BACKGROUND/AIMS: Refractory gastroesophageal reflux disease (GERD) is very common, affecting up to 40% of the patients receiving proton pump inhibitor (PPI) therapy. However, there is not much information about the clinical characteristics of these patients. The aim of the study is to compare the clinical characteristics of PPI responders vs non-responders. METHODS: Consecutive GERD patients receiving PPI once or twice daily were evaluated by a questionnaire and a personal interview regarding their demographics, habits, clinical characteristics and endoscopic findings. The patients were divided into 3 groups: Patients who fully responded to PPI once daily (Group A, n = 111), patients who failed PPI once daily (Group B, n = 78) and patients who failed PPI twice daily (Group C, n = 56). RESULTS: A total of 245 patients (59.3% females, 52 +/- 17.2 years of age) were included in this study. Cross-group differences (A vs B vs C) were detected for hiatal hernia (33% vs 51% vs 52%, P = 0.011); erosive esophagitis (19% vs 51% vs 30%, P < 0.0001); cough (24% vs 44% vs 43%, P = 0.007); sleep disturbances (19% vs 30% vs 38%, P = 0.033); chest symptoms (21% vs 35% vs 41%, P = 0.010); Helicobacter pylori status (25% vs 33% vs 48%, P < 0.0001), disease duration (1.6 +/- 0.8 vs 1.9 +/- 1.0 vs 2.0 +/- 1.1 years, P = 0.007), performed lifestyle interventions (68.5% vs 46.7% vs 69.6%, P = 0.043) and compliance (84% vs 55% vs 46%, P < 0.0001). CONCLUSIONS: PPI failure (either once or twice daily) appears to be significantly associated with atypical GERD symptoms, disease duration and severity, H. pylori status, obesity, performed lifestyle interventions and compliance as compared with PPI responders.
Compliance ; Cough ; Demography ; Esophagitis ; Female ; Gastroesophageal Reflux ; Helicobacter pylori ; Hernia, Hiatal ; Humans ; Life Style ; Obesity ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Surveys and Questionnaires ; Thorax

BACKGROUND/AIMS: Gastroesophageal reflux disease is a highly prevalent disease. Assessing treatment efficacy is critical in that clinical endpoints are properly evaluated. Clinical tools for symptoms severity assessment should be discriminative, predictive and evaluative. METHODS: In this study we compared a patient-oriented symptoms evaluation (ReQuest(TM)) vs a structured interview assessment initiated by a physician (sickness impact profile [SIP]). Both questionnaires were analyzed in a multidimensional space using latent factors. Five dimensions were found: 1 for the short ReQuest(TM) questionnaire and 4 for SIP. RESULTS: We included 1,522 women and 1,296 men; mean age was 36 +/- 7 years, and mean body mass index was 26 +/- 4. The score questionnaire assessment evaluation by physicians and patients did not correlate between them (between r = 0.03 and 0.26) except nausea and sleep disorder (r = 0.45 and 0.51) but both were sensitive enough to detect changes after treatment (P < 0.05). Medical specialty of the physician showed effect on the score of both, ReQuest(TM) and SIP evaluation. Questionnaire variance decomposition due to specialist was only 2% (P < 0.05). CONCLUSIONS: While both evaluations are orthogonal (non-correlated), meaning patients and physicians measured diverse aspects of the same disease, they both were able to measure patient's improvement with treatment.
2-Pyridinylmethylsulfinylbenzimidazoles ; Body Mass Index ; Female ; Gastroesophageal Reflux ; Humans ; Monitoring, Physiologic ; Nausea ; Surveys and Questionnaires ; Specialization ; Treatment Outcome

