symptom severity, demographic features, and gastric dysmotility in a large series of patients with functional dyspepsia.METHODS:Severity of individual digestive symptoms, demographic features, and scintigraphic gastric emptying of solids were evaluated in 483 patients with chronic unexplained dyspepsia.RESULTS:Two main subgroups were identified. The first was characterized by predominant epigastric pain, male gender (61%), and normal gastric emptying. The second subgroup was characterized by predominant nonpainful symptoms, female gender (60%), a high frequency of associated irritable bowel syndrome (30%), and delayed gastric emptying (42%). A third group included approximately one-third of patients who did not present with any predominant symptom, and was characterized by a high frequency of delayed gastric emptying (30%), overlapping irritable bowel syndrome (28%), and gastroesophageal reflux disease (41%).CONCLUSIONS:Different subgroups exist among patients with functional dyspepsia seen in a referral center. They can be identified by the predominant symptom and are characterized by different demographic, clinical, and pathophysiological features.

Dyspeptic symptoms and gastric emptying in the irritable bowel syndrome

OBJECTIVES:Irritable bowel syndrome (IBS) and dyspepsia often overlap. Delayed gastric emptying has been reported in IBS patients, although conflicting results exist. Whether overlapping dyspepsia correlates with gastric emptying abnormalities in IBS patients has not been clarified. This study aimed to evaluate gastric emptying of solids and its relationship with dyspeptic symptoms in IBS patients.METHODS:A total of 146 IBS outpatients seen in a referral center were evaluated for dyspeptic symptoms using a validated questionnaire. Gastric emptying of solids was evaluated scintigraphically in all patients and in 50 healthy controls.RESULTS:Overlapping dyspepsia was diagnosed in 96 (66%) IBS patients. On average, gastric emptying rates were lower in IBS patients (mean ± SEM, 33%± 1%/h) compared with controls (40%± 2%/h; p < 0.01). Specifically, gastric emptying was delayed in IBS patients with overlapping dyspepsia (31%± 1%/h; p < 0.01), whereas IBS patients without dyspeptic complaints showed gastric emptying rates (37%± 2%/h) that were similar to those of healthy controls (40%± 2%/h). Relevant postprandial fullness (OR = 4.7, 95% CI = 1.8–12.5) and relevant nausea (OR = 3.3, 95% CI 1.2–9.3) were independently associated with delayed gastric emptying.CONCLUSIONS:IBS patients without overlapping dyspepsia have normal gastric emptying of solids. A significant association exists in IBS patients between delayed gastric emptying and overlapping relevant postprandial fullness and nausea.

New Developments in the Treatment of Functional Dyspepsia

Functional dyspepsia is a clinical syndrome defined by chronic or recurrent pain or discomfort in the upper abdomen of unknown origin. Although generally accepted, investigators differently interpret this definition and clinical trials are often biased by inhomogeneous inclusion criteria.The poorly defined multifactorial pathogenesis of dyspeptic symptoms has hampered efforts to develop effective treatments. A general agreement exists on the irrelevant role played by Helicobacter pylori in the pathophysiology of functional dyspepsia. Gastric acid secretion is within normal limits in patients with functional dyspepsia but acid related symptoms may arise in a subgroup of them. Proton pump inhibitors appear to be effective in this subset of patients with dyspepsia. Non-painful dyspeptic symptoms are suggestive of underlying gastrointestinal motor disorders and such abnormalities can be demonstrated in a substantial proportion of patients. Postprandial fullness and vomiting have been associated with delayed gastric emptying of solids, and early satiety and weight loss to postcibal impaired accommodation of the gastric fundus. Prokinetics have been shown to exert beneficial effects, at least in some patients with dyspepsia. In contrast, drugs enhancing gastric fundus relaxation have been reported to improve symptoms, although conflicting results have also been published. An overdistended antrum may also generate symptoms, but its potential pathogenetic role and the effects of drugs on this abnormality have never been investigated formally. Visceral hypersensitivity plays a role in some dyspeptic patients and this abnormality is also a potential target for treatment. Both chemo- and mechanoreceptors can trigger hyperalgesic responses. Psychosocial abnormalities have been consistently found in functional digestive syndromes, including dyspepsia. Although useful in patients with irritable bowel syndromes (IBS), antidepressants have been only marginally explored in functional dyspepsia.Among the new potentially useful agents for the treatment of functional dyspepsia, serotonin 5-HT4 receptor agonists have been shown to exert a prokinetic effect. Unlike motilides, 5-HT4 receptor agonists do not appear to increase the gastric fundus tone and this may contribute to improve symptoms. 5-HT3 receptor antagonists have been investigated mainly in the IBS and the few studies performed in functional dyspepsia have provided conflicting results. Also, κ-opioid receptor agonists might be useful for functional digestive syndromes because of their antinociceptive effects, but available results in functional dyspepsia are scanty and inconclusive. Other receptors that represent potential clinical targets for antagonists include purinoceptors (i. e., P2X2/3 receptors), NMDA receptors (NR2B subtype), protease-activated receptor-2, the vanilloid receptor-1, tachykinin receptors (NK1/NK2) and cholecystokinin (CCK)1 receptors.

Dyspeptic symptoms in primary care. An observational study in general practice.

