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Biomedical subjects

V Stanghellini

Publications and source records attributed to V Stanghellini.

At least 73 records · Page 4Linked to original sources

Upper gastrointestinal motor activity in patients with slow-transit constipation. Further evidence for an enteric neuropathy.

Recent evidence indicates that patients complaining of severe chronic idiopathic constipation may have motor abnormalities not limited to the colon. We studied by manometric means gastric and small bowel motility in a homogeneous group of patients with chronic idiopathic constipation, ie, the slow transit type. Twenty-one patients were recruited for the study and compared to 33 healthy subjects. Manometric examination was carried out for about 5 hr fasting and 1 hr after a standard meal. Analysis of the manometric tracings revealed during fasting no abnormalities in number and configuration of migrating motor complex with respect to controls. However, in 70% of patients motor abnormalities were detected, represented by bursts of nonpropagated contractions and discrete clustered contractions. After feeding, the patient group displayed a significantly shorter antral motor response to the meal with respect to controls; moreover, intestinal bursts of nonpropagated contractions were found in 19% of patients, and 14% of them had an early return of the activity fronts. We conclude that patients with slow transit constipation frequently display motor abnormalities of the upper gut. These findings further strengthen the concept that this condition may represent a panenteric disorder.

Adult↗

Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia.

BACKGROUND & AIMS: Although gastric dysmotility and dyspeptic symptoms are often associated, their relationship remains unclear. The aim of this study was to evaluate the relationship between gastric emptying abnormalities and clinical features in functional dyspepsia. METHODS: In 343 patients with functional dyspepsia, the gastric emptying of solids was measured by a radioisotopic technique and four dyspeptic symptoms (epigastric pain and burning, postprandial fullness, nausea, and vomiting) were measured as absent, mild, relevant, and severe, according to their influence on patients' usual activities. RESULTS: Delayed gastric emptying was detected in 33.5% of dyspeptics. Delayed gastric emptying was particularly frequent in patients characterized by female sex, low body weight, presence of relevant and severe postprandial fullness, nausea, vomiting, and absence of relevant and severe epigastric pain. Logistic regression showed that delayed gastric emptying was invariably associated with female sex and postprandial fullness (odds ratio, 2.34; 95% confidence interval, 1.45-3.75) and vomiting (odds ratio, 4.04; 95% confidence interval, 1.30-12.54) when coded as severe and only postprandial fullness (odds ratio, 3.78; 95% confidence interval, 1.78-8.01) when coded as relevant and severe. CONCLUSIONS: Female sex, relevant and severe postprandial fullness, and severe vomiting are independently associated with delayed gastric emptying of solids in patients with functional dyspepsia seen in a referral center.

Adult↗

Gastric emptying of solids in morbid obesity.

OBJECTIVE: To evaluate the effect of weight loss induced by dietetic treatment, with or without an intragastric balloon, on gastric emptying of obese subjects. SUBJECTS: 20 morbidly obese subjects (21-54 years, 45.3-58.0 kg/m2) and 20 healthy controls (21-56 years, 20.3-24.8 kg/m2). DESIGN: Parallel study of a 4 month, low calorie dietetic treatment with or without a 500 ml intragastric balloon. RESULTS: In basal conditions, obese subjects had accelerated gastric emptying as compared to healthy controls. At the end of the dietetic treatment period, a significant decrease of body weight was obtained. Patients also showed a slowing of gastric emptying. Both the weight loss and the slowing of gastric emptying occurred irrespective of the presence or absence of the intragastric balloon. CONCLUSION: The present findings are compatible with the hypothesis that gastric emptying, food intake and body weight are integrated parameters in subjects with morbid obesity.

Adult↗

[New etiopathogenic, clinical and therapeutic findings in multiple endocrine neoplasia type 1].

Multiple Endocrine Neoplasia type 1 (MEN 1) syndrome comprises tumors or hyperplasia of different glands, including parathyroid, pituitary, adrenal cortex and the gastroenteropancreatic system. The vast majority of MEN 1 are found in familial clusters, although a few cases are sporadic. Hypercalcemia and/or nephrocalcinosis are the first and most common clinical manifestation in familial MEN 1 syndrome, followed by islet cell tumors (especially those secreting gastrin or insulin) and pituitary dysfunction due to either functioning or non-functioning microadenomas. Genetic studies indicate that familial MEN 1 syndrome is inherited through a dominant gene with incomplete penetrance and variable expression. The diagnosis of MEN 1 syndrome is mainly based on the careful assessment of the clinical history, symptoms physical evaluation along with the assay of serum electrolytes (i.e., calcium, phosphorus, etc.) and hormonal substances (i.e., gastrin, insulin, pancreatic polypeptide, prolactin, adrenocorticotropic hormone, etc.). In addition, several provocative tests have been used to identify endocrine tumors (particularly those of the gastroenteropancreatic system) and imaging techniques play a crucial role for the diagnostic approach in MEN 1 syndrome. Even though in the long term, the prognosis of MEN 1 syndrome is unfavourable. Recently, however, many therapeutic strategies, including both surgical and pharmacological options, have been developed to reduce the size of the neoplasm and control symptoms associated with hormone oversecretion.

