Showing papers in "Alimentary Pharmacology & Therapeutics in 2007"

Review article: the role of butyrate on colonic function

Abstract: BACKGROUND: Butyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis. AIM: To provide an overview on the present knowledge of the bioactivity of butyrate, emphasizing effects and possible mechanisms of action in relation to human colonic function. METHODS: A PubMed search was performed to select relevant publications using the search terms: 'butyrate, short-chain fatty acid, fibre, colon, inflammation, carcinogenesis, barrier, oxidative stress, permeability and satiety'. RESULTS: Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis, reinforcing various components of the colonic defence barrier and decreasing oxidative stress. In addition, butyrate may promote satiety. Two important mechanisms include the inhibition of nuclear factor kappa B activation and histone deacetylation. However, the observed effects of butyrate largely depend on concentrations and models used and human data are still limited. CONCLUSION: Although most studies point towards beneficial effects of butyrate, more human in vivo studies are needed to contribute to our current understanding of butyrate-mediated effects on colonic function in health and disease.

Increasing prevalence of coeliac disease over time.

Abstract: SUMMARY Background The number of coeliac disease diagnoses has increased in the recent past and according to screening studies, the total prevalence of the disorder is around 1%. Aim To establish whether the increased number of coeliac disease cases reflects a true rise in disease frequency. Methods

Chronic constipation: a survey of the patient perspective.

Abstract: Summary Background Constipation is a common, often chronic, gastrointestinal motility disorder characterized by such symptoms as straining, hard stool, and infrequent defecation. Published literature is limited regarding symptom prevalence, healthcare-seeking behaviour, and patient satisfaction with traditional therapies for chronic constipation. Aim To assess the prevalence of chronic constipation among a random sample of Americans, to identify the frequency, severity and bothersomeness of their symptoms, and to assess satisfaction levels with traditional treatments. Methods All members (N = 37 004) of the Knowledge Networks Panel, representative of the US population, participated in a web-based survey. Eligibility was established using a six-question screener. Results Of the 24 090 panellists consenting to participate, 557 met eligibility requirements and took the 45-question survey. The most prevalent symptom was straining (79%). Hard stool and straining were the top two severe symptoms, and bloating, straining and hard stool were the top three bothersome symptoms. Symptoms affected quality of life of more than half (52%) the respondents. Among those who worked or went to school, 12% experienced reduced productivity and a mean of 2.4 days of absence in the month before the survey. Most respondents had used (96%) or were using (72%) constipation relief therapy; however, nearly half (47%) were not completely satisfied, mainly because of efficacy (82%) and safety (16%) concerns. Conclusions Chronic constipation is common. Individual symptoms are often severe and bothersome, and many patients are dissatisfied with traditional treatment options, primarily because of lack of efficacy.

Review article: lactose intolerance in clinical practice--myths and realities.

Abstract: Summary Background Approximately 70% of the world population has hypolactasia, which often remains undiagnosed and has the potential to cause some morbidity. However, not everyone has lactose intolerance, as several nutritional and genetic factors influence tolerance. Aims To review current clinical practice and identify published literature on the management of lactose intolerance. Methods PubMed was searched using the terms lactose, lactase and diet to find original research and reviews. Relevant articles and clinical experience provided the basis for this review. Results Lactose is found only in mammalian milk and is hydrolysed by lactase in the small intestine. The lactase gene has recently been identified. ‘Wild-type’ is characterized by lactase nonpersistence, often leading to lactose intolerance. Two genetic polymorphisms responsible for persistence have been identified, with their distribution concentrated in north Europeans. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhoea. Diagnosis is most commonly by the lactose hydrogen breath test. However, most people with hypolactasia, if given appropriate advice, can tolerate some lactose-containing foods without symptoms. Conclusion In clinical practice, some people with lactose intolerance can consume milk and dairy foods without developing symptoms, whereas others will need lactose restriction.

