Comparison of Lactase Variant MCM6 -13910 C>T Testing and Self-report of Dairy Sensitivity in Patients With Irritable Bowel Syndrome.

GOALS: To evaluate agreement of MCM6-13910 with self-report of dairy sensitivity (DS) and lactose hydrogen methane breath test (LHMBT) results in subjects with irritable bowel syndrome (IBS). BACKGROUND: IBS is a functional gastrointestinal disorder with symptoms including abdominal pain, variable bowel habits, and bloating. Adult patients with lactose malabsorption may present with similar symptoms. Patients with lactose malabsorption have a lactase nonpersistent (LNP) phenotype. Recent studies found 2 single nucleotide polymorphisms associated with LNP: G/A-22018 and C/T-13910. STUDY: Genotyping the MCM6-13910 variant of LNP in 538 IBS patients and 317 controls (without IBS). Subjects completed questionnaires pertaining to gastrointestinal problems and dietary consumption, with charts abstracted. RESULTS: Self-reported DS was higher in IBS (45%) than controls (9.8%, odds ratio=6.46, P<0.001). The C/C-13910 genotype was similar in IBS cases and controls, 81 (15.1%) and 47 (14.8%). Among subjects reporting DS, 49 (18.0%) had the C/C genotype. Overall agreement between genotype and self-reported DS was 0.06 in IBS and 0.07 in controls. There were 20 subjects with LHMBT results; 3 had positive results, 17 were negative. LNP genotypes were found in all 3 of positive LHMBT results; 16 had negative LHMBT among the 17 who were lactase persistent. Agreement between C/C-13910 genotype and LHMBT was excellent with κ-statistic of 0.83 (0.50-1.00). CONCLUSIONS: In IBS patients, self-report of lactose intolerance are highly prevalent but are a poor indicator of underlying C/C-13910 genotype. LHMBT had excellent agreement with C/C-13910 genotype.

Lack of familial aggregation in chronic constipation excluding irritable bowel syndrome: a population-based study.

BACKGROUND: Despite strong evidence supporting a genetic and gene-environment interaction in the irritable bowel syndrome (IBS), the role of genes and early life in another common functional bowel disorder, chronic constipation (CC), have been little studied. AIM: To determine whether familial aggregation occurs in CC and whether risk factors differed in those with family members. METHODS: A randomly selected population-based cohort from Olmsted County, MN, was surveyed (n = 8,006); 3,831 completed questionnaires (response rate 48 %). Cases were identified based upon their responses to a validated questionnaire and meeting Rome criteria for CC. Controls were matched one to one by age and gender. IBS (by Rome II criteria) was excluded. Recruitment of case and control probands occurred in 2010-2011 by mailing a family information form; then, first-degree relatives (FDR) were mailed a questionnaire. All potential proband participants were not informed of CC status. RESULTS: Overall 1,185 cases who met criteria for CC without symptoms of IBS and 1,185 controls were surveyed; 309 case and 336 control probands provided data. The proportion of family members having CC was not associated with case status, and the constipation status of FDR was not significantly associated with case-controls status of the respective probands. Symptom burden in FDR was associated with gender and SSC score, but not age or proband status. CONCLUSIONS: No evidence of familial aggregation was observed in adults from the community with CC (excluding IBS). Our data suggest environmental factors in later life more likely account for adult CC.

Effects of Birth Cohorts on the Irritable Bowel Syndrome Support Early-Life Risk Factors.

