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Biomedical subjects

V Stanghellini

Publications and source records attributed to V Stanghellini.

106 records · Page 6Linked to original sources

Effect of opiate and adrenergic blockers on the gut motor response to centrally acting stimuli.

Labyrinthine stimulation and cold pain inhibit feeding antral pressure activity, delay gastric emptying, and increase blood concentrations of beta-endorphin and norepinephrine. Further, labyrinthine stimulation induces, in approximately one-third of healthy individuals, a migrating burst of motor activity in the proximal intestine that interrupts the normal fed pattern. Our hypothesis was that endogenous opiates and catecholamines act as mediators of such disruptive effects of centrally acting stressful stimuli on gut motility. Thus, we studied feeding gastrointestinal pressure activity in healthy volunteers who were exposed to labyrinthine stimulation or cold pressure test, or both (both stimuli being either in their active or in their control forms), while receiving an intravenous infusion of either placebo (saline), or an opioid blocker (naloxone), or a combination of alpha- and beta-adrenergic blockers (phentolamine and propranolol), or all the drugs together. Neither opioid nor adrenergic blockers affected motility during control stimulations. Active stressful stimuli (labyrinthine stimulation, cold pain, or both) significantly inhibited antral feeding activity (p less than 0.05), but these effects were prevented by concomitant infusion of naloxone (p less than 0.05). Adrenergic blockade also prevented the antral motor inhibition caused by stress (p less than 0.05), but it was more effective for cold pain than for labyrinthine stimulation, and, when performed concomitantly with opiate blockade, the preventive effects disappeared. Furthermore, during adrenergic blockade labyrinthine stimulation invariably induced the appearance of a migrating duodenal burst of motor activity. Neither opioid nor adrenergic blockers modified the stress-induced rise of plasma beta-endorphin and norepinephrine. Our results suggest that opioids and catecholamines are involved in the mediation of the disruptive effects induced by centrally acting stressful stimuli on postprandial motor activity in the proximal human gut.

Adult↗

Effect of ranitidine and cimetidine on gastric emptying of a mixed meal in man.

The effect of acute and chronic crossover administration of ranitidine and cimetidine on gastric emptying was studied in healthy volunteers and in duodenal ulcer patients, respectively. In the first series of experiments, intravenous ranitidine (50 mg) significantly (p less than 0.05) delayed emptying of both solids and liquids, whereas cimetidine (300 mg i.v.) was totally ineffective. In the second set of experiments, neither ranitidine (150 mg bd orally for two weeks) nor cimetidine (400 mg bd) significantly modified emptying rate. These results, therefore, suggest that only high blood levels of ranitidine, as elicited by intravenous administration, are able to affect gastric emptying. On the contrary, at steady state levels elicited by conventional therapeutic doses, no effect on gastric emptying is evident.

Administration, Oral↗

Hypersensitivity of gastric parietal cells to selective H2-receptor stimulation in duodenal ulcer.

According to previous studies, duodenal ulcer patients not only secrete more acid than normal subjects, but are also more sensitive to pentagastrin stimulation. The aim of this study was to investigate whether hypersensitivity of parietal cells also occurs with specific H2-receptor agonists such as impromidine. Twelve duodenal ulcer patients and 12 healthy volunteers were admitted to the study. After 30 minutes of basal secretion, impromidine was infused at increasing doses (2.5; 5.0; 10.0; 20 micrograms/kg-1/h-1) in both groups of subjects. The gastric acid secretion was significantly higher in the duodenal ulcer group. The percentage, for each dose, of the calculated maximal response (CMR) was always higher in the patient group, and the difference with respect to the control group, was always higher in the patient group, and the difference, with respect to the control group, was statistically significant. Also, the average D50 was significantly lower in the duodenal ulcer group. Drug safety evaluation confirmed the presence of reversible dose-dependent pharmacological side effects. This study showed that parietal cells are more sensitive to highly selective H2-receptor agonists such as impromidine. These results add further information to the physiopathological features of duodenal ulcer.

Adult↗

Gastric manometric abnormalities in patients with dyspeptic symptoms after fundoplication.

We describe six patients in whom severe dyspeptic symptoms developed after fundoplication. The symptoms began immediately after operation (three patients) or shortly thereafter (three and eight months). There were no other known predisposing factors to gastroparesis. Seven, age-matched, healthy volunteers served as controls. Pressure activity from antrum (two sites), duodenum (two sites), and jejunum (one site) was recorded by a low compliance perfusion system connected to external strain gauge transducers. Activity was recorded for three hours during fasting and for two hours after the ingestion of a solid and a liquid meal. To determine whether an inadvertent vagotomy had been performed, basal acid output and the response to insulin (Hollander's test) were measured on a separate day. Manometric studies revealed postprandial hypomotility in these patients, whereas fasting antral and intestinal activities were normal. Acid output increased in all patients during insulin induced hypoglycaemia. In three patients, an antrectomy was subsequently performed, and they were relieved of their symptoms. We conclude that, after fundoplication, symptoms associated with postprandial antral hypomotility may develop in some patients. The pathophysiologic mechanism is unknown, but a positive acid response to insulin induced hypoglycaemia does not support the occurrence of incidental vagotomy. We do not know the prevalence of this motor abnormality among asymptomatic patients with prior fundoplication. A favourable symptomatic response to antrectomy in several of our patients, however, suggests that the symptoms were related to antral motor dysfunction.