Review article: yeast as probiotics-saccharomyces boulardii

Abstract: ummary Background Probiotics are defined as live micro-organisms which confer a health benefit on the host. Although most probiotics are bacteria, one strain of yeast, Saccharomyces boulardii, has been found to be an effective probiotic in double-blind clinical studies. Aims To compare the main properties that differentiates yeast from bacteria and to review the properties of S. boulardii explaining its potential benefits as a probiotic. Methods The PubMed and Medline databases were searched using the keywords ‘probiotics’, ‘yeast’, ‘antibiotic associated diarrhea’, ‘Saccharomyces boulardii’,‘bacterial diarrhea’ and ‘inflammatory bowel disease’ in various combinations. Results Several clinical studies have been conducted with S. boulardii in the treatment and prevention of various forms of diarrhoea. Promising research perspectives have been opened in terms of maintenance treatment of inflammatory bowel diseases. The mechanism of S. boulardii’s action has been partially elucidated. Conclusion Saccharomyces boulardii is a strain of yeast which has been extensively studied for its probiotic effects. The clinical activity of S. boulardii is especially relevant to antibiotic-associated diarrhoea and recurrent Clostridium difficile intestinal infections. Experimental studies clearly demonstrate that S. boulardii has specific probiotic properties, and recent data has opened the door for new therapeutic uses of this yeast as an ‘immunobiotic’.

Systematic review and meta‐analysis: the incidence and prognosis of post‐infectious irritable bowel syndrome

Abstract: Summary Background Individual studies suggest that post-infectious irritable bowel syndrome is common, but symptoms gradually improve. Aim To review evidence for an association between intestinal infection and development of irritable bowel syndrome, assess the prognosis of post-infectious irritable bowel syndrome and explore factors that increase the risk. Methods MEDLINE (1966–2007) and EMBASE (1980–2007) databases were searched to identify the studies of post-infectious irritable bowel syndrome epidemiology. Data were extracted by two independent reviewers. Pooled odds ratios (POR) and corresponding 95% CI for incidence of irritable bowel syndrome were estimated among the exposed and unexposed groups. Results Eighteen of 26 studies identified were eligible for inclusion. Intestinal infection was associated with increased odds of developing irritable bowel syndrome at study end (POR = 5.86; 95% CI: 3.60–9.54). In subgroup analysis, the odds of developing irritable bowel syndrome was increased at 3 months (POR = 7.58; 95% CI: 4.27–13.45), 6 months (POR = 5.18; 95% CI: 3.24–8.26), 12 months (POR = 6.37; 95% CI: 2.63–15.40) and 24–36 months (POR = 3.85; 95% CI: 2.95–5.02). Among all studies (controlled and uncontrolled), the pooled incidence of irritable bowel syndrome at study conclusion was 10% (95% CI: 9.4–85.6). Subjects with post-infectious irritable bowel syndrome were younger and more anxious and depressed than those without post-infectious irritable bowel syndrome. Conclusion The odds of developing irritable bowel syndrome are increased sixfold after acute gastrointestinal infection. Young age, prolonged fever, anxiety and depression are risk factors for post-infectious irritable bowel syndrome.

Adipokines and cytokines in non-alcoholic fatty liver disease

Abstract: Summary Background Several adipocytokines have been implicated in the pathogenesis non-alcoholic fatty liver disease (NAFLD). Aim To assess adipocytokines in NAFLD patients and controls. Methods A total of 95 patients (26 non-alcoholic steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non-obese controls) were included. Fasting serum insulin, glucose, visfatin, resistin, adiponectin, tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used to compare groups and determine associations. Results Serum TNF-α and IL-8 were higher in NAFLD patients when compared with both obese and non-obese controls. Analysis involving all patients revealed a significant correlation between serum TNF-α and IL-8 (P < 6.319e−08), and between IL-6 and IL-8 (P < 5.271e−15). Homeostatic model assessment scores negatively correlated with adiponectin in NAFLD (P < 0.0032). Serum visfatin was higher in all three obese groups than in non-obese controls (P < 0.02, P < 0.002 and P < 0.008). Visfatin in NASH patients was lower than SS and obese controls. Although TNF-α was associated with NAFLD (P < 0.02), it was interdependent on visfatin. In comparison to SS, four factors were independently associated with NASH: age, alanine aminotransferase, IL-8 and adiponectin (P < 0.05). Multivariate analysis indicated that TNF-α was the only independent predictor of fibrosis in NASH (P < 0.0004). Conclusion These findings support a complex interaction between adipocytokines and the pathogenesis of NAFLD.

