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Nicholas J Talley

Publications and source records attributed to Nicholas J Talley.

At least 37 records · Page 2Linked to original sources

Is there an association between GNbeta3-C825T genotype and lower functional gastrointestinal disorders?

BACKGROUND & AIMS: GNbeta3 influences G-protein translation of a majority of ligand-receptor activations. It has been reported that functional dyspepsia (FD) is associated with homozygous genotypes of the C825T polymorphism in the GNbeta3 gene. It is unknown whether the GNbeta3 genotype is associated with lower functional gastrointestinal disorders (FGID). We aimed to compare the prevalence of the different GNbeta3-C825T genotypes in patients with lower FGID and healthy controls and to test the associations of these genetic variations with subgroups of irritable bowel syndrome (IBS), functional abdominal pain (FAP), lower FGID-FD overlap, and high somatic symptom scores. METHODS: GNbeta3-C825T polymorphism was analyzed in DNA from blood samples of 233 patients with lower FGID and 152 healthy controls. A validated bowel questionnaire characterized the FGID phenotype: 82 with IBS constipation, 94 with IBS diarrhea, 38 with IBS alternating bowel function, and 19 with FAP. There were 159 patients with lower FGID and overlap FD using Rome II criteria. Regression analyses assessed associations of the GNbeta3 genotypes with lower FGID as a group, and subgroups of FGID and somatic symptom scores. RESULTS: GNbeta3-C825T genotype distributions were similar between healthy controls (50.7% CC, 40.8% TC) and patients with lower FGID (8.6% TT, 51.5% CC, 40.8% TC, and 7.7% TT). There were no significant associations of GNbeta3-C825T polymorphism with lower FGID overall or with the separate symptom subgroups including IBS, FAP, lower FGID-FD overlap, or high somatic symptom scores. CONCLUSIONS: In contrast to the reported association with FD, GNbeta3-C825T polymorphism is not associated significantly with lower FGID, with different IBS or FAP phenotypes, or lower FGID-FD overlap.

Adolescent↗

Limited value of alarm features in the diagnosis of upper gastrointestinal malignancy: systematic review and meta-analysis.

BACKGROUND & AIMS: Alarm features such as dysphagia, weight loss, or anemia raise concern of an upper gastrointestinal malignancy in patients with dyspepsia. The aim of this study was to determine the diagnostic accuracy of alarm features in predicting malignancy by performing a metaanalysis based on the published literature. METHODS: English-language studies were identified by searching MEDLINE, EMBASE, Cochrane Controlled Trials Register, and CINAHL. Cohort studies that measured alarm features and compared them with the endoscopic findings were included. Studies were screened for inclusion by 2 authors who independently extracted the data. Sensitivity, specificity, and likelihood ratios were calculated by comparing the alarm feature with the endoscopic diagnosis. The summary receiver operating characteristic curve method was used to summarize test characteristics across studies. Individual alarm features were also assessed when the study report permitted. RESULTS: Eighty-three of 2600 studies met the initial screening criteria; 15 met inclusion criteria after detailed review. These 15 studies evaluated a total of 57,363 patients, of whom 458 (.8%) had cancer. The sensitivity of alarm symptoms varied from 0% to 83% with considerable heterogeneity between studies. The specificity also varied significantly from 40% to 98%. A clinical diagnosis made by a physician was very specific (range, 97%-98%) but not very sensitive (range, 11%-53%). CONCLUSIONS: Alarm features have limited predictive value for an underlying malignancy. Their use in dyspepsia management strategies needs further refinement and study.

Anemia↗

Low social class is linked to upper gastrointestinal symptoms in an Australian sample of urban adults.

OBJECTIVE: The epidemiology of gastrointestinal (GI) symptoms has been described in population surveys, yet their distribution by socio-economic (social) class remains largely uninvestigated. The aim of this study was to evaluate the influence of social class on GI symptoms in an urban sample of Australian adults. MATERIAL AND METHODS: The prevalence of 25 GI symptoms was determined by postal questionnaire. Five latent symptom groups were identified by a principal components analysis (PCA) (Esophageal, Dysmotility-like, Nausea/vomiting, Constipation and Diarrhea). These components were used to model the association between GI symptoms and adult social class. Social class was assigned according to a census-based measure of area disadvantage, and to highest level of completed education. Age- and sex-adjusted odds ratios - as identified by unconditional logistic regression - were used to describe the relationship between symptom groups and adult social class. RESULTS: The effects of area disadvantage and education on Esophageal and Dysmotility-like symptoms were pronounced, with persistent trends for elevated symptom rates amongst the lower social classes (all p<0.01 on age- and sex-adjusted effects). When defined by area disadvantage, the odds ratios for Nausea/vomiting were significantly elevated among the lowest social class group (p=0.01), whereas the odds for Constipation were significantly elevated among the upper-middle social class when defined by education (p=0.001). Diarrhea was not associated with social class whether defined by area disadvantage or education. CONCLUSIONS: Low social class is a risk factor for upper GI complaints.

