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L'atteinte digestive au cours de la sclérodermie systémique peut être sévère et occasionner une véritable pseudo-obstruction intestinale chronique, secondaire à des troubles profonds de la motilité de l'intestin grêle. Elle est associée à certaines caractéristiques cliniques et biologiques, notamment la positivité des anticorps anti fibrillarine/U3RNP. La pseudo-obstruction intestinale chronique se complique d'une pullulation microbienne qui nécessite une antibiothérapie cyclique. Elle entraîne nécessairement une réduction du bol alimentaire compte-tenu des symptômes douloureux, nausées et vomissements engendrés par les repas et, in fine , une dénutrition sévère. La stratégie de fractionnement des repas n'est souvent que transitoirement efficace et les patients nécessitent un authentique support nutritionnel, principalement par voie parentérale. La sclérodermie systémique ne constitue pas un frein à l'initiation et la poursuite de ce traitement dans le temps. Les dispositifs veineux implantables ne s'accompagnent pas d'un surrisque de complications locales ou infectieuses. La poursuite d'une nutrition parentérale au long cours nécessite toutefois un suivi conjoint dans un centre expert en nutrition, afin d'adapter les volumes et apports nutritifs et d'en limiter les complications cardiaques et hépatobiliaires potentiellement mortelles. À la nutrition s'associent des traitements prokinétiques dont les effets secondaires – notamment antagonistes sur la motilité digestive – doivent être connus, ainsi que des procédures invasives dont la balance bénéfice-risque doit être évaluée avec précaution. Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively. [ABSTRACT FROM AUTHOR]

The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR). The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders–Quality of Life scores. Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P =.003), nausea (P =.003), and fullness subscales (P =.005), upper abdominal pain score (P =.04), Gastroesophageal Reflux Disease score (P =.05), and Patient Assessment of Upper Gastrointestinal Disorders–Quality of Life score (P =.05). Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM. [ABSTRACT FROM AUTHOR]

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid suppressing therapy is widespread in intensive care units to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus include opioid analgesics, catecholamines and α 2 -adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin, either alone or in combination, though their effectiveness in clinical practice is limited. A range of further medications, with different drug targets, are being investigated as alternatives. These include specific motilin receptor agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5HT 4 antagonists and cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]

Background and study aims Several studies have demonstrated the superiority of proton-pump inhibitors (PPIs) in resolving erosive gastro-oesophageal reflux disease (GORD). However, this first line of treatment can fail to control symptoms in around 30% of cases, especially in the presence of non-erosive GORD. In situations where the first line of treatment fails, there is a lack of concordance regarding the best strategy to apply. This study presents a systematic review of the trials which have tested second-line treatments after PPI failure. Methods The study was conducted according to the PRISMA statement. The systematic review included medical trials written in English which were published between 2000 and 2016 and were retrieved from PubMed and Scopus using the keywords ‘PPI-resistant gastro-oesophageal reflux’, ‘alginate AND gastro-oesophageal reflux’, ‘hyaluronic acid AND gastro-oesophageal reflux’, ‘prokinetics AND gastro-oesophageal reflux’, ‘sucralfate AND gastro-oesophageal reflux’ and ‘baclofen AND gastro-oesophageal reflux’. Results Ten randomised and non-randomised studies were included, which included 1515 patients of both sexes (mean age = 49.19 years, age range = 18–85, males = 700; 46.2%). Conclusions A personalised choice of the best treatment for PPI-resistant GORD should be based on the results of an upper endoscopy and pH/MII monitoring. For patients in situations where the first line of treatment fails, we encourage the execution of trials for testing double doses of PPIs against alternative medicaments. [ABSTRACT FROM AUTHOR]

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid suppressing therapy is widespread in intensive care units to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus include opioid analgesics, catecholamines and α 2 -adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin, either alone or in combination, though their effectiveness in clinical practice is limited. A range of further medications, with different drug targets, are being investigated as alternatives. These include specific motilin receptor agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5HT 4 antagonists and cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]