GI Epidemiology: nonalcoholic fatty liver disease

Abstract: Summary Background Nonalcoholic fatty liver disease (NAFLD) is a common diagnosis in clinical practice Insulin resistance and oxidative stress play an important role in NAFLD development and progression Aim To review the data available on the epidemiology and natural history of NAFLD as well as the risk factors for its development and the areas where future research is necessary Results/Conclusions NAFLD may affect individuals of any age range and race/ethnicity NAFLD affects one in three adults and one in ten children/adolescents in the United States Mortality in patients with NAFLD is significantly higher than in the general population of same age and gender with liver-related complications being a common cause of death Liver-related morbidity and mortality in NAFLD occurs when the disease has progressed to advanced fibrosis and cirrhosis Further studies are necessary to determine the impact of NAFLD on health-related quality of life and resources utilization, and to the extent to which preventing the development of the metabolic syndrome would prevent NAFLD development and reduce liver-related morbidity and mortality Lifestyle intervention may improve NAFLD, but medications that increase insulin sensitivity and the antioxidant defenses in the liver deserve evaluation in carefully controlled trials

Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change

Abstract: Summary Background Capsule endoscopy can identify small bowel mucosal inflammatory change. However, there has been no validated index for capsule endoscopy findings. This manuscript documents the development of such an index. Aim To develop a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Methods The index was created in four separate steps. First, parameters and descriptors of inflammatory change were identified. Secondly, blinded readers prospectively graded the presence or absence of each parameter on de-identified videos and graded a perceived global assessment of overall severity. Thirdly, the individual parameters and descriptors were ranked in order of severity. Fourthly, values for each parameter were created using the descent gradient methodology. The premise was to assure that the final numerical score reflected the global assessment and that the global assessment agreed with the ranking of finding severity. Results were compiled for the three categories: no or clinically insignificant change, mild change, and moderate or severe change. Thresholds were determined. Results The final index includes three parameters: villous oedema, ulcer and stenosis. A score <135 is designated normal or clinically insignificant mucosal inflammatory change, a score between 135 and 790 is mild, and a score ≥790 is moderate to severe. Conclusion This capsule endoscopy score provides a common language to quantify small bowel inflammatory changes.

Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial.

Abstract: SUMMARY Background Health-related quality of life (HRQoL) has been rarely evaluated as a primary endpoint in the assessment of the effect of probiotics on the irritable bowel syndrome (IBS). Aim To study the effects of fermented milk containing Bifidobacterium animalis DN-173 010 and yoghurt strains on the IBS in a multicentre, double-blind, controlled trial. Methods A total of 274 primary care adults with constipation-predominant IBS (Rome II) were randomized to consume for 6 weeks either the test fermented milk or a heat-treated yoghurt (control). HRQoL and digestive symptoms were assessed after 3 and 6 weeks on an intention-to-treat population of 267 subjects. Results The HRQoL discomfort score, the primary endpoint, improved (P < 0.001) in both groups at weeks 3 and 6. The responder rate for the HRQoL discomfort score was higher (65.2 vs. 47.7%, P < 0.005), as was the decrease in bloating score [0.56 (s.d.)1.01 vs. 0.31 0.87, P = 0.03], at week 3 in the test vs. the control group. In those subjects with <3 stools ⁄ week, stool frequency increased (P < 0.001) over 6 weeks in the test vs. control group.

Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori.

