Abstract: Background and Aim The efficacy of treatment with multispecies probiotics on irritable bowel syndrome (IBS) symptoms and the alterations of gut microbiota in patients who have taken probiotics were investigated. Methods This randomized, double-blind, placebo-controlled trial involved 49 IBS patients (probiotics: 25, placebo: 24) diagnosed according to the Rome III criteria. Patients were randomly assigned to two groups: either to receive multispecies probiotics (a mixture of Bifidobacterium longum, B. bifidum, B. lactis, Lactobacillus acidophilus, L. rhamnosus, and Streptococcus thermophilus) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks. The primary efficacy end-point was the proportion of participants whose IBS symptoms were substantially relieved at week 4. Secondary end-points were the intensity of abdominal pain/discomfort, bloating, stool frequency/consistency, alterations in fecal microflora over the 4 weeks. Fecal microflora were analyzed in 34 patients (probiotics: 17, placebo: 17) by quantitative real-time polymerase chain reaction assays. Results The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group: 68.0% (17/25) versus 37.5% (9/24) (P < 0.05). Secondary end-points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group. Fecal analysis revealed that B. lactis, L. rhamnosus, and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group. Conclusions Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota.

Abstract: Background The characteristics of patients who suffer from noncancer pain and opioid-induced constipation are not well understood. Methods Cross-sectional patient survey and chart review data from the baseline assessment of an ongoing longitudinal study in the USA, Canada, Germany, and the UK were evaluated via descriptive statistics. Participants had confirmation of daily opioid therapy ≥30 mg for ≥4 weeks and self-reported opioid-induced constipation. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response to one laxative agent and two or more agents from at least two different laxative classes. Outcomes included the Patient Assessment of Constipation-Symptoms, Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, EuroQOL 5 Dimensions, and Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue. Results Patients reported a mean of 1.4 bowel movements not preceded by laxatives and 3.7 bowel movements with laxative use per week; 83% wanted at least one bowel movement per day. Most commonly reported on Patient Assessment of Constipation-Symptoms were straining/squeezing to pass bowel movements (83%), bowel movements too hard (75%), flatulence (69%), and bloating (69%). Eighty-four percent were taking natural or behavioral therapies; 60% were taking at least one over-the-counter laxative; and 19% were taking at least one prescription laxative. Prevalence of inadequate response to one laxative agent was 94%; inadequate response to two or more agents from at least two different laxative classes was 27%. Mean Work Productivity and Activity Impairment Questionnaire-Specific Health Problem values for percent work time missed, percent impairment while working, and percent activity impairment were 9%, 32% (equivalent of 14 hours of lost productivity per week), and 38%. Mean EuroQOL 5 Dimensions index and visual analog scale scores were 0.49 and 50.6, respectively. Forty-four percent reported being satisfied with their treatment for constipation. Conclusion Patients treated with opioids for noncancer pain commonly endure constipation symptoms that limit their work productivity and overall health-related quality of life while adhering to treatments that provide little relief. Further research is needed to identify more efficacious constipation therapies for this patient population.

Abstract: Systemic sclerosis is an autoimmune chronic disease characterised by microvascular, muscular and immunologic abnormalities that lead to progressive and systemic deposition of connective tissue in the skin and internal organs. The gastrointestinal tract is often overlooked by physicians but it is the most affected organ after the skin, from the mouth to the anus. Indeed, 80% of SSc patients may present with gastrointestinal involvement. Gastrointestinal manifestations range from bloating and heartburn to dysphagia and anorectal dysfunction to severe weight loss and malabsorption. However, the gastrointestinal involvement is rarely the direct cause of death, but has great impact on quality of life and leads to several comorbidities that subsequently affect patients' survival. Treatments, including nutritional support and prokinetics provide limited benefits and do not arrest the progressive course of the disease, but earlier detection of gastrointestinal involvement may reduce the risk of complications such as malnutrition.