Adult↗

Stress-induced gastroduodenal motor disturbances in humans: possible humoral mechanisms.

The objectives of this study were threefold. First, we investigated the effects of acute stressful stimuli on gastroduodenal feeding activity after a physiologic meal. Second, we explored the possible role of humoral mediators of these effects by measuring concurrently plasma levels of beta-endorphin, catecholamines, and several gut peptides. Third, we wished to determine whether or not the gut responded selectively to different types of central stimuli. Thus, in 12 healthy volunteers we studied the effects of vertigo and cold pain on the gastrointestinal motor response to a solid meal. Pressure activity was recorded by a low-compliance perfusion system. Plasma concentrations of beta-endorphin and gut peptides were measured by radioimmunoassay, whereas catecholamine levels were measured by high-pressure liquid chromatography. Blood pressure, pulse rate, and skin conductance were also monitored. Labyrinthine vertigo (by otic stimulation with 10 degrees C water; control, 37 degrees C water) and cold pain (immersing hand in 4 degrees C water; control, 37 degrees C water) were simultaneously induced after the meal in each subject according to a 2 X 2 factorial experimental design. Cold pain and labyrinthine stimulation alone or in combination significantly reduced the antral phasic pressure response to solids while elevating plasma levels of beta-endorphin and norepinephrine. These effects occurred within the first 20 min poststimulus and were associated with changes in blood pressure, pulse rate, and skin conductance. Further, in 2 of 6 individuals in whom vertigo was induced by labyrinthine stimulation, a phase 3-like burst of motor activity appeared in the duodenum and migrated aborally. We conclude that centrally acting external stimuli may severely disrupt antral feeding activity. Furthermore, concurrent elevations in plasma levels of beta-endorphin and norepinephrine raise the possibility that these substances may be involved as mediators of the central effects on the gut.

Adult↗

Endocrine effects of the H2-receptor antagonists cimetidine and ranitidine.

This paper reviews investigations on the endocrine effects of two H2-receptor antagonists, cimetidine and ranitidine. Cimetidine has hyperprolactinaemic properties and interferes with the peripheral activity of the sexual hormone (DHT) and probably with the pituitary LH secretion. A possible effect on TSH and thyroid hormone secretion or peripheral metabolism is suggested. Ranitidine seems to have no central or peripheral effects (after both acute and chronic administration) on sexual hormones. High doses (300 mg i.v. bolus) of the drug induce a significant increase in prolactin basal levels, whereas no effects follow oral administration. The effects on PRL are sex-related and less marked than those obtained with cimetidine. The chronic administration of this drug does not affect basal or TRH-stimulated PRL levels. No effects were apparent on TSH serum levels after either oral or i.v. acute administration, whereas lower basal and TRH-stimulated T4 values were registered after chronic treatment. On the basis of these results, a possible interference of ranitidine on iodothyronine metabolism can be suggested.

Animals↗

Gastric secretion and emptying of liquids in reflex esophagitis.

We have investigated the gastric secretory activity and the emptying half-time of a liquid meal in 17 selected patients with reflex esophagitis compared to 10 controls. The basal acid output and the basal and maximal secretory volume were higher in the patient group (P less than 0.05, P = 0.05, and P less than 0.01, respectively), while the maximal acid output and the basal and maximal acid concentration were not different in the two groups. The gastric emptying half-time of a liquid meal was higher in the patient group (P less than 0.001). Our results show that gastric function may be altered in reflux esophagitis patients and suggest particularly that a delayed emptying of liquids may play a role in the pathogenesis of the disease in some patients.

Adult↗

Inhibition by pirenzepine of nocturnal gastric acid secretion in duodenal ulcer patients.

Ten patients with endoscopically proven duodenal ulcers participated in a double-blind, placebo-controlled, cross-over trial to investigate the effect of pirenzepine on nocturnal gastric acid secretion. Pirenzepine, 50 mg orally at bedtime, inhibited acid secretion all night long: the overall volume secreted and acid output (midnight to 7 a.m.) were significantly less than after placebo. The decrease in acid output per hour was significant at 1,2,3,6, and 7 a.m. It was concluded that controlled clinical trials of maintenance therapy for prevention of relapse of healed duodenal ulcers should be carried out with pirenzepine taken at bedtime.

