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Notes: Motor changes could be involved in the pathogenesis of diarrhoea that complicates the treatment of ulcer disease by prostaglandins. Our aim was to assess the effect of enprostil, a synthetic analogue of PGE2, on duodeno-jejunal motility. During this randomized double-blind crossover study, two manometric recordings, each lasting 20 h (12.00-08.00 hours), were carried out during dosing with 35 μg enprostil b.d. or placebo (eight volunteers: part 1), or during dosing with 35 or 70 μg enprostil b.d. (nine volunteers: part 2). Subjects were only allowed a standard dinner at 18.00 hours.During fasting, in part 1, the number of phase 3 activity patterns (PIIIs) was higher with enprostil than with placebo (P 〈 0.01), without any difference in their characteristics; the overall duration of phase 1 activity was longer with enprostil than with placebo (P 〈 0.01). In part 2, during fasting the number and characteristics of the PIIIs were not different, but there was a dose-related increase in PI, and decrease in PII activity. Fed motor patterns did not differ between the two doses of enprostil.

Notes: Rabeprazole has been shown to be more potent and faster than other proton pump inhibitors in in vitro studies and highly effective in decreasing oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD).〈section xml:id="abs1-2"〉〈title type="main"〉Aim:This study was a multicentre, double-blind, placebo-controlled, randomized, parallel-group comparison of three active treatment regimens utilizing two different proton pump inhibitors, or placebo, administered over 7 days in patients with GERD.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Eighty-two patients with symptomatic GERD were given placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m., or omeprazole 20 mg o.m. for 7 days. Twenty-four hour oesophageal pH monitoring was performed at baseline and repeated at the conclusion of the treatment period.〈section xml:id="abs1-4"〉〈title type="main"〉Results:At the end of study, the percentage time (mean ± s.d.) with pH 〈 4 over a 24-h period was significantly decreased by the three active regimens but without significant difference between them (9.27 ± 4.77; 2.53 ± 4.27; 2.02 ± 1.71 and 2.91 ± 4.06 for placebo, rabeprazole 10 mg b.d., rabeprazole 20 mg o.m. and omeprazole 20 mg o.m., respectively). Acid exposure was normalized in 90% of patients treated with rabeprazole 10 mg b.d., 95% treated with rabeprazole 20 mg o.m., 78% treated with omeprazole 20 mg o.m., and only 9.5% of patients treated with placebo. Both rabeprazole and omeprazole were well-tolerated.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Although rabeprazole 20 mg o.m. showed greater activity numerically, this study demonstrates that rabeprazole 10 mg b.d. and 20 mg o.m. are equivalent to omeprazole 20 mg o.m. in decreasing oesophageal acid exposure.

Notes: Motilin-receptor agonists are prokinetics; whether they relieve the symptoms of functional dyspepsia is unknown. We aimed to test the efficacy of the motilin agonist ABT-229 in functional dyspepsia patients with and without delayed gastric emptying.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Patients were randomized with postprandial symptoms and documented functional dyspepsia by endoscopy (n=589 in intention-to-treat analysis). Patients were assigned to either the delayed or normal gastric emptying strata, based on a validated 13C octanoic acid breath test. Patients were then further randomized within each strata, to receive one of four doses of ABT-229 (1.25, 2.5, 5 or 10 mg b.d. before breakfast and dinner) or placebo for 4 weeks, following a 2-week baseline. The primary outcome was the assessment of change in symptom severity over the 2 weeks from baseline to final visit, based on a self-report questionnaire measuring severity on visual analogue scales.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Baseline characteristics across the treatment arms were very similar. No significant differences in the upper abdominal discomfort severity score (maximum 800 mm) were observed for any active treatment arm vs. placebo (mean change from baseline −139, −141, −145, −160 and −134 mm for placebo, 1.25, 2.5, 5, and 10 mg, respectively, at 4 weeks by intention-to-treat). More patients on placebo reported a good or excellent global response than patients on 1.25 or 5 mg of active therapy (both P 〈 0.05). The results were very similar in those with and without delayed gastric emptying. Helicobacter pylori status did not predict response. Excluding patients with any baseline heartburn (total remaining n=240), ABT-229 10 mg was inferior to placebo in relief of upper abdominal discomfort.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:ABT-229 was of no value for relief of symptoms in functional dyspepsia, compared with placebo.

Notes: Background : Impedance-pH monitoring is the most sensitive method for detection and characterization of gastro-oesophageal reflux episodes. Normal values from European subjects are lacking.Aim : To build a database of gastro-oesophageal reflux patterns from French and Belgian healthy subjects.Methods : Seventy-two healthy subjects (35 men, mean age 35 years, 18–72) underwent 24-h ambulatory impedance-pH studies. Gastro-oesophageal reflux episodes were detected using impedance and characterized by pH as acid, weakly acidic, or weakly alkaline. Analysis was performed visually and effects of age, gender and intra-individual reproducibility were evaluated.Results : The total number of gastro-oesophageal reflux episodes was 44 (25,58,75) of which 59% were acid, 28% were weakly acidic and 10% weakly alkaline. Half of gastro-oesophageal reflux episodes were mixed (liquid/gas) and 22% reached 15 cm above the lower oesophageal sphincter. The bolus clearance time was 11 s while acid was chemically cleared in 34 s. Male gender was associated with increased number and proximal extent of total and acid gastro-oesophageal reflux. Repeated studies in 27 subjects showed good reproducibility for number, acidity and air–liquid composition of reflux (Kendall's W-values = 0.72–0.85).Conclusions : This study demonstrates good reproducibility of 24-h ambulatory impedance-pH studies and provides values of reflux patterns in healthy subjects for comparisons with European gastro-oesophageal reflux disease patients.

