Age-dependent association of idiopathic achalasia with vasoactive intestinal peptide receptor 1 gene.

Idiopathic achalasia is a rare disorder of the oesophagus of unknown aetio-pathogenesis characterized by a myenteric inflammation, aperistalsis and insufficient lower oesophageal sphincter relaxation. Vasoactive intestinal peptide (VIP), present in the myenteric plexus, is involved in smooth muscle relaxation and acts as an anti-inflammatory cytokine. The human VIP receptor 1 gene (VIPR1) is highly polymorphic and may play a role in idiopathic achalasia. One hundred and four consecutive patients and 300 random controls from the same geographic area were typed for five SNPs mapping in the VIPR1 gene. Patients with idiopathic achalasia show a significant difference in allele, genotype and phenotype distribution of SNP rs437876 mapping in intron 4. This association, however, was almost entirely due to the group of patients with late disease onset (P = 0.0005). These results strongly suggest that idiopathic achalasia is a heterogeneous disease with a different aetiology in cases with early or late disease onset.

Effect of wheat bran in treatment of chronic nonorganic constipation. A double-blind controlled trial.

After a two-week basal period, 24 patients were randomly allocated to receive, with a crossover double-blind design, for two consecutive four-week periods, bran (20 g/24 hr) or placebo. The daily intake of water and dietary fibers was standardized. Symptomatology, oroanal transit time, bowel frequency, and stool weight were assessed in basal conditions and at week 4 and 8 of the treatment. Oroanal transit time decreased and bowel frequency and stool weight increased significantly during both bran and placebo administration in comparison with basal period. Bran treatment was more effective than placebo in improving bowel frequency and oroanal transit. During bran treatment oroanal transit time became normal only in patients with slow colonic transit and not in those with slow rectal transit. Neither the occurrence nor the severity of the most frequent accompanying symptoms of chronic constipation differed significantly between placebo and bran treatments.

Effects of intraluminal acidification on oesophageal motor activity.

This study assessed the effect of prolonged intraluminal acidification on the motor activity of the entire oesophageal body (under controlled conditions). Intraoesophageal pressures were recorded in 13 endoscopy negative subjects with gastro-oesophageal reflux disease in whom saline, HC1 0.1 N, and saline solutions were infused (1.5 ml/min) blindly in the oesophageal body, 6 cm distal to the upper oesophageal sphincter for three consecutive periods of 45 minutes each. These findings were compared with those of a control group. Intraoesophageal acidification caused an increase in the deglutition frequency (p < 0.02), the occurrence of multipeaked waves (p < 0.04) as well as a decrease of the propagating velocity (p < 0.04) of the primary peristaltic contractions. Furthermore, intraoesophageal acidification determined an increase, at all levels of the oesophagus, of the duration (p < 0.04) and, more noticeable in the proximal oesophageal body, of the amplitude (p < 0.02) of primary peristaltic contraction waves. In conclusion prolonged intraoesophageal acidification can considerably affect frequency of deglutition, morphology, and propagating patterns of primary peristaltic contractions. This study shows that these effects are independent from volume distension of the oesophagus and supports the presence of acid sensitive receptors in the oesophageal mucosa.

Effects of cisapride on distal esophageal motility in humans.

