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Notes: Background: Psyllium is widely used in the symptomatic therapy of constipation. Its effects on colonic function and their correlation with symptomatic response have not been defined. Methods: After a 4-week baseline, placebo, run-in phase, 22 subjects with idiopathic constipation confirmed by prospectively administered stool diaries were randomly assigned to receive either psyllium (5 g b.d., 11 patients) or placebo (11 patients) for 8 weeks, followed by another 4-week wash-out, placebo phase. A colon transit study and anorectal manometry were performed at the beginning and at the end of each study phase. Subjects recorded, in diaries, their daily stool frequency, difficulty with defecation and weekly stool weight. Results: Stool frequency increased significantly after 8 weeks of psyllium treatment (3.8 ± 0.4 vs. 2.9 ± 0.1 stools/week, P 〈 0.05) as did stool weight (665.3 ± 95.8 g vs. 405.2 ± 75.9 g, P 〈 0.05). Subjects also reported an improvement in stool consistency (stool consistency score: 3.2 ± 0.2 vs. 3.8 ± 0.2, P 〈 0.05) and pain on defecation (pain score: 2.0 ± 0.4 vs. 2.6. ± 0.5, P 〈 0.05) on psyllium. Colon transit and anorectal manometry parameters were unchanged on psyllium. Subjects treated with placebo did not show any change in either subjective or objective measures of constipation. Conclusions: Psyllium increases stool frequency and weight and improves stool consistency in idiopathic constipation. These effects are not associated with significant changes in either colonic or rectal motor function. We suggest that the beneficial effects of psyllium in constipation are primarily related to a facilitation of the defecatory process.

Notes: The purpose of this review is to explore issues relating to quality of life in gastro-oesophageal reflux disease, examining the range of generic and disease-specific instruments available, their applicability and limitations and to overview the effect of gastro-oesophageal reflux disease on quality of life. Whereas instruments have been developed to assist researchers, there is a paucity of reliable instruments for pragmatic use in the clinical setting. The situation is complicated because there is not necessarily a direct correlation between endoscopic findings and symptom severity and non-erosive reflux disease is now recognized as an important manifestation of gastro-oesophageal reflux disease. However, quality-of-life instruments are useful in evaluating the impact of therapies and interventions, although these are limited, particularly in surgical interventions. Impaired quality of life now forms part of a definition of gastro-oesophageal reflux disease, the impact of which goes beyond the symptoms alone. While the symptoms themselves have a negative effect on sufferers’ lives, there are secondary effects caused by impaired physical, emotional and social functioning on productivity. Non-gastrointestinal problems caused by gastro-oesophageal reflux disease also impair quality of life. There is an ongoing need to develop instruments which truly measure the impact of gastro-oesophageal reflux disease and which are readily interpretable to the individual patient and clinician.

Notes: Although delayed gastric emptying has been described in several functional gastrointestinal disorders, and appears to be especially common in functional dyspepsia, the relationship of this finding to symptoms and basic pathophysiology is difficult to define. The delineation of the interactions between delayed gastric emptying, on the one hand, and symptom pathogenesis, on the other, has been hampered by several factors. These include the limitations of the methodology itself, the extent of overlap between the various functional disorders and the sensitivity of gastric emptying to factors external to the stomach, be they elsewhere within the gastrointestinal tract, in the central nervous system or in the environment. In many instances, delayed gastric emptying is an epiphenomenon, reflecting the overlap between inadequately defined functional syndromes, shared pathophysiology or the activation of physiological interactions between the various organs of the gut. In others, it may imply a truly diffuse motor disorder. The disappointments attendant on attempts to alleviate symptoms through approaches designed to accelerate gastric emptying should therefore not come as a surprise. Pending the definition of the true significance of delayed gastric emptying in all functional gastrointestinal disorders, caution should be exerted in the interpretation of this finding in a patient with functional symptoms.

