Search PubMed⌕ Search

Biomedical subjects

G Basilisco

Publications and source records attributed to G Basilisco.

At least 37 records · Page 2Linked to original sources

High spontaneous chromosomal damage in lymphocytes from patients with hereditary megaduodenum.

Chromosomal aberration and micronucleus assays were used to investigate the extent of cytogenetic damage in peripheral blood lymphocytes from four patients in two unrelated families with hereditary megaduodenum. The frequencies of total chromosomal aberrations, which significantly correlated with those of micronuclei, were higher in the patients than in sex- and age-matched controls, with no overlapping between the two groups. The considerable chromosomal fragility in patients with hereditary megaduodenum may be a genotypic marker for preclinical diagnosis predictive of increased cancer risk.

Adult↗

Tonic responses of canine proximal colon: effects of eating, nutrients, and simulated diarrhea.

Our hypothesis was that the proximal colon relaxes to accommodate flow from the ileum. Therefore, we recorded tonic responses of the canine proximal colon to flow through the ileum and colon stimulated by 1) an 840-kcal meal, 2) nutrients perfused into the ileum and colon, or 3) rapid infusion of saline into the ileum with overflow into the colon. Saline infusion was considered to be a model of diarrhea, and the effects of an antidiarrheal (morphine sulfate) were therefore assessed. Proximal colonic tone was measured with a barostat. Tone increased before and after the arrival of chyme in the ileocolonic region. Perfusion of nutrients into the ileum and colon also significantly increased (P < 0.05) colonic tone compared with equal volumes of saline. Rapid perfusion of the ileocolonic segment with saline increased colonic tone; this increase was significantly greater (P < 0.01) when preceded by morphine. In contrast to our hypothesis, tone of the canine proximal colon increased in response to ileal flow. The increase in colonic tone during the late response to food was at least partly attributable to stimulation by intraluminal contents.

Animal Nutritional Physiological Phenomena↗

Manometric patterns of rat colonic motor activity and defecation. Effect of selective 5HT1A agonist 8-OH-DPAT.

We investigated in conscious and unrestrained rats, the major patterns of colonic pressure waves, as related to defecation. A manometric low compliance perfusion system, which was set at a very low flow rate (0.03 ml/min), permitted simultaneous recordings of intraluminal pressure in the proximal, transverse, and distal colon. Pressure waves in control rats reflected two types of motor activity: short-duration waves (< 15 sec), that were frequent throughout the colon (about 40-90/hr with aborally decreasing frequency), and propulsive, long-duration, high-amplitude waves (> 15 sec, > 15 mm Hg) that occurred only occasionally (1/hr or less) in the transverse and distal, but not in the proximal colon; these waves appeared to migrate aborally and were associated with defecation. The serotonin 5HT1A agonist 8-OH-DPAT dramatically and dose-dependently increased the frequency of long-duration, high-amplitude waves in the transverse and distal colon, and concurrently promoted defecation; these effects were prevented by the putative 5HT1A antagonist pindolol. We conclude that 5HT1A agonists such as 8-OH-DPAT may promote defecation and occurrence of propulsive waves through the same serotoninergic mechanism.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Ileal distention relaxes the canine colon: a model of megacolon?

BACKGROUND/AIMS: Reflex relaxation is a mechanism whereby the colon can show short-term dilatation in the absence of mechanical obstruction. This study investigated the tonic response of the canine colon to ileal distention and its pharmacological control. METHODS: In four dogs, the tone of the proximal colon was recorded by a barostat during distention of the terminal ileum. RESULTS: Ileal distention inhibited ileal motility and relaxed the colon. Adrenergic blockade by propranolol plus phentolamine, nicotinic blockade by hexamethonium, and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methylester significantly increased resting tone of the colon but did not inhibit relaxation induced by ileal distention. Muscarinic blockade by atropine completely relaxed the colon, and no further decrease in tone was observed after ileal distention. The neurokinin 2 antagonist SR48968 did not alter colonic tone. CONCLUSIONS: The barostat was able to monitor resting tone of the canine colon, which was shown to be under inhibitory control by adrenergic, cholinergic-nicotinic, and nitric oxide-like transmitters. Inhibition of colonic tone by ileal distention was not mediated solely by adrenergic, cholinergic-nicotinic, or nitric oxide mechanisms. Reflex relaxation, possibly predisposing to acute colonic dilatation, may be activated by multiple mechanisms that may differ from those controlling resting tone.