Adult↗

Somatization an independent psychosocial risk factor for irritable bowel syndrome but not dyspepsia: a population-based study.

BACKGROUND: A psychosocial conceptualization for irritable bowel syndrome and unexplained dyspepsia has been proposed, but remains untested. We conducted a comprehensive population-based study to determine what psychiatric and psychosocial factors, if any, are important in irritable bowel syndrome and dyspepsia. METHODS: Two hundred and seven participants identified from two previous Australian population surveys who also met Rome I criteria for irritable bowel syndrome (n=156) or unexplained dyspepsia (n=51) were included in the study. Consulters (n=103) were those who had had visited their general practitioner for gastrointestinal symptoms at least once in the prior 12 months. Nonconsulters had not sought medical care for gastrointestinal symptoms in the past year. Controls (n=100) did not report having any abdominal pain in a previous population survey. Psychosocial variables were assessed using structured interviews and validated self-report measures. RESULTS: Psychiatric diagnoses, neuroticism, more highly threatening life event stress, an external locus of control and ineffectual coping styles were significantly associated with having a diagnosis of irritable bowel syndrome and/or dyspepsia. Only somatization (odds ratio=5.28, 95% confidence interval 1.57-17.68), however, was independently associated with irritable bowel syndrome. Psychosocial factors did not discriminate between consulters and nonconsulters. CONCLUSIONS: Somatization is likely play a key role in explaining irritable bowel syndrome but not dyspepsia.

Adaptation, Psychological↗

Antimicrobial susceptibility of Helicobacter pylori strains in a random adult Swedish population.

BACKGROUND AND AIM: Antimicrobial resistance in Helicobacter pylori is a growing problem and has become an important factor leading to eradication failure. Information on antimicrobial susceptibility is important for selection of an optimum treatment regimen. The resistance rate in a random population has not been studied previously. METHODS: A random Swedish population sample (n = 3000, age 20-1 years) was surveyed using a mailed validated questionnaire assessing gastrointestinal symptoms (response rate of 74%). One-third of the responders was invited, in random order, and accepted an esophagogastroduodenoscopy with biopsies for H. pylori culture and histology. Subjects were not treated for their H. pylori infection but a minimum inhibitory concentration of metronidazole, clarithromycin, amoxicillin, and tetracycline for the H. pylori isolates (n = 333) was determined by agar dilution. Prescribed antibiotic in the area was recorded. RESULTS: Irrespective of symptomatology, 16.2% of the isolated H. pylori strains were resistant to metronidazole, 1.5% to clarithromycin, 0% to amoxicillin, and 0.3% to tetracycline. The antibiotic consumption was low from an international perspective. CONCLUSION: The resistance to the antibiotics was lower than expected from patient sample studies, especially for clarithromycin, most probably due to a restrictive prescription policy in the area. Introduction of a test-and-treat strategy in Sweden would only marginally affect the usage of clarithromycin.

Adult↗

Hypothesis driven research and molecular mechanisms in functional dyspepsia: the beginning of a beautiful friendship in research and practice?

There is accumulating evidence of a genetic predisposition in at least a subset of patients with functional GI symptoms. Hence, hunting for genes in irritable bowel syndrome and functional dyspepsia has become fashionable of late. Unfortunately, as in other fields, replication of gene association studies has most often been problematic. In this issue of the Journal, independent corroboration of an association of dyspepsia with GNbeta3 is reported. Other carefully selected putative genes including polymorphisms in the alpha2A adrenoreceptor, the serotonin reuptake transporter, and the 5-HT1A receptor were not associated. The study raises three key questions all considered in this editorial: (a) if GNbeta3 is truly associated with functional and uninvestigated dyspepsia, why might this be the case, (b) what molecular mechanisms may be of most relevance, and (c) perhaps most importantly, does or will this finding translate into clinical practice in terms of diagnosis or treatment? New knowledge of gene associations like GNbeta3 and their pathophysiological relevance may ultimately lead to better targeted therapy as well as new disease modifying treatments.