Abstract: Hydrogen breath tests are widely used to explore pathophysiology of functional gastrointestinal (GI) disorders. Small intestinal bacterial overgrowth (SIBO) and carbohydrate malabsorption are disorders detected by these tests that have been proposed to be of great importance for symptoms of GI diseases. Glucose hydrogen breath test is more acceptable for diagnosis of SIBO whereas lactose and fructose hydrogen breath tests are used for detection of lactose and fructose maldigestion respectively. Lactulose hydrogen breath test is also used widely to measure the orocecal transit time for GI motility. These methods are noninvasive and inexpensive. Many patients with functional gut disorders are unaware of the relationship between diet and GI symptoms they present. In particular, patients with chronic symptoms may regard their condition as normal and may not be aware that their symptoms can be effectively managed following a proper diagnosis. Patients with symptoms of abdominal pain, bloating, flatulence and altered bowel movements (diarrhea and constipation), or with a medical diagnosis of irritable bowel syndrome or celiac disease, may have undiagnosed carbohydrate malabsorption or SIBO. Hydrogen breath tests are specific and sensitive diagnostic tests that can be used to either confirm or eliminate the possibility of carbohydrate malabsorption or SIBO in such patients. Breath tests, though valuable tools, are underutilized in evaluating dyspepsia and functional bloating and diarrhea as well as suspected malabsorption. However, because of their simplicity, reproducibility and safety of procedure they are now being substituted to more uncomfortable and expensive techniques that were traditionally used in gastroenterology.

Abstract: Objective Patients with irritable bowel syndrome and abdominal bloating exhibit abnormal responses of the abdominal wall to colonic gas loads We hypothesised that in patients with postprandial bloating, ingestion of a meal triggers comparable abdominal wall dyssynergia Our aim was to characterise abdominal accommodation to a meal in patients with postprandial bloating Design A test meal (08 kcal/ml nutrients plus 27 g/litre polyethylenglycol 4000) was administered at 50 ml/min as long as tolerated in 10 patients with postprandial bloating (fulfilling Rome III criteria for postprandial distress syndrome) and 12 healthy subjects, while electromyographic (EMG) responses of the anterior wall (upper and lower rectus, external and internal oblique via bipolar surface electrodes) and the diaphragm (via six ring electrodes over an oesophageal tube in the hiatus) were measured Means +/− SD were calculated Results Healthy subjects tolerated a meal volume of 913±308 ml; normal abdominal wall accommodation to the meal consisted of diaphragmatic relaxation (EMG activity decreased by 15±6%) and a compensatory contraction (25±9% increase) of the upper abdominal wall muscles (upper rectus and external oblique), with no changes in the lower anterior muscles (lower rectus and internal oblique) Patients tolerated lower volume loads (604±310 ml; p=0030 vs healthy subjects) and developed a paradoxical response, that is, diaphragmatic contraction (14±3% EMG increment; p Conclusions In functional dyspepsia, postprandial abdominal distension is produced by an abnormal viscerosomatic response to meal ingestion that alters normal abdominal accommodation

Abstract: Background: Constipation is an intestinal dysfunction. Prebiotics, such as inulin, can improve bowel function by positively influencing intestinal biota. Aim: To analyze the scientific evidence for the role of inulin in improving bowel function in patients with chronic constipation. Methods: A meta-analysis of randomized controlled clinical trials was conducted, grounded on a literature search for the period 1995-2013 (descriptors: inulin & constipation) on PubMed, ScieLo and Central Trials Register Cochrane databases. A total of 24 articles were found, 5 of them were selected for this meta-analysis, involving 252 subjects (experimental group: n = 144, control group: n = 108). The quality of the studies was assessed using the Jadad scale. Results: We found a significant overall effect of inulin on stool frequency (DEM = 0.69, 95%CI: 0.04, 1.34), stool consistency (Bristol scale) (DEM = 1.07, 95% CI: 0.70, 1.45), transit time (DEM = -0.57, 95% CI: -0.99, -0.15) and hardness of stool (RR = 0.42, 95% CI: 0.26, 0.70). Pain and bloating do not improve with inulin intake. Conclusions: inulin intake has a positive effect on bowel function.

Abstract: Breath tests are non-invasive tests and can detect H₂ and CH₄ gases which are produced by bacterial fermentation of unabsorbed intestinal carbohydrate and are excreted in the breath. These tests are used in the diagnosis of carbohydrate malabsorption, small intestinal bacterial overgrowth, and for measuring the orocecal transit time. Malabsorption of carbohydrates is a key trigger of irritable bowel syndrome (IBS)-type symptoms such as diarrhea and/or constipation, bloating, excess flatulence, headaches and lack of energy. Abdominal bloating is a common nonspecific symptom which can negatively impact quality of life. It may reflect dietary imbalance, such as excess fiber intake, or may be a manifestation of IBS. However, bloating may also represent small intestinal bacterial overgrowth. Patients with persistent symptoms of abdominal bloating and distension despite dietary interventions should be referred for H₂ breath testing to determine the presence or absence of bacterial overgrowth. If bacterial overgrowth is identified, patients are typically treated with antibiotics. Evaluation of IBS generally includes testing of other disorders that cause similar symptoms. Carbohydrate malabsorption (lactose, fructose, sorbitol) can cause abdominal fullness, bloating, nausea, abdominal pain, flatulence, and diarrhea, which are similar to the symptoms of IBS. However, it is unclear if these digestive disorders contribute to or cause the symptoms of IBS. Research studies show that a proper diagnosis and effective dietary intervention significantly reduces the severity and frequency of gastrointestinal symptoms in IBS. Thus, diagnosis of malabsorption of these carbohydrates in IBS using a breath test is very important to guide the clinician in the proper treatment of IBS patients.

