Addition of prokinetics to PPI therapy in gastroesophageal reflux disease:A meta-analysis

AIM: To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD).

Comparison of PPIs and H_2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM： To compare efficacy of proton pump inhibitors （PPIs） with H2-receptor antagonists （H2RA$） plus pro- kinetics （Proks） for dysmotility-like symptoms in func- tional dyspepsia （FD）. METHODS： Subjects were randomized to receive openlabel treatment with either rabeprazole 10 mg od （n = 57） or famotidine 10 mg bid plus mosapride 5 mg tid （n = 57） for 4 wk. The primary efficacy endpoint was change （%） from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment. RESULTS： The improvement in dysmotility-like dyspep- sia symptom score on day 28 was significantly greater in the rabeprazole group （22.5% ± 29.2% of baseline） than the famotidine ＋ mosapride group （53.2%±58.6% of baseline, P 〈 0.0001）. The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine ＋ mosapride group （87.7% vs 59.6%, P = 0.0012）. Rabeprazole therapy was the only significant predictor of treatment response （P 〈 0.0001）, defined as a total symptom score improvement ≥ 50%. CONCLUSION： PPI monotherapy improves dysmotil- ity-like symptoms significantly better than H2RAs plus Proks, and should be the treatment of first choice for Japanese FD.

Consensus statement AIGO/SICCR diagnosis and treatment of chronic constipation and obstructed defecation(Part Ⅱ:Treatment)

The second part of the Consensus Statement of the Italian Association of Hospital Gastroenterologists and Italian Society of Colo-Rectal Surgery reports on the treatment of chronic constipation and obstructed defecation. There is no evidence that increasing fluid intake and physical activity can relieve the symptoms of chronic constipation. Patients with normal-transit constipation should increase their fibre intake through their diet or with commercial fibre. Osmotic laxatives may be effective in patients who do not respond to fibre supplements. Stimulant laxatives should be re- served for patients who do not respond to osmotic laxatives. Controlled trials have shown that serotonin- ergic enterokinetic agents, such as prucalopride, and prosecretory agents, such as lubiprostone, are effec- tive in the treatment of patients with chronic constipa- tion. Surgery is sometimes necessary. Total colectomy with ileorectostomy may be considered in patients with slow-transit constipation and inertia coil who are resistant to medical therapy and who do not have defecatory disorders, generalised motility disorders or psychological disorders. Randomised controlled trials have established the efficacy of rehabilitative treat- ment in dys-synergic defecation. Many surgical proce- dures may be used to treat obstructed defecation in patients with acquired anatomical defects, but none is considered to be the gold standard. Surgery should be reserved for selected patients with an impaired quality of life. Obstructed defecation is often associated with pelvic organ prolapse. Surgery with the placement of prostheses is replacing fascial surgery in the treatment of pelvic organ prolapse, but the efficacy and safety of such procedures have not yet been established.

Efficacy of mosapride citrate with polyethylene glycol solution for colonoscopy preparation

AIM:To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. METHODS:We conducted a randomized,double-blind, placebo-controlled study with mosapride in addition to polyethylene glycol(PEG)-electrolyte solution.Of 250 patients undergoing colonoscopy,124 were randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group),and 126 received 2 L PEG plus placebo(placebo group).Patients completed a questionnaire reporting the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed by colonoscopists using a 5-point scale based on Aronchick's criteria.The primary end point was optimal bowel preparation rates(scores of excellent/good/fair vs poor/inadequate). RESULTS:A total of 249 patients were included in the analysis.In the mosapride group,optimal bowel preparation rates were significantly higher in the left colon compared with the placebo group(78.2%vs 65.6%,P<0.05),but not in the right colon(76.5%vs 66.4%,P=0.08).After excluding patients with severe constipation,there was a significant difference in bowel preparation in both the left and right colon(82.4%vs 66.7%,80.8%vs 67.5%,P<0.05,P<0.01).The incidence of adverse events was similar in both groups. Among the subgroup who had previous colonoscopy experience,a significantly higher number of patients in the mosapride group felt that the current preparation was easier compared with patients in the placebo group(34/72 patients vs 24/74 patients,P<0.05). CONCLUSION:Mosapride citrate may be an effective and safe adjunct to PEG-electrolyte solution that leads to improved quality of bowel preparation,especially in patients without severe constipation.