Dyspepsia↗

Measuring successful treatment of irritable bowel syndrome: is "satisfactory relief " enough?

The treatment options for the irritable bowel syndrome (IBS) are expanding as new therapies, including probiotics and serotonin receptor agents, become available. Before any new agents gain widespread use, they must be studied in appropriately designed clinical trials. Symptom improvement remains the key clinically but the best technique to measure symptom improvement is unclear. Many IBS therapy studies have used a binary endpoint such as "Have you had satisfactory relief of your IBS symptoms in the past week? Yes/No?" The study by Whitehead and colleagues in this issue suggests that "satisfactory relief" is affected by baseline symptom severity and may not always truly reflect the symptom burden. Future research needs to determine whether "satisfactory relief" is truly adequate, or whether alternatives such as the proportion of patients achieving a > or = 50% reduction in symptom severity would represent a superior approach to capture clinically important improvement.

Humans↗

Case-control genetic association studies in gastrointestinal disease: review and recommendations.

As our knowledge of genetic variation grows, our ability to use this information to unravel the mysteries of human disease expands. Identification of genes and inexpensive methods to sequence them has resulted in a rising interest in evaluating specific variants and whether they may result in clinical manifestations or symptoms. Genetic variants include restriction fragment length polymorphisms, variable number tandem repeats, DNA microsatellites, and single nucleotide polymorphisms. Using these variants, genetic association studies, also referred to as candidate gene association or genotype-disease association studies are being performed by clinical and basic researchers alike. They are relatively easy to perform, but as a result of their deceivingly simple design, can be conducted or interpreted poorly. A positive association between a genotype and a GI disease of interest may be because the genotype causes (or increases susceptibility to) the disease, but may also be the result of the genotype being in linkage disequilibrium with the actual disease susceptibility gene, or be a false positive due to chance or bias in study design. An excellent understanding of the genetic and methodological issues surrounding these studies is therefore essential. We provide an overview of terminology and provide insight into the complexities underlying these studies. Recommendations for reporting the results of a genetic association study are provided to assist with study planning and manuscript preparation.

Case-Control Studies↗

A unifying hypothesis for the functional gastrointestinal disorders: really multiple diseases or one irritable gut?

The functional gastrointestinal disorders are defined by the Rome criteria as a heterogeneous group of symptom-based conditions that have no structural or biochemical explanation. However, this definition now seems outdated, because structural and molecular abnormalities have begun to be recognized in subsets of patients with the irritable bowel syndrome (IBS), the prototypic functional bowel disease. A complex classification system based arbitrarily on symptom criteria does not fit in with a number of emerging facts. For example, the symptom overlap of IBS with gastroesophageal reflux disease is not due to chance, and the emergence of post-infectious IBS, dyspepsia, or both after Salmonella gastroenteritis fits better with a 1-disease model. A new paradigm seems to be needed. All of these disorders may arise after infection or gut inflammation, but the phenotype depends on localized neuromuscular dysfunction in the predisposed human host (the "irritable gut").

Age Factors↗

Best of DDW 2006.

Highlights from the 2006 Digestive Disease Week May 20-25, 2006, Los Angeles, CA. In this meeting review, many of our editorial board members report on Digestive Disease Week 2006. They highlight the most noteworthy presentations in their respective areas of expertise, including the latest treatments, technologies, and diagnostic advances in ulcerative colitis, Crohn's disease, Helicobacter pylori infection, gastroesophageal reflux disease, irritable bowel syndrome, colorectal cancer, pancreatic and biliary disease, and liver disease.

Digestive System Diseases↗

Overlapping abdominal symptoms: why do GERD and IBS often coexist?

Gastroesophageal reflux disease (GERD), functional dyspepsia and irritable bowel syndrome (IBS) often coexist and may share a common pathophysiological mechanism. An association between GERD and asthma has been reported, and IBS patients have been shown to have an excess prevalence of bronchial hyperresponsiveness. Patients with overlapping IBS and dyspepsia have delayed gastric emptying rates as well as increased visceral hypersensitivity in both the colon and the stomach. Postinfectious occurrence of concomitant dyspepsia and IBS has also been reported, as has a familial association in functional gastrointestinal disorders. Although GERD, dyspepsia and IBS are highly prevalent conditions, overlapping symptoms should be not be attributed to their high prevalence but to a possible common disease process in a subset of patients.

