Gabrio Bassotti

Twenty four hour manometric recording of colonic motor activity in healthy man.

The motor activity of the transverse, descending, and sigmoid colon was recorded for 24 hours in 14 healthy volunteers with a colonoscope positioned catheter. During the study the patients ate two 1000 kcal mixed meals and one continental breakfast. Colonic motor activity was low before meals and minimal during sleep; the motility index increased significantly after meals and at morning awakening. Most of the motor activity was represented by low amplitude contractions present singly or in bursts, which showed no recognisable pattern. All but two subjects also showed isolated high amplitude (up to 200 mmHg) contractions that propagated peristaltically over long distances at approximately 1 cm/sec. Most of these contractions occurred after morning awakening, and some in the late postprandial period, with a mean of 4.4/subject/24 h. The peristaltic contractions were often felt as an urge to defecate or preceded defecation, and could represent the manometric equivalent of the mass movements.

Colonic mass movements in idiopathic chronic constipation.

As relatively little is known of human colonic motor activity either in health, or in pathological conditions, we investigated mass movements in 14 chronically constipated patients and 18 healthy volunteers. Mass movements were recorded from proximal and distal colon during 24 h (12 noon-12 noon) by a colonoscopically positioned multilumen manometric probe and low compliance infusion system. Patients and controls differed significantly in the number (mean 2.6 (0.7) v 6.1 (0.9) (SE), p = 0.02) and duration (mean 8.2 (1.6) v 14.1 (0.8) s, p = 0.04) of mass movements. The data suggest that one pathophysiological mechanism of constipation may be decreased propulsive activity. A circadian pattern, with a significant difference between day and night distribution, was documented in both groups. The patients reported decreased defecatory stimulus concomitant with the mass movements.

A multicentre randomised study of intrasphincteric botulinum toxin in patients with oesophageal achalasia

BACKGROUND Intrasphincteric injection of botulinum toxin (Botx) has been proposed as treatment for oesophageal achalasia. However, the predictors of response and optimal dose remain unclear. AIMS To compare the effect of different doses of Botx and to identify predictors of response. PATIENTS/METHODS A total of 118 achalasic patients were randomised to receive one of three doses of Botx in a single injection: 50 U (n=40), 100 U (n=38), and 200 U (n=40). Of those who received 100 U, responsive patients were reinjected with an identical dose after 30 days. Clinical and manometric assessments were performed at baseline, 30 days after the initial injection of botulinum toxin, and at the end of follow up (mean 12 months; range 7–24 months). RESULTS Thirty days after the initial injection, 82% of patients were considered responders without a clear dose related effect. At the end of follow up however, relapse of symptoms was evident in 19% of patients who received two injections of 100 U compared with 47% and 43% in the 50 U and 200 U groups, respectively. Using Kaplan-Meier analysis, patients in the 100×2 U group were more likely to remain in remission at any time (p<0.04), with 68% (95% CI 59–83) still in remission at 24 months. In a multiple adjusted model, response to Botx was independently predicted by the occurrence of vigorous achalasia (odds ratio 3.3) and the 100×2 U regimen (odds ratio 3.2). CONCLUSIONS Two injections of 100 U of Botx 30 days apart appeared to be the most effective therapeutic schedule. The presence of vigorous achalasia was the principal determinant of the response to Botx.

The role of glial cells and apoptosis of enteric neurones in the neuropathology of intractable slow transit constipation

