Dysaccommodation of the stomach: therapeutic nirvana?

Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder and has a complex pathophysiology. Impaired fundic relaxation in response to a meal is present in 40% of patients with FD. This review focuses on impaired gastric accommodation of the stomach as a pathophysiological mechanism and the possible therapeutic targets that can be derived from the current knowledge of the neuroregulation of the accommodation reflex. First the different means of gastric accommodation assessment are described and the relationship between symptoms and impaired gastric accommodation. The different therapeutic options are subsequently discussed in view of their molecular target, based on the different receptor subtypes involved in the accommodation reflex. Although impaired gastric accommodation is highly prevalent in dyspeptic patients and basic knowledge about the accommodation reflex enables to develop pathophysiologically targeted therapies, it is unlikely that therapies aimed at dysaccommodation of the stomach will lead to symptom relief in all dyspeptic patients. A major challenge is the development of methods that readily identify impaired accommodation in clinical practice.     

Motility Disorders after Roux-en-Y Gastrojejunostomy

About 30% of patients who have a Roux-en-Y gastrojejunostomy after gastrectomy suffer from abdominal pain, nausea, vomiting of food and bloating made worse by eating. This syndrome, called the Roux stasis syndrome, is caused, in part, by a motility disorder of the Roux limb. Transection of the jejunum during the construction of the limb separates the limb from the natural small intestinal pacemaker located in the duodenum. Ectopic pacemakers then appear in the limb and trigger retrograde contractions in its proximal portion. These contractions slow transit through the limb and result in Roux stasis. Current nonsurgical treatment of the syndrome includes the use of prokinetic agents and intestinal pacing, neither of which has demonstrated long-term benefits. A near-total gastrectomy may speed upper gastrointestinal transit somewhat, but stasis in the Roux limb often persists. Our current approach aims at preventing the syndrome by the use of an ‘uncut’ Roux limb, an operation which preserves myoneural continuity between the duodenal pacemaker and the Roux limb and so prevents the appearance of ectopic pacemakers and stasis in the limb.     

Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial

INTRODUCTION: Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with and without delayed gastric emptying. METHODS: Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C(13) octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Patients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual analogue scales; the primary outcome was assessment of change in the total upper abdominal symptom severity score (range 0-800 mm) from baseline to the final visit. RESULTS: The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvement on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to treat). The results were not significantly different in those with and without delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dependently in a greater number of patients receiving ABT-229 than placebo. Overall, 63% of patients on placebo reported a good or excellent global response, and this was not different from the active treatment arms. CONCLUSIONS: The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.     

Quality of Life in Functional Dyspepsia

Our purpose was to assess the quality of life of functional dyspepsia patients using the SF-36 generic scale and the Gastrointestinal Symptoms Rating Scale (GSRS). In all, 328 dyspeptic patients were included in a multicenter, prospective, observational study. Both scales were filled out at baseline and one and three months after a prokinetic agent was given as a single-drug therapy. A total of 250 patients completed the study. An improvement in all SF-36 dimensions was observed, although the final scores were lower than the population reference values. Physical role (27% change), emotional role (20%), and physical pain (16%) dimensions showed the greater change. The GSRS total and domain scores also showed significant decreases. The best predictors of quality of life improvement were certain basal symptoms, drug compliance, and the absence of idiopathic dyspepsia. In conclusion, both the generic and the specific scales provide useful and sensitive measures of quality of life in functional dyspepsia patients on single-drug treatment.     

Chronic Gastric Electrical Stimulation for Gastroparesis Reduces the Use of Prokinetic and/or Antiemetic Medications and the Need for Hospitalizations