Abstract: Functional abdominal pain in the context of irritable bowel syndrome (IBS) is a challenging problem for primary care physicians, gastroenterologists and pain specialists. We review the evidence for the current and future non-pharmacological and pharmacological treatment options targeting the central nervous system and the gastrointestinal tract. Cognitive interventions such as cognitive behavioral therapy and hypnotherapy have demonstrated excellent results in IBS patients, but the limited availability and labor-intensive nature limit their routine use in daily practice. In patients who are refractory to first-line therapy, tricyclic antidepressants (TCA) and selective serotonin reuptake inhibitors are both effective to obtain symptomatic relief, but only TCAs have been shown to improve abdominal pain in meta-analyses. A diet low in fermentable carbohydrates and polyols (FODMAP) seems effective in subgroups of patients to reduce abdominal pain, bloating, and to improve the stool pattern. The evidence for fiber is limited and only isphagula may be somewhat beneficial. The efficacy of probiotics is difficult to interpret since several strains in different quantities have been used across studies. Antispasmodics, including peppermint oil, are still considered the first-line treatment for abdominal pain in IBS. Second-line therapies for diarrhea-predominant IBS include the non-absorbable antibiotic rifaximin and the 5HT3 antagonists alosetron and ramosetron, although the use of the former is restricted because of the rare risk of ischemic colitis. In laxative-resistant, constipation-predominant IBS, the chloride-secretion stimulating drugs lubiprostone and linaclotide, a guanylate cyclase C agonist that also has direct analgesic effects, reduce abdominal pain and improve the stool pattern.

Abstract: BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder in Iran with challenging treatment. Although trials have suggested that probiotics alleviate the complaints of patients with minimal side effects, they have not been investigated in Iranian adults. METHODS: In a randomized double-blind study, 108 eligible IBS patients (Rome III Criteria) aged 20 – 70 years who referred consecutively to a clinical center in Tehran with abdominal bloating from 2010 to 2012 received a combination probiotics or placebo twice daily for 4 weeks. The objective was to evaluate the efficacy and safety of a multi-strain probiotics combination. One week prior to and throughout the treatment, the participants recorded their abdominal symptoms on a daily basis, using visual analogue scale and reported satisfactory relief of general symptoms at the end of each week. Adverse events were evaluated by self-reporting and physical examination. Continuous variables were analyzed by independent t-test and chi-square was used for binomials. RESULTS: The baseline characteristics were balanced (60% female, mean age 36.7 ± 11.5). A total of 97 (51 intervention, 46 control) completed the treatment. Intention to treat analysis was done on 108 allocated subjects. 85% of the probiotic group reported satisfactory relief of general symptoms compared with 47% in the control group (P < 0.01). A reduction in abdominal bloating and pain with probiotic was superior to placebo [-13.0 vs. -3.7 (P < 0.01), -8.2 vs. -2.1 (P = 0.02), respectively]. No severe adverse drug reaction was seen in either group. CONCLUSIONS: A 4-week period of treatment with the combination probiotics twice daily was safe, well tolerated, and effective in our patients. Further investigation is recommended for other subgroups of IBS. Trial Registration: IRCT.ir IRCT2012071010230N1

Abstract: BACKGROUND: Small intestinal bacterial overgrowth (SIBO) may have a role in the pathophysiology of irritable bowel syndrome (IBS). So, the aim of this study was to assess the association between SIBO and IBS by using glucose breath test (GBT) in Kerman city as the first study in Iranian population. METHOD: 107 patients with IBS and 107 healthy individualswere enrolled in our study. All the participants underwent GBT. A peak of H2 values >20 p.p.m above the basal value after glucose ingestion was considered suggestive of SIBO. SPSS software version 17 was used for data analysis.P value < 0.05 was considered as statistically significant. RESULTS: Of the 107 patients with IBS, 40 had positive GBT (37.4%) compared with 14 (12.1%) out of the 107 control participants( p < 0.001). Dominant symptoms in patients with IBS were diarrhea in 36(33.6%), constipation in 12(11.2%), abdominal pain in 22(20.6%), bloating in 28(26.2%), and change in bowel habit in 9(8.4%) patients. There was not statistically significant difference among any of this IBS subgroups and positive GBT (P=0.44). CONCLUSION: There is a positive association between IBS and SIBO. We suggest a Placebo-controlled bacterial eradication study for identifying the role of SIBO in IBS.