Aim Commonly, neuroleptics and prokinetics induce a prolonged QTc interval. In this study, stable gastric pentadecapeptide BPC 157 counteracts the prolongation of the QTc interval in Wistar rats that underwent daily administration of dopamine neuroleptics or prokinetics. Previously, in rats and mice, BPC 157 counteracted neuroleptic-induced catalepsy and gastric ulcers. Main methods To counteract neuroleptic- or prokinetic-induced prolongation of the QTc interval, rats were given a BPC 157 regimen once daily over seven days (10 μg, 10 ng/kg ip) immediately after each administrations of haloperidol (0.625, 6.25, 12.5, and 25.0 mg/kg ip), fluphenazine (0.5, 5.0 mg/kg ip), clozapine (1.0, 10.0 mg/kg ip), quetiapine (1.0, 10.0 mg/kg ip), sulpiride (1.6, 16.0 mg/kg ip), metoclopramide (2.5, 25.0 mg/kg ip) or (1.0, 10.0 mg/kg ip). Controls simultaneously received saline (5 ml/kg ip). To assess the ECG presentation before and after neuroleptic/prokinetic medication, the assessment was at 1, 2, 3, 4, 5, 10, 15, 20 and 30 min (first administration) as well as at 30 min, 60 min and 24 h (first administration and subsequent administrations) and the ECG recording started prior to drug administration. Key findings Since very early, a prolonged QTc interval has been continually noted with haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats as a central common effect not seen with domperidone. Consistent counteraction appears with the stable gastric pentadecapeptide BPC 157. Thus, BPC 157 rapidly and permanently counteracts the QTc prolongation induced by neuroleptics and prokinetics. Significance Pentadecapeptide BPC 157 is suited for counteracting a prolonged QT interval. [ABSTRACT FROM AUTHOR]

This review of the pathophysiologic basis for gastroparesis and recent advances in the treatment of patients with gastroparesis shows that there are several novel approaches to advance treatment of gastroparesis including diet, novel prokinetics, interventions on the pylorus, and novel forms of gastric electrical stimulation. The field of gastroparesis is likely to advance with further studies, with help from a guidance document from the Food and Drug Administration on gastroparesis, and with recent approval of the stable isotope gastric emptying test to ensure eligibility of participants in multicenter trials. Clinical experience and a formal, randomized, controlled trial provide insights on optimizing dietary interventions in patients with gastroparesis. This review addresses the biologic rationale of these different treatments, based on known physiology and pathophysiology of gastric emptying. The novel medications include the motilin agonist, camicinal; 5-HT 4 receptor agonists, such as velusetrag; and the ghrelin agonist, relamorelin. New approaches target pylorospasm by stent placement, endoscopic pyloric myotomy, or laparoscopic pyloroplasty. These approaches offer the opportunity to achieve more permanent reduction of resistance to flow at the pylorus over the intrapyloric injection of botulinum toxin, which typically has to be repeated every few months if it is efficacious. A novel device, deployed in porcine stomach, involved per-endoscopic electrical stimulation. These promising approaches require formal, randomized, controlled trials and deployment in patients. The presence of concomitant antral hypomotility may be a significant factor in the responsiveness to interventions at the pylorus. [ABSTRACT FROM AUTHOR]

Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid-suppressing therapy is widespread in critical care. The aim is to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus, include opioid analgesics, catecholamines and α 2 -adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin either alone or in combination. Limited efficacy has been demonstrated with these medications. A range of further medications, with different drug targets, are being investigated as alternatives. These include motilin agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5-HT 4 antagonists and cholinesterase inhibitors. [ABSTRACT FROM AUTHOR]