BACKGROUND: Irritable bowel syndrome (IBS) is common with prevalence reported between 10 and 20 %. IBS clusters in families but it is unknown whether this is explained by a common environment, genes, or both. If early-life factors are important, IBS might be expected to demonstrate a birth cohort phenomenon. AIM: To investigate whether there is a birth cohort phenomenon for subjects with IBS. METHODS: Validated questionnaires were sent to a random sample of Olmsted County, Minnesota, residents who recorded gastrointestinal symptoms; IBS diagnosis was based on the modified Rome criteria. Birth cohorts were chosen a priori based on historical national trends in birth weights using 10-year increments. Logistic regression was used to develop odds ratios to assess the association of IBS with calendar period, birth cohort, age, gender, and somatic symptom score. RESULTS: A total of 4,893 surveys were completed with an overall survey response rate of 58 %. The survey responders were between 25 and 94 years of age and 53 % were female. The overall prevalence of IBS was 16.2 % (95 % CI 15.3-17.4). The univariate association of IBS with birth cohort was significant (p < 0.001) as was the association adjusted for age and gender. The prevalence of IBS was highest for the birth cohort 1963-1972 with an odds ratio of 2.6 (95 % CI 0.97-7.0, p = 0.058). CONCLUSIONS: Population-based data support a possible birth cohort phenomenon in IBS. If correct, early-life risk factors likely play a key role in the development of IBS.

An update on irritable bowel syndrome: from diagnosis to emerging therapies.

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal discomfort or pain that is accompanied by a disturbance in defecation. Although the exact etiopathogenesis is not completely understood, recent advances in the understanding of the biochemical, physiologic, and biopsychosocial mechanisms of IBS have resulted in exciting new insights as well as therapies. This article will review the recent developments in pathogenesis, diagnosis, and treatment. RECENT FINDINGS: IBS may be the product of various pathogenic mechanisms which include IBS as a serotonergic disorder; the role of genetics; IBS as an inflammatory state and the potential role of mast cells; IBS as a result of bacterial overgrowth and altered gastrointestinal microbiome; and abnormal pain processing and pain memory. Emerging therapies have developed targeting these mechanisms. SUMMARY: IBS remains a symptom-based diagnosis that can usually be made comfortably based on clinical history without testing in the absence of alarm features. Novel and emerging therapies that are based upon the evolving understanding of the pathophysiology of IBS hold significant promise and for the first time there are potential therapies that may alter the natural history of this disorder.

A shift in the clinical spectrum of eosinophilic gastroenteritis toward the mucosal disease type.

BACKGROUND & AIMS: Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal (GI) tract. Despite the increasing prevalence of eosinophilic GI disorders, the epidemiology of EG has not been well studied. We evaluated the clinical spectrum of EG. METHODS: We reviewed data from patients diagnosed with EG, allergic gastroenteropathy, or eosinophilia and referred to gastroenterologists from 1987 to 2007 (n = 59; 52 with mucosal, 3 with muscularis, and 4 with subserosal disease). The study included subjects diagnosed with EG and those with a history that suggested EG, defined by GI symptoms; eosinophilic infiltration of the GI tract, eosinophilic ascites, or characteristic radiographic findings with eosinophilia; and no parasitic or extraintestinal disease. Findings were compared with those from patients with unexplained GI symptoms and peripheral eosinophilia (n = 11). RESULTS: Associations between clinical variables and EG subgroups did not differ between patients with EG and peripheral eosinophilia. Fifty percent of patients with EG who underwent food allergy testing had a positive test result; only 32% of those with EG who underwent radiographic imaging had positive test results. Patients with EG received steroid therapy; 75% with mucosal, 67% with muscle, and 100% with subserosal disease received prednisone. Eighty-eight percent of patients who received only steroids (mean follow-up period, 7 mo) and 94% of patients who received steroids in combination with another therapy (mean follow-up period, 4 mo) had improved or resolved disease. CONCLUSIONS: Unlike eosinophilic esophagitis, EG is rare. Results from this large study suggest that EG disease type has shifted toward that of the mucosal layer.

Impact of functional gastrointestinal disorders on survival in the community.