Notes: Background : Beidellitic montmorillonite is a purified clay containing a double aluminium and magnesium silicate.Aim : To assess the efficacy and the safety of beidellitic montmorillonite (3 g, t.d. for 8 weeks) in patients with irritable bowel syndrome (IBS).Methods : A multicentre, double-blind, placebo-controlled, randomized study with parallel groups, was performed in IBS patients selected according to ROME I criteria. Patients were included after a 1-week washout period to confirm that abdominal pain and/or discomfort was rated at least 2 on a 0–4 graded Likert scale. Patients were then randomized and stratified according to their predominant bowel habit profile into three groups. The use of rescue medication was allowed: polyethylene glycol 4000 (10–20 g/day) as a laxative agent in case of stool absence for three consecutive days, phloroglucinol (80 to a maximum of 320 mg/day) as a spasmolytic agent for no more than 8 days. The main end-point was the improvement of abdominal pain and/or discomfort by at least 1 point on the Likert scale.Results : A total of 524 patients constituted the overall intent-to-treat population (ITT), 263 were assessed in the beidellitic montmorillonite group, i.e. 93 diarrhoea-predominant IBS (D-IBS), 83 constipation-predominant IBS (C-IBS), 87 alternating constipation/diarrhoea-IBS (A-IBS); 261 in the placebo group, i.e. 81 D-IBS, 92 C-IBS and 88 A-IBS. Initial analysis in the ITT population demonstrated a higher rate of success with beidellitic montmorillonite (51.7%) when compared with the placebo group (45.2%); however, the difference was not statistically significant. Improvement was significant in C-IBS both in ITT (beidellitic montmorillonite group = 49.4%, placebo group = 31.5%, P 〈 0.016) and per protocol populations (59.4% vs. 37.8%) (P 〈 0.01). The time to improvement of abdominal pain and/or discomfort (log Rank test) was also significantly in favour of beidellitic montmorillonite, (P 〈 0.04). The average number of stools per day was not different from baseline, either in all patients or in C-IBS patients. Spasmolytic and laxative agent intakes were not different between the two groups. Subjective evaluation by patients of treatment efficacy and visual analogue scale test of treatment efficacy by investigators were significantly better in the beidellitic montmorillonite group (P 〈 0.05). Tolerance of beidellitic montmorillonite was considered optimal without any significant adverse event.Conclusions : Although pain or discomfort was not significantly improved in the entire IBS population treated with beidellitic montmorillonite in comparison with placebo, this study demonstrates that beidellitic montmorillonite is efficient for C-IBS patients (P 〈 0.016). This effect of beidellitic montmorillonite on pain cannot be explained by changes in bowel habits. The efficacy of this well-tolerated therapy warrants further confirmatory therapeutic trials in C-IBS patients.

Notes: Background : Proton pump inhibitors control gastric acidity better during the day than at night, when nocturnal acid breakthrough can occur. Tenatoprazole is a novel proton pump inhibitor with a seven-fold longer plasma half-life.Aim : To compare the effects of tenatoprazole 20 mg (T20), tenatoprazole 40 mg (T40) and esomeprazole 40 mg (E40) on intragastric acidity in healthy volunteers.Methods : This randomized, three-period, cross-over study enrolled 18 Helicobacter pylori-negative volunteers, who received E40, T20 and T40 once daily for 7 days with a 14-day washout between periods. Twenty-four-hour gastric pH monitoring was performed on day 7. Serum gastrin was assessed on day 8.Results : T40 induced a more potent acid inhibition than T20 (24-h median pH: 4.6 vs. 4.0, P 〈 0.01; daytime: 4.5 vs. 3.9, P 〈 0.01; night-time: 4.7 vs. 4.1, P 〈 0.05). T40 was more potent than E40 (24-h median pH: 4.6 vs. 4.2, P 〈 0.05; night-time: 4.7 vs. 3.6, P 〈 0.01); the pH 〉 4 holding time was higher during the night for T40 than for E40: 64.3% vs. 46.8%, P 〈 0.01; the nocturnal acid breakthrough duration was significantly shorter for T40 than for E40. No significant gastrin increase was observed and all drugs were well tolerated.Conclusion : T40 is significantly more potent than T20 and E40 during the night. The therapeutic relevance of this pharmacological advantage deserves further study.