Abstract: Depression could hardly get a satisfactory effect from the currently available antidepressants. To get a more effective treatment, antidepressant effect and monoaminergic mechanism of Fructus Aurantii (FRA) in the rat forced swimming test (FST) and open field test (OFT), and its prokinetics were examined. FST and OFT were respectively used to evaluate the antidepressant effect and locomotor activity of FRA. We observed the effects of monoamine receptor antagonists on FRA-induced antidepressant effect in rat. The effects of FRA on intestinal transit, gastric emptying and in vitro jejunum contractile activity were assessed. FRA decreased significantly the immobility time (32.6±8.5, 30.3±5.2 vs 56.4±9.4, all p <0.01) in FST, dose-dependent increased the locomotor activity (102±17.5, 120±18.5 vs 89±9.8, p <0.05 or 0.01), significantly accelerated gastric emptying (GE: 48.1±6.3, 39.5±5.7 vs 19.5±3.8, p <0.01) and intestinal transit (IT: 67.3±9.1, 64.2±6.3 vs 49.1±8.2, p <0.01) of the semi-liquid meal, compared with vehicle. And FRA (1μM, 10μM) significantly increased the mean amplitude (0.24±0.021 and 0.281±0.015) of contraction in jejunum of rat compared with vehicle (0.149±0.011) in vitro. FRA (10μM) could induce a largest amplitude (0.281±0.015) of contraction in jejunum. The anti-immobility effect of FRA in FST was prevented by pre-treatment of rat with p-chlorophenylalanine methyl ester, WAY100635, ketanserin, haloperidol, SCH233390, sulpiride, yohimbine, but not prazosin. FRA could simultaneously induce prokinetics and antidepressant effect, deserves further to investigate. [Copyright &y& Elsevier]

Abstract: Gastric disorders have clinical implications in both anaesthesia and critical care medicine. Aspiration of acidic gastric contents in the perioperative setting is linked to pneumonitis and later development of pneumonia. Pharmacological strategies to minimize this risk include histamine-2 receptor antagonists, sucralfate, proton pump inhibitors and sodium citrate. Use of gastric acid-suppressing therapy is widespread in critical care. The aim is to reduce the incidence of stress-related mucosal bleeding. Intestinal failure is common in critical illness. Medications that decrease gastric motility and contribute to ileus, include opioid analgesics, catecholamines and α2-adrenoceptor antagonists. Current pharmacological strategies for increasing gastric motility include the use of metoclopramide and erythromycin either alone or in combination. Limited efficacy has been demonstrated with these medications. A range of further medications, with different drug targets, are being investigated as alternatives. These include motilin agonists, peripherally acting opioid receptor antagonists, cholecystokinin antagonists, 5-HT4 antagonists and cholinesterase inhibitors. [Copyright &y& Elsevier]

Abstract: Selective serotonin reuptake inhibitors (SSRIs), one of popular antidepressants as “one-compound-one-target” paradigm, cannot but discontinue because of inhibiting gut movement. Traditional Chinese medicine (TCM) Chaihu–Sugan–San (CSS) can simultaneously exert anti-depression and prokinetics. From this thread, we aimed to find a new antidepressant with polypharmacological mechanisms. In vivo antidepressive and prokinetic comparisons between CSS and its absorbed compound ferulic acid (FA) were made. And FA''s action mechanisms involved in monoaminergic systems, HPA axis and gastrointestinal peptide ghrelin was then studied in forced swimming test (FST) of rat. Lastly, the jejunal contraction activity evoked by FA was measured in vitro. Compared with vehicle, FA reduced immobility time, increased locomotor activity, accelerated gastric emptying and intestinal transit similar to CSS whose absorbable component FA was identified in hippocampus and jejunum. FA''s prokinetics in vivo was further supported by its jejunal contraction in vitro. FA-induced anti-immobility was prevented by pretreated with PCPA, WAY-100635, ketanserin, sulpiride, SCH233390, haloperidol and yohimbine, respectively. CRH, ACTH and 5-HT were significantly decreased, but ghrelin was apparently increased compared with vehicle. In summary, FA induced anti-depression and prokinetics similar to CSS via inhibiting serotonin, norepinephrine and dopamine reuptakes, regulating HPA axis, increasing ghrelin and stimulating jejunal contraction simultaneously. [Copyright &y& Elsevier]