Antineoplastic Agents, Hormonal↗

[The innervation of the digestive tract: its morphofunctional and neurochemical aspects].

The innervation of the alimentary tract (or enteric nervous system, ENS) represents the third division of the autonomic nervous system and it appears to be unique for its intrinsic ability to mediate reflex activity even when disconnected from the central nervous system. Enteric nerve cells can be classified in subclasses according to combined classic morphological criteria (Dogiel type I, II and III) and electrophysiological properties (type S and AH). A further major feature of the ENS lies in the variety of chemical messengers expressed in its neuronal elements. These substances can act either as neurotransmitters or neuromodulators. A common finding of enteric neurons is to synthetize and store several chemical messengers, a phenomenon known as neurochemical coding. As a consequence, neurotransmission involves the release and action of more than one messenger, an event referred to as plurichemical transmission. Recently, the use of combination of methods (such as immunohistochemical, pharmacological and electrophysiological techniques) has led to the identification of specific functionally distinct categories of enteric neurons. Thus, inhibitory and excitatory motor neurons, interneurons, vasomotor and sensory neurons are now recognized to constitute the complex network of the ENS. These neuronal elements are synaptically connected to form microcircuits which play a pivotal role to control digestive functions, including motility, blood flow, secretion and absorbtion.

Animals↗

Nitric oxide modulates pepsinogen secretion induced by calcium-mediated agonist in guinea pig gastric chief cells.

BACKGROUND & AIMS: Nitric oxide, a putative cellular messenger synthesized from L-arginine, is a powerful modulator of gastric motility and secretions. The aim of this study was to investigate whether (1) guinea pig gastric chief cells express NO synthase, (2) NO modulates the pepsinogen secretion and guanosine 3',5'-cyclic monophosphate (cGMP) generation induced by calcium (Ca2+)-mediated agents, and (3) NO donors and cGMP analogues stimulate pepsinogen release. METHODS: Chief cells were prepared by sequential digestion with collagenase and Ca2+ chelation. NO generation was measured by determining the NO coproduct citrulline. RESULTS: NO synthase immunoreactivities were constitutively expressed in approximately 70% chief cells. Carbachol (10 mumol/L) caused a 4- 6-fold increase in pepsinogen release, citrulline generation, intracellular Ca2+ concentration ([Ca2+]i) and cGMP concentration. These effects were concentration dependently inhibited by NG-monomethyl-L-arginine (L-NMMA). As gastrin, cholecystokinin, thapsigargin, and Ca2+ ionophore increased NO generation, [Ca2+]i seemed to regulate NO synthase activity. [Ca2+]i chelator and calmodulin antagonist inhibited the carbachol-induced pepsinogen secretion and NO generation. Preincubating the cells with L-NMMA had no effect on carbachol-stimulated inositol triphosphate generation or [Ca2+]i or Ca(2+)-dependent adenosine triphosphatase levels. Nitrovasodilator agents and 8-bromo-cGMP stimulated pepsinogen release. CONCLUSIONS: Gastric chief cells express a Ca2+/calmodulin-dependent NO synthase. NO modulates the stimulatory effect of Ca(2+)-mediated agonists on pepsinogen release.

Animals↗

Chronic oral administration of lansoprazole does not affect the hypothalamic pituitary gonadal axis in healthy young men.

OBJECTIVE: To assess the effects of chronic oral administration of standard doses of lansoprazole on the luteinizing hormone pulsatile pattern and on follicle stimulating hormone (FSH) and testosterone levels in young men. DESIGN AND METHODS: Eleven healthy volunteers were studied on three separate occasions, before and after two 3-week periods of treatment with lansoprazole (30 mg every morning) or a placebo, according to a randomized, double-blind, double-dummy, cross-over design. On each study day, blood samples were taken every 15 min for 8 h. The pulsatile pattern of luteinizing hormone, mean concentrations of FSH and total testosterone plasma levels were determined for each patient using specific radioimmunoassays. RESULTS: Lansoprazole did not significantly affect mean plasma levels, the pulsatile pattern of luteinizing hormone, or mean plasma concentrations of FSH and testosterone compared with the placebo. CONCLUSIONS: This study indicates that chronic oral administration of standard doses of lansoprazole does not affect the concentrations of gonadal hypothalamic pituitary or sex steroid hormones.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Effects of acute cold pressor test on vagally stimulated gastric acid secretion and circulating levels of human pancreatic polypeptide and gastrin.