Chronic intestinal pseudo-obstruction

Chronic intestinal pseudo-obstruction (CIPO) is a se- vere digestive syndrome characterized by derangement of gut propulsive motility which resembles mechanical obstruction, in the absence of any obstructive process. Although uncommon in clinical practice, this syndrome represents one of the main causes of intestinal failure and is characterized by high morbidity and mortality. It may be idiopathic or secondary to a variety of diseases. Most cases are sporadic, even though familial forms with either dominant or recessive autosomal inheritance have been described. Based on histological features in- testinal pseudo-obstruction can be classified into three main categories:neuropathies, mesenchymopathies, and myopathies, according on the predominant involvement of enteric neurones, interstitial cells of Cajal or smooth muscle cells, respectively. Treatment of intestinal pseu- do-obstruction involves nutritional, pharmacological and surgical therapies, but it is often unsatisfactory and the long-term outcome is generally poor in the majority of cases.

Can mosapride citrate reduce the volume of lavage solution for colonoscopy preparation?

AIM:To evaluate the possibility of reducing the volume of polyethylene glycol(PEG)-electrolyte solution using adjunctive mosapride citrate for colonoscopy preparation. METHODS:This was a single-center,prospective, randomized,investigator-blinded,non-inferiority study involving 252 patients of both sexes,aged from 20 to 80 years,scheduled for screening or diagnostic colonoscopy in our department.A total of 126 patients was randomized to receive 1.5 L PEG-electrolyte solution plus 15 mg of mosapride(1.5 L group),and 126 received 2 L PEG-electrolyte solution plus 15 mg of mosapride(2 L group).Patients completed a questionnaire on the acceptability and tolerability of the bowel preparation process.The efficacy of bowel preparation was assessed using a 5-point scale based on the Aronchick scale.The primary end point was adequate bowel preparation rates(score of excellent/good/fair) vs(poor/inadequate).Acceptability and tolerability,as well as disease detection,were secondary end points. RESULTS:A total of 244 patients was included in the analysis.There were no significant differences between the 2 L and 1.5 L groups in age,sex,body mass index, number of previous colonoscopies,and the preparation method used previously.The adequate bowel preparation rates were 88.5%in the 2 L group and 82.8%in the 1.5 L group[95%lower confidence limit(LCL)for the difference=-14.5%,non-inferiority P=0.019]in the right colon.In the left colon,the adequate bowel preparation rates were 89.3%in the 2 L group and 81.1%in the 1.5 L group(95%LCL=-17.0%,non-inferiority P=0.066).Compliance,defined as complete (100%)intake of the PEG solution,was significantly higher in the 1.5 L group than in the 2 L group(96.8% vs 85.7%,P=0.002).The proportion of abdominal distension(none/mild/moderate/severe)was significantly lower in the 1.5 L group than in the 2 L group (36/65/22/3 vs 58/48/18/2,P=0.040).Within the subgroup who had undergone colonoscopy previously, a significantly higher number of patients in the 1.5 L group than in the 2 L group felt that the current preparation was easier than the previous one(54.1%vs 28.0%,P=0.001).The disease detection rate was not significantly different between the two groups. CONCLUSION:Although the 1.5 L group had better acceptability and tolerability,15 mg of mosapride may be insufficient to compensate for a 0.5-L reduction of PEG solution.

Implications of small-bowel transit time in the detection rate of capsule endoscopy: A multivariable multicenter study of patients with obscure gastrointestinal bleeding

AIMTo define the role of small-bowel transit time in the detection rate of significant small-bowel lesions.METHODSSmall-bowel capsule endoscopy records, prospectively collected from 30 participating centers in the Lombardy Registry from October 2011 to December 2013, were included in the study if the clinical indication was obscure gastrointestinal bleeding and the capsule reached the cecum. Based on capsule findings, we created two groups: P2 (significant findings) and P0-1 (normal/negligible findings). Groups were compared for age, gender, small-bowel transit time, type of instrument, modality of capsule performance (outpatients vs inpatients), bowel cleanliness, and center volume.RESULTSWe retrieved and scrutinized 1,433 out of 2,295 capsule endoscopy records (62.4%) fulfilling the inclusion criteria. Patients were 67 &#x000b1; 15 years old, and 815 (57%) were males. In comparison with patients in the P0-1 group, those in the P2 group (n = 776, 54%) were older (P &#x0003c; 0.0001), had a longer small-bowel transit time (P = 0.0015), and were more frequently examined in low-volume centers (P &#x0003c; 0.001). Age and small-bowel transit time were correlated (P &#x0003c; 0.001), with age as the sole independent predictor on multivariable analysis. Findings of the P2 group were artero-venous malformations (54.5%), inflammatory (23.6%) and protruding (10.4%) lesions, and luminal blood (11.5%).CONCLUSIONIn this selected, prospectively collected cohort of small-bowel capsule endoscopy performed for obscure gastrointestinal bleeding, a longer small-bowel transit time was associated with a higher detection rate of significant lesions, along with age and a low center volume, with age serving as an independent predictor.

Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

Gastroparesis:New insights into an old disease

Gastroparesis(Gp)is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical obstruction.Although this condition has been reported in the literature since the mid-1900s,only recently has there been renewed clinical and scientific interest in this disease,which has a potentially great impact on the quality of life.The aim of this review is to explore the pathophysiological,diagnostic and therapeutical aspects of Gp according to the most recent evidence.A comprehensive online search for Gp was carried out using MEDLINE and EMBASE.Gp is the result of neuromuscular abnormalities of the gastric motor function.There is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or telocytes.As regards diagnostic approach,99-Technetium scintigraphy is currently considered to be the gold standard for Gp.Its limits are a lack of standardization and a mild risk of radiation exposure.The C13 breath testing is a valid and safe alternative method.13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic kits.The wireless motility capsule is a promising technique,but its use is limited by costs and scarce availability in many countries.Finally,therapeutic strategies are related to the clinical severity of Gp.In mild and moderate Gp,dietary modification and prokinetic agents are generally sufficient.Metoclopramide is the only drug approved by the Food and Drug Administration for Gp.However,other older and new prokinetics and antiemetics can be considered.As a second-line therapy,tricyclic antidepressants and cannabinoids have been proposed.In severe cases the normal nutritional approach can be compromised and artificial nutrition may be needed.In drug-unresponsive Gp patients some alternative strategies(endoscopic,electric stimulation or surgery)are available.

Personalized medicine in functional gastrointestinal disorders:Understanding pathogenesis to increase diagnostic and treatment efficacy

There is overwhelming evidence that functional gastrointestinal disorders(FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms(UGI Sx). Among patients with UGI Sx, approximately equal proportions(25%) of patients have delayed gastric emptying(GE), reduced gastric accommodation(GA), both impaired GE and GA,or neither, presumably due to increased gastric or duodenal sensitivity.Treatments targeted to the underlying pathophysiology utilize prokinetics,gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia(with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome(IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2 D6, 2 C19 and 3 A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here;pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of genetics in the management of FGIDs.

Gastric electrical stimulation: An emerging therapy for children with intractable gastroparesis

Management of gastroparesis remains challenging,particularly in pediatric patients.Supportive care and pharmacological therapies for symptoms remain the mainstay treatment.Although they are effective for mild and some moderately severe cases,often time they do not work for severe gastroparesis.There are a few prokinetics available,yet the use of these drugs is limited by a lack of persistent efficacy and/or safety concerns.Currently,the only modality for adult patients with severe intractable gastroparesis is surgery,e.g.,pyloroplasty and partial gastrectomy,however,this option is generally considered too radical for a growing child.Novel therapeutic approaches,particularly those which are less invasive,are needed.This article explores gastric electrical stimulation(GES),a new therapy for gastroparesis.Unlike others,it neither needs medications nor gastrectomy;rather,it treats through the use of microelectrodes to deliver high-frequency low energy electric stimulation to the pacemaker area of the stomach.Thus,it is tolerated and safe in children.Like in adult patients,GES appears to work in releasing symptoms,improving nutrition,and enhancing the quality of life;it also helps wean off medications and eliminate many needs for hospitalization.Considering the transient nature of gastroparesis in children in many occasions,GES is considered a“bridging”therapy after failed medical interventions and before surgery.

Gastroparesis: Current diagnostic challenges and management considerations

Gastroparesis refers to abnormal gastric motility characterized by delayed gastric emptying in the absence of mechanical obstruction. The most common etiologies include diabetes, post-surgical and idiopathic. The most common symptoms are nausea, vomiting and epigastric pain. Gastroparesis is estimated to affect 4% of the population and symptomatology may range from little effect on daily activity to severe disability and frequent hospitalizations. The gold standard of diagnosis is solid meal gastric scintigraphy. Treatment is multimodal and includes dietary modification, prokinetic and anti-emetic medications, and surgical interventions. New advances in drug therapy, and gastric electrical stimulation techniques have been introduced and might provide new hope to patients with refractory gastroparesis. In this comprehensive review, we discuss gastroparesis with emphasis on the latest developments; from the perspective of the practicing clinician.

Mechanisms underlying feed intolerance in the critically ill: Implications for treatment

Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.

