Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After Helicobacter pylori eradication was introduced and largely eliminated the need for maintenance therapy for peptic ulcer disease, gastroesophageal reflux disease (GERD) became the main indication for prolonged gastric acid inhibition. The drug effect on GERD depends on the degree of acid inhibition, thus the efficacious proton pump inhibitors are preferred. The proton pump inhibitors have few immediate side effects, the main concern being the profound hypoacidity and hypergastrinaemia they induce. In short-term, hypergastrinaemia causes rebound hyperacidity, possibly worsening GERD and reducing the efficacy of histamine H(2) blockers. In the long-term, hypergastrinaemia causes enterochromaffin-like cell hyperplasia and carcinoids. Since enterochromaffin-like cells may be important in gastric carcinogenesis, iatrogenic hypergastrinaemia may predispose to carcinoma. Gastric hypoacidity also increases gut bacterial infections, and the barrier function of acid against viral and prion infections requires further assessment.
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PMID:Long-term safety of proton pump inhibitors: risks of gastric neoplasia and infections. 1290 57

Gastroesophageal reflux disease is the most common malady of the esophagus, affecting 7% of the United States population. Histological assessment demonstrates classic inflammatory mechanisms including selective leukocyte recruitment and hemorrhage, suggesting a prominent role for the microvasculature. We isolated and characterized human esophageal microvascular endothelial cells (EC) (HEMEC), examined inflammatory activation in response to cytokines, LPS, and acidic pH exposure, and identified signaling pathways that underlie activation. HEMEC displayed characteristic morphological and phenotypic features including acetylated LDL uptake. TNF-alpha/LPS activation of HEMEC resulted in upregulation of the cell adhesion molecules (CAM) ICAM-1, VCAM-1, E-selectin, and mucosal addressin CAM-1 (MAdCAM-1), increased IL-8 production, and enhanced leukocyte binding. Both acid and TNF-alpha/LPS activation lead to activation of SAPK/JNK in HEMEC that was linked to VCAM-1 expression and U-937 leukocyte adhesion. Expression of constitutive inducible nitric oxide synthase in HEMEC was in marked contrast to intestinal microvascular endothelial cells. In this study, we demonstrate that HEMECs are phenotypically and functionally distinct from lower gut-derived endothelial cells and will facilitate understanding of inflammatory mechanisms in esophageal inflammation.
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PMID:Isolation and characterization of human esophageal microvascular endothelial cells: mechanisms of inflammatory activation. 1291 42

Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.
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PMID:Stress and the gastrointestinal tract. 1574 Apr 74

Functional chest pain is a common, yet poorly understood entity. The focus of this review is to explore the evolving research and clinical approaches with a particular emphasis on the sensory or afferent neuronal dysfunction of the esophagus as a key player in the manifestation of this pain syndrome. Although once regarded as a psychologic or esophageal motility disorder, recent advances have shown that many of these patients have visceral hyperalgesia. Whether visceral hypersensitivity is a central or peripheral perturbation of the gut-brain axis remains debatable. Response to empirical therapy with high-dose proton pump inhibitors, upper endoscopy, or prolonged recording of esophageal pH may identify gastroesophageal reflux disease as a source of chest pain. Esophageal balloon distension study can serve as a useful test for identifying hypersensitivity. Newer techniques, including functional magnetic resonance imaging, magnetoencephalogram, and cortical evoked potentials, are being investigated. High doses of proton pump inhibitors and low doses of tricyclic antidepressants or trazadone remain the mainstay of therapy, although several new approaches including theophylline have been shown to be beneficial.
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PMID:Functional chest pain: nociception and visceral hyperalgesia. 1579 86