Notes: Abstract Endoscopic adrenaline-hypertonic injection was attempted in 40 patients admitted for oesophagogastroduodenal ulcer haemorrhage unresponsive to conventional medical treatment and presenting with severe underlying disease or advanced age (〈80 years). The results were compared with our own historical controls (43 patients) treated by conventional therapy, meeting the same inclusion criteria. Permanent haemostasis was achieved in 32 patients in the injection group and 30 in the control group (NS) but emergency surgery was less frequent in the injection group (2 vs 25,p〈0.001). Blood transfusion requirements were less in the injection group (8.5±6.2 vs 10.2±5.4,p〈0.05) but length of hospital stay was not really different (15.7 days±9.3 vs 20.9±14.4). Unfortunately, mortality was not reduced in the injection group (14/40 vs 17/43). Two lethal complications attributable to injection treatment occurred. This treatment could represent an alternative to conventional haemostatic treatment in high surgical risk patients with severe clinical bleeding, avoiding emergency surgery. In spite of the fact that we selected high-risk patients, endoscopic treatment was not able to lower the mortality (about 37%). Due to severe unpredictable side effects and potential risks of long-term massive rebleeding, this treatment should be performed electively in patients with severe clinical bleeding, as first line treatment when surgical risk factors exist or immediately before surgery in low risk patients.

Notes: Abstract The aim of this study was to assess (a) the incidence of perineal descent and (b) the relationship between radiological abnormalities of the pelvic floor and rectoanal manometric disturbances in patients consulting for constipation. Lateral radiographs in both the left lateral and supine positions studied pelvic floor descent. Results obtained in the 25 patients (mean age 47 years) studied were compared with those of 12 controls (mean age 58 years). Pelvic floor descent, never seen in controls, was demonstrated in 14 patients who were older (53±3 years, mean ±SD) than the 11 with a normal radiological examination (38±3 years,p〈0.05). Anal low pressures (3 cases) and a low amplitude of rectoanal inhibitory reflex (RAIR) (5 cases) were shown only in patients with perineal descent and anal high pressures only in those with normal radiology. Our results suggest that (a) perineal descent is a common finding in over 50% of constipated patients and (b) anorectal motility is related to pelvic floor function.

Notes: Abstract. The aim of this study was to assess the reliability of cortical evoked potentials after electrical stimulation of the anal canal. Cortical evoked potentials were recorded on 243 patients presenting with perineal pain (28 patients), impotence (55 patients), anal incontinence (52 patients), urinary continence (30 patients), constipation (49 patients), and on 29 neurological patients, by stimulating the external anal sphincter and penis (or clitoris). The inter- and intra-observer reproducibility was studied by coding recordings interpreted by three different observers on two separate occasions. The influence of recording characteristics and clinical data were assessed. To study operator dependence, five operators investigated the patients. Only one of them was well trained in this technique. The interpretation of the coded curves by the observers was poorly reproducible in about 15% of cases, depending on time between the two readings and the quality of recordings. The interpretation of cerebral responses after anal stimulation were observer-dependent and influenced by the knowledge of clinical data. This was also observed with cortical evoked potentials after electrical stimulation of the penis or clitoris, but to a lesser extent. The cerebral evoked potentials method was also operator-dependent, mainly after anal stimulation. When a study of cortical evoked potentials by perineal stimulation is needed in clinical practice, it seems logical to prefer cortical evoked potentials by penile or clitoral stimulation as they seem easier to obtain than those evoked by anal stimulation if the investigators are not well trained for the performance of electrophysiological studies as the former are much less operator- and observer-dependent.

Notes: Abstract Six patients with complete transection of the spinal cord and six healthy volunteers were examined by using anorectal manometry together with electromyographic (EMG) recording of the external anal sphincter composed of striated muscle. Anal pressure and EMG activity of the external anal sphincter were continuously-recorded at rest and during gradual rectal distention (10, 20, 30, 40, and 50 ml) by means of an air-filled balloon eliciting a rectoanal inhibitory reflex (RAIR) at the upper part, and an inflation reflex (IR) at the lower part of the anal canal. All patients and controls had a RAIR for each rectal distention volume. A relationship between the duration of the RAIR and the rectal distention volume was present in controls only. In controls the IR was present for each rectal distention volume, whereas it was present in only one patient for a 40-ml volume. During the resting period, all controls showed continuous tonic EMG activity of the external anal sphincter, but after 30 minutes all the patients showed a decrease and ultimately in five cases a disappearance of the tonic EMG activity of the external anal sphincter. In spinal patients, the presence or absence of EMG activity of the external anal sphincter did not modify the anal canal pressure. These results indicate that: 1) the tonic EMG activity of the external anal sphincter seems to be under the control of supraspinal structures, because in spinal patients it disappears in the absence of sensitive inputs toward the spinal cord; 2) the absence of EMG activity at rest indicates that the external anal sphincter is not implicated in the RAIR disturbances observed in spinal patients; 3) the IR is not a spinal reflex but is under voluntary control, because it is not present in spinal humans; 4) in spinal humans the tonic EMG activity of the external anal sphincter does not play a role in the maintenance of the anal pressure at rest.