S. Passaretti

Longterm oral cisapride improves interdigestive antroduodenal motility in dyspeptic patients.

We have evaluated the effect of cisapride on interdigestive antroduodenal motility during a prolonged oral therapy in 20 consecutive dyspeptic subjects. Individuals with less than two migrating motor complexes (MMCs) starting from the antral region in 240 minutes and without evidence of upper gastrointestinal tract diseases were randomly treated with either cisapride (10 cases), or placebo (10 cases) for 15 days. Computerised manometry of antroduodenal region was performed for 240 minutes, in basal conditions and on the 15th day of therapy. Symptomatic evaluation of patients was also performed before and after treatment. After cisapride administration, a significant increase in the incidence of antral migrating motor complexes was noticed (p = 0.022); likewise, the motility index, calculated for phase-2 periods, appeared to be significantly higher both in the antrum and in the duodenum (p less than 0.001). Symptomatic improvement was observed in both groups, with a hardly significant (p = 0.049) reduction of dyspeptic symptoms severity only but not of frequency in cisapride treated patients v controls. We conclude that longterm oral therapy with cisapride improves interdigestive antroduodenal motor activity.

Esophageal Motility in Cirrhotics with and without Esophageal Varices

Esophageal manometry was performed in 45 cirrhotics with varices, in 15 cirrhotics without varices, and in 20 normal subjects, to define the effect of varices on esophageal motility. Cirrhotics with varices showed a decreased amplitude of motor waves in the lower half of the esophagus (p less than 0.01), an increased duration of primary peristaltic waves along the entire length of the esophagus (upper esophagus, p less than 0.05; lower esophagus, p less than 0.01), and an increased peak-to-peak speed of primary peristaltic waves (p less than 0.01). Resting lower esophageal sphincter pressure and duration of sphincter relaxation were similar in patients and controls. The above-mentioned abnormalities might be due to the mechanical effect of the presence of varices.

Effects of cimetropium bromide on gastrointestinal transit time in patients with irritable bowel syndrome

Cimetropium bromide is a new antimuscarinic compound with strong antispasmodic activity. The aim of this study was to evaluate the effects of oral cimetropium bromide on total gut transit time in patients with irritable bowel syndrome. Forty patients, divided according to their initial total gastrointestinal transit times and presenting symptoms, were treated with cimetropium bromide 50 mg t.d.s. or placebo for 1 month according to a double‐blind, parallel group design. Before and after treatment all subjects ingested 24 radio‐opaque markers. The total intestinal transit time was determined by evaluating the rate of disappearance of markers from plain X‐ray films of the abdomen taken every 24 h for 4 days. Pain and bowel habits were also monitored. Seven patients did not complete the study. Cimetropium bromide significantly (P < 0.01) shortened the whole gut transit time in patients with prolonged transit time (80.8 ± 4.0 h before vs 60.8 ± 6.7 h after treatment) and improved the global clinical condition significantly compared with placebo (P= 0.029). In patients with a short total intestinal transit time, cimetropium bromide had no effect on whole gut transit time and did not significantly improve symptoms. The results of this study indicate that oral cimetropium bromide is effective both objectively and subjectively in a subgroup of irritable bowel syndrome patients with constipation.

Area under pH 4: a more sensitive parameter for the quantitative analysis of esophageal acid exposure in adults

Objective:Traditional quantitative analysis of 24-h esophageal pH monitoring data does not include the pH of reflux episodes. Area under pH 4 (AU4) is a recently introduced parameter that describes the acid exposure rate through both duration and depth of pH falls.Methods:In Study A, we enrolled 20 healthy controls and 42 patients (18 without esophagitis, 24 with Savary I–III esophagitis) in a study evaluating reference values for 24-h reflux time at pH <4 (RT) and 24-h AU4 by means of receiver operating characteristic (ROC) discriminant analysis. For Study B, we next prospectively applied the resulting cutoffs to 16 healthy controls and to 110 gastroesophageal reflux (GERD) patients (55 with esophagitis) to adjust sensitivity, specificity, and predictive values of both RT and AU4.Results:In Study A, the best cutoff values were 5.1% for RT (Area Index ± SE, 0.899 ± 0.038; 95% confidence interval [C.I.], 0.796 ± 0.961) and 36.1 pH × min for AU4 (Area Index ± SE, 0.935 ± 0.03; 95% C.I., 0.842 ± 0.981); AU4 gave the best performance (p= 0.038vs RT) in discriminating controls and GERD patients. In Study B, RT was abnormal in three controls and 79 patients; AU4 identified all the controls and patients with abnormal RT and also 10/31 patients (32.3%) with so-called “normal” acid exposure (according to RT). In the whole GERD group of patients, AU4 and RT specificity was 81.2%, whereas sensitivity was 71.8% for RT and 80.9% for AU4 (χ2, 61.831; DF, 1; p < 0.005); PPV/NPV were 96.3%/29.5% for RT, and 96.7%/38.2% for AU4.Conclusions:AU4 appears to be a simple and sensitive quantitative parameter to measure the esophageal acid exposure in adults submitted to 24-h pH monitoring, and it could be an useful clinical aid in evaluating normal RT tests where, from a clinical point of view, a reflux disease is highly likely.

Manometric evaluation of the interdigestive antroduodenal motility in subjects with fasting bile reflux, with and without antral gastritis.