To investigate the effect of chronic gastric electrical stimulation (GES) on the daily use of prokinetics and antiemetics, hospitalizations, total symptom score (TSS), SF-36 status for health-related quality of life (HQOL), and gastric emptying of a solid meal, we evaluated 37 gastroparetic patients preoperatively and 1 year after undergoing GES implant. Prokinetic and antiemetic use was significantly reduced. Of 27 patients on at least one prokinetic at baseline, 8 were off at 1 year. Twenty-six patients requiring antiemetics before surgery decreased to 17. Mean TSS was significantly reduced and the reduction for patients off medications was significantly better than for patients still on medications. Overall SF-36 scores for HQOL were significantly improved, and patients off antiemetics had a significantly higher HQOL score than for patients on antiemetics at 1 year. Hospitalizations decreased from 50 ± 10 days for the year prior to GES therapy to 14± 3 days (P < 0.05). However, gastric emptying was not significantly improved. Conclusions are as follows. (1) Chronic GES significantly reduced the use of prokinetic/antiemetic medications and the need for hospitalization in gastropraretic patients, whose clinical and quality of life outcomes also significantly improved (2) These data provide evidence of the positive economic impact of this new therapy on long-term clinical outcomes in gastroparetic patients not responding to standard medical therapy.This study was supported in part by Medtronic, Inc. Part of this work was presented orally at the 2002 Annual AGA/DDW Meeting in San Francisco, California.     

红霉素化学修饰研究的新进展

近期的红霉素化学修饰研究导致了新型酮基内酯类抗生素和新的动能内酯类消化道动力药物的发现，前者具有抗大环内酯耐药菌活性，而后者放大了红霉素的消化道运动促进作用。本文针对酮基内酯和动能内酯研究的新进展做一简单综述。     

Effect of mosapride on gastrointestinal transit time and diagnostic yield of capsule endoscopy

BACKGROUND AND AIM: Since its introduction, capsule endoscopy (CE) has made it possible to visualize the small intestine mucosa directly. However, owing to the limited battery life, only 60-80% of the capsules could reach the cecum and would possibly affect the diagnostic yield. The aim of this study was to determine the effect of oral mosapride on gastrointestinal transit time and the diagnostic yield of CE. METHOD: Sixty patients were involved in this randomized, prospective and controlled study. The patients were randomly allocated to groups receiving either mosapride citrate or nothing. Patients in the mosapride group (n = 30) received 10 mg mosapride citrate 1 h before CE examination, while patients in the control group (n = 30) received no preparation. The gastrointestinal transit time, the number of CE reaching the cecum, and the diagnostic yield of each group were assessed in a single-blinded fashion. RESULT: Gastric emptying time was significantly shorter in the mosapride group than in the control group (13.5 min vs 34 min P = 0.035). Compared with the control group, the complete transit rate was significantly higher in the mosapride group (93.3% vs 66.7% P = 0.021). There was no significant difference between the two groups on the small bowel transit time and diagnostic yield. CONCLUSION: Mosapride citrate accelerates the gastric emptying and completion rate of small bowel examination in patients undergoing CE.     

State-of-the-Art Management of Acute Bleeding Peptic Ulcer Disease

The management of patients with non variceal upper gastrointestinal bleeding has evolved, as have its causes and prognosis, over the past 20 years. The addition of high-quality data coupled to the publication of authoritative national and international guidelines have helped define current-day standards of care. This review highlights the relevant clinical evidence and consensus recommendations that will hopefully result in promoting the effective dissemination and knowledge translation of important information in the management of patients afflicted with this common entity.     

Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region: First Asian Pacific working party on functional dyspepsia

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro-oesophageal reflux, or gastric cancer but is most often due to functional (or non-ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia-Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new-onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2–4 weeks with an empirical anti-secretory or prokinetic agent, followed by investigation using non-invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost-effectiveness of the approaches recommended.     

肝硬化合并肠功能紊乱的临床治疗观察

目的探讨肝硬化合并肠功能紊乱的有效治疗方法。方法将50例肝硬化合并肠功能紊乱患者,随机分成治疗组(26例)与对照组(24例),治疗组在对照组治疗方案的基础上给予口服贝飞达、双迪28d,同时给予心理干预治疗。观察两组治疗前后临床症状及主要的肝功能指标。结果对照组肠道功能改善总有效率70%,治疗组总有效率92%,治疗组疗效优于对照组(P<0.05)。两组患者治疗后主要肝功能指标均明显改善,治疗组治疗后ALT、T-BiL值低于对照组(P<0.05)。结论肝硬化合并肠功能紊乱的患者给予微生态制剂、肠动力药及心理干预治疗可有效改善患者临床症状,并降低肝功能指标。