Abstract: Objective:To evaluate total annual all-cause, gastrointestinal-related, and symptom-related healthcare costs among chronic constipation (CC) patients and estimate incremental all-cause healthcare costs of CC patients relative to matched controls.Methods:Patients aged ≥18 years with continuous medical and pharmacy benefit eligibility in 2010 were identified from the HealthCore Integrated Research Database. CC patients had ≥2 medical claims for constipation (ICD-9-CM code 564.0x) ≥90 days apart or ≥1 medical claim for constipation plus ≥1 constipation-related pharmacy claim ≥90 days apart, and no medical claims for irritable bowel syndrome (IBS). Sub-groups with and without abdominal symptoms were classified according to the presence/absence of abdominal pain (ICD-9-CM code 789.0x) and bloating (ICD-9-CM code 787.3x). Controls without claims for constipation, abdominal pain, bloating, or IBS or constipation-related prescriptions were randomly selected and matched 1:1 with CC patients on age, gender,...

Abstract: AIM: To ascertain whether caecal pH is different in patients with irritable bowel syndrome (IBS), whose primary symptoms are bloating and distension, to healthy controls.

Abstract: Irritable bowel syndrome (IBS) is common in the society. Among the putative pathogeneses, gut dysmotility results in pain and disturbed defecation. The latter is probably caused by the effect of abnormal gut water secretion. The interaction between abnormal gas accumulation, abdominal pain and bloating remains controversial. Visceral hypersensitivity and its modification along with the central transmission are the characteristics of IBS patients. The identification of biologic markers based on genetic polymorphisms is undetermined. Imbalanced gut microbiota may alter epithelial permeability to activate nociceptive sensory pathways which in turn lead to IBS. Certain food constituents may exacerbate bowel symptoms. The impact of adult and childhood abuses on IBS is underestimated. Using the concept of biopsychosocial dysfunction can integrate multidimensional pathogeneses. Antispasmodics plus stool consistency modifiers to treat the major symptoms and defecation are the first-line drug treatment. New drugs targeting receptors governing bowel motility, sensation and secretion can be considered, but clinicians must be aware of their potential serious side effects. Psychiatric drugs and modalities may be the final options for treating intractable subjects. Probiotics of multi-species preparations are safe and worth to be considered for the treatment. Antibiotics are promising but their long-term safety and effectiveness are unknown. Diet therapy including exclusion of certain food constituents is an economic measure. Using relatively safe complementary and alternative medicines (CAMs) may be optional to those patients who failed classical treatment. In conclusion, IBS is a heterogeneous disorder with multidimensional pathogeneses. Personalized medicines with multidisciplinary approaches using different classes of drugs, psychiatric measures, probiotics and antibiotics, dietary therapy, and finally CAMs, can be considered.

Abstract: The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

Abstract: Prospective study. The objective of this study was to assess the prevalence of small intestinal bacterial overgrowth (SIBO), methane (CH4) production and orocecal transit time (OCTT) in children affected by myelomeningocele. This study was conducted at the Catholic University in Rome, Italy. Eighteen (6M/12F; 16.4±7.6 years) children affected by myelomeningocele were enrolled. All subjects underwent H2/CH4 lactulose breath tests to assess SIBO and OCTT. All patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. A nephro-urological clinical evaluation of the number of urinary tract infections (UTIs) and neurogenic bowel disease score were also performed. Thirty-nine percent (7/18) of the children showed SIBO and 61% (11/18) presented a delayed OCTT. Moreover 44.4% (8/18) produced high levels of CH4. Interestingly, all myelomeningocele children who produced CH4 showed a delayed OCTT and a higher incidence of UTI, with a lower frequency of evacuation, compared with those with a normal or accelerated OCTT. The association between CH4 and constipation suggests that CH4 has an active role in the development of constipation. One of the most interesting features of our study is to identify a correlation between myelomeningocele, CH4, delayed OCTT and UTI. The intestinal decontamination with locally acting drugs in these children may reduce the number of UTIs and improve intestinal motility.