Abstract: Advances in the understanding of the pathophysiology of stress explain the risk of specific nutrients deficiency because of the changes in metabolic patterns during the acute phase. The advantages of early enteral nutrition (EEN) over other modalities of nutrition (parenteral nutrition or delayed enteral nutrition) are widely acknowledged. More physiological, EEN preserves the gut integrity, its immune function and reduces infectious complication rate. Antioxidants, conditionally essential amino-acids (glutamine, cysteine) seem to be useful during the acute phase. EEN is the way to provide nutrients to the gut, which plays a key role in inflammation homeostasis. Despite the potential benefits of EEN, limits and requirements due to particular conditions in intensive care must be kept in mind. To be successful and safe, EEN must be integrated in the healthcare process. Stress, use of sedative agents and opioids, impair the gastric emptying and intestinal motility. The quality of nutritional care, the rational use of prokinetics, algorithm based sedation and analgesia, must be combined to prevent the risk of ventilator-associated pneumonia. EEN becomes a goal for improving quality in critical care. In high risk patients, EEN combined with parenteral nutrition (PN) allows to avoid underfeeding. [Copyright &y& Elsevier]

Abstract: Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide. [Copyright &y& Elsevier]

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a Ca-free solution and thapsigargin, a Ca-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by GDP-β-S, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external Ca influx, phospholipase C activation, and Ca release from internal storage in a G protein-independent and protein kinase C-independent manner. [ABSTRACT FROM AUTHOR]

Abstract: To develop a therapeutic for functional dyspepsia (FD), a prokinetic agent, DA-9701 has been newly formulated with Pharbitis Semen and Corydalis Tuber and we evaluated the gastroprokinetic effects of DA-9701 in comparison with conventional prokinetics. Oral administration with DA-9701 not only significantly accelerated gastric emptying in normal rats but also restored the delayed gastric emptying caused by apomorphine and cisplatin up to almost normal levels. For gastrointestinal transit, DA-9701 caused FITC-dextran to travel a significantly longer distance than the control, and in the delayed GI transit models induced by laparotomy and atopine, DA-9701 considerably increased the values of mean geometric center (MGC), while the conventional prokinetics rarely showed significant effects. Furthermore, DA-9701 drastically increased the gastric accommodation in Beagle dogs, shifting the pressure–volume curve toward considerably higher volume compared to the control, which was comparable to that of cisapride. These results indicate that DA-9701 has potential as a safe and effective therapeutic for FD patients with abnormalities in GI motor function. [Copyright &y& Elsevier]

Chronic intestinal pseudo-obstruction (CIPO) is a severe functional digestive syndrome characterised by a derangement of gut propulsive motility which resembles mechanical obstruction. It may be associated with disabling and potentially life-threatening complications. CIPO can be secondary to a variety of diseases, but it is more frequently idiopathic. Most cases are sporadic, but familial forms have also been described. Based on histological features CIPO can be classified into three major entities: neuropathies, mesenchymopathies, and myopathies depending on the predominant involvement of enteric neurones, interstitial cells of Cajal (ICC) or smooth muscle cells, respectively. Mitochondriopathies may be responsible for a syndromic form of CIPO, i.e. mitochondrial neurogastrointestinal encephalomyopathy. Management of CIPO involves nutritional, pharmacological and surgical therapies, but the long-term outcome turns out to be poor in the vast majority of cases. The main pathogenetic and clinical features of the syndrome, together with current management recommendations are reviewed in this chapter. [Copyright &y& Elsevier]

