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Biomedical subjects

V Stanghellini

Publications and source records attributed to V Stanghellini.

At least 91 records · Page 5Linked to original sources

Pseudo-obstruction syndromes.

Chronic intestinal pseudo-obstruction (CIP) is a clinical syndrome characterized by symptoms and signs of intestinal occlusion, in absence of any mechanical obstruction of the gut lumen. It causes impaired transit of intestinal contents and is determined by abnormalities of motor activity. The term CIP is used to indicate a heterogeneous group of disorders with many different pathogenic mechanisms. The defect in the regulation of intestinal transit can be at any level of motility control. Two main types of CIP are recognized, termed respectively myogenic (when smooth muscle cells are affected) and neurogenic (caused by abnormalities of extrinsic and/or intrinsic nervous supplies). Both types may be secondary to a variety of recognizable diseases or idiopathic. In myogenic CIP, intestinal transit is impaired because of lack of propulsive strength; in the neurogenic form, contractions are powerful but not sufficiently co-ordinated to propel intestinal contents aborally in an organized fashion. CIP belongs to the large and loosely defined group of digestive functional disorders. These disorders probably share common pathogenic mechanisms but with different expressiveness. The reasons why only some patients present recurrent symptomatological bouts resembling mechanical occlusion has not been clarified. This aspect is of great clinical relevance and deserves attention, as CIP patients, unlike other patients with severe functional disorders, may undergo repeated, useless and potentially dangerous operations. The diagnosis of CIP may be suggested by clinical features and is based on radiological, endoscopic, manometric, and histological findings. Recent technological improvements facilitate the recognition of this intriguing syndrome. In particular, manometric recording of the small bowel motility, which has long been considered an important research technique, can now also be regarded as a useful diagnostic tool.

Chronic Disease↗

Chronic idiopathic intestinal pseudo-obstruction: clinical and intestinal manometric findings.

We report the clinical and intestinal manometric findings in a group of 42 patients with chronic idiopathic intestinal pseudo-obstruction evaluated at the Mayo Clinic. The main clinical manifestations in these patients were nausea and vomiting (83%), abdominal pain (74%), distension (57%), constipation (36%), diarrhoea (29%), and urinary symptoms (17%). These symptoms preceded surgery in all patients. Air fluid levels or distended bowel loops occurred in 57% and a dilated bladder or urinary excretory pathway in 17%. All patients showed intestinal manometric abnormalities none of which are seen in healthy individuals: aberrant configuration or propagation of interdigestive motor complexes in 25 patients; bursts (greater than 2 min duration) of non-propagated phasic pressure activity in fasting and/or fed state in 30 patients; sustained incoordinated fasting pressure activity in 15 patients; and inability of an ingested meal to convert fasting into fed pattern in 28 patients. We conclude that qualitative analysis of intestinal manometry provides evidence of gut dysmotility in patients with the clinical syndrome of chronic intestinal pseudo-obstruction. These abnormalities of motility can help to establish the correct diagnosis.

Adolescent↗

Effect of chronic administration of cisapride on gastric emptying of a solid meal and on dyspeptic symptoms in patients with idiopathic gastroparesis.

In a double blind crossover comparison with placebo, the effects of cisapride (10 mg tid for two weeks), a non-antidopaminergic gastrointestinal prokinetic drug, on gastric emptying times and on symptoms were evaluated in 12 patients with chronic idiopathic dyspepsia and gastroparesis. Gastric emptying was studied by a radioisotopic gamma camera technique. The test meal was labelled in the solid component (99mTc-sulphur colloid infiltrated chicken liver). Nine symptoms (nausea, belching, regurgitations, vomiting, postprandial drowsiness, early satiety, epigastric pain or burning, heartburn) were graded weekly on a questionnaire. Cisapride was significantly more effective than placebo in shortening the t1/2 of gastric emptying (p2 = 0.04), but no significant difference was observed between the two treatments with regard to the improvement of total symptom score (p2 = 0.09). No side effects were reported during the study.

Adult↗

Effects of short- and long-term administrations of famotidine and ranitidine on some pituitary, sexual and thyroid hormones.