OBJECTIVES: Functional gastrointestinal disorders (FGIDs) comprise a constellation of symptoms that have no identifiable structural or biochemical abnormality. In view of the lack of data from large-scale population-based studies evaluating the effects of these disorders on survival, we aimed to examine whether FGIDs are associated with impaired survival. METHODS: Between 1988 and 1993, valid self-report questionnaires that recorded gastrointestinal symptoms required for the diagnosis of irritable bowel syndrome (IBS), chronic constipation, chronic diarrhea, dyspepsia, and abdominal pain were mailed to randomly selected cohorts of Olmsted County, Minnesota residents. Minnesota administrative death records were used to identify which of the survey respondents had died over the follow-up period (through April 2008). The association between survival and each FGID was assessed using proportional hazards regression models with univariate and adjusted hazard ratios (HRs, 95% confidence intervals (CIs)), adjusting for age at time of survey, gender, smoking, alcohol, marital status, and Charlson Comorbidity Index (CCI). RESULTS: Of the 5,262 randomly selected eligible subjects who received a questionnaire, a total of 4,176 responded to the surveys (overall response rate 79%). From these respondents, 243 subjects were excluded because of lack of research authorization (or were registered solely at a different medical institution in Olmsted County, MN), resulting in 3,933 eligible subjects for analysis (eligible response rate 75%); 10% reported symptoms of IBS; 16% chronic constipation; 18% chronic diarrhea; 2% dyspepsia; and 15% abdominal pain. At baseline, the mean (s.d.) age was 54 (18) years, and 52% were female. No association with overall survival was detected for IBS (HR=1.06 (95% CI: 0.86-1.32)), chronic diarrhea (HR=1.03 (95% CI: 0.90-1.19)), abdominal pain (HR=1.09 (95% CI: 0.92-1.30)), or dyspepsia (HR=1.08 (95% CI: 0.58-2.02)). Reporting symptoms of chronic constipation was associated with poorer survival (HR=1.23 (95% CI: 1.07-1.42)). This association remained significant after adjusting for the CCI (HR=1.19 (95% CI: 1.03-1.37)). CONCLUSIONS: In this large population-based cohort study with over 30,000 person-years of follow-up, no significant association was observed between survival and IBS, chronic diarrhea, dyspepsia, or abdominal pain. Furthermore, no association was found between increasing burden of FGIDs and survival. However, in contrast to these other FGIDs, subjects with symptoms of chronic constipation were found to be at increased risk of poorer survival. Further investigation is required to determine the cause of this observed association.

Adsorption of perfluoroalkyl substances (PFAS) in groundwater by granular activated carbons: Roles of hydrophobicity of PFAS and carbon characteristics.

The adsorption breakthrough behavior of nine perfluoroalkyl substances (PFAS) in groundwaters by four bituminous coal-based granular activated carbons (F400, Carbsorb 40, HPC and CMR400) was studied using rapid small-scale column tests (RSSCTs). The half breakthrough bed volume (BV50), an indicator of apparent adsorption capacity, correlated with the hydrophobicity of PFAS at a given pH (i.e., Log Dow) for F400, indicating that hydrophobic interaction is important for apparent adsorption capacity of PFAS in groundwater with low dissolved organic concentrations (DOC < 1 mg C/L) and low specific UV absorbances at 254 nm (SUVA254 < 2 L mg-1m-1). Higher empty bed contact time (EBCT) caused steeper PFAS breakthrough curves with respect to throughput, but did not affect apparent adsorption capacity. Three different sizes of F400 (0.13, 0.17, and 0.20 mm) exhibited similar breakthrough profiles of PFAS, indicating that the intraparticle diffusivity was independent of adsorbent diameter in the given conditions. Among the tested carbons, the positively charged adsorbents (F400, HPC, and CMR400) showed higher apparent adsorption capacities for hydrophilic (Log Dow at pH 7 < 0) and marginally hydrophobic PFAS (Log Dow at pH 7 between 0 and 1) than the negatively charged adsorbent (Carbsorb 40). In addition, activated carbons with higher micropore surface areas exhibited higher apparent adsorption capacities of hydrophilic and marginally hydrophobic PFAS among the positively-charged activated carbons, whereas the mesoporous carbon (HPC) exhibited an increasingly larger adsorption capacity for more hydrophobic PFAS compared to the microporous carbon (F400) at a later breakthrough possibly due to less pore blockage.