Abstract: Functional dyspepsia is a common chronic disorder with non-specific upper abdominal symptoms which can not be explained by organic or biochemical abnormalities. The dyspeptic symptoms are very compromising and bothersome and result in a substantial reduction of quality of life. The substantial direct and indirect medical and economical costs induce a high socioeconomic interest in the pathogenesis and the treatment options of this disease. Over the past 30 years several theories about the etiology of the symptoms in functional dyspepsia patients have been put forward. These include disorders of gastrointestinal motility, acid secretion, visceral hypersensitivity, adaptation and accommodation, Hp-infection, mucosal inflammation and finally genetic predisposition. There is increasing evidence that functional dyspepsia is a multi-causal disorder, which leads to altered processing of afferent information from the gastrointestinal tract to the CNS. Autonomic hypersensitivity and altered central processing could be a common phenomenon whereas motility changes, inflammation or altered secretion could increase neural afferent inputs. Treatment of this complex disorder could and should involve these different levels of symptom generation. Thus different approaches with anti-secretory, spasmolytic, prokinetic and anti-inflammatory effects and most preferably reduction of visceral hypersensitivity seem logical. This could explain the variety of drugs which show a positive symptomatic response. This could also offer the conclusion, whether a combination of these drugs could be clinically superior which remains to be proven. And this could offer a logical approach for the use of substances with a multi-target action, e.g. STW 5. [Copyright &y& Elsevier]

Abstract: Background:: Quality of life (QOL) is impaired in functional dyspepsia (FD). Little is known about the effects of different therapies on the QOL profile in patients with this condition. Objectives:: The aims of this study were to measure baseline QOL in patients with FD and to assess changes in QOL over time associated with Helicobacter pylori eradication and prokinetic treatment. The primary and secondary end points were the improvement in QOL 6 weeks and 1 year after successful eradication of the infection or prokinetic therapy. Methods:: This 1-year, single-center, prospective, open-label, controlled, parallel-group trial was conducted at the Department of Gastroenterology, Ferencvdros Health Centre, Budapest, Hungary. The Functional Digestive Disorder Quality of Life (FDDQoL) Questionnaire (MAPI Research Institute, Lyon, France) was translated and validated previously in Hungarian. Male and female subjects aged 20 to 60 years were enrolled and classified as H pylori positive (HP+), H pylori negative (HP-) with FD, or healthy (control group). The HP+ patients received pantoprazole 40 mg BID + amoxicillin 1000 mg BID + clarithromycin 500 mg BID for 7 days, followed by on-demand ranitidine (150–300 mg/d) for 1 year. The HP- patients received the prokinetic cisapride 10 mg TID for 1 month, followed by on-demand cisapride (10–20 mg/d) for 1 year. The FDDQoL questionnaire was completed by all 3 groups on enrollment, at 6 weeks, and 1 year. Results:: A total of 101 HP+ patients, 98 HP- patients, and 123 healthy controls were included in the study (185 women, 137 men; mean age, 39.0 ears). The mean (SD) baseline QOL scores were significantly lower in the HP+ group (53.3 [9.6]; 95% CI, 54.4-58.2) and the HP- groups (50.0 [9.8]; 95% CI, 58.0–62.0) compared with that in healthy controls (76.2 [8.7]; 95% CI, 74.6–77.8) (both, P < 0.001). Analysis of the short-term domain scores found that the HP+ group had significantly decreased scores in 6 of 8 domains: daily activities (P = 0.005), anxiety level (P = 0.02), diet (P = 0.008), sleep (P < 0.001), discomfort (P = 0.004), and disease control (P = 0.02); the HP- group had significantly decreased scores in 5 of 8 domains: daily activities (P < 0.001), diet (P = 0.004), sleep (P = 0.005), discomfort (P < 0.001), and disease control (P = 0.02). Eradication of the infection was successful in 77/101 (76.2%) of the patients on intent-to-treat analysis and 77/94 (81.9%) on per-protocol analysis. Eradication was associated with an increase in mean (SD) QOL score to 70.8 (10.7) at 6 weeks (95% CI, 63.3–73.2; P < 0.001 vs baseline) and to 75.3 (9.3) at 1 year (95% CI, 73.2–77.5; P= 0.05 vs 6 weeks). In the HP- group, the QOL score increased to 73.3 (9.7) (95% CI, 71.3–75.4; P < 0.001 vs baseline) at 6 weeks of cisapride treatment and to 76.5 (8.5) at 1 year (95% CI, 74.5–78.4; P = 0.06 vs 6 weeks). Most of the impaired domain scores improved significantly after both treatments. The short-term effect size was 1.48 in HP+ and 1.35 in HP− patients. Adverse events (AEs) occurred in 22 (21.8%) patients in the HP+ group (nausea, 8 [7.9%] patients; diarrhea, 5 [5.0%]; loss of appetite, 5 [5.0%]; stomatitis, 5 [5.0%]; abdominal pain, 4 [4.0%]; bloating, 4 [4.0%]; headache, 4 [4.0%]; vomiting, 4 [4.0%]; constipation, 3 [3.0%]; and vaginitis, 3 [3.0%]). In HP− cases, AEs occurred in 9 (9.2%) patients (abdominal cramps, 7 [7.1%]; diarrhea, 4 [4.1%]; and nausea, 3 [3.1%]). Conclusion:: In this study in patients with FD and healthy controls, eradication of H pylori infection in infected patients and cisapride treatment in uninfected patients reversed low QOL scores during the 1-year follow-up period. [Copyright &y& Elsevier]