The endocrine effects of short-term (4 weeks) and long-term (6 months) oral administration of famotidine (40 and 20 mg nocte, respectively) and ranitidine (300 and 150 mg nocte, respectively), were investigated in 20 male patients with duodenal ulcers. Basal PRL, LH, FSH and TSH serum levels were evaluated and their response to specific releasing factors, and basal blood levels of some sexual (E2, P, T) and thyroid (T3, T4) hormones. None of the treatments modified basal and RH-stimulated levels of PRL, LH, FSH and TSH, nor basal levels of sexual hormones. Regarding the thyroid hormones, no effect was observed during the administration of famotidine. On the contrary, short-term treatment with ranitidine induced a significant decrease in thyroxine serum levels, while no effect was observed during maintenance treatment.

Adult↗

Protective effect of sulglycotide on human gastric mucosa exposed to taurocholic acid.

Sulglycotide is a non-systemic drug used in the treatment of peptic ulcer. It seems also to possess cytoprotective action. A double-blind cross-over study on the influence of oral sulglycotide on gastric mucosal cell loss induced by taurocholic acid (20 mM + HCl 7mM in 100 ml normal saline) was carried out in sixteen healthy volunteers by means of the DNA-loss technique. Each subject received either sulglycotide (400 mg thrice daily) or a placebo in random order on the basis of a double-blind cross-over design. Sulglycotide appeared to reduce the gastric cell loss induced by taurocholic acid. These results can explain the therapeutic effect of sulglycotide in peptic disease.

Adult↗

[Effect of tiropramide on solid gastric emptying time in man].

The influence of Thyropramide, a recently developed spasmolytic on the gastric emptying times of a solid meal was assessed in 10 healthy subjects aged 23-54. Thyropramide (300 mg per diem for 3 days per os) does not significantly modify gastric emptying time compared to the placebo though a slight average increase in T 1/2 was noted. No side effects were noted during the study. Thyropramide therefore appears to have a spasmolytic effect on the large intestine without in any way influence the stomach either proximally or distally.

Adult↗

Dose-related effects of synthetic human beta-endorphin and naloxone on fed gastrointestinal motility.

In humans, plasma beta-endorphin levels rise during application of acute stressful stimuli (vertigo, cold pain, and transcutaneous electrical stimulation) that induce gut motor disturbances. Whereas it is possible that circulating beta-endorphin participates in the mediation of these central effects on gut motility, its role cannot be established solely on the basis of changes in plasma levels. Therefore, we designed the present study to investigate 1) the dose-related effects of intravenous synthetic human beta-endorphin and naloxone on gastrointestinal pressure activity in fed healthy individuals; and 2) the interactions of the opiate agonist and antagonist. Infusion of beta-endorphin increased pyloric phasic pressure activity (P less than 0.001) and induced intestinal bursts of rhythmic activity (P less than 0.05) which interrupted normal fed motility. These effects were dose related, with the pyloric dose-response profile being essentially linear. The effects in the proximal intestine were obtained with doses of beta-endorphin at 250 ng X kg-1 X min-1 or greater. In the antrum, there was an overall reduction in phasic pressure activity (P less than 0.02), which was predominantly an effect of the highest dose of beta-endorphin infused (2,500 ng X kg-1 X min-1). Naloxone by itself had no significant effect on fed upper gut motility. However, naloxone significantly inhibited the effect of the lower doses of beta-endorphin on the pylorus. In addition, naloxone significantly reduced the probability of beta-endorphin, triggering intestinal bursts of rhythmic activity. These data suggest that beta-endorphin may play a humoral role in the stimulation of fed pyloric contraction at physiological levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The evolution of anti-ulcer therapy with cimetidine. Is a single large nocturnal dose of cimetidine the right therapy for duodenal ulcer?

Peptic ulcer results from the prevalence of agents causing endoluminal lesions over the defence mechanisms of the mucosa of the upper GI tract. Particularly, in the case of duodenal ulcer, the pathogenetic relevance of non-buffered acid secretion of the early nighttime period has been emphasized. This is indeed confirmed by the fact that a single night dose of 800 mg cimetidine has apparently been proved able--in numerous controlled clinical trials--to provide results that are similar to those obtained with the classic dose of 1 g daily or 400 mg twice daily. Our centre carried out a crossover double-blind controlled trial aimed at evaluating titrable acidity and pH during the 24-h period in seven patients with active duodenal ulcer. The single nighttime dose of cimetidine resulted in a significant and long-lasting inhibition of acid secretion during the entire night. During the day, secretory values returned to levels similar to those obtained with placebo, hence allowing normal digestive functions.