Adult↗

Clinical use of manometry for the diagnosis of intestinal motor abnormalities.

Digestive symptoms suggestive of intestinal motor disorders, such as abdominal pain and distension, fullness, vomiting, constipation and diarrhoea, are very common and non-specific, and may be clinical manifestations of both organic and functional diseases. Both radiology and endoscopy are important in the diagnosis of structural gastrointestinal lesions that can affect motility and offer indirect signs of impaired gastrointestinal functions, but the diagnosis of gut motility disorders currently relies on the manometric assessment of contractile activities. Small bowel manometry helps to identify normal motility features and consequently to identify abnormal motor patterns. Small bowel manometry can help to differentiate mechanical obstruction from pseudo-obstruction and neurogenic from myogenic motor disorders. Manometry is an invasive technique which is not well accepted by patients and requires specific skills from investigators. Also, manometric assessment is limited to referral centres with a specific interest in the field of digestive functions, in general, and motility, in particular. Only patients who remain undiagnosed after extensive traditional work-up and fail repeated courses with medical therapy should be referred for the manometric test. Understanding the underlying pathophysiologic mechanisms of abnormal motility and developing new therapies are the goals of the current research in this fascinating field of medicine.

Diagnosis, Differential↗

Standards for non-invasive methods for gastrointestinal motility: scintigraphy. A position statement from the Gruppo Italiano di Studio Motilità Apparato Digerente (GISMAD).

Scintigraphic techniques are well established methods to assess gastrointestinal transit patterns. The main advantages are represented by the possibility to evaluate, in a relatively non-invasive manner, the transit time of specific components of physiological meals as well as of some digestive secretions. These techniques are generally well accepted by the patients and results are largely not operator dependent. Their main limitation is the use of a radioisotope, that prevents repeated applications in all subjects and immediate exclusion of women of childbearing potential. Due to the high costs of these tests and the limited availability of Nuclear Medicine Departments, scintigraphic techniques should be reserved for well-selected patients. A review is made of the technical requirements and indications for scintigraphic tests currently available for clinical purposes (gastric emptying study, oesophageal transit time, evaluation of gastro-oesophageal reflux, intestinal and colonic transit time, evaluation of biliary motility and of duodenogastric reflux).

Colon↗

Evaluation of Helicobacter pylori sensitivity to amoxycillin and metronidazole in dyspeptic patients.

We evaluated the "in vitro" sensitivity to amoxycillin and metronidazole of 193 Helicobacter pylori strains isolated from the gastric mucosa of dyspeptic patients. Susceptibility was determined by disc diffusion on agar plates. All the isolates were found to be sensitive to amoxycillin. On the contrary, 12% of the strains isolated from patients never treated for Helicobacter pylori infection and 73% of those isolated from patients who had previously received unsuccessful treatment for Helicobacter pylori infection were found to be resistant to metronidazole. Resistance was more common in women (17%) than in men (4%: p < 0.01) and was not correlated with age. The occurrence of Helicobacter pylori resistance to metronidazole is relatively common in Italy. In vitro testing of Helicobacter pylori sensitivity seems to be important before embarking on treatments aimed at eradicating the bacterium.

Adult↗

Rifaximin and Helicobacter pylori eradication.

In this study, we tested the effectiveness of Rifaximin, a surface antibiotic which is not absorbed when given orally, in the eradication of Helicobacter pylori (HP). The drug was combined in triple therapy either with Amoxicillin and Omeprazole or with Erythromycin-ethylsuccinate and Omeprazole. Twenty-three patients complaining of dyspeptic symptoms and gastric infection due to HP were evaluated. The patients were randomly given one of the following therapeutic protocols: Rifaximin susp. 600 mg/day x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Amoxicillin tab. 1 g x 2/day (at least two hours after meals: 10:00 am, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol A) and Rifaximin susp. 600 mg/day x 3/day and Erythromycin-ethylsuccinate tab. 600 mg x 3/day (at least two hours after meals: 10:00 am, 2:00 pm, 9:00 pm), Omeprazole tab. 40 mg/day (in the morning before breakfast) (protocol B). Both therapeutic protocols were prescribed for two weeks. At least one month after the end of the treatment the patients were controlled to ascertain eradication of the infection. The follow-up carried out after treatment showed that HP infection was eradicated in 6 of 10 patients in the first group (protocol A) and in 1 of 10 in the second group (protocol B). These patients were HP-negative in all the tests performed: histological, CP-TEST, culture test. The data collected showed a reasonable level of effectiveness of the protocol using the combination Rifaximin-Amoxicillin and Omeprazole. However, they do not differ from the reported data in the literature which show a similar effectiveness of the combination Omeprazole-Amoxicillin at the same doses. Different formulations that makes it possible for the drug to reach these "protected areas" would probably be more effective.

Adolescent↗