BACKGROUND/AIMS: Dysfunction of the gastrointestinal tract occurs in about 76% of patients who are diabetic for more than 10 years. Although diabetes-related dysfunctions of the stomach such as gastroparesis have been extensively studied over the recent years, studies about the mechanism underlying colonic symptoms in long-term diabetes models are rare. Therefore, the goal of our study was to clarify the nature of colonic dysfunction in a long-term diabetic rat model. METHODS: The characteristics of colonic smooth muscle were investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. These results were compared to those obtained from Long-Evans Tokushima Otsuka (LETO) control rats. RESULTS: Spontaneous contractility of the proximal colon was significantly decreased in the diabetic rats compared to the controls, while the spontaneous contractility of the distal colon was not. The number of interstitial cells of Cajal networks in the proximal colon was greatly decreased in diabetic rats compared to the controls. Contractility of the proximal colon in response to carbachol, an acetylcholine receptor agonist, was significantly weaker in the diabetic rats. In addition, the degree of relaxation in response to nitric oxide in the proximal colon of diabetic rats also appeared to be attenuated. CONCLUSIONS: The results from our study suggest that the decrease of interstitial cells of Cajal network, cholinergic receptors, and neuronal nitric oxide synthase in the proximal colon plays important roles in diabetes-related dysfunction of colon.
Acetylcholine ; Animals ; Carbachol ; Colon ; Diabetes Mellitus ; Gastrointestinal Motility ; Gastrointestinal Tract ; Gastroparesis ; Humans ; Interstitial Cells of Cajal ; Models, Animal ; Muscle, Smooth ; Nitric Oxide ; Nitric Oxide Synthase Type I ; Rats ; Receptors, Cholinergic ; Relaxation ; Stomach

Functional dyspepsia is a group of disorders featuring symptoms believed to be derived from the stomach and duodenum such as upper abdominal discomfort, pain, postprandial fullness and early satiety. A key diagnostic requisite is the absence of organic, metabolic, or systemic disorders to explain "dyspeptic symptoms." Therefore, when peptic ulcer diseases (including scars), erosive esophagitis and upper gastrointestinal malignancies are found at endoscopic examinations, the diagnosis of functional dyspepsia is excluded. One notable exception, however, is Helicobacter pylori infection. According to the Rome III definition, H. pylori infection is included in functional dyspepsia. This is an obvious deviation from the diagnostic principle of functional dyspepsia, since H. pylori infection is a definite cause of mucosal inflammation, which affects a number of important gastric physiologies such as acid secretion, gastric endocrine function and motility. The chronic persistent nature of infection also results in more dramatic mucosal changes such as atrophy or intestinal metaplasia, the presence of which in the esophagus (Barrett's esophagus) precludes the diagnosis of functional dyspepsia. Since careful endoscopic examination can diagnose reliably H. pylori infection not only in Japan but also in Western contries, it is now feasible and more logical to exclude patients with chronic gastritis caused by H. pylori infection as having dyspeptic symptoms. It is time to establish the Asian consensus to declare that H. pylori infection should be separated from functional dyspepsia.
Asian Continental Ancestry Group ; Atrophy ; Consensus ; Duodenum ; Dyspepsia ; Esophagitis ; Esophagus ; Gastric Acid ; Gastritis ; Helicobacter ; Helicobacter pylori ; Humans ; Inflammation ; Japan ; Logic ; Metaplasia ; Peptic Ulcer ; Rome ; Stomach ; Ulcer

Among functional gastrointestinal (GI) disorders, functional dyspepsia (FD) and irritable bowel syndrome (IBS) are important to public health around the world and are frequently encountered in general practice. Upper GI symptoms such as heartburn, postprandial fullness, early satiety, epigastric pain or burning and lower GI symptoms such as constipation and diarrhea often coexist. Although the prevalence of FD-IBS overlap would be influenced by the selection of the study population, the overlap rate of FD-IBS could be in the range of 11%-27%. Specifically, FD-IBS overlap is associated with more severe symptoms than FD alone or IBS alone. Since clinical overlap, especially FD-IBS overlap, is very common, the 2 syndromes should not be treated in a mutually exclusive fashion.
Burns ; Constipation ; Diarrhea ; Dyspepsia ; General Practice ; Heartburn ; Irritable Bowel Syndrome ; Prevalence ; Public Health