Abstract: Summary Background Information regarding the effects of drug resistance on therapies for Helicobacter pylori is limited. Aims To determine the effect of drug resistance on the efficacy of first-line treatment regimens for H. pylori and identify the most efficacious treatments in the presence of drug resistance. Methods We searched for studies using the keywords: ‘Helicobacter pylori’,‘resistance’ and ‘treatment’ or ‘therapy’. Multilevel meta-regression models were used to determine the effect of drug resistance on treatment efficacy. Results We analysed data from 93 studies with 10 178 participants. For triple therapies, clarithromycin resistance had a greater effect on treatment efficacy than nitroimidazole resistance. Metronidazole resistance reduced efficacy by 26% in triple therapies containing a nitroimidazole, tetracycline and bismuth, while efficacy was reduced by only 14% when a gastric acid inhibitor was added to the regimen. Quadruple therapies containing both clarithromycin and metronidazole were the most efficacious; >80% of H. pylori infections were consistently eradicated with these regimens. Conclusions Drug resistance was a strong predictor of efficacy across triple therapies for the eradication of H. pylori in adults. Resistance to either clarithromycin or metronidazole, but not both simultaneously, may be overcome by using quadruple therapies, especially those containing both clarithromycin and metronidazole.

Review article: the burden of hepatic encephalopathy

Abstract: Hepatic encephalopathy, a challenging complication of advanced liver disease, occurs in approximately 30-45% of patients with cirrhosis and 10-50% of patients with transjugular intrahepatic portosystemic shunt, while minimal hepatic encephalopathy affects approximately 20-60% of patients with liver disease. Although the total direct and indirect costs of hepatic encephalopathy have not been formally quantified, data from the Healthcare Cost and Utilization Project suggest that hepatic encephalopathy-related hospitalizations are associated with substantial costs. In 2003, there were over 40 000 patients hospitalized in the United States for a primary diagnosis of hepatic encephalopathy, resulting in total charges of approximately $932 million. Furthermore, trends over the past 10 years suggest that the burden of hepatic encephalopathy is increasing, as indicated by increases in hospital admissions and higher charges per stay. Because of inconsistencies in coding for hepatic encephalopathy, the prevalence and cost data from this data source are believed to significantly underestimate the true burden of hepatic encephalopathy. In addition, expenditures for physician fees and out-patient care, as well as indirect costs attributable to lost work days and decreased productivity, have not been quantified. Thus, there is need for future studies to more accurately define the burden of hepatic encephalopathy, including minimal hepatic encephalopathy.

Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota

Abstract: Summary Background Irritable bowel syndrome is the most common diagnosis in gastroenterology. Trials suggest certain probiotics to be beneficial. Aim To investigate the effects of multispecies probiotic supplementation (Lactobacillus rhamnosus GG, L. rhamnosus Lc705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium animalis ssp. lactis Bb12) on abdominal symptoms, quality of life, intestinal microbiota and inflammatory markers in irritable bowel syndrome. Methods Eighty-six irritable bowel syndrome patients (Rome II criteria) participated in this randomized, placebo-controlled 5-month intervention. Patients were randomized to receive daily either multispecies probiotic supplementation or placebo. Irritable bowel syndrome symptoms, quality of life, microarray-based intestinal microbiota stability (n = 20), serum cytokines and sensitive C-reactive protein were monitored. Results The composite irritable bowel syndrome score had at 5 months decreased 14 points (95% CI: −19 to −9) from baseline with the multispecies probiotic vs. three points (95% CI: −8 to 1) with placebo (P = 0.0083). Especially, distension and abdominal pain were affected. A stabilization of the microbiota was observed, as the microbiota similarity index increased with the probiotic supplementation (1.9 ± 3.1), while it decreased with placebo (−2.9 ± 1.7). No differences were seen in C-reactive protein. Conclusions This multispecies probiotic seems to be an effective and safe option to alleviate symptoms of irritable bowel syndrome, and to stabilize the intestinal microbiota.

The burden of constipation on quality of life: results of a multinational survey

Abstract: SUMMARY Background The impact of constipation on quality of life (QoL) may vary in different cultural or national settings. Aim We studied QoL in a multinational survey to compare different social and demographic groups with and without constipation (defined according to Rome III criteria) and to detect country-specific differences among the groups studied. Methods Health-related QoL (HRQoL) was assessed with the Short Form 36 (SF-36) questionnaire in 2870 subjects in France, Germany, Italy, UK, South Korea, Brazil and USA. Results Respondents were mainly middle-aged, married or living together and part- or full-time employed. General health status, measured by the SF-36 questionnaire, was significantly worse in the constipated vs. nonconstipated populations. Results were comparable in all countries. QoL scores correlated negatively with age. Constipated women reported more impaired HRQoL than constipated men. Brazilians were most affected by constipation as to their social functioning (35.8 constipated vs. 51.3 non-constipated) and general health perception (29.4 constipated vs. 54.4 non-constipated). Conclusions There are significant differences in HRQoL between constipated and non-constipated individuals and a significant, negative correlation between the number of symptoms and complaints and SF-36 scores. The study detected a correlation of constipation with QoL and the influence of social and demographic factors on HRQoL in constipated people.

Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis.

Abstract: Summary Background Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking. Aim To perform a controlled study of botox injection in gastroparesis. Methods Twenty-three gastroparesis patients (five men, age 45 ± 3, 19 idiopathic) underwent two upper endoscopies with 4-week interval, with injection of saline or botox 4 × 25 U in a randomized double-blind-controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal-related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student’s t-test. Results Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t1/2 (3.4 ± 7.4 vs. 16.3 ± 8.3, N.S.) and liquid t1/2 (8.2 ± 13.7 vs. 22.5 ± 7.7, N.S.), meal-related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 ± 1.5 vs. 3.8 ± 1.5, N.S.). Conclusion In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying.

Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects.

Abstract: Summary Background Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET). Aims To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics. Methods Eighty-seven healthy subjects and 61 gastroparetics enrolled with simultaneous SmartPill and GES. Fasted subjects were ingested capsule and [99mTc]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. Results Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. Conclusion SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy.

The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study.

Abstract: Summary Background Lifelong adherence to a strict gluten-free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT-1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae. Aim To determine the safety and tolerability of 12 mg doses of AT-1001 in coeliac disease subjects challenged with gluten. Methods An in-patient, double-blind, randomized placebo-controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy. Results Compared to placebo, no increase in adverse events occurred in patients exposed to AT-1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group. Interferon-γ levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT-1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT-1001 group (P = 0.018). Conclusions AT-1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.

Systematic review: Endoscopic dilatation in Crohn's disease.

Abstract: Summary Background Endoscopic dilatation for Crohn’s disease has been evaluated only in some small and heterogeneous studies. Aim To evaluate any association between the main clinical variables and endoscopic variables and the efficacy and safety of endoscopic dilatation in Crohn’s disease. Methods A Medline search regarding pneumatic dilatation in Crohn’s disease was performed. Several technical and clinical variables were extracted from each study to build up a descriptive, pool-data analysis. Data on individual patients were extracted from suitable studies to create a simulated population upon which a multivariate statistical analysis was performed. Results Thirteen studies enrolling 347 Crohn’s disease patients were reviewed. Endoscopic dilatation was mainly applied to postsurgical strictures, being technically successful in 86% of the cases. Long-term clinical efficacy was achieved in 58% of the patients. Mean follow-up was as long as 33 months, corresponding to 800 patient years of follow-up. Major complication rate was 2%, being higher than 10% in two series. At multivariate analysis, a stricture length ≤4 cm was associated with a surgery-free outcome (OR: 4.01; 95% CI: 1.16–13.8; P < 0.028). Conclusions Endoscopic dilatation is an effective and safe treatment for short strictures caused by Crohn’s disease, impacting substantially on the natural history of these patients.

The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases

Abstract: Summary Background The validity of International Classification of Diseases-9 codes for liver disease has not been determined. Aim To examine the accuracy of International Classification of Diseases-9 codes for cirrhosis with hepatitis C virus or alcoholic liver disease and HIV or hepatitis B virus coinfection with hepatitis C virus in Veterans Affairs data. Methods We conducted a retrospective study comparing the Veterans Affairs administrative data with abstracted data from the Michael E. DeBakey VA Medical Center’s medical records. We calculated the positive predictive value, negative predictive value, per cent agreement and kappa. Results For cirrhosis codes, the positive predictive value (probability that cirrhosis is present among those with a code) and negative predictive value (probability that cirrhosis is absent among those without a code) were 90% and 87% with 88% agreement and kappa = 0.70. For hepatitis C virus codes, the positive predictive value and negative predictive value were 93% and 92%, yielding 92% agreement and kappa = 0.78. For alcoholic liver disease codes, the positive predictive value and negative predictive value were 71% and 98%, with 89% agreement and kappa = 0.74. All parameters for HIV coinfection with hepatitis C virus were >89%; however, the codes for hepatitis B virus coinfection had a positive predictive value of 43–67%. Conclusion These diagnostic codes (except hepatitis B virus) in Veterans Affairs administrative data are highly predictive of the presence of these conditions in medical records and can be reliably used for research.

