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Nicholas J Talley

Publications and source records attributed to Nicholas J Talley.

At least 19 recordsLinked to original sources
PubMed2006

Gut-brain neuropeptides in the regulation of ingestive behaviors and obesity.

The prevalence of obesity has increased to epidemic proportions and has become an urgent public health problem. Obesity causes significant morbidity and mortality and its impact on health-care costs in the United States is growing dramatically. Apart from bariatric surgery treatment, options are limited. Future advances in treatment will rely on a better understanding of the pathogenesis and physiology of obesity. Alterations in gastrointestinal (GI) sensory-motor function and symptoms have been associated with obesity. GI neuroendocrine communications between the periphery and the brain regulate energy balance and ingestive behaviors. These interactions are largely mediated by the gut-brain peptides through negative and positive feedback loops that maintain energy homeostasis. Bariatric surgery has been shown effective, but the mechanisms of weight loss following these procedures clearly require further studies and a better understanding of the affects of bariatric surgery on the gut-brain neuropeptide homeostasis. Gut-brain peptides may provide attractive therapeutic targets in the fight against this very morbid disease. We review alterations in GI function and some of the more important gut-brain neuropeptides that occur in obesity.

Brain↗
PubMed2006

Incidence of presentation of common functional gastrointestinal disorders in children from birth to 5 years: a cohort study.

BACKGROUND & AIMS: Gastroesophageal reflux disease (GERD), abdominal pain of unknown origin, and constipation are thought to be causes for frequent medical visits during childhood. The aim of this study was to estimate the incidences, repeat presentation, clinical symptoms, and sociodemographic risk factors in children who medically presented for GERD, abdominal pain of unknown origin, and constipation from birth to 5 years. METHODS: This was a population-based, retrospective birth cohort study of all children born to mothers residing in Rochester, Minnesota who remained in the area until at least age 5 (n = 5718). The medical records of all individuals were searched for relevant diagnostic billing codes for GERD, abdominal pain of unknown origin, and constipation, without another underlying diagnosis, and manually reviewed. Parental sociodemographic factors collected from birth certificate records on patients and matched controls were compared. RESULTS: The incidence for childhood (age, <5 y) presentation of GERD, abdominal pain of unknown origin, and constipation was .9/1000 person-years, 4.5/1000 person-years, and 6.8/1000 person-years, respectively; there were no significant differences between boys and girls. Three or more medical visits by age 5 occurred in 11%, 19%, and 24% of children who were seen for abdominal pain of unknown origin, constipation, and GERD, respectively. Single parentage, maternal age (<18 y), and maternal education (<high school) were not associated with abdominal pain or constipation presentation. CONCLUSIONS: The incidences of presentation for GERD, abdominal pain of unknown origin, and constipation are among the highest for pediatric disorders, and a cause for repeated medical consultations.

Abdominal Pain↗
PubMed2006

Gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease refers to reflux of gastric contents into the oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality of life, or long-term complications. Transient relaxation of the lower oesophageal sphincter is believed to be the primary mechanism of the disease although the underlying cause remains uncertain. Obesity and smoking are weakly associated with the disease and genetic factors might be important. A negative association with Helicobacter pylori exists, but eradication of H pylori does not seem to cause reflux disease. Diagnosis is imprecise as there is no gold standard. Reflux symptoms are helpful in diagnosis but they lack sensitivity. Ambulatory oesophageal pH monitoring also seems to be insensitive despite high specificity. Empirical acid suppression with a proton-pump inhibitor (PPI) has reasonable sensitivity but poor specificity. Some evidence suggests that once patients develop the disease, severity is determined early and patients seem to continue with that phenotype long term. Unfortunately, most patients do not respond to life-style advice and require further therapy. H2 receptor antagonists and PPIs are better than placebo in oesophagitis, with a number needed to treat of five and two, respectively. In non-erosive reflux disease, acid suppression is better than placebo but the response rate is lower. Most patients need long-term treatment because the disease usually relapses. The role of endoscopic therapy is uncertain. Anti-reflux surgery is probably as effective as PPI therapy although there is a low operative mortality and morbidity.

Antacids↗
PubMed2006

In patients with Helicobacter pylori gastritis and functional dyspepsia, a biopsy from the incisura angularis provides useful diagnostic information.