The interdigestive antroduodenal motor activity was studied in 15 patients with bile reflux without gastritis (group A), 17 with bile reflux and chronic antral superficial gastritis (group B) and in nine healthy controls (group C), by manometric recording of phases of the interdigestive motility complex (IDMC) over 240 minutes, or until two consecutive migrating motor complexes (MMCs) had been recorded, whichever the shorter. In the patients with bile reflux the occurrence of MMCs was decreased and median duration of the IDMC was significantly prolonged (group A = 162.5 min; group B = 185.0 min), compared with controls (group C = 92.0 min; p less than 0.01 v groups A and B). There were no differences in motility pattern between patients with and without gastritis, suggesting that motor abnormalities are not caused by gastritis, but may precede its occurrence. Delayed occurrence of motor activity fronts increases duodenogastric reflux, but correlation with gastric mucosal lesions was not shown, suggesting that other mechanisms are involved.

Effects of Gabexate Mesilate, a Protease Inhibitor, on Human Sphincter of Oddi Motility

Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 ± 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 ± 1 vs 3.6 ± 1; P < 0.05) and amplitude (157.4 ± 44 vs 80.0 ± 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results.

Interdigestive Motility Pattern in Subjects with Duodenogastric Bile Reflux

The role of antroduodenal motility in the pathogenesis of duodenogastric biliary reflux is widely accepted, but few and conflicting data are available on the possible motor abnormalities related to this phenomenon in the fed and in the fasting state. In an attempt to define the motility pattern of the antroduodenal region associated with bile reflux in the fasting state, 20 subjects with proven duodenogastric reflux and without disorders of the upper gastrointestinal tract have been studied, and the results have been compared with those observed in 6 control subjects without evidence of reflux. The interdigestive motility complex (IDMC) has been evaluated (mean duration of IDMC and frequency and site of onset of migrating motor complexes). In subjects with duodenogastric reflux a significant increase (p less than 0.01) in the mean duration of IDMCs (179 +/- 22.19 min) was observed, in comparison with controls (108.5 +/- 37 min). A considerable reduction in the frequency of migrating motor complexes (MMC) was also observed, while no differences in the site of onset and the propagation of MMCs and in the percentage of time recorded occupied by the single phases of IDMC were found. This evidence suggests a strict relationship between duodenogastric reflux and the occurrence of phase III of IDMC and supports the hypothesis that the IDMC abnormalities are the cause and not the consequence of biliary reflux. The reduced incidence of MMC may also account for the high incidence of chronic gastritis due to prolonged contact in the fasting state between the gastric mucosa and the duodenal content.

Towards a better assessment of reflux oesophagitis.

SIR,-We read with interest the exhaustive and balanced overview by Dr Colin-Jones on gastro-oesophageal reflux. We were particularly pleased to see that an authoritative reviewer has at last officially suggested an adaptation of the notorious endoscopic classification of oesophagitis by Savary and Miller.2 For reasons which are beyond our understanding, the oesophageal mucosa is the only one in the digestive system (or, better, in the whole body), the lesions of which were graded starting from erosions. Thus, in clinical practice, when patients with symptoms of gastrooesophageal reflux have endoscopic evidence of erythematous areas in the distal oesophagus the term of grade 0 oesophagitis is often used. In our opinion mild (non-erosive) oesophagitis should be graded from longitudinal red streaks to circumferential erythema, but any attempt to include non-erosive lesions within the concept of oesophagitis is welcome. On the other hand in clinical trials the endoscopic evaluation criteria are often at variance with Savary and Millers classification and tend to include non-erosive forms as well, in order to obtain a more realistic approach to the problem.` As for the possibility ofimproving the results of H2 receptor blockers in the treatment of reflux oesophagitis, we believe that the time of administration can also play a major role. Contrary to that reported in the past,6 daytime reflux has been claimed to be an important factor in the pathogenesis of the disease. Therefore a single dose of a H2 blocker at night might not be ideal in some subjects. The results of a recent cooperative study performed in northern Italy seem to support this view. A group of 33 healthy controls was initially examined by means of 24 hour ambulatory pHmetry to determine the upper normality limit, on the basis of De Meesters criteria6 (mean ±2SD) ofthe percentage oftime with pH below 4. Accordingly, 112 consecutive subjects with abnormal pH-metry were detected and could be divided in upright (53%) or supine (11%) refluxers and in patients with reflux in both positions (36%).6 These figures differ from De Meesters findings and in particular the number of upright refluxers is substantially higher (53% v 9%). The reasons for those discrepancies are unclear. It must be noted, however, that the Italian study was carried out in outpatients and not subjected to dietary restrictions, whereas DeMeester examined only hospitalised patients on a standard diet. At any rate, the high number of upright refluxers in the Italian series makes the habit of indiscriminately treating reflux oesophagitis with a single bedtime dose of a H2 receptor blocker questionable. To achieve better results, the choice of administering the drug in the morning and at bedtime or only at night should be based on the results of 24-hour pHmetry. For practical reasons we cannot expect that each and every subject with reflux oesophagitis can have previously been submitted to the test in order to obtain a personalised therapy. On the other hand, at least in patients who fail to respond to treatment, the time of administration of H2blockers should be adjusted to the results of pHmetry. This does not apply to omeprazole, the long lasting action of which makes it irrelevant the time of administration. The superior results observed with omeprazole, including healing of most cases resistant to H2blockers, possibly rely not only upon its greater antisecretory effect, but also upon its ability to suppress the acidity of refluxate throughout the whole day. M GUSLANDI S PASSARETII A TITTOBELLO Gastroentology Unit, Institute ofInternal Medicine, University ofMilan, Via Pace 9, 20122 Milan, Italy