Meta-analysis: enteral nutrition in active Crohn's disease in children.

Abstract: SUMMARY Background Controversy exists surrounding the optimal treatment for inducing remission in active Crohn’s disease. Aim To review and update evidence on the effectiveness of enteral nutrition (EN) in treating active Crohn’s disease in children. Methods

Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children.

Abstract: SUMMARY Aim To review evidence for the effectiveness of Lactobacillus GG (LGG) in treating acute infectious diarrhoea in children. Methods

Review article: drug hepatotoxicity.

Abstract: SUMMARY Background Drug toxicity is the leading cause of acute liver failure in the United States. Further understanding of hepatotoxicity is becoming increasingly important as more drugs come to market. Aims (i) To provide an update on recent advances in our understanding of hepatotoxicity of select commonly used drug classes. (ii) To assess the safety of these medications in patients with pre-existing liver disease and in the post-liver transplant setting. (iii) To review relevant advances in toxicogenomics which contribute to the current understanding of hepatotoxic drugs. Methods A Medline search was performed to identify relevant literature using search terms including ‘drug toxicity, hepatotoxicity, statins, thiazolidinediones, antibiotics, antiretroviral drugs and toxicogenomics’. Results Amoxicillin-clavulanic acid is one of the most frequently implicated causes of drug-induced liver injury worldwide. Statins rarely cause clinically significant liver injury, even in patients with underlying liver disease. Newer thiazolidinediones are not associated with the degree of liver toxicity observed with troglitazone. Careful monitoring for liver toxicity is warranted in patients who are taking antiretrovirals, especially patients who are co-infected with hepatitis B and C. Genetic polymorphisms among enzymes involved in drug metabolism and HLA types may account for some of the differences in individual susceptibility to drug hepatotoxicity. Conclusions Drug-induced hepatotoxicity will remain a problem that carries both clinical and regulatory significance as long as new drugs continue to enter the market. Future results from ongoing multicentre collaborative efforts may help contribute to our current understanding of hepatotoxicity associated with drugs.

Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis.

Abstract: Summary Background The cancer risk of low-grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious. Aim To determine the risk of cancer or any advanced lesion once LGD is diagnosed. Methods A MEDLINE, EMBASE and Pub Med search was conducted using the key words ‘surveillance’, ‘colorectal cancer’, ‘low-grade dysplasia’ and ‘ulcerative colitis’. A random effects model of meta-analysis was used. Results Twenty surveillance studies had 508 flat LGD or LGD with dysplasia-associated lesion or mass. An average of 4.3 colonoscopies was performed/patient post-LGD diagnosis (range: 3–7.6). An average of 18 biopsies taken per colonoscopy (range: 9–24) detected 73 advanced lesions (cancer or high-grade dysplasia) pre-operatively. The cancer incidence was 14 of 1000 (95% CI: 5.0–34) person years duration (pyd) and the incidence of any advanced lesion was 30 of 1000 pyd (95% CI: 12–76). When LGD is detected on surveillance there is a ninefold risk of developing cancer (OR: 9.0, 95% CI: 4.0–20.5) and 12-fold risk of developing any advanced lesion (OR: 11.9, 95% CI: 5.2–27). Conclusions The risk of developing cancer in patients with LGD is high. These estimates are valuable for decision-making when LGD is encountered on surveillance.

pH-profile and regional transit times of the normal gut measured by a radiotelemetry device.