The aim of this study was to assess whether the taking of an additional biopsy from the incisura angularis increases the chance of detecting maximal degrees of atrophy and intestinal metaplasia (IM) in patients with Helicobacter pylori gastritis and functional dyspepsia. At entry into a randomised trial, biopsies were taken from 328 patients (mean age 48 years), two from both the gastric antrum and corpus, and one from the incisura angularis, and comparative grading of gastritis variables was carried out. Biopsy material from the gastric antrum, corpus, and the incisura angularis revealed no notable differences in atrophy or an incidence of IM and mucosa-associated lymphatic tissue. However, when the incisura biopsies were classified histologically, 58% contained antral mucosa (AM), 18% corpus mucosa (CM), and 24% intermediate zone mucosa. AM at the incisura was associated with considerably more severe gastritis in both the incisura and antrum (14% atrophy, 20% IM) than in CM of incisura (2% atrophy, 6% IM). Corpus atrophy and IM were rare in the AM group and absent from the CM group. Incisura angularis biopsy in patients with H. pylori gastritis and functional dyspepsia does give additional information regarding the severity of gastritis expected in the corpus and antrum. Antral-type mucosa in the incisura angularis region seems to indicate an increased risk for the development of atrophy and/or IM.

Biopsy↗
PubMed2006

Can the clinical history distinguish between organic and functional dyspepsia?

CONTEXT: Upper gastrointestinal symptoms occur in 40% of the population. An accurate diagnosis would help rationalize investigation and treatment. OBJECTIVE: To systematically review the literature of the accuracy of primary care physicians, gastroenterologists, or computer models in diagnosing organic dyspepsia. DATA SOURCES: A search of Cochrane Controlled Trials Register (December 2003), MEDLINE (1966-December 2003), EMBASE (1988-December 2003), and CINAHL (1982-December 2003) for studies that reported on cohorts of patients attending for endoscopy that had symptoms, clinical opinion, or both recorded before investigation. STUDY SELECTION: Studies that prospectively compared the diagnosis reached by a clinician, computer model, or both with results of upper gastrointestinal endoscopy in adult patients with upper gastrointestinal symptoms. DATA EXTRACTION: Two authors independently assessed studies (n = 79) for eligibility and abstracted data for estimating likelihood ratios (LRs) of clinical opinion, computer models, or both in diagnosing an organic cause for dyspepsia. DATA SYNTHESIS: Fifteen studies were identified that evaluated 11 366 patients, with 4817 patients (42%) classified as having organic dyspepsia. The computer models performed similarly to the clinician; therefore, the 2 approaches were combined. The diagnosis reached by the clinician or computer model suggesting organic dyspepsia had an LR of 1.6 (95% confidence interval [CI], 1.4-1.8), and a negative result decreased the likelihood of organic dyspepsia (LR, 0.46; 95% CI, 0.38-0.55). A diagnosis of peptic ulcer disease performed similarly with an LR of 2.2 (95% CI, 1.9-2.6), but an evaluation that suggested the absence of peptic ulcer disease had an LR of 0.45 (95% CI, 0.38-0.53). A clinical history suggesting esophagitis had an LR of 2.4 (95% CI, 1.9-3.0) vs a negative history that had an LR of 0.50 (95% CI, 0.42-0.60). CONCLUSION: Neither clinical impression nor computer models that incorporated patient demographics, risk factors, history items, and symptoms adequately distinguished between organic and functional disease in patients referred for endoscopic evaluation of dyspepsia.

Diagnosis, Computer-Assisted↗
PubMed2006

Peptic ulcer disease in a general adult population: the Kalixanda study: a random population-based study.