Background and aims Dyspepsia frequently causes patients to consult a general practitioner, but is generally investigated in referral centres. This study describes features of dyspepsia and its relationship with demographic, clinical and socio-economic factors in patients seen by general practitioners in Italy. Patients and methods In Italy, 10 000 general practitioners were asked to recruit up to 10 consecutive dyspeptic patients during a 1-month period. Painful and non-painful dyspeptic symptoms, retrosternal pain/burning and visible abdominal distension were graded 0–3 by a validated questionnaire. Demographics and clinical features were also recorded. Results During the test period, 43 446 patients were included (55% were men; 50% were over 45 years old; 49% were smokers; 45% had experienced symptoms for ⩾ 1 month; 28% had a history of peptic ulcer). Dyspepsia accounted for 8.3% (range 3–11%) of the consultations of a subset of participating doctors. Epigastric pain and fullness were reported in 84% and 79% of patients, respectively. Dyspeptic symptoms were moderate-severe (graded ⩾ 2) in 69% of patients. Predominant epigastric pain and predominant discomfort were reported in 21% and 25% of the cases, respectively. Male gender, smoking, nocturnal awakening, overlapping reflux symptoms and a history of peptic ulcer were more frequent in patients with predominant pain, while female gender and overlapping abdominal distension were more common in patients with predominant discomfort. Age, educational level and working status were not related to any symptom pattern. Young patients presenting for the first time with uncomplicated dyspepsia accounted for 10% of the dyspepsia workload. Conclusions Dyspepsia accounts for a relevant workload for general practitioners. A considerable overlap exists among digestive symptoms. The proportion of patients that can be empirically treated according to current guidelines may be lower than expected.

Predictors of gastroparesis in out-patients with secondary and idiopathic upper gastrointestinal symptoms

BACKGROUND Delayed gastric emptying occurs frequently in patients with upper gastrointestinal symptoms associated with functional or organic diseases. AIMS To evaluate whether: (i) the prevalence of delayed gastric emptying is influenced by the presence of organic disease; (ii) demographic or clinical factors predict modestly or markedly (gastroparesis) delayed emptying. PATIENTS A total of 327 consecutive out-patients with upper gastrointestinal symptoms. METHODS Routine diagnostic work-up and evaluation of demographic factors, gastrointestinal symptom evaluation and scintigraphic gastric emptying of solids were performed. RESULTS Organic diseases were detected in 227/327 (65%) patients: 33% had delayed emptying and 20% gastroparesis. Female gender (OR: 2.1; 95% C.I.: 1.3-3.4). overweight (0.5; 0.3-0.9), relevant postprandial fullness (1.8; 1.1-3.2) and relevant epigastric bloating (1.8; 1.1-2.9), but not the presence of organic diseases, were associated with delayed emptying. Female gender (3.9; 1.3-11.9) and relevant postprandial fullness (4.1; 1.7-10.2) were associated with gastroparesis. CONCLUSIONS (i) There is a high prevalence of delayed gastric emptying and gastroparesis in out-patients with upper gastrointestinal symptoms, which is not influenced by the presence of organic disease; (ii) female gender, low body weight, relevant fullness and bloating are associated with delayed emptying; female gender and relevant postprandial fullness predict gastroparesis.

A survey of pharmacological and nonpharmacological treatment of functional gastrointestinal disorders

Background Treatment of functional gastrointestinal disorders (FGIDs) is based on symptoms relieve by conventional drugs, but increasingly complementary and alternative medicine (CAM) is used. Objective This survey aimed to investigate the current treatments used by FGIDs patients. Methods A total of 25 Italian gastroenterologists interviewed outpatients on gastrointestinal symptoms and treatments (pharmacological, CAM, diet/dietary supplements) used during the last year to relieve FGIDs. Consecutive adults with FGIDs according to Rome III were included. Results Of the 199 patients, 81% used conventional drugs, 64.3% diet/dietary supplements, and 48.7% CAM. Conventional drugs, diet/dietary supplements, or CAM as exclusive treatment were used by 24.6, 6, and 2.5% of patients, respectively. Two-thirds used more than one treatment: 34.7% conventional drugs, CAM, and diet/dietary supplements, 17.1% conventional drugs and diet/dietary supplements, 10.1% diet and CAM, and 5% conventional drugs and CAM. Benefits and adverse effects were similar for conventional drugs and nonpharmacological treatments. Males (OR 2.4) without lower GI symptoms (OR 5.4) used more frequently exclusive pharmacological treatment of FGIDs. Conclusions Conventional drugs are the preferred treatment for FGID. CAM and dietary modifications are more likely used as an adjunct to rather than instead of conventional drugs. Adverse effects occurred in all treatments.

The effect of different dosage schedules of cisapride on gastric emptying in idiopathic gastroparesis

SummaryThe aim of this study was to determine the optimal dosage regimen of cisapride for the treatment of idiopathic gastroparesis.We studied 17 patients with documented idiopathic gastroparesis in a three-way, cross-over, double-blind study with three 4-day treatment periods separated by at least 3 days without treatment. In each period, the patients were preloaded with cisapride (10 mg tid) for three days. On the fourth day (the test day) they took either 10 mg or 20 mg before breakfast and placebo before lunch (1×10 mg), (1×20 mg), or 10 mg before breakfast and 10 mg before lunch (2×10 mg). The medications were taken 30 min before meals. Gastric emptying of solids (99mTc-sulphur colloid) was measured at lunch time under basal conditions and during each treatment period. Plasma concentrations of cisapride were determined before the breakfast dose, before the lunch dose, and at 1, 2, 3, 4 and 5 h after.The greatest acceleration in gastric emptying occurred with the 2×10 mg regimen. Although the single morning dose of 20 mg also significantly accelerated gastric emptying (P=0.05), the reduction was not as substantial.Plasma concentrations of cisapride were significantly higher after 2×10 mg than after 1×20 mg or 1×10 mg. There was a significant relation between cisapride plasma concentrations and changes in gastric emptying. Peak concentrations of cisapride greater than 60 ng·ml−1 were invariably associated with acceleration of gastric emptying.We conclude that cisapride 10 mg tid before meals is the optimal dose for the treatment of idiopathic gastroparesis.