The aims of our study were 3-fold: (1) to determine the effect of an acute cold pressor test on vagally stimulated gastric acid secretion, (2) to evaluate whether adrenergic blockers are able to prevent the stress-induced alterations of vagally stimulated gastric acid secretion, and (3) to assess the effect of stress and adrenergic blockers on serum levels of vagally stimulated pancreatic polypeptide and gastrin. Twenty-eight studies were carried out on 7 healthy subjects, each one of them being evaluated on four separate occasions. Active (4 degrees C) or control (37 degrees C) cold pressor tests were applied in random order after an interval of 15 min following completion of a vagal stimulation represented by modified sham feeding. Each stressful stimulus was preceded by an intravenous bolus plus an infusion of either adrenergic blockers (propranolol and phentolamine) or placebo. Modified sham feeding significantly stimulated gastric acid secretion and circulating hormonal levels, compared to basal values. Cold pressor test significantly stimulated gastric acid secretion 30 min after the beginning of the stressful stimulus. This stress-induced secretory response was completely prevented by infusions of adrenergic blockers. No effect was induced by stressful stimuli or by adrenergic blockers on human pancreatic polypeptide and gastrin circulating levels. The present study demonstrates that the cold pressor test induces a late increase of vagally stimulated gastric acid secretion suggesting a possible role mediated by adrenergic neural pathways.

Adult↗

Evaluation of two therapeutic regimens for the treatment of Helicobacter pylori infection.

In the present study we evaluated the efficacy and tolerability of two different therapeutic schedules in eradicating Helicobacter pylori. Forty-six consecutive patients (suffering from either peptic ulcer or non-ulcer dyspepsia) with helicobacter pylori infection were randomly allocated to one of the following two groups: group 1 (n = 23) 2 weeks of treatment with bismuth subcitrate tablets (120 mgx4) + amoxycillin capsules (500 mgx4) + metronidazole tablets (250 mgx4); group 2 (n = 23) 2 weeks of treatment with amoxycillin capsules (500 mgx4) + metronidazole tablets (250 mgx4). Endoscopy, histology and bacterial culture were performed at entry, and 30 and 90 days after treatment. Two group 1 patients and one group 2 patient did not complete the treatment. Successful eradication was obtained in 20/21 (95%) patients treated with triple therapy (group 1) and in 17/22 (77%) patients treated with double therapy (group 2) (p = 0.2). Side-effects occurred in 9/21 (43%) patients of group 1 and in 9/22 (41%) patients of group 2 (p = 0.9). These were all self-limiting and required no specific treatment. These data suggest that combined therapy with amoxycillin and metronidazole, with or without bismuth subcitrate, represents a safe and effective therapeutic approach for the treatment of Helicobacter pylori infection. In our series, triple therapy determined a numerically higher eradication rate than double therapy.

Adult↗

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

The 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 x 10 mg), (1 x 20 mg), or 10 mg before breakfast and 10 mg before lunch (2 x 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 x 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 x 10 mg than after 1 x 20 mg or 1 x 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.

Adult↗

One-day therapy for treatment of Helicobacter pylori infection.

The present study evaluated the effect of a one-day high-dose combined therapy on Helicobacter pylori infection. Thirty-two consecutive patients (suffering from either peptic ulcer or nonulcer dyspepsia) with Helicobacter pylori infection received omeprazole (40 mg) + bismuth subcitrate (240 mg x 4) + amoxicillin suspension (2000 mg x 4) + metronidazole (500 mg x 4), for only one day. Endoscopy, histology, culture, and susceptibility studies were done at entry and 30 and 90 days after the treatment day. Successful eradication was obtained in 23/32 (72%) patients and gastritis had resolved in 95% of these. Side effects were induced by the treatment in 6/32 (19%) patients, but these were all self-limiting, short-lasting, and did not require any specific treatment. Development of bacterial resistance to metronidazole occurred in 6/9 (67%) non-eradicated patients. These data suggest that one-day treatment with high doses of amoxicillin, metronidazole, bismuth, and omeprazole represents an effective, safe, and inexpensive therapeutic approach for the treatment of H. pylori infection.

Adult↗

Fat-induced ileal 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.

Adult↗

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.

Adult↗

Fasting and postprandial gastrointestinal motility in ulcer and non-ulcer dyspepsia.

This study aimed to compare fasting and postprandial gastrointestinal motor patterns in patients with ulcer and non-ulcer dyspepsia. Forty five subjects were studied: 10 with uncomplicated gastric ulcer, eight with uncomplicated duodenal ulcer, 18 with chronic idiopathic dyspepsia, and nine healthy asymptomatic controls. Gastrointestinal fasting and postprandial motor patterns were recorded using a low compliance perfusion technique. The interdigestive antral cumulative motility index, computed for 30 minutes before the appearance of duodenal activity fronts, and the number of activity fronts with an antral component were significantly less in patients with ulcers and those with non-ulcer dyspepsia compared with asymptomatic controls. The patient groups also had a reduced antral motor response to a solid-liquid test meal compared with healthy controls. Intestinal motor abnormalities (bursts of non-propagated phasic pressure activity and discrete clustered contractions) were recorded in a minority of patients, all with associated irritable bowel symptoms. In conclusion, antral hypomotility is a frequent but nonspecific motor abnormality in dyspepsia; abnormal motor patterns of the small bowel are less frequent and seem to be confined to patients with concomitant irritable bowel syndrome.

Adolescent↗