Animals↗

A selective NK-2 antagonist blocks the increase of canine colonic tone and ileal contractions induced by the NK-2 selective receptor agonist, [beta Ala8] neurokinin A-(4-10).

BACKGROUND: The regulatory roles of tachykinins in intestinal motor function may be clarified by use of novel, stable and selective antagonists of neurokinin receptors. We studied the effects of the non-peptide NK-2 receptor antagonist SR48968 on canine colonic tone under resting conditions and after stimulation by the selective NK-2 receptor agonist [beta Ala8] neurokinin A-(4-10). METHODS: Experiments were performed in three conscious female dogs. Proximal colonic tone was recorded by a barostat and intraluminal pressures were recorded in the terminal ileum. 10, 15 and 20 cm orad to the ileocaecal junction. In separate experiments, and in a random sequence, dogs received an i.v. injection of the NK-2 antagonist SR48968, 10, 100, 1000 micrograms/kg, followed after 30 min by 2 micrograms/kg of the agonist [beta Ala8] neurokinin A-(4-10). Experiments were replicated twice in each dog. RESULTS: The NK-2 agonist increased colonic tone, and SR48968 antagonized these effects in a dose-dependent fashion (Spearman's rank, r = 0.86; P < 0.01); antagonism was complete at the highest dose. SR48968 alone had no effect on colonic tone and ileal motility. When given during phase I or II of the interdigestive motor complex, [beta Ala8] neurokinin A-(4-10) increased ileal contractions: pre-treatment with SR48968 blocked this increase in ileal motility. When given during phase III, [beta Ala8] neurokinin A-(4-10) interrupted the motility front; this effect was not antagonized by SR48968. CONCLUSIONS: SR48968 antagonizes the increase in canine colonic tone and ileal motility induced by activation of NK-2 receptors. However, SR48968 by itself had no effect on the control of colonic tone and ileal motility under unstimulated conditions. SR48968 may be useful for investigating the physiological role of tachykinins on the gastrointestinal tract.

Animals↗

Anorectal dysfunction and delayed colonic transit in patients with progressive systemic sclerosis.

We studied 14 unselected patients with progressive systemic sclerosis (PSS), six with constipation, and eight with normal bowel habits. A control group, matched for age and sex, comprised six patients with idiopathic constipation and seven healthy subjects. Anorectal manometry was performed with perfused catheters and segmental colonic transit was measured by a radiopaque marker technique. The resting pressure of the anal canal was significantly reduced in PSS with constipation (P < 0.05). The rectoanal inhibitory reflex was detected in only one PSS patient with constipation, but was present in seven of eight PSS patients with normal bowel habits and in all controls (P < 0.01). Total and right colonic transit times were significantly delayed in PSS with constipation and in patients with idiopathic constipation (P < 0.05). In patients with PSS, colonic transit was delayed and anal sphincter function was impaired in constipated patients, suggesting involvement of both the colon and the anorectum by the disease.

Adult↗

Acid clearance and oesophageal sensitivity in patients with progressive systemic sclerosis.

This study examined the hypothesis that impaired oesophageal peristalsis was associated with delayed oesophageal clearance of acid in patients with progressive systemic sclerosis (PSS), some of whom are thought to have impaired oesophageal sensitivity to acid. Sixteen patients with PSS had: (a) oesophageal manometry and endoscopy; (b) acid perfusion of the oesophagus with simultaneous measurement of intraoesophageal pH during perfusion and for the next 10 minutes; (c) 22 hour monitoring of intraoesophageal pH; and (d) an evaluation of reflux symptoms during and after perfusion and during overnight pH monitoring. By oesophageal manometry, eight patients had normal peristalsis and eight patients had impaired peristalsis. Oesophageal endoscopy was unremarkable in patients with normal peristalsis, whereas all patients with impaired peristalsis had oesophagitis. The time needed to clear the oesophagus of perfused acid was shorter (p < 0.01) in patients with normal peristalsis and acid clearance time was significantly correlated (p < 0.01) with acid exposure time during overnight pH monitoring. During and after oesophageal perfusion, the nature, duration, and severity of symptoms did not differ between the groups, but overnight symptoms lasted longer (p < 0.05) in patients with impaired peristalsis. It is concluded that in PSS: (1) Impaired oesophageal motility delayed the clearance of acid and increased the exposure time to acid. (2) Acid clearance time is a useful parameter of impaired oesophageal motor function. The assessment of acid clearance time can be used as an alternative to overnight pH monitoring, to assess the impairment of oesophageal acid clearance. (3) Oesophageal sensitivity to acid was preserved in patients with impaired peristalsis and oesophagitis. (4) Reflux symptoms lasted longer in patients with prolonged oesophageal acid exposure but were still reported for a small fraction of the total acid exposure time. Thus, reflux symptoms reflect poorly prolonged exposure of the oesophagus to acid and are not a reliable guide to acid injury of the oesophagus in PSS.