The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches.
Abdominal Pain ; Animals ; Antibodies ; Biomarkers ; Celiac Disease ; Cell Culture Techniques ; Cytokines ; Diet ; Diet, Gluten-Free ; Gastroenteritis ; Genetic Predisposition to Disease ; Humans ; Immune System ; Inflammatory Bowel Diseases ; Intestine, Large ; Irritable Bowel Syndrome ; Mast Cells ; Metagenome ; Risk Factors ; T-Lymphocytes ; Tight Junctions

The paradigm for the control of feeding behavior has changed significantly. In this review, we present evidence that the separation of function in which cholecystokinin (CCK) controls short-term food intake and leptin regulate long-term eating behavior and body weight become less clear. In addition to the hypothalamus, the vagus nerve is critically involved in the control of feeding by transmitting signals arising from the upper gut to the nucleus of the solitary tract. Among the peripheral mediators, CCK is the key peptide involved in generating the satiety signal via the vagus. Leptin receptors have also been identified in the vagus nerve. Studies in the rodents clearly indicate that leptin and CCK interact synergistically to induce short-term inhibition of food intake and long-term reduction of body weight. The synergistic interaction between vagal CCK-A receptor and leptin is mediated by the phosphorylation of signal transducer and activator of transcription3 (STAT3), which in turn, activates closure of K+ channels, leading to membrane depolarization and neuronal firing. This involves the interaction between CCK/SRC/phosphoinositide 3-kinase cascades and leptin/Janus kinase-2/phosphoinositide 3-kinase/STAT3 signaling pathways. It is conceivable that malfunctioning of these signaling molecules may result in eating disorders.
Appetite ; Body Weight ; Cholecystokinin ; Eating ; Feeding and Eating Disorders ; Feeding Behavior ; Fires ; Hypothalamus ; Leptin ; Membranes ; Neurons ; Nodose Ganglion ; Phosphorylation ; Receptor, Cholecystokinin A ; Receptors, Leptin ; Rodentia ; Signal Transduction ; Solitary Nucleus ; Transducers ; Vagus Nerve

No abstract available.
Gastroesophageal Reflux ; Humans

No abstract available.
Colon ; Interstitial Cells of Cajal ; Receptors, Cholinergic

BACKGROUND/AIMS: There are limited data about the relation between belching and irritable bowel syndrome (IBS). We aim to evaluate belching in patients with IBS. METHODS: Twenty-five patients with IBS and 12 healthy volunteers were enrolled in the study. IBS was diagnosed in accordance with the Rome III criteria. All patients were questioned about the presence of symptoms for belching, gastroesophageal reflux disease, and dyspepsia. Esophageal manometry and 24-hour pH-impedance were performed in all patients and healthy volunteers. Each of the patients with IBS underwent gastroscopy and colonoscopy. RESULTS: Demographic features were similar in both groups (P > 0.05). The belching rate was 32% in patients with IBS. The mean DeMeester score was significantly higher in IBS patients (13.80 ± 14.40 vs 6.04 ± 5.60, P = 0.027) and 24% of patients had pathologic acid reflux (DeMeester score > 14). Gastroscopy was normal in all patients. Symptom association probability positivity was detected in 24% of patients in the impedance study. The rate of weak acid reflux was also significantly higher in patients with IBS (97.00 ± 56.20 vs 58.20 ± 29.30, P = 0.025). The number of supine gas reflux (7.50 ± 6.40 vs 2.42 ± 2.80, P = 0.001) and supragastric belches was significantly higher in patients with IBS (51.20 ± 41.20 vs 25.08 ± 15.20, P = 0.035). Although the number of gastric belching was higher in controls, the difference did not reach statistical significance (12.10 ± 17.60 vs 4.90 ± 3.80, P = 0.575). We did not find any correlation between belching and any symptoms of IBS. CONCLUSIONS: Belching is frequent in patients with IBS. Non-erosive reflux disease is frequent in IBS, which may be related to supragastric belching.
Colonoscopy ; Dyspepsia ; Electric Impedance* ; Eructation* ; Gastroesophageal Reflux ; Gastroscopy ; Healthy Volunteers ; Humans ; Irritable Bowel Syndrome* ; Manometry