Background: Idiopathic slow transit constipation is one of the most severe and often intractable forms of constipation. As motor abnormalities are thought to play an important pathogenetic role, studies have been performed on the colonic neuroenteric system, which rules the motor aspects of the viscus. Aims: We hypothesised that important neuropathological abnormalities of the large bowel are present, that these are not confined to the interstitial cells of Cajal and ganglion cells, and that the previously described reduction of enteric neurones, if confirmed, might be related to an increase in programmed cell death (apoptosis). Patients and methods: Surgical specimens from 26 severely constipated patients were assessed by conventional and immunohistochemical methods. Specific staining for enteric neurones, glial cells, interstitial cells of Cajal, and fibroblast-like cells associated with the latter were used. In addition, gangliar cell apoptosis was evaluated by means of indirect and direct techniques. Data from patients were compared with those obtained in 10 controls. Results: Severely constipated patients displayed a significant decrease in enteric gangliar cells, glial cells, and interstitial cells of Cajal. Fibroblast-like cells associated with the latter did not differ significantly between patients and controls. Patients had significantly more apoptotic enteric neurones than controls. Conclusion: Severely constipated patients have important neuroenteric abnormalities, not confined to gangliar cells and interstitial cells of Cajal. The reduction of enteric neurones may in part be due to increased apoptotic phenomena.

Gastrointestinal motor dysfunction, symptoms, and neuropathy in noninsulin-dependent (type 2) diabetes mellitus

Although relatively frequent. diabetic involvement of digestive tract motility has not been investigated extensively in different organs. The authors studied esophageal, gastric, and gallbladder motor function in 35 type 2 (noninsulin-dependent) diabetic patients to determine the extent of gut involvement. Of these patients, 27 (77%) had peripheral neuropathy, 12 (34%) had both peripheral and autonomic neuropathy, and 22 (63%) had gastrointestinal symptoms. Esophageal manometric abnormalities were recorded in 18 patients, and delayed radionuclide emptying of the esophagus was documented in 16 patients, with a 83% concordance between the two tests. Scintigraphic gastric emptying of solids was delayed in 56% of patients, whereas gallbladder emptying after cholecystokinin stimulation was reduced in 69% of them. In 74% of patients at least one of the viscera under investigation showed abnormal motor function; however, only 36% of patients displayed involvement of the three organs. Gastrointestinal symptoms, duration and therapy of diabetes, previous poor glycemic control, and retinopathy did not correlate with the presence or the extent of motor disorders. Neuropathy was not predictive of gastrointestinal involvement and its extent; however, when motor abnormalities were present in patients with neuropathy, these were usually more severe. Gastrointestinal motor disorders are frequent and widespread in type 2 diabetics, regardless of symptoms. Autonomic neuropathy has a poor predictive value on motor disorders (0.75 for the esophagus, 0.5 for the stomach, 0.8 for the gallbladder), thus suggesting the coexistence of other pathophysiologic mechanisms.

Coeliac disease: a histological follow‐up study

Aims:  To assess the histological response to a gluten‐free diet (GFD) in a series of coeliac patients in clinical remission, of different ages and with varying degrees of mucosal damage at diagnosis.

Anorectal manometric abnormalities and colonic propulsive impairment in patients with severe chronic idiopathic constipation

Idiopathic chronic constipation is a frequent and disabling symptom, but its pathophysiological grounds are still poorly understood. In particular, there is little knowledge about the relationships between distal (anorectal area) and proximal (colonic area) motor abnormalities in this condition, especially concerning high-amplitude propagated colonic activity. For this purpose, we studied 25 patients complaining of severe idiopathic constipation and categorized them as normal- or slow-transit constipation according to colonic transit time. Twenty-five age-matched controls were also studied. Investigations included standard anorectal motility testing and prolonged (24-hr) colonic motility studies. Analysis of results showed that both groups of constipated patients displayed significantly different (P<0.05) minimum relaxation volumes of the internal anal sphincter, defecatory sensation thresholds, and maximum rectal tolerable volumes with respect to controls. Patients with normal-transit constipation also showed lower internal anal sphincter pressure with respect to slow-transit constipation and controls (P<0.001 andP<0.02, respectively). The daily number of high-amplitude propagated contractions (mass movements) as well as their amplitude and duration, was significantly reduced in both subgroups of constipated patients (P<0.02 vs controls). We conclude that (1) in normal-transit constipation, motor abnormalities are not limited to the anorectal area; (2) patients with slow-transit constipation probably have a severe neuropathic rectal defect; (3) prolonged colonic motility studies may highlight further the functional abnormalities in constipated subjects; and (4) an approach taking into account proximal and distal colon motor abnormalities might be useful to understand pathophysiological grounds of chronic constipation and lead to better therapeutic approaches.