Diagnosis, Differential↗

Effects of desipramine and escitalopram on postprandial symptoms induced by the nutrient drink test in healthy volunteers: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Antidepressants are widely used to treat functional gastrointestinal disorders but their effect on postprandial symptoms remains unstudied. We hypothesized that desipramine and escitalopram would enhance the maximum tolerated volume of nutrient ingested and decrease postprandial symptoms. METHODS: Healthy participants (n=45) all underwent an assessment of symptoms, anxiety and depression, and a standard nutrient drink test (Ensure). Participants were randomized to 11 days of desipramine (50 mg once daily), escitalopram (10 mg once daily) or identical placebo. RESULTS: The maximum tolerated gastric volumes were not significantly different on day 11 for desipramine (1,136+/-478 ml, mean+/-SD), escitalopram (1,198+/-422 ml) and placebo (1,231+/-318 ml). A univariate analysis indicated significant treatment group effects on total symptom scores (p=0.049), but after adjusting for age, gender, BMI and baseline scores, treatment effects were no longer significant (p=0.15). CONCLUSIONS: While this study does not rule out a beneficial effect of tricyclics or selective serotonin reuptake inhibitors in functional dyspepsia, neither desipramine nor escitalopram significantly altered the nutrient volume ingested or symptoms induced by the nutrient drink test in healthy volunteers.

Adult↗

A history of abuse in community subjects with irritable bowel syndrome and functional dyspepsia: the role of other psychosocial variables.

BACKGROUND/AIMS: Why abuse is associated with irritable bowel syndrome and functional dyspepsia remains unclear but other psychosocial factors may be important. We hypothesized that other psychosocial variables may confound the association. METHODS: 207 subjects identified from a previous population survey who also met Rome I criteria for IBS (n=156) or functional dyspepsia (n=51) were included in the study. Controls (n=100) did not report having any abdominal pain in a previous population survey. Sexual, physical, emotional/verbal abuse as a child ( or=14 years) was assessed using validated self-report questions. Other psychological variables were assessed via validated self-report. RESULTS: Adulthood abuse was significantly more common in IBS and/or functional dyspepsia (40%) compared with healthy controls (25%). Abuse was not an independent predictor for IBS or functional dyspepsia when psychological and buffering factors were controlled for in the analyses. Having a diagnosis of depression and using a self-controlling coping style were significantly associated with having a history of abuse. CONCLUSIONS: Abuse occurring as an adult was significantly associated with IBS and/or functional dyspepsia, but it was not an important factor when psychosocial factors were controlled for in these disorders.

Case-Control Studies↗

Helicobacter pylori serology in a birth cohort of New Zealanders from age 11 to 26.

AIM: To determine seroprevalence of Helicobacter pylori (H pylori) in the Dunedin Multidisciplinary Health and Development Study (DMHDS) at age 26 in order to investigate seroconversion and seroreversion from age 11 to 26 and the association of seropositivity with risk factors for H pylori infection. METHODS: Participants in the DMHDS at age 26 and retrospectively at age 21 were tested for H pylori antibodies using two commercially available ELISA kits. Gender, socioeconomic status (SES), smoking, educational attainment and employment at age 26 were tested for association with H pylori seropositivity. RESULTS: At ages 21 and 26, seroprevalence of H pylori using one or other kit was 4.2% (n = 795) and 6.3% (n = 871) respectively. Seroreversion rate was lower than seroconversion rate (0.11% vs 0.53% per person-year) in contrast to the period from age 11 to 21 when seroreversion rate exceeded seroconversion rate (0.35% vs 0.11% per person-year). Serology in those tested at ages 11, 21, and 26 remained unchanged in 93.6% of the sample. Seroprevalence at age 26 was lower among those with a secondary school qualification (P = 0.042) but was not associated with gender, SES, smoking or employment status. CONCLUSION: H pylori seroprevalence in a New Zealand birth cohort remains low between ages 11 and 26. H pylori infection remains stable from childhood to adulthood although seroreversion seems to be more common in the adolescent years than in young adults.

Adolescent↗