Notes: Tegaserod (HTF 919), a 5-HT4 receptor partial agonist, has prokinetic effects that might be useful in decreasing acid reflux in gastro-oesophageal reflux disease (GERD).〈section xml:id="abs1-2"〉〈title type="main"〉Methods:To investigate the potential clinical utility of tegaserod in GERD, a five-period crossover study (balanced Latin square) was designed to evaluate the efficacy of 4 b.d. doses of tegaserod vs. placebo. Four-hour manometry (1 h fasting and 3 h postprandial) with continuous recording of lower oesophageal sphincter pressure and distal oesophageal pH, was performed at the end of each 2-week treatment period in 19 patients with mild-to-moderate GERD. Recordings were scored for mean lower oesophageal sphincter pressure, number of transient lower oesophageal sphincter relaxations, and distal oesophageal acid exposure.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Tegaserod (1 mg/day and 4 mg/day) caused a more than 50% decrease in acid exposure in the postprandial period in patients with abnormal acid exposure, although only the 1 mg/day tegaserod treatment elicited statistically significant decreasing (P 〈 0.05) for the entire treatment group (percentage time for which pH 〈 4: placebo=13%; 1 mg/day dose=5%; 4 mg/day dose=8%). A decreased number of reflux episodes was demonstrated with both the 1 mg/day and 4 mg/day tegaserod doses. There was no apparent effect on mean lower oesophageal sphincter pressure, whilst transient lower oesophageal sphincter relaxations frequency decreased in the 1–2.5 h post-dose.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Tegaserod in a dose of 1 mg/day causes a significant decrease in postprandial oesophageal acid exposure. The reduction in oesophageal acid exposure with tegaserod treatment may result from enhanced oesophageal acid clearance, improved gastric emptying, and/or reduced transient lower oesophageal sphincter relaxations.

Notes: Disordered motility has been considered fundamental to the pathophysiology of gastro-oesophageal reflux disease and a number of dyspeptic syndromes. Motor activity is certainly essential for the homeostasis of the oesophagus and stomach - in the oesophagus, the lower oesophageal sphincter and peristalsis are fundamental components of the ‘normal’ anti-reflux defence mechanism, whereas, in the stomach, contractile activity regulates the orderly emptying of the various components of a meal.Recent studies have clarified considerably the role of the lower oesophageal sphincter in permitting reflux to occur under both physiological and pathological situations, and transient relaxation of the lower oesophageal sphincter is now regarded as the most important mechanism of reflux.Interest has also been renewed in the role of hiatus hernia in the pathogenesis of reflux disease. By moving the lower oesophageal sphincter into the thorax, a hiatus hernia deprives this sphincter of the beneficial effects of intra-abdominal pressure and crural augmentation. Altered anatomical relationships also predispose the patient with a non-reducing hiatus hernia to impaired clearance of acid, thus exacerbating reflux.Relationships between disordered peristalsis and reflux are complex. Primary disorders of peristalsis, such as scleroderma, are associated with severe and often complicated reflux disease. It is also evident that reflux may itself result in impaired peristalsis, particularly in the distal oesophagus. Whether aggressive treatment of reflux disease by either medical or surgical means can restore peristaltic function remains uncertain.The importance of co-ordinated function of the antrum, pylorus and duodenum in the regulation of gastric emptying is being increasingly recognized. Foregut motor dysfunction is implicated in dyspepsia. Abnormalities in patients with dyspepsia include gastroparesis, antral hypomotility, gastric dysrhythmias, duodenal dysmotility, and duodeno-gastric reflux. The true prevalence of these disorders is uncertain, and the reported relationship between these abnormalities and symptoms has often been inconsistent. The specificity of the abnormalities for dyspepsia is also open to question. In many instances, it remains unclear whether the motor abnormality is truly primary or rather an epi-phenomenon. It seems reasonable to conclude that while considerable advances have been made in our understanding of both foregut motor physiology and the role of motor dysfunction in patients with reflux disease, the role of dysmotility in dyspeptic patients remains uncertain.

Notes: The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high-performance liquid chromatography with UV detection.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Erythromycin passed across all skin types tested. Steady-state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to ≈28 cm2 should provide therapeutic levels of drug within 3 h.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.

Notes: Gastro-oesophageal reflux disease (GERD) has been associated with a variety of supra-oesophageal symptoms, including asthma, laryngitis, hoarseness, chronic cough, frequent throat clearing and globus pharyngeus. GERD may be overlooked as the underlying mechanism for these symptoms because typical GERD symptoms may be absent, despite abnormal oesophageal acid exposure. Two basic mechanisms linking GERD with laryngeal symptoms have been proposed: direct contact of gastric acid with the upper airway, in some cases due to micro-aspiration, and a vagovagal reflex triggered by acidification of the distal portion of the oesophagus. Gastro-oesophageal reflux (GER) during sleep is believed to be an important mechanism for the development of supra-oesophageal complications of GERD, such as asthma and idiopathic pulmonary fibrosis (IPF). Several physiological changes during sleep, including prolonged oesophageal acid contact time, decreased upper oesophageal sphincter pressure, increased gastric acid secretion, decreased salivation, decreased swallowing and a decrease in conscious perception of acid, render an individual more susceptible to reflux-induced injury. Supra-oesophageal symptoms often improve in response to aggressive acid-suppressive therapy. However, many unanswered questions remain regarding the appropriate approach to diagnosis and treatment of patients with GERD-related supra-oesophageal symptoms. In this article we review the relationship between supra-oesophageal symptoms and GERD and, where possible, highlight the evidence supporting the role of night-time reflux as a contributing factor to these symptoms.