Adult↗

Single doses of ritodrine delay orocaecal transit in patients with irritable bowel syndrome.

The lactulose hydrogen breath test was used to assess the effect of a single dose of the beta 2-adrenoceptor agonist ritodrine on orocaecal transit time in 11 patients (three men) with irritable bowel syndrome. Transit time (median values, range) was significantly longer (P less than 0.01) after ritodrine than after placebo (120, 50-200 vs 75, 40-100 min). Median heart rate was similar before treatments whereas the maximal increase in heart rate was significantly greater (P less than 0.01) after ritodrine than after placebo.

Adult↗

Intragastric and intraoesophageal pH monitoring in duodenal ulcerpatients: effect of the new histamine H2-receptor antagonist ramixotidine.

The effect of the new histamine H2-receptor antagonist ramixotidine 750 mg p.o., administered at 22.00 h, on intragastric and intraoesophageal pH monitored from 22.00 h to 08.00 h, was studied in a double-blind cross-over trial in 11 duodenal ulcer patients. Placebo and ramixotidine were given to each patient on 2 consecutive days in a randomized sequence. Three patients were excluded from the intragastric pH analysis as the records on the second study day were technically inadequate. No significant carry-over or sequence effect was noted. Intragastric hydrogen ion activity was significantly lower (p = 0.01) after ramixotidine than after placebo: median (range) 24 (9-100) vs 97 (27-188) mmol/l. The percentage of time with intraoesophageal pH less than 4 was less than 5% in all but three recordings, with a maximum value of 12%, and it was not significantly different after the two treatments.

Adult↗

Orocecal transit delay in obese patients.

Orocecal transit time was assessed with lactulose hydrogen breath test in 12 obese patients during intravenous infusion of placebo or naloxone 40 micrograms/kg/hr given in randomized order and in double-blind conditions. Transit time was also evaluated in 22 healthy controls. Orocecal transit was significantly (P less than 0.01) longer in the obese patients, during placebo treatment (median 130, range 100-200 min) than in the healthy controls (median 75, range 40-170 min). Compared with placebo, transit time in the obese subjects was delayed (P less than 0.05) during naloxone treatment (median 150, range 100-230 min).

Adult↗

Risk factors for first operation in Crohn's disease.

We studied 267 consecutive Italian patients (146 male, 121 female) with Crohn's disease. Median time from the first symptom to diagnosis at our center was 21 months (range 1-372), whereas median follow-up from the first visit was 38 months (range 1-180). The disease affected the small bowel in 93 (35%) cases, the ileum and colon in 76 (28%), and the colon in 98 (37%). Forty-nine percent of the patients underwent major abdominal surgery for the disease at least once. The cumulative probability of abdominal surgery was 36% and 55%, 60 and 120 months after the onset of symptoms, respectively. Univariate analysis indicated that patients with colon involvement (p less than 0.0001), those with a longer interval between first symptom and diagnosis (p less than 0.0001), and those at an older age at diagnosis (p less than 0.0003) had a significantly greater probability of escaping abdominal surgery. The interval between first symptom and diagnosis, the site of disease, and the age at diagnosis were confirmed as risk factors for surgery, in decreasing order of importance, by multivariate analysis with Cox's proportional hazard model. A prognostic index for first operation based on these variables is proposed.

Adolescent↗

Plasma prolactin, sex steroids and gastrin in human volunteers treated for 2 weeks with therapeutic doses of cimetidine or the new histamine H2-receptor antagonist ramixotidine (CM 57755A).

Three groups of eight healthy male volunteers received placebo for 2 days, then daily morning doses either of cimetidine 800 mg, ramixotidine 750 mg (CM 57755A), or placebo, for 14 days, and then were all returned to placebo for one more day. Plasma levels of prolactin, testosterone and 17 beta-estradiol were measured on Days 2, 3, 16 and 17 in blood samples taken 30 and 15 min before and 0, 60, 120, 180, 240 and 300 min after treatment. Gastrin was assayed in blood collected on the same days 180 min after treatment. Mean pre- and post-treatment areas under the time-concentration curves of the first three hormones were not significantly different in the three groups on any test day, or within the same group throughout the four test days. Mean plasma gastrin levels ranged between 27 and 42 pg/ml, respectively, in the placebo and cimetidine treated groups on test day 3, and intermediate values were found in the group receiving CM 57755A. There was no statistically significant difference in gastrin level between the groups on any test day or within the same group throughout the four test days. No subjective side-effects attributable to the treatments were reported, and there were no abnormalities in blood pressure, heart rate or standard laboratory tests.