Peristaltic contractions of the distal esophageal body and lower esophageal sphincter tone were evaluated in patients affected by gastroesophageal reflux disease after either acute intravenous (8.0 mg) administration or two oral doses (5.0 mg and 10.0 mg) of cisapride and in healthy controls after a 10.0-mg oral dose of cisapride. Intravenous cisapride administration enhanced the amplitude and duration of primary peristalsis and the lower esophageal sphincter tone, which reached normal control values. Likewise, the 10.0-mg oral dose effectively enhanced the lower esophageal sphincter resting pressure in both controls and in reflux patients, whereas the amplitude and duration of primary peristalsis was improved only in controls. The 5.0-mg oral dose of cisapride proved ineffective on distal esophageal motor activity in reflux patients. To evaluate whether atropine is capable of modifying the effects of cisapride on distal esophageal motor activity, cisapride was administered intravenously before and during intravenous atropine administration. Effects of cisapride on peristaltic contractions were completely blocked by atropine, irrespective of whether atropine was administered before or after cisapride. The lower esophageal sphincter pressure response to cisapride varied according to the sequence of drug administration, showing no effect when cisapride followed atropine administration and, when this sequence was reversed, no significant atropine-induced inhibition on cisapride-stimulated lower esophageal sphincter pressure. It is suggested that cisapride enhances distal esophageal motor activity by means of a muscarinic receptor mechanism at the level of the distal esophageal body and, at least in part, via a muscarinic-independent mechanism at the level of the lower esophageal sphincter.

Rectal sensitivity in chronic constipation.

Rectal sensitivity is often reduced in patients affected by chronic constipation, but it is not known whether this alteration differs according to the severity and the site(s) of the slowing of gastrointestinal transit. Moreover, it is not known whether alteration precedes or follows bowel complaints. In this study, perception of intrarectal distension was evaluated in 28 healthy controls, in 20 patients complaining of constipation and with a normal gastrointestinal transit time (less than 96 hr), and in 44 patients complaining of constipation and with a prolonged gastrointestinal transit time (greater than 96 hr). Within the latter group, perception to intrarectal distension was analyzed in patients with slowing of transit in the rectum only, in the colon only, and in both the rectum and the colon. In a subgroup of 22 patients, rectal sensitivity was evaluated before and after treatment. Rectal sensitivity was found to be reduced significantly in constipated patients; it was more severely reduced in patients with objective evidence of prolonged gastrointestinal transit time and with slow transit in the rectum. Rectal sensitivity improved in patients who responded to treatment and did not vary significantly in nonresponders.

Intraluminal pH and oesophageal motility in patients with gastro-oesophageal reflux.

The effect of intraluminal pH on motor activity of the lower oesophageal body was studied in patients with pathological gastro-oesophageal reflux. Liquid boluses with a pH range of 6.98-1.1, infused in the distal oesophagus of 21 patients during manometric recording of motor activity, elicited either secondary peristalsis or simultaneous contractions. Acid pH did not affect the threshold of distension required to elicit secondary peristalsis. Oesophageal responses to volumes of instillate did not differ in patients with normal and abnormal acid clearing test, nor in patients with a negative and positive acid perfusion test.

Melanosis of the rectum in patients with chronic constipation.

In patients with constipation the prevalence of melanosis in rectal biopsies was evaluated in an attempt to correlate its occurrence with laxative consumption and intestinal stasis. Melanosis was present in 58 percent of the patients and in none of a control group. Melanosis was present in 73.4 percent of patients consuming anthracene laxatives and in 26.6 percent of those not consuming anthracene laxatives (P less than 0.01). No correlation was found between the occurrence (and grading) of melanosis and pattern of transit through the large bowel, bowel movements, and duration of symptoms. Results of this study seem to indicate that intestinal stasis is not a cause of melanosis of the colon and rectum and confirm that melanosis may well be due only to the consumption of anthracene laxatives; melanosis coli does not appear to be a sensitive marker of impairment of motor function in the "cathartic colon."

Motor activity of the distal oesophagus and gastrooesophageal reflux.