Abstract: The term ‘functional disorders’ was previously used to describe a wide range of disorders characterized by symptoms in the absence of known structural or functional abnormalities. Diagnosis must be based on symptoms and a consensus group has agreed a set of definitions called the ‘Rome criteria’ (www.romecriteria.org). This review discusses the two most common functional disorders: functional dyspepsia and irritable bowel syndrome. They share many features with other, rarer conditions and between them account for about 50% of gastroenterology outpatient referrals in the UK. [Copyright &y& Elsevier]

The objectives of the study were to determine whether retrospective data can be used to answer questions about the efficacy of prokinetic agents when used to treat horses with post-operative ileus (POI). We describe prevalence and mortality of POI with reference to treatment with four prokinetic agents. By combining data from two Hospitals a study population of 55 horses with POI following pedunculated lipoma obstruction (PLO) was established. Univariable and multivariable associations were determined between short term survival and potential explanatory variables. With death as outcome in multivariable models, breed and hospital were significantly associated with outcome but the use of prokinetic agents was not (P = 0.15). However, sample size estimates indicate the low power of this study to detect differences in outcome. It was not possible definitively to evaluate the efficacy of prokinetics as treatment for POI following PLO using retrospective data. The data were suggestive of limited efficacy of prokinetics as treatment for POI. It is postulated that the identified association between hospital and survival reflects differences in clinician decision making. The study highlights the need for further prospective studies using randomised clinical trials to evaluate accurately the efficacy of prokinetic agents. This report illustrates difficulties with performing retrospective analysis of clinical data to determine the efficacy of treatment regimes. [ABSTRACT FROM AUTHOR]

Currently, few herbal pharmacokinetic (PK) parameters have been applied successfully for therapeutic monitoring because of the complexity of consistency when there are multiple chemicals and efficacies. The present study aims to evaluate the herbal PK properties by investigating the PK parameters of the 8 absorbed bioactive compounds (ABCs), which can represent its parent herbal holistic efficacy, to achieve a PK therapeutic monitoring of herbs. First, we tested the hypothesis that the antidepressant and prokinetic effects and related anti-inflammation and anti-oxidation activity (APIO) by Fructus aurantii-Magnolia Bark (FM) formula are related to 8 compounds according to the absorbable evidence and the determined contents. Subsequently, stable and representative APIO from 8ABCs allowed us to develop a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 8 compounds following the oral administration of FM decoction (20 g/kg) in rats. Result: 8 compounds either including Meranzin hydrate (MH) or MH alone almost identically (8 compounds: 91.62–108.82%)or nearly(MH: 65.38–88.41%) replicated the parent formula FM in terms of efficacy for inducing APIO. This unifying strategy shows how multi-herb formulas pharmacokinetic therapeutic monitoring can be achieved by the method we established. Image 1 • The activity by Fructus aurantii-Magnolia Bark formula are related to 8 compounds. • 8 compounds almost replicated the parent formula FM in terms of efficacy. • The Pharmacokinetic of the 8 absorbed compounds in rats are studied. [ABSTRACT FROM AUTHOR]