Abstract: Symptoms compatible with IBS, that is, abdominal pain and discomfort, bloating, abdominal distention and an erratic bowel function, are very common reasons for GI consultations in primary care1 and patients with IBS are one of the most frequent patient categories in gastroenterology outpatient clinics.2 Despite being very common and in spite of considerable research effort during the last decades, the pathophysiology of IBS is still considered to be complex and incompletely understood3 ,4 and even though our understanding of this disabling condition arguably has increased tremendously, we still cannot use knowledge from pathophysiology studies to subgroup IBS patients in a clinically meaningful way. In everyday clinical work, we still rely on subgrouping patients based on the predominant bowel habit when we decide how to manage and treat the patients.5 Even though we have new pharmacological treatment options targeting specific molecules in the GI tract,6–9 only a subset of patients will respond favourably when we choose patients based on the current imperfect system to subgroup patients, that is, into patients with predominant diarrhoea, constipation or mixed bowel habit.5 Ideally, clinical subgrouping based on the underlying pathophysiology should have the potential to lead to targeted …

Abstract: Aerophagia is a functional gastrointestinal disorder characterized by repetitive air swallowing, abdominal distension, belching and flatulence. Pathologic aerophagia is a condition caused by the swallowing of excessive volumes of air with associated various gastrointestinal symptoms, such as burping, abdominal cramps, flatulence and a reduced appetite. It is a clinical entity that can simulate pediatric gastrointestinal motility disorders, such as gastroparesis, megacolon and intestinal pseudo-obstruction, and presents more frequently in children with mental retardation. Early recognition and diagnosis of functional aerophagia or pathologic aerophagia is required to avoid unnecessary, expensive diagnostic investigations or serious clinical complications. Functional aerophagia is frequent in the adult population, but rarely discussed in the pediatric literature. We present two pediatric clinical cases with a history of functional constipation in whom gaseous abdominal distension was the most important symptom. Mechanical intestinal obstruction, chronic intestinal pseudo-obstruction, malabsorption and congenital aganglionic megacolon were ruled out. Extensive gaseous abdominal distension was due to aerophagia, and treatment consisted of parents' reassurance and psychological counseling.

Abstract: New Findings What is the central question of this study? Does stress sensitivity and susceptibility to inflammation innate to certain rat strains make them vulnerable to bowel dysfunction? What is the main finding and its importance? Of four different rat strains, the Lewis rat, which displays both susceptibility to gastrointestinal inflammation and sensitivity to stress, exhibits the most aberrant gastrointestinal morphology and visceral pain sensitivity. Given the similarities to human functional bowel disorders, such as irritable bowel syndrome, this may make it a good model of this disease. Irritable bowel syndrome is a common, debilitating gastrointestinal (GI) disorder characterized by episodic exacerbations of symptoms such as abdominal pain, bloating and altered bowel habit. Contributory factors for the development of irritable bowel syndrome include genetics, childhood trauma and prior GI infection leading to chronic low-grade inflammation or immune activation. Additional considerations in comprehending the chronic relapsing pattern that typifies irritable bowel syndrome symptoms are the effects of both psychosocial and infection-related stresses. Background stress and immune profiles can influence gut permeability and visceral pain sensitivity. This study examined whether innate susceptibility to inflammation and stress sensitivity in four rat strains is associated with bowel dysfunction. The pain threshold to colorectal distension was assessed in Lewis, Fischer (F344) and spontaneously hypertensive rats and compared with Sprague–Dawley control animals. Colons were subsequently excised and morphologically assessed for total length, goblet cell hyperplasia and muscle and mucosal thickness. Lewis rats displayed visceral hypersensitivity compared with other strains. At a morphological level, the gastrointestinal tract from these rats displayed mucosal goblet cell hyperplasia and alterations in muscle layer thickness. The Lewis rat strain, which is reported to have increased susceptibility to GI inflammation in addition to stress sensitivity, had the most prominent features of physiological and morphological GI dysfunction. These data support the hypothesis that background strain is a key factor in the development and exacerbation of bowel dysfunction in rodent models.