Management of non-variceal upper gastrointestinal tract hemorrhage:Controversies and areas of uncertainty

Upper gastrointestinal tract hemorrhage （UGIH） remains a common presentation requiring urgent evaluation and treatment. Accurate assessment, appropriate intervention and apt clinical skills are needed for proper management from time of presentation to discharge. The advent of pharmacologic acid suppression, endoscopic hemostatic techniques, and recognition of Helicobacter pylori as an etiologic agent in peptic ulcer disease （PUD） has revolutionized the treatment of UGIH. Despite this, acute UGIH still carries considerable rates of morbidity and mortality. This review aims to discuss current areas of uncertainty and controversy in the management of UGIH. Neoadjuvant proton pump inhibitor （PPI） therapy has become standard empiric treatment for UGIH given that PUD is the leading cause of non variceal UGIH, and PPIs are extremely effective at promoting ulcer healing. Howeve, neoadjuvant PPI administration has not been shown to affect hard clinical outcomes such as rebleeding or mortality. The optimal timing of upper endoscopy in UGIH is often debated. Upon completion of volume resuscitation and hemodynamic stabilization, upper endoscopy should be performed within 24 h in all patientswith evidence of UGIH for both diagnostic and therapeutic purposes. With rising healthcare cost paramount in today＇s medical landscape, the ability to appropriately triage UGIH patients is of increasing value. Upper en- doscopy in conjunction with the clinical scenario allows for accurate decision making concerning early discharge home in low risk lesions or admission for further moni toring and treatment in higher risk lesions. Concomitant pharmacotherapy with non steroidal antiinflammatory drugs （NSAIDs） and antiplatelet agents, such as clopidogrel, has a major impact on the etiology, severib/, and potential treatment of UGIH. Long term PPI use in patients taking chronic NSAIDs or clopidogrel is discussed thoroughly in this review.

Effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy

AIM： To determine the effect of oral erythromycin on gastric and small bowel transit time of capsule endoscopy. METHODS： Consecutive patients who underwent capsule endoscopy during the 16-mo study period were either given 250 mg oral erythromycin, 1 h prior to swallowing the capsule endoscope or nothing. The gastric and small bowel transit time, and the small bowel image quality were compared. RESULTS： Twenty-four patients received oral erythromycin whereas 14 patients were not given any prokinetic agent. Patients who received erythromycin had a significantly lower gastric transit time than control （16 min vs70 min, P= 0.005）, whereas the small bowel transit time was comparable between the two groups （227 rain vs 183 min, P= 0.18）. Incomplete small bowel examination was found in three patients of the control group and in one patient of the erythromycin group. There was no significant difference in the overall quality of small bowel images between the two groups. A marked reduction in gastric transit time was noted in two patients who had repeat capsule endoscopy after oral erythromycin. CONCLUSION： Use of oral erythromycin significantly reduces the gastric transit time of capsule endoscopy.

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

AIM： To study the effect of combined omeprazole（Ome） and domperidone（Dom） therapy on asthma symptoms and pulmonary function in asthmatics with gastroesoph- ageal reflux. METHODS： We selected 198 asthmatics with gastro- esophageal reflux diagnosed by 24-h esophageal pH moni- toring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk （1：1 double-blind randomization）. Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were： mean daily daytime and nighttime asthma symptom scores. Mean daily reflux symptom scores, albuterol use as rescue medication （number of puffs）, daytime and nighttime peak expiratory flow rate （PEFR）, postbronchodilator forced expiratory volume in 1 second （FEVl） and postbronchodilator forced vital capacity （FVC） were secondary outcome measures. RESULTS： Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score （17.4% vs 8.9 %）, nighttime asthma symptom score （19.6% vs 5.4%）, reflux symptom score （8.7% vs 1.6%） and rescue medication use （23.2% vs 3.1%） after antireflux therapy compared to mean change in placebo group （P 〈 0.001）. There was significant improvement in morning PEFR （7.9% vs 0.2%）, evening PEFR （9.8% vs 0.5%）, FEW （11.1% vs 3.78%） and FVC （9.3%vs 1.52%） in the antireflux therapy group compared to placebo on comparng the mean change from baseline after 16 wk （P 〈 0.01） CONCLUSION： Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal reflux may be beneficial by reducing asthma symptoms, rescuing medi- cation use, and improving pulmonary function.