Abstract: The pH of the gut lumen was measured in 39 healthy persons using a pH-sensitive, radiotransmitting capsule Thirteen persons were studied twice The location of the capsule was determined by X-ray The pH rose from 64 in the duodenum to 73 in the distal part of the small intestine In 17 persons the pH dropped by 01-08 pH units during the last hours of the small intestinal transit The pH was 57 in the caecum, but rose to 66 in the rectum Gastric residence time was 11 h, small intestinal transit was 8 h, and colonic transit time was 175 h (median values) The results provide a firmer basis for prediction of the level, and the rate of release of active substance from pH-dependent sustained-release oral preparations

The role of hepatitis E virus testing in drug-induced liver injury.

Abstract: Summary Background Locally acquired hepatitis E is an emerging infection in developed countries and can be misdiagnosed as drug-induced liver injury. Aim To study the role of hepatitis E virus (HEV) testing in drug-induced liver injury. Methods Retrospective review of a cohort of patients with suspected drug-induced liver injury (n = 69) and hepatitis E (n = 45). The standard criteria for drug-induced liver injury were applied. Patients with suspected drug-induced liver injury who met these criteria were retrospectively tested for HEV on stored sera taken at the time of presentation. The two cohorts were compared to determine variables that predicted either of the diagnoses. Results Forty-seven out of 69 patients had criterion-referenced drug-induced liver injury. 22/47 were HEV negative and thus had confirmed drug-induced liver injury. 19/47 were not tested for HEV, as there was no sera available from the time of presentation. 6/47 were HEV positive and thus did not have drug-induced liver injury, but had hepatitis E infection. Compared to patients with confirmed drug-induced liver injury, patients with hepatitis E were significantly more likely to be male (OR 3.09, CI 1.05–9.08); less likely to present in November and December (0.03, CI 0.01–0.52); have lower serum bilirubin (P = 0.015); and higher serum alanine aminotransferase (P < 0.001) and alanine aminotransferase/alkaline phosphatase ratio (P < 0.001). Conclusion The diagnosis of drug-induced liver injury is not secure without testing for HEV.

Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin

Abstract: SUMMARY Background Inulin and oligofructose promote selective growth of saccharolytic bacteria with low inflammatory potential. Objective To test the effect of oligofructose-enriched inulin in patients with active ulcerative colitis. Design Prospective, randomized, placebo controlled pilot trial. Eligible patients had been previously in remission with mesalazine as maintenance therapy or no drug, and presented with a relapse of mild to moderate activity. They were treated with mesalazine (3 g ⁄ day) and randomly allocated to receive either oligofructose-enriched inulin (12 g ⁄ day, p.o., n = 10) or placebo (12 g ⁄ day of maltodextrin, p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as determined by reduction of calprotectin and human DNA in faeces. Results Rachmilewitz score decreased in both groups, reaching statistical significance at day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic symptoms scale decreased significantly with active treatment but not with placebo. At day 7, an early significant reduction of calprotectin was observed in the group receiving oligofructose-enriched inulin (day 0: 4377 659 lg ⁄g; day 7: 1033 393 lg ⁄g, P < 0.05) but not in the placebo group (day 0: 5834 1563 lg ⁄g; day 7: 4084 1395 lg ⁄g, n.s.). Changes in faecal concentration of human DNA were not significant. Conclusion In active ulcerative colitis, dietary supplementation with oligofructose-enriched inulin is well tolerated and is associated with early reduction in faecal calprotectin.

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety.

Abstract: Summary Background Lubiprostone, a locally acting type-2 chloride channel activator, induces intestinal fluid secretion. Aim To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation. Methods A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked. Results Over the double-blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea. Conclusions Lubiprostone improved SBM rates in a dose-dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk-to-benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

The actions of peppermint oil and menthol on calcium channel dependent processes in intestinal, neuronal and cardiac preparations