Population screening for barrett esophagus: a prospective randomized pilot study.

OBJECTIVE: To assess the feasibility of unsedated transnasal endoscopy (uTNE) and video capsule endoscopy (VCE) as alternatives to sedated endoscopy (sEGD) as screening tools for Barrett esophagus (BE) and to obtain preliminary estimates of participation rates for sEGD, uTNE, and VCE when used for community BE screening in a population cohort. PATIENTS AND METHODS: From February 1, 2009, to May 31, 2010, patients from Olmsted County, Minnesota, who were older than 50 years and had no history of known BE were randomized (stratified by age, sex, reflux symptoms noted in a validated questionnaire) into 3 groups for esophageal evaluation with sEGD, uTNE, or VCE. Participation rates and safety profiles were estimated. RESULTS: We contacted 127 patients to recruit 20 for each procedure arm (60 total). The probability of participation was 38% (95% confidence interval [CI], 26%-51%) for sEGD, 50% (95% CI, 35%-65%) for uTNE, and 59% (95% CI, 42%-74%) for VCE. Both uTNE and VCE were well tolerated without adverse effects. BE was identified in 3 patients and esophagitis in 8. CONCLUSION: Unsedated techniques may be acceptable, feasible, and safe alternatives to sEGD to screen for BE in the community. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00943280.

Current and emerging therapies in irritable bowel syndrome: from pathophysiology to treatment.

Irritable bowel syndrome is a common functional gastrointestinal disorder with characteristic symptoms of abdominal pain/discomfort with a concurrent disturbance in defecation. It accounts for a significant healthcare burden, and symptoms may be debilitating for some patients. Traditional symptom-based therapies have been found to be ineffective in the treatment of the entire syndrome complex, and do not modify the natural history of the disorder. Although the exact etiopathogenesis of IBS is incompletely understood, recent advances in the elucidation of the pathophysiology and molecular mechanisms of IBS have resulted in the development of novel therapies, as well as potential future therapeutic targets. This article reviews current and emerging therapies in IBS based upon: IBS as a serotonergic disorder; stimulating intestinal chloride channels; modulation of visceral hypersensitivity; altering low-grade intestinal inflammation; and modulation of the gut microbiota.

Clinical subtypes of lone atrial fibrillation.

AIMS: In the face of increasing evidence of underlying genetic heterogeneity for lone atrial fibrillation (LAF), we undertook a clinical analysis of subjects to identify the phenotypic subsets of this arrhythmia. METHODS AND RESULTS: We evaluated serial patients who presented with LAF between July 5, 2001 and December 19, 2003. Subjects underwent a standardized interview to elicit a detailed medical history, prior therapies, and precipitants of atrial fibrillation. The results of a physical exam, electrocardiogram and echocardiogram were reviewed. One hundred and eighty subjects with a mean age of 45 years (15-67 years) at the time of diagnosis were enrolled. The majority of patients originally presented with paroxysmal fibrillation (94%), and 7.8% progressed to permanent AF. Reported triggers for AF included sleeping (44%), exercise (36%), alcohol use (36%), and eating (34%). Women with LAF had distinct symptoms, triggers for episodic AF, and over one-fourth had an underlying rheumatologic condition. Several subsets of AF including familial AF (39%), exercise-induced AF (32%), and conduction system disease requiring pacemaker implantation (7%), were identified. CONCLUSIONS: Family history, exercise as a trigger of AF, and a history of a pacemaker identified subtypes of LAF.

New lanostanoids from the mushroom Ganoderma lucidum.

From a lipophilic extract of the fruiting body of Ganoderma lucidum, three new lanostanoids, 8beta,9alpha-dihydroganoderic acid J (1), methyl 8beta,9alpha-dihydroganoderate J (2), and 20-hydroxylganoderic acid G (3), along with 12 known lanostanoids and two ergostane sterols were isolated. The structures of 1-3 were determined by interpretation of their spectroscopic data.