Colonic motility and gastric emptying in patients with irritable bowel syndrome effect of pretreatment with octylonium bromide

This study was undertaken to evaluate (1) the colonic response to eating for a prolonged time in healthy subjects and patients with the irritable bowel syndrome (IBS); (2) the effect of octylonium bromide, a new smooth muscle relaxant acting by interfering with calcium ion mobilization, on the postprandial colonic motility; and (3) whether chronic gastric stasis could be responsible for both the dyspeptic symptoms often complained of by IBS patients and the faulty colonic response to eating. The colonic response to a 1000-kcal mixed meal in ten healthy subjects was characterized by two transient (from 0 to 60 and from 120 to 150 min postprandially, respectively) increases in colonic motor activity; ten IBS patients showed a continuous postprandial increase in colonic motor activity that was not terminated 180 min after eating. Treatment of IBS patients with octylonium bromide (80 mg, qid,per os) for 5–7 days reduced their colonic response to eating to a very short increase in colonic motor activity limited to the first 30 min. Finally, gastric emptying was not different in the two groups.

Enteric nervous system abnormalities in inflammatory bowel diseases

Abstract  Various studies have described abnormalities of the enteric nervous system (ENS) in tissue samples from patients with chronic idiopathic inflammatory bowel diseases (IBD). The distribution of density of the different cell types of the ENS was however not studied in a systematic way. The aim of this study was to examine the density of neurons, enteroglial cells and interstitial cells of Cajal (ICC) in the different plexuses of the ENS in samples from patients with Crohn’s disease (CD), ulcerative colitis (UC) and controls. Tissue samples from 16 patients with CD (ileum) and 16 patients with UC obtained in involved and non‐involved areas were studied using immunohistochemistry with antibodies directed against neuron‐specific enolase, S100, C‐Kit and CD3. Sections were analysed blindly by two pathologists and the number of positive cells was counted for each type. Overall, an increase was noted for neuronal cell bodies, enteroglia and ICC in the deep muscular plexus in CD. In uninvolved areas of CD patients, the number of enteroglial cells was decreased. In UC, an increase of ICC in the muscularis propria and enteroglial cells was observed in diseased tissue. The study confirms the presence of abnormalities of the different cells of the ENS in IBD. The presence of lesions in samples from uninvolved areas, such as a reduction of enteroglia, supports a pathogenetic role of the ENS.

Clinical and morphofunctional features of idiopathic myenteric ganglionitis underlying severe intestinal motor dysfunction: a study of three cases

Ganglionitis, i.e., the inflammatory neuropathy characterized by a marked lymphoplasmacellular infiltrate in the myenteric plexus, may underlie a variety of paraneoplastic, infectious, or neurological disorders, although occasional cases are idiopathic in origin. We report clinical, manometric, morphofunctional, and immunological features of three cases of idiopathic ganglionitis. All patients had megacolon and underwent surgery for repeated episodes of intestinal subocclusion. Esophageal, GI, and colonic manometry performed in one patient showed dysmotility of the whole gut. Histological examination of colonic and ileum specimens identified a prominent lymphoplasmacellular infiltrate within the myenteric plexus along with a marked decrease of a wide array of neuronal peptides/transmitters. In one patient, tissue analysis revealed progressive neuronal changes up to marked myenteric neuron damage. The inflammatory infiltrate in all patients comprised CD4+ and CD8+ T lymphocytes. Abundance of both subclasses of lymphocytes suggests that immune-mediated mechanisms were responsible for neuronal degeneration. In one patient, systemic steroid therapy brought a significant clinical improvement. The immunosuppressive approach deserves further investigation in patients with severe gut motor abnormalities attributable to idiopathic myenteric ganglionitis.