Abstract: The activities of menthol and peppermint oil were determined in guinea-pig ileal smooth muscle, in rat and guinea-pig atrial and papillary muscle, in rat brain synaptosomes and in chick retinal neurones by pharmacological 45Ca2+ uptake and radioligand binding assays. Menthol is a major constituent of peppermint oil and is approximately twice as potent as peppermint oil as an inhibitor of K+ depolarization-induced and electrically stimulated responses in ileum and electrically stimulated atrial and papillary muscles. IC50 values in the ileal preparation ranged from 7.7 to 28.1 micrograms ml-1 and in the cardiac preparations from 10.1 to 68.5 micrograms ml-1. Similar potencies were demonstrated against K+ depolarization-induced 45Ca2+ uptake in synaptosomes and against K+ depolarization and Bay K 8644-induced uptake in chick retinal neurons. IC50 values for menthol inhibition of K+ and Bay K 8644 responses in the retinal neurons were 1.1 x 10(-4) M (17.2 micrograms ml-1) and 1.75 x 10(-4) M (26.6 micrograms ml-1), respectively, and for peppermint oil were 20.3 and 41.7 micrograms ml-1 respectively. Both menthol and peppermint oil inhibited specific [3H]nitrendipine and [3H]PN 200-110 binding to smooth and cardiac muscle and neuronal preparations with potencies comparable to, but slightly lower than, those measured in the pharmacological and 45Ca2+ uptake experiments. Binding of menthol and peppermint oil, studied at 78 micrograms ml-1, was competitive against [3H]nitrendipine in both smooth muscle and synaptosome preparations. The data indicate that both menthol and peppermint oil exert Ca2+ channel blocking properties which may underlie their use in irritable bowel syndrome. Ca2+ channel antagonism may not be the only pharmacological effect of menthol and peppermint oil contributing to intestinal smooth muscle relaxation.

Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain.

Abstract: Summary Aim To provide estimates of actual costs to deliver health care to patients with functional bowel disorders, and to assess the cost impact of symptom severity, recency of onset, and satisfaction with treatment. Methods We enrolled 558 irritable bowel (IBS), 203 constipation, 243 diarrhoea and 348 abdominal pain patients from primary care and gastroenterology clinics at a health maintenance organization within weeks of a visit. Costs were extracted from administrative claims. Symptom severity, satisfaction with treatment and out-of-pocket expenses were assessed by questionnaires. Results Average age was 52 years, 27% were males, and 59% participated. Eighty percent were seen in primary care clinics. Mean annual direct health care costs were $5049 for IBS, $6140 for diarrhoea, $7522 for constipation and $7646 for abdominal pain. Annual out-of-pocket expenses averaged $406 for treatment of IBS symptoms, $294 for diarrhoea, $390 for constipation and $304 for abdominal pain. Lower gastrointestinal costs comprised 9% of total costs for IBS, 9% for diarrhoea, 6.5% for constipation and 9% for abdominal pain. In-patient care accounted for 17.5% of total costs (15.2% IBS). Conclusion Costs were affected by disease severity (increased), recent exacerbation of bowel symptoms (increased), and whether the patient was consulting for the first time (decreased).

Short-chain fatty acid topical treatment in distal ulcerative colitis

Abstract: SUMMARY Background: Some evidence indicates that short-chain fatty acid (SCFA) enemas are effective in the treatment of distal ulcerative colitis. Methods: In a randomized, double-blind, placebo-controlled study, we tested the efficacy of a 6-week course of topical SCFA (100 mL, twice daily enemas of sodium acetate 80 mmol/L, sodium propionate 30 mmol/L and sodium butyrate 40 mmol/L) in 40 patients with mild to moderate distal colitis. Clinical, endoscopic and histological data were collected at the beginning and end of the study. Results: Fourteen patients on SCFA improved (overall score 11.3 ± 2.0 vs. 7.4 ± 3.5) as compared to five in the placebo group (overall score 10.0 ± 1.9 vs. 8.9 ± 2.5). In the SCFA-treated group all parameters significantly improved except the number of bowel motions, whereas no significant changes were recorded in the control group. A statistically significant difference between the two treatment regimens, however, was observed only for intestinal bleeding (P < 0.05), urgency (P < 0.02) and the patient self-evaluation score (P < 0.05). This was probably due to the random inclusion of more patients with moderate disease into the SCFA-treated group, thus causing pre-trial differences between the two groups. Conclusion: the present study confirms that irrigation with SCFA enemas is effective in distal colitis, and may represent an alternative therapeutic tool in the treatment of the disease.