Notes: The spectrum of gastro-oesophageal reflux disease (GERD) has expanded; indeed the majority of individuals with symptomatic GERD do not have erosive reflux disease (ERD); this group has been referred to as nonerosive or negative-endoscopy reflux disease (NERD). There may be important differences between NERD and ERD in terms of pathophysiology and management. Thus, NERD patients appear relatively resistant to proton pump inhibitors and may not be good surgical candidates. The clinician caring for patients with GERD must therefore be aware of the full spectrum of GERD and of the pathophysiological and therapeutic implications of NERD. Recent twin studies have revealed that genetic factors play a role in GERD and form the basis for future studies on the role of inheritance in the various manifestations of GERD. Several recent investigations have reaffirmed the primacy of acid reflux in the pathogenesis of GERD and have also provided insights into the pathophysiology of postprandial heartburn. Transient lower oesophageal sphincter relaxations and hiatal hernias have emerged as major and interacting factors in the genesis of reflux events and in the potentiation of acid exposure; the former are attracting considerable attention as a potential therapeutic target. Nocturnal acid breakthrough, which has been implicated in the failure of some patients to respond to high doses of proton pump inhibitors, appears, on further examination, to be a gastric rather than an oesophageal phenomenon, and may not be of clinical or therapeutic importance.

Notes: Background : Patients report that the prophylactic consumption of a proton pump inhibitor minimizes gastrointestinal symptoms expected to be provoked by late-night food and alcohol consumption. The efficacy of this practice has not been studied formally.Aim : To perform a randomized, double-blind, placebo-controlled trial of a single dose of lansoprazole (30 mg) taken prior to a large meal and alcohol consumption.Methods : Study subjects were recruited randomly from local primary care and hospital physicians. Each participant (n = 56; 37 male, 19 female; mean age, 38 years) completed questionnaires before and after the meal. Approximately 90 min prior to the provocative meal, participants were witnessed taking either placebo or 30 mg lansoprazole. Bar tokens were dispensed to permit the accurate quantification of alcohol consumption (mean, 15 units).Results : Forty per cent of subjects reported significant reflux symptoms. For the entire group, there was no significant difference between lansoprazole and placebo. Post-prandial reflux was more frequent in those consuming 〉 15 units of alcohol (13/26, 50%) compared with those consuming 〈 15 units (7/30, 24%; P 〈 0.05). In the group who consumed 〉 15 units of alcohol, lansoprazole was associated with a lower rate of heartburn (5/15, 33%) compared with placebo (8/11, 73%; P 〈 0.05).Conclusion : A single dose of a proton pump inhibitor prior to indulgence was only associated with reduced heartburn in those consuming 〉 15 units of alcohol.

Notes: Background/aim: To define the possible contribution of altered small intestinal motor activity to side-effects of bulking fibres, we sought to compare the relative effects of intraduodenal and intracolonic administration of the bulking fibre psyllium and the anthraquinone laxative senna on canine small intestinal motor activity. Methods: Motor activity was recorded by serosal strain gauges implanted along the small intestine in 6 dogs. In random order, the motor responses to the instillation of psyllium (in doses of 5 or 10 g), senna (10 mg/kg) or appropriate vehicle (200 ml water infusion or saline 5 ml bolus) into either the proximal duodenum or proximal colon were assessed. Results: The intra-duodenal administration of psyllium in either dose consistently induced a prolonged burst of‘clustered’contractions; in contrast, clusters were infrequent and of short duration following instillation of either vehicle or senna (P 〈 0.05). Intraduodenal instillation of psyllium inhibited migrating motor complex (MMC) migration and consistently delayed the onset of the next MMC cycle; a similar inhibition occurred with vehicle, however. Neither senna nor its vehicle inhibited MMC migration. None of these agents had any effect on small intestinal motor activity when instilled directly into the colon. Conclusions: Psyllium administered directly into the duodenum inhibits MMC activity and consistently induces‘clustered’contractions. Whilst the MMC-inhibitory effect appears to be a non-specific volumerelated phenomenon, the induction of clusters is independent of volume or laxation. These motor effects of psyllium may contribute to the gastrointestinal symptomatology related to such agents and could be avoided by the preferential release of psyllium in the colon.