The authors' aim in this study was to explore the prevalence, symptomatology, and risk factors for peptic ulcer in a general adult population. Between December 1998 and June 2001, the authors surveyed a random sample (n=3,000) of the adult population (n=21,610) in two communities in northern Sweden using a validated questionnaire, the Abdominal Symptom Questionnaire (response rate=74%). A subsample (n=1,001) of the responders was randomly invited to undergo esophagogastroduodenoscopy and symptom assessment (response rate=73%). The prevalence of peptic ulcer was 4.1% (20 gastric ulcers and 21 duodenal ulcers). Nausea and gastroesophageal reflux were significant predictors of peptic ulcer disease, but epigastric pain/discomfort was not. Six persons with gastric ulcer and two persons with duodenal ulcer were asymptomatic. Eight subjects with duodenal ulcer (38%) lacked evidence of current Helicobacter pylori infection. Five (25%) of the gastric ulcers and four (19%) of the duodenal ulcers were idiopathic (no use of aspirin or nonsteroidal antiinflammatory drugs, no H. pylori infection). Smoking, aspirin use, and obesity were risk factors for gastric ulcer; smoking, low-dose (<or=160 mg) aspirin use, and H. pylori infection were risk factors for duodenal ulcer. Peptic ulcer disease often coexists with atypical symptoms or no symptoms at all, and idiopathic duodenal ulcer may be more common than anticipated.

Adult↗
PubMed2006

Psychological stress and the severity of post-inflammatory visceral hyperalgesia.

OBJECTIVES: Lowered visceral sensory thresholds are a key finding in at least a subgroup of patients with functional bowel disorders. Stress and inflammation contribute to this altered visceral sensory function. We aimed to elucidate the role of repetitive stress and acute mucosal inflammation, alone and in combination, on sensory function. METHODS: In randomized order, trinitrobenzenesulfonic acid (TNBS) plus the equal amount of ethanol or saline were instilled into the colorectum of female Lewis rats. Colorectal distensions (CRD) were performed with a barostat device (3 min/40 mmHg); to quantify the visceromotor response (VMR) to CRD, electromyographic activity (EMG) of the abdominal muscles was recorded. In randomized order, equal numbers of both treatment groups underwent either seven days (1 h/day) repetitive water avoidance stress (WAS) or sham WAS. CRD's were conducted 28 days later. Colonic tissue samples were obtained to characterize inflammation and blood samples were taken at day 28 to measure plasma IL-2 levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to controls (662+/-114 microV) TNBS (1081+/-227 microV), WAS (1366+/-125 microV) and the combination of both (1477+/-390 microV) significantly augmented the VMR to CRD. TNBS and/or WAS caused significant inflammatory changes at day 5, while only TNBS+WAS also showed signs of mucosal inflammation on day 14 and significantly elevated IL-2 levels on day 28. CONCLUSIONS: Stress and inflammation cause long lasting alterations of visceral sensory function. Concomitant stress further increases post-inflammatory visceral hyperalgesia.

Abdominal Muscles↗
PubMed2006

A placebo-controlled trial of itopride in functional dyspepsia.

BACKGROUND: The treatment of patients with functional dyspepsia remains unsatisfactory. We assessed the efficacy of itopride, a dopamine D2 antagonist with anti-acetylcholinesterase [corrected] effects, in patients with functional dyspepsia. METHODS: Patients with functional dyspepsia were randomly assigned to receive either itopride (50, 100, or 200 mg three times daily) or placebo. After eight weeks of treatment, three primary efficacy end points were analyzed: the change from baseline in the severity of symptoms of functional dyspepsia (as assessed by the Leeds Dyspepsia Questionnaire), patients' global assessment of efficacy (the proportion of patients without symptoms or with marked improvement), and the severity of pain or fullness as rated on a five-grade scale. RESULTS: We randomly assigned 554 patients; 523 had outcome data and could be included in the analyses. After eight weeks, 41 percent of the patients receiving placebo were symptom-free or had marked improvement, as compared with 57 percent, 59 percent, and 64 percent receiving itopride at a dose of 50, 100, or 200 mg three times daily, respectively (P<0.05 for all comparisons between placebo and itopride). Although the symptom score improved significantly in all four groups, an overall analysis revealed that itopride was significantly superior to placebo, with the greatest symptom-score improvement in the 100- and 200-mg groups (-6.24 and -6.27, vs. -4.50 in the placebo group; P=0.05). Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo (73 percent vs. 63 percent, P=0.04). CONCLUSIONS: Itopride significantly improves symptoms in patients with functional dyspepsia. (ClinicalTrials.gov number, NCT00272103.).

Adolescent↗
PubMed2006

Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors.