Abstract: Gastrointestinal (GI) discomfort, e.g. bloating or rumbling, is a common symptom in otherwise healthy adults. Approximately 20% of the population, particularly women suffer from gastrointestinal discomfort and this affects quality of life. Recent studies discovered a link between the body and mind, called the gut-brain axis. Psychosocial factors, such as e.g. daily stress may cause altered gut physiology leading to ileum contractions and consequently gastrointestinal symptoms. In vitro and ex vivo studies clearly showed that a Perilla frutescens extract combines prokinetic, antispasmodic and anti-inflammatory effects. The aim of the intervention was to investigate the effects of the proprietary Perilla extract on GI discomfort in healthy subjects with gastrointestinal discomfort and reduced bowel movements in comparison to a placebo product. The pilot study was performed according to a double-blind, randomized, placebo-controlled parallel design. Fifty healthy subjects with gastrointestinal discomfort and reduced bowel movements, 30-70 years, documented their GI symptoms, stool frequency and consistency daily during a 2-week run-in phase and a 4-week intervention phase with Perilla frutescens extract or placebo. GI symptoms were assessed on a 5-point scale daily and average scores over 14 days intervals were calculated. All GI symptoms were significantly improved over time by Perilla frutescens extract during the intervention phase (bloating: -0.44 ± 0.56, p = 0.0003; passage of gas: -0.30 ± 0.66, p = 0.0264; GI rumbling: -0.55 ± 0.87, p = 0.0014; feeling of fullness: -0.36 ± 0.72, p = 0.0152; abdominal discomfort: -0.54 ± 0.75, p = 0.004), whereas in the placebo group only abdominal discomfort was significantly improved (-0.31 ± 0.55, p = 0.0345). In the subgroup of women results were strengthened and a subscore out of bloating and abdominal discomfort was significantly improved against placebo (95%CI 0.003 to 0.77; p = 0.048). The demonstrated effects of Perilla frutescens extract to improve GI complaints offer very promising results, taking into consideration the challenging set up of a nutritional human study with healthy subjects and in the area of digestive health, which is known for high placebo effects. NCT01931930 at ClinicalTrials.gov, Registration date 23rd August 2013.

Abstract: Irritable bowel syndrome is a prevalent and chronic disorder, characterized by recurrent abdominal pain/discomfort, bloating and altered bowel habits. This condition affects an estimated 10-15% of the population worldwide and impacts heavily on a patient's daily life and ability to work, as well as healthcare resource utilization. Drug therapy aimed at correcting the primary symptoms of diarrhea/constipation/bloating may have little effect on abdominal pain, which results from visceral hypersensitivity. Smooth muscle relaxants or antispasmodics decrease the tone and contractility of intestinal smooth muscle, effectively managing abdominal pain. Otilonium bromide has been widely used worldwide and has been found to be safe and well tolerated, and superior to placebo for the reduction of symptoms and the prevention of symptom relapse in patients with irritable bowel syndrome.

Abstract: The review article published in the present issue of Intern Emerg Med, from Corazza’s group [1], is an in-depth description of the up-to-date clinical features of small bowel malabsorption, but at the same time offers a practical clinical approach to this difficult diagnosis. Small bowel malabsorption often overlaps complex clinical scenarios, and is one of the most challenging diagnoses in gastroenterology. A key factor is the differential diagnosis, and this is presented starting with the pathological mimics of coeliac disease (CD), where the interplay between genes and environment (i.e. gluten) is described, and finishing with irritable bowel syndrome (IBS). The relationships between IBS and non-motility-related gastrointestinal disorders continue to be the subject of much debate. Population-based studies have shown that many of the symptoms reported by IBS patients (particularly in the tertiary care setting) overlap with symptoms suggestive of coeliac disease or intestinal malabsorption, including lactose malabsorption [2]. One study shows that IBS-like symptoms are present in 20 % of the celiac disease population studied (n = 150) [3]. In a recent metaanalysis, no specific complaint could predict lactose malabsorption, with sensitivities ranging from 0 to 90 % and specificities ranging from 18 to 96 % for symptoms such as bloating, diarrhoea, flatulence, and abdominal pain in individual studies [4]. Upper gastrointestinal symptoms reported by patients with functional dyspepsia are described in CD. Prevalence of biopsy-proven CD in subjects with dyspepsia is around 1 % and is higher than in controls, but this difference is not statistically significant in a recent meta-analysis [5]. In this complex scenario, no serological clinical markers validated in clinical practice are available. However, in the review by Papadia et al., a new research tool that could change the fate of intestinal malabsorption diagnosis is described. Plasma citrulline concentration is a new single marker whose role in the field is widely debated. Papadia et al. [6] show that plasma citrulline is not affected by intestinal inflammation; moreover, the citrulline assay provides a reliable clinical index of global function, and so the nutritional prognosis, of a compromised intestine and is independent from the nutritional status. Other recent markers, such as IgA F-actin and intestinal fatty acid-binding protein (I-FABP), in the light of some recent interesting results, may also contribute to assessing the extent of villous atrophy. As awareness, detection, and treatment for small bowel atrophy and malabsorption all improve, the laboratory’s role in facilitating follow-up and monitoring is sure to increase in the near future.