Gastric electrical stimulation for gastroparesis:A goal greatly pursued,but not yet attained

The lack of an effective medical treatment for gastroparesis has pushed the research of new techniques of gastric electrical stimulation (GES) for nearly half a century of experimentation with a large variety of electrical stimuli delivered to the gastric wall of animals and patients with gastroparesis. Three principal methods are currently available: gastric low-frequency/high-energy GES with long pulse stimulation, high-frequency/low-energy GES with short pulse stimulation and neural sequential GES. The first method aims to reset a regular slow wave rhythm, but has variable effects on contractions and requires devices with large and heavy batteries unsuitable for implantation. High-frequency/low-energy GES, although inadequate to restore a normal gastric electro-mechanical activity, improves dyspeptic symptoms, such as nausea and vomiting, giving patients a better quality of life together with a more satisfactory nutritional status and is suitable for implantation. Unfortunately, the numerous clinical studies using this type of GES, with the exception of two, were not controlled and there is a need for definitive verification of the effectiveness of this technique to justify the cost and the risks of this procedure. The last method, which is neural sequential GES, consists of a microprocessor-controlled sequential activation of a series of annular electrodes along the distal two thirds of the stomach and is able to induce propagated contractions causing forceful emptying of the gastric content. The latter method is the most promising, but has been used only in animals and needs to be tested in patients with gastroparesis before it is regarded as a solution for this disease.

Finding the solution for incomplete small bowel capsule endoscopy

AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February 2013.Capsule location was systematically checked one hour after ingestion using RTV.If it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min.If the capsule remained in the stomach a second dose of10 mg of domperidone was administered orally.After another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)endoscopy.The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical history.The control group included 307 patients,with 48(15.6%)IE.The RTV group included 82 patients,with3(3.7%)IE,P=0.003.In the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=0.736.Domperidone did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.

Pharmacological therapy of feed intolerance in the critically ills

Feed intolerance in the setting of critical illness is associated with higher morbidity and mortality,and thusrequires promptly and effective treatment. Prokineticagents are currently considered as the first-line therapygiven issues relating to parenteral nutrition and post-pyloric placement. Currently,the agents of choice areerythromycin and metoclopramide,either alone or incombination,which are highly effective with relativelylow incidence of cardiac,hemodynamic or neurologicaladverse effects. Diarrhea,however,can occur in up to 49% of patients who are treated with the dual prokinetic therapy,which is not associated with Clostridiumdifficile infection and settled soon after the cessation ofthe drugs. Hence,the use of prokinetic therapy over along period or for prophylactic purpose must be avoided,and the indication for ongoing use of the drug(s)must be reviewed frequently. Second line therapy,suchas total parenteral nutrition and post-pyloric feeding,must be considered once adverse effects relating theprokinetic therapy develop.

Mangiferin,a natural xanthone,accelerates gastrointestinal transit in mice involving cholinergic mechanism

AIM： To investigate the effects of mangiferin on gas- trointestinal transit （GIT） in normal and constipated mice, together with the possible mechanism.METHODS： Intragastrically-administered charcoal mealwas used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin （3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po） or tegaserod （1 mg/kg, ip） were administered 30 min before the char- coal meal to study their effects on normal transit. In the second series, mangiferin （30 mg/kg） was tested on delayed GIT induced by several different pharma- cological agonists （morphine, clonidine, capsaicin） or antagonists （ondansetron, verapamil, and atropine） whereas in the third series, mangiferin （30 mg/kg, 100 mg/kg and 300 mg/kg） or tegaserod （1 mg/kg） were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS： Mangiferin administered orally significantly （P 〈 0.05） accelerated GIT at 30 mg/kg and 100 mg/kg （89% and 93%, respectively）, similarly to 5-hydroxytrypta- mine4 （5-H%） agonist tegaserod （81%） when compared to vehicle-treated control （63%）. Co-administered man- giferin （30 mg/kg） totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by ~2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses （245.5±10.43 mg vs 161.9±10.82 mg and 227.1±20.11 mg vs 161.9±10.82 mg of vehicle-treated control, at 30 and 100 mg/ kg, P 〈 0.05, respectively）, the effect of tegaserod was more potent （297.4±7.42 mg vs 161.9±10.82 mg of vehicle-treated control, P 〈 0.05）. Unlike tegaserod, which showed an enhanced water content in fecal pel- lets （59.20%±1.09% vs 51.44%±1.19% of control, P 〈 0.05）, mangiferin evidenced no such effect, indi-cating that it has only a motor and not a secretomotor effect. CONCLUSION： Our data indicate the prokinetic action of mangiferin. It can stimulate the normal GIT and also overcome the drug-induced transit delay, via a choliner- gic physiological mechanism.