Adult↗

Repeatability of lactulose hydrogen breath test in subjects with normal or prolonged orocecal transit.

The within-subject repeatability of orocecal transit assessed with lactulose hydrogen breath test was evaluated in 15 healthy volunteers and 16 constipated or obese patients. The test was repeated twice in each subject. Mean (SD) transit time was 105 (63) and 103 (60) min in the first and second series of tests, respectively, showing that the first measurement did not affect the second. The within-subject repeatability of the test was related to the length of transit, the scatter of the differences between the first and second test being greater with the increase of the mean gastrointestinal transit time. The 95% coefficient of repeatability was 84 min for all measurements and 30 and 118 min, respectively, for transit times under and over 100 min. The lowest reproducibility of the test was found in constipated patients with prolonged orocecal transit.

Adult↗

Inhibition of pentagastrin-stimulated gastric acid secretion and plasma levels of the new histamine H2-receptor antagonist ramixotidine dihydrochloride (CM 57755) in human volunteers.

The new competitive histamine H2-receptor antagonist, ramixotidine 2 HCl (CM 57755), has been tested in healthy male volunteers for its ability to inhibit pentagastrin-stimulated gastric acid secretion. In the first study, in 8 subjects, pentagastrin 6 micrograms.kg-1 was injected s.c., 90 min after the following 4 oral treatments given in random order at weekly intervals: placebo, 100, 200 and 400 mg CM 57755. Gastric contents were collected over 15-min periods during the 2 h after pentagastrin stimulation. In a second, similar study, 8 subjects received placebo, 0.5 and 1.0 g CM 57755 and 800 mg cimetidine, 120 min before a 2 h i.v. infusion of 6 micrograms.kg-1.h-1 pentagastrin. Cumulative gastric secretion in placebo-treated subjects was 46 +/- 14 and 62 +/- 11 mmol H+.2 h-1 (mean +/- SD), respectively, in the first and second studies. It was significantly reduced only after 400 mg CM 57755 in the first study. In the second study either dose of CM 57755 and cimetidine caused a significant reduction in gastric acid secretion. Average plasma levels of ramixotidine were dose-related after 0.2 and 1.0 g and ranged from 0.3 and 1.6 micrograms/ml, respectively, at 60 min to 0.5 and 3.7 micrograms/ml at 180 min. The peak cimetidine level averaged 3.6 micrograms/ml at 150 min. Individual CM 57755 plasma levels throughout the test period were fairly consistent with the inhibition of cumulative gastric acid secretion scored concurrently in each subject. No subjective side-effects attributable to the treatments were reported, and no abnormal findings were seen in the ECG or in laboratory tests.

Adult↗

Oral naloxone antagonizes loperamide-induced delay of orocecal transit.

Orocecal transit time was determined by the lactulose hydrogen breath test in nine healthy volunteers after administration of placebo, loperamide (16 mg per os), and loperamide (16 mg per os) followed by oral naloxone at doses of 16 and 32 mg. The four tests were performed in double-blind conditions and in random sequences. Transit time (mean, SD) after loperamide (128.8 min, 32.9) was significantly increased (P less than 0.05) compared with placebo (85.5 min, 35.7), loperamide followed by naloxone 16 mg (88.8 min, 46.2), and loperamide followed by naloxone 32 mg (84.4 min, 40.6). These results show that the peripheral opioid agonist loperamide delays orocecal transit in healthy subjects and that naloxone per os at adequate doses antagonizes this effect.

Administration, Oral↗

Effect of loperamide and naloxone on mouth-to-caecum transit time evaluated by lactulose hydrogen breath test.

The effect of loperamide and naloxone on mouth-to-caecum transit time was evaluated by the lactulose hydrogen breath test in four men and four women. Each subject underwent tests during the administration of placebo, loperamide (12-16 mg po), naloxone (40 micrograms/kg/h by a three-hour intravenous infusion), and loperamide plus naloxone, carried out at intervals of one or two weeks. The transit time was significantly longer after loperamide, and this effect was antagonised by the concomitant administration of naloxone whereas naloxone administered alone had no effect on mean transit time. No clinically important side effects were reported.

Adult↗