Abstract: Background: While chronic constipation (CC) clinical trials have focused primarily on bowel symptoms (symptoms directly related to bowel movements), abdominal symptoms are also prevalent among patients. The United States Food and Drug Administration’s (FDA’s) guidance on the use of patient-reported outcome measures to support product approvals or labeling claims recommends that endpoints be developed with direct patient input and include all symptoms important to patients. Aim: To identify a comprehensive set of CC symptoms that are important to patients for measurement in clinical trials. Methods: Following a targeted literature review to identify CC symptoms previously reported by patients, 28 patient interviews were conducted consistent with the FDA’s guidance on patientreported outcomes. Subsequent to open-ended questions eliciting descriptions of all symptoms, rating and ranking methods were used to identify those of greatest importance to patients. Results: All 67 studies reviewed included bowel symptoms; more than half also addressed at least one abdominal symptom. Interview participants reported 62 potentially distinct concepts: 12 bowel symptoms; 21 abdominal symptoms; and 29 additional symptoms/impacts. Patients’ descriptions revealed that many symptom terms were highly related and/or could be considered secondary to CC. The rating and ranking task results suggest that both bowel (for example, stool frequency and consistency) and abdominal symptoms (for example, bloating, abdominal pain) comprise patients’ most important symptoms. Further, improvements in both bowel and abdominal symptoms would constitute an improvement in patients’ CC overall. Conclusion: Abdominal symptoms in CC patients are equal in relevance to bowel symptoms and should also be addressed in clinical trials to fully evaluate treatment benefit.

Abstract: Background : Upper gastrointestinal (GI) symptoms are common complaints affecting 25--40% of the general population and are common causes of health care utilisation and substantially affect the quality of life. In day-to-day practice our clinicians have to face good number of patients with various upper GI symptoms. But we have limited data on the prevalence of different upper GI symptoms in our community. Objective : The present study aimed to find out the prevalence of different upper GI symptoms in the general population of a district in Bangladesh. Materials and Methods : This population-based observational study was conducted in a selected district of Bangladesh. Three thousand subjects selected by cluster sampling method were interviewed by a valid bowel disease questionnaire. Student’s t test and chi-square tests were used for comparison of different variables with significance level set at 0.05. Results : Among the study population 1523 were men and 1477 were women with a mean age of 33.91 ± 16.43 years. A total of 2273 (75.8%) persons had at least one upper GI symptom, 2072 (69.1%) had 2 or more symptoms and 1705 (56.8%) had 3 or more symptoms in the prior 3 months. Nine hundred sixty three subjects (32.1%) had upper abdominal pain, 1265 (42.16%) had bloating, 1354 (45.13%) had heart-burn, 1166 (38.87%) had chest pain, 1347 (44.9%) had early satiation and 258 (8.6%) had vomiting. Around 249 (8.3%, male 123, female 126, P=0.691) was diagnosed as functional dyspepsia, 187 (6.2%, male 82, female 105, P=0.059) as gastroesophageal reflux disease (GERD) and 55 (1.83%, male 27, female 28, P=0.892) as upper abdominal bloating. Only one woman fulfilled the criteria for functional gallbladder or sphincter of Oddi dysfunction. Approximately 40.56% dyspeptic patients had overlapping GERD symptoms. Symptom prevalence was found to decrease with increased number, frequency and duration of symptoms. Conclusion : Upper GI symptoms are prevalent in our community. Multiple upper GI symptoms do exist simultaneously. Symptom prevalence varies with number, frequency and duration of symptoms. DOI: http://dx.doi.org/10.3329/jemc.v4i2.19458 J Enam Med Col 2014; 4(2): 79--88

Abstract: Primary epiploic appendagitis (PEA) is a rare cause of abdominal acute or subacute complaints. Diagnosis of PEA is made when computed tomography (CT) reveals a characteristic lesion. We report on contrast-enhanced CT images of a patient with PEA and regression of inflammation and the reduction in size of the inflamed appendage over the time period of 4 months. Patients with PEA usually recover without medication or surgical treatment within a few weeks. However, due to continuing bloating and irregular bowel movements we investigated carbohydrate malabsorption and diagnosed a fructose malabsorption. Bloating and irregular bowel movements in this patient with PEA were correlated to carbohydrate malabsorption and were treated successfully with a diet free of culprit carbohydrates.