OBJECTIVES: Proton pump inhibitors reduce ulcer recurrence in non-steroidal anti-inflammatory drug (NSAID) users, but their impact in at-risk ulcer-free patients using the current spectrum of prescribed agents has not been clearly defined. We assessed esomeprazole for ulcer prevention in at-risk patients (> or = 60 yr and/or ulcer history) taking NSAIDs, including COX-2 inhibitors. Such studies are particularly relevant, given that concerns regarding adverse cardiovascular outcomes among COX-2 inhibitor users may prompt re-evaluation of their use. METHODS: We conducted two similar double-blind, placebo-controlled, randomized, multicenter studies; VENUS (United States) and PLUTO (multinational). A total of 844 and 585 patients requiring daily NSAIDs, including COX-2 inhibitors were randomized to receive esomeprazole (20 or 40 mg) or placebo, daily for 6 months. RESULTS: In the VENUS study, the life table estimated proportion of patients who developed ulcers over 6 months (primary variable, intent-to-treat population) was 20.4% on placebo, 5.3% on esomeprazole 20 mg (p < 0.001), and 4.7% on esomeprazole 40 mg (p < 0.0001). In the PLUTO study, the values were 12.3% on placebo, 5.2% with esomeprazole 20 mg (p = 0.018), and 4.4% with esomeprazole 40 mg (p = 0.007). Significant reductions were observed for users of both non-selective NSAIDs and COX-2 inhibitors. Pooled ulcer rates for patients using COX-2 inhibitors (n = 400) were 16.5% on placebo, 0.9% on esomeprazole 20 mg (p < 0.001) and 4.1% on esomeprazole 40 mg (p= 0.002). Esomeprazole was well tolerated and associated with better symptom control than placebo. CONCLUSIONS: For at-risk patients, esomeprazole was effective in preventing ulcers in long-term users of NSAIDs, including COX-2 inhibitors.

Aged↗
PubMed2006

Novel mechanisms in functional dyspepsia.

Functional dyspepsia (FD) is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antro-duodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.

Dyspepsia↗
PubMed2006

Aerophagia and rumination: recognition and therapy.

Aerophagia and rumination syndrome are functional upper gastrointestinal disorders that are becoming increasingly recognized in otherwise-healthy children and adults. Aerophagia is primarily characterized by troublesome repetitive belching and abdominal symptoms that result from air sucking and swallowing. Rumination syndrome is primarily characterized by regurgitation occurring shortly after meal intake. Physiologic studies suggest that both disorders are a result of habitual behavior with associated esophageal and gastric physiologic deviations. However, the underlying etiology of these disorders remains unclear. Studies examining optimal treatments are lacking. However, therapeutic approaches utilizing biofeedback may be helpful in alleviating symptoms for patients with these conditions.

Journal Article↗
PubMed2006

Design of treatment trials for functional gastrointestinal disorders.

This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.

Clinical Trials as Topic↗
PubMed2006

Functional gastroduodenal disorders.

A numerically important group of patients with functional gastrointestinal disorders have chronic symptoms that can be attributed to the gastroduodenal region. Based on the consensus opinion of an international panel of clinical investigators who reviewed the available evidence, a classification of the functional gastroduodenal disorders is proposed. Four categories of functional gastroduodenal disorders are distinguished. The first category, functional dyspepsia, groups patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation. Based on recent evidence and clinical experience, a subgroup classification is proposed for postprandial distress syndrome (early satiation or postprandial fullness) and epigastric pain syndrome (pain or burning in the epigastrium). The second category, belching disorders, comprises aerophagia (troublesome repetitive belching with observed excessive air swallowing) and unspecified belching (no evidence of excessive air swallowing). The third category, nausea and vomiting disorders, comprises chronic idiopathic nausea (frequent bothersome nausea without vomiting), functional vomiting (recurrent vomiting in the absence of self-induced vomiting, or underlying eating disorders, metabolic disorders, drug intake, or psychiatric or central nervous system disorders), and cyclic vomiting syndrome (stereotypical episodes of vomiting with vomiting-free intervals). The rumination syndrome is a fourth category of functional gastroduodenal disorder characterized by effortless regurgitation of recently ingested food into the mouth followed by rechewing and reswallowing or expulsion. The proposed classification requires further research and careful validation but the criteria should be of value for clinical practice; for epidemiological, pathophysiological, and clinical management studies; and for drug development.

Child↗
PubMed2006

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↗
PubMed2006

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↗
PubMed2006

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↗