Administration, Oral↗

The role of colloidal bismuth subcitrate in the short-term treatment of duodenal ulcer.

Colloidal bismuth subcitrate (CBS) is a drug used in the treatment of duodenal ulcer; it acts mainly by increasing mucosal resistance against endoluminal aggressive agents, without inhibiting gastric secretion. In previous clinical trials, CBS solution induced healing rates significantly higher than placebo and similar to those observed with cimetidine. In spite of these promising results, the drug has never been widely employed, mainly because of its unpleasant taste, which greatly reduced patient compliance. For this reason, chewing tablets have been introduced. CBS tablets have been reported to induce healing rates significantly higher than placebo and similar to those obtained with CBS solution, cimetidine, and ranitidine. CBS may therefore represent an important alternative to antisecretory drugs in the therapy of duodenal ulcer patients.

Bismuth↗

Comparison between two different posologies of ranitidine on 24-hour gastric acidity in duodenal ulcer patients.

Eight outpatients with active duodenal ulcer, endoscopically proven, entered a controlled double-dummy cross-over study aimed at comparing the effects of ranitidine 150 mg b.i.d. and 300 mg nocte on 24-h intragastric titratable acidity and pH. Both treatments markedly inhibited (p less than 0.01) gastric acid secretion when the mean 24-h results were compared. When the effects of two posologies on nocturnal and diurnal periods were considered separately, 300 mg appeared to control nocturnal acid secretion more actively, while during the day 150 mg b.i.d. seemed to be the more active. Since nocturnal hypersecretion can be considered an important determinant of duodenal ulcer, a large bedtime dose of ranitidine seems to represent a valid therapeutic approach to this disease.

Adult↗

Gastrointestinal motility disturbances in patients with orthostatic hypotension.

Orthostatic hypotension syndromes may be associated with visceral denervation, resulting in disturbances of the gastrointestinal and urinary systems. This report analyzes the findings in 9 patients with neurogenic orthostatic hypotension and gastrointestinal symptoms. Antral and proximal small intestinal motor dysfunction was demonstrated in all patients: a significant reduction (p = 0.007) in the number of interdigestive motor complexes during 3 h of fasting (mean 0.4 vs. 1.3 controls); absence of gastric component in interdigestive motor complexes observed; incoordination of fasting and fed antral activity; and development of nonpropagating bursts of phase III-like activity in the intestine that were of at least 2-min duration, high amplitude and frequency, and associated with tonic elevations in baseline pressure. These motor abnormalities may provide a potential means for the diagnosis of impaired autonomic supply to the upper gut.

Adult↗

Manometric evaluation of functional upper gut symptoms.

Pressure activity in the stomach and upper intestine was studied in 104 patients referred to the Mayo Clinic for evaluation of functional symptoms (nausea, vomiting, upper abdominal pain, or other dyspeptic symptoms in the absence of structural gut abnormalities). Manometric abnormalities were found in 75 patients. Forty-three of these had gastric abnormalities and 32 patients had both gastric and intestinal abnormalities. In the stomach, decreased antral phasic pressure activity after a solid meal was the most common abnormality. In the upper intestine, unpropagated bursts of phasic and tonic contractile activity were a relatively frequent abnormality but a number of other altered manometric patterns also were observed. Digestive tract symptoms were not good predictors of the presence or site of the gastrointestinal manometric abnormalities. Patients with associated neurologic, urologic, or metabolic (diabetes) disease were more likely to exhibit manometric abnormalities than were those without evidence of disease outside the gut. Almost two-thirds of the patients with symptoms and normal manometry presented features suggestive of psychiatric disease. We conclude that in patients with severe functional-type symptoms gastrointestinal manometry is a useful technique to evidence the underlying gut motor disturbance that is present in a relatively high proportion of these patients.

Adolescent↗

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↗