Abstract: Background: Measures assessing treatment outcomes in previous CC clinical trials have not met the requirements described in the US Food and Drug Administration’s guidance on patient‐ reported outcomes. Aim: Psychometric analyses using data from one Phase IIb study and two Phase III trials of linaclotide for the treatment of chronic constipation (CC) were conducted to document the measurement properties of patient‐reported CC Symptom Severity Measures. Study methods: Each study had a multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group design, comparing placebo to four doses of oral linaclotide taken once daily for 4 weeks in the Phase IIb dose‐ranging study (n=307) and to two doses of linaclotide taken once daily for 12 weeks in the Phase III trials (n=1,272). The CC Symptom Severity Measures addressing bowel function (Bowel Movement Frequency, Stool Consistency, Straining) and abdominal symptoms (Bloating, Abdominal Discomfort, Abdominal Pain) were administered daily using interactive voice‐response system technology. Intraclass correlations, Pearson cor‐ relations, factor analyses, F‐tests, and effect sizes were computed. Results: The CC Symptom Severity Measures demonstrated satisfactory test–retest reliability and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known‐groups F‐tests substantiated the discriminating ability of the CC Symptom Severity Measures. Responsiveness statistics were moderate to strong, indicating that these measures are capable of detecting change. Conclusion: In large studies of CC patients, linaclotide significantly improved abdominal and bowel symptoms. These psychometric analyses support the reliability, validity, discriminating ability, and responsiveness of the CC Symptom Severity Measures for evaluating treatment outcomes in the linaclotide clinical studies.

Abstract: A 23-year-old male with an over 10-year history of chronic iron-deficiency anemia and gastroschisis at birth was initially evaluated at an outpatient Gastroenterology clinic with complaints of generalized malaise and fatigue lasting for several days. Although he denied abdominal pain, he had experienced intermittent bloating and epigastric discomfort for several years. He also reported chronic diarrhea, which he described as foul smelling, loose stools that occurred three to six times per day for several years. He denied fevers, chills, nausea, vomiting, hematemesis, or rectal bleeding. Additionally, he denied dyspnea on exertion or chest discomfort. On examination, tachycardia and normotension were noted. A hemoglobin of 4.4 g/dL prompted admission for further evaluation. His past medical history included asthma. The patient had been hospitalized for 3 months after birth (at 36 weeks gestation), largely due to an inability to tolerate oral intake, having received total parenteral nutrition prior to being discharged tolerating oral feeds. Charts from that time noted that he ‘‘...had gastroschisis with intestine, spleen and stomach outside of the abdomen.’’ A few days after birth, he underwent non-resective surgical repair. Intraoperatively, there was no evidence of intestinal atresia. At the age of five, he had one episode of a small bowel obstruction that resolved with medical management. An upper gastrointestinal series (UGIS) with small bowel follow through (SBFT) at that time showed slightly dilated small bowel segments with normal transit time throughout. In 1994, at the age of six, his hemoglobin and mean corpuscular volume (MCV) were within normal limits. Nevertheless, even in 2001, the patient had a history of heme-positive stool, along with bloating, diarrhea, and anemia (hemoglobin 9.1 g/dL and MCV 60). His anemia was evaluated at that time with panendoscopy without abnormal findings. The duodenum was reported as being ‘‘patulous.’’ Biopsies revealed mild chronic active gastritis (antral biopsies were negative for Helicobacter pylori), mild reflux esophagitis, and a normal duodenum. Biopsies throughout the right and left colon were normal. Overall, his endoscopic evaluation did not reveal any abnormalities that explained his anemia. He was prescribed oral iron replacement therapy, which, however, was not tolerated and thus not taken regularly. Given his history of asthma and poor growth as a child, he was evaluated for cystic fibrosis (CF) with sweat chloride and genetic testing which were normal. In 2001 another UGIS with SBFT showed a somewhat dilated distal jejunum. Pancreatic enzyme supplements were prescribed for unclear reasons, which, however, initially improved his bloating and diarrhea. By 2004, the diarrhea recurred with non-bloody, loose stools reported two to three times a week. There was no clear explanation for the patient’s diarrhea, anemia, or hemepositive stools; he was lost to follow-up until being seen at our institution. The patient’s social history was unremarkable in that he denied any drug, alcohol, or tobacco use. He also denied foreign travel or unusual environmental exposures. He did not have any pertinent family history; his three siblings S. R. Sinha (&) G. Triadafilopoulos N. Shah Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 300 Pasteur Dr., Always Bldg. M211, Stanford, CA 94305-5187, USA e-mail: sidsinha@stanford.edu