The relationship between intraoesophageal pH value and motor activity of the lower oesophageal body and sphincter was investigated by simultaneous evaluation of intraluminal pressure and pH in 13 patients complaining of heartburn and regurgitation. One hundred and thirty one episodes of gastro-oesophageal reflux were recorded. One hundred and eighteen (90.1%) were preceded by a swallow (one to 12 seconds), 13 reflux episodes (9.9%) were not preceded by a swallow. Gastro-oesophageal refluxes preceded by swallow were accompanied by an equal number of normal and abnormal primary peristaltic sequences and, while recording at level of the lower oesophageal sphincter, occurred during inhibition of the sphincter. Frequency of abnormal primary peristalsis increased (p less than 0.01) during periods of low intraluminal pH (less than 5.0). An increase of at least 0.5 U in intraluminal pH occurred with 45.2% of normal primary peristalsis, 29.3% of abnormal primary peristalsis, 4.3% of secondary peristalsis, 3.5% of non-peristaltic contractions. The results of this study indicate that in patients with symptoms of reflux oesophagitis, gastro-oesophageal reflux appears to be related to swallow-induced lower oesophageal sphincter inhibition and not related to abnormal motor activity of the distal oesophageal body where an increased frequency of abnormal primary peristalsis appears to occur during low intraluminal pH and primary peristalsis appears to be the most important mechanism of oesophageal clearing.

Effect of bombesin on lower esophageal sphincter pressure in humans.

Intravenous infusion of bombesin in humans results in increased serum gastrin levels and increased lower esophageal sphincter pressure. To differentiate a gastrin- from a nongastrin-mediated mechanism, the effect of intravenous bombesin infusion on lower esophageal sphincter pressure was studied in 5 healthy subjects and in 5 antrectomized patients. Lower esophageal sphincter pressure was recorded by three continuously perfused catheters with side-openings located 5 mm apart. Blood samples were taken at regular intervals during the study periods to assay gastrin and pancreatic polypeptide. Manometric tracings and blood samples were coded and evaluated blindly. Lower esophageal sphincter pressure increased during bombesin infusion both in normal and antrectomized subjects. The increase had a delayed onset and persisted after discontinuation of bombesin. No correlation was found between lower esophageal sphincter pressure and serum gastrin or pancreatic polypeptide values. These data indicate that the effect of bombesin on lower esophageal sphincter pressure is not gastrin or pancreatic polypeptide mediated.

Lower oesophageal sphincter response to intravenous infusions of pentagastrin in normal subjects, antrectomised and achalasic patients.

Lower oesophageal sphincter response to infusion of graded doses (0.003--0.050 microgram kg-1min-1) of pentagastrin was evaluated in four antrectomised patients as well as in six healthy subjects and seven achalasic patients in whom inhibition of antral gastrin release was maintained by continuous acidification (HC1 0.1 N) and aspiration of gastric antrum. In normal subjects and in antrectomised patients doses of pentagastrin required for half-maximal gastric acid secretion (0.012 microgram kg-1min-1) produced statistically significant increases of LES pressure. In achalasic patients, the infusion of pentagastrin did not affect LES pressure. These data seem to indicate that gastrin plays, at least in some degree, a physiological role in the regulation of LES tone. Insensitivity of LES to pentagastrin in achalasia suggests that the raised sphincter pressure in this disorder can not be attributed to gastrin.

Intraluminal pH esophageal motility.

The aim of the present study was to investigate the effect of intraluminal pH on motor activity of the lower esophageal body. Liquid boluses of different pH values (7 to 2) were infused in the esophagus of 14 normal subjects during manometric recording of motor activity. Each test infusion elicited an esophageal motor response, either secondary peristalsis or simultaneous contractions. Secondary peristalsis was elicited by similar volumes of perfusates at pH 7, 6, 5, but significantly less volumes were needed with perfusates pH 4, 3, and 2. Simultaneous motor activity was not affected by intraesophageal pH value in the range investigated.

Functional evaluation of colon transplants used in esophageal reconstruction.

Studies were performed on the mechanical activity of iso- and antiperistaltic colon segments used to replace the esophagus. Transplants were challenged with a semiliquid bolus and/or a 0.1 N HCl solution, considered as common stimuli for an in situ esophagus, and the mechanical activity was investigated by means of synchronized manometric and cinefluorographic recordings. Basal activity of the interposed colon was limited to occasional monophasic waves of the segmenting type; the acid solution and the semiliquid bolus constantly elicited a peristaltic motor response transporting the contents to the gastric fundus or, in antiperistaltic colon, from the distal to the proximal part.