Duodeno-gastro-esophageal reflux has been thought to induce Barrett's esophagus. Recently, we designed a new duodenal reflux model using rats, and studied sequential morphological changes of esophageal mucosa leading to Barrett's esophagus. A specialized columnar epithelium (SCE) developed 20 weeks after operation. Barrett's epithelium originated from pyloric-foveolar metaplasia of stem cells in the basal layer of the esophageal squamous epithelium. The pyloric-foveolar metaplasia was then followed by the appearance of goblet cells, becoming a typical SCE. The expression of homeobox gene Cdx2 was seen in this process, thereby suggesting a role of Cdx2 in intestinal differentiation of Barrett's esophagus. We noticed the pyloric-foveolar metaplasia followed by the appearance of goblet cells is common to entire gut in regenerative process, and proposed a concept of GRCL (gut regenerative cell lineage), and an implication of GRCL in digestive tract carcinogenesis was discussed.
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PMID:[Pathogenesis of Barrett's esophagus--new findings in the experimental studies of duodenal reflux models]. 1610 Dec 19

Most asthmatics have GER, and the evidence is strong that GER plays an important role in some patients who have asthma. Despite sophisticated study methods and technologically advanced diagnostic tests, the results of published studies on mechanisms have failed to provide a diagnostic test with a degree of certainty great enough to identify which patients have GER-induced or GER-exacerbated asthma and which patients will respond to antireflux therapy. The difficulties involved in establishing a definite cause-and-effect relationship between GER and asthma are real. Even positive results on such direct tests as sputum inspection and scintigraphic monitoring, both of which establish reflux into the tracheobronchial tree, do not necessarily establish cause or effect and cannot be used to predict outcomes. Ambulatory esophageal pH testing can suggest, but cannot prove, the diagnosis of GER-induced asthma, and pH testing cannot be relied on safely to make clinical decisions. A trial of a proton pump inhibitor (PPI) is indicated to assess if asthma improves subjectively and objectively, but the dose must be high enough to prevent even silent esophageal acid exposure, and the duration must be long enough to allow for detection of even subtle trends in subjective and objective respiratory improvement. Antireflux surgery remains a therapeutic option and should not be withheld if GER is a reasonable suspect in asthma exacerbations. Although strong opinions have been voiced as to whether or not a good response to PPI therapy predicts a good response to antireflux surgery, the opinions, although logical, are based on personal experience and gut feelings; a good PPI response may not necessarily predict a good surgery response. Opinions suggesting that a poor response to PPI predicts a poor response to antireflux surgery also may seem logical but are not based on clinical data; a poor PPI response may not necessarily predict a poor antireflux surgery response. When the method is found that predicts which patients who have GER and asthma will respond to antireflux treatment, the results could be profound: fewer hospitalizations for respiratory complications, less pulmonary morbidity and mortality, less need for pulmonary medications, less time lost from work, fewer visits to physicians' offices, and less illness associated with corticosteroid therapy. For the present, however, clinical judgment and good sense still are our best friends. It is not unreasonable to urge patients to alter their lifestyle: the huge volume, calorie-dense, high-fat meals eaten before bedtime are not likely to prevent GER or add to their life expectancy.
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PMID:The spectrum of pulmonary symptoms due to gastroesophageal reflux. 1610 26

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").
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PMID:A unifying hypothesis for the functional gastrointestinal disorders: really multiple diseases or one irritable gut? 1669 76

Dyspepsia itself is not a diagnosis but stands for a constellation of symptoms referable to the upper gastrointestinal tract. It consists of a variable combination of symptoms including abdominal pain or discomfort, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation. Patients with heartburn and acid regurgitation invariably have gastroesophageal reflux disease and should be distinguished from those with dyspepsia. There is a substantial group of patients who do not have a definite structural or biochemical cause for their symptoms and are considered to be suffering from functional dyspepsia (FD). Gastrointestinal motor abnormalities, altered visceral sensation, dysfunctional central nervous system-enteral nervous system (CNS-ENS) integration and psychosocial factors have all being identified as important pathophysiological correlates. It can be considered as a biopsychosocial disorder with dysregulation of the brain-gut axis being central in origin of disease. FD can be categorized into different subgroups based on the predominant single symptom identified by the patient. This subgroup classification can assist us in deciding the appropriate symptomatic treatment for the patient.
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PMID:Reassessment of functional dyspepsia: a topic review. 1671 48

An increasing body of evidence has accumulated in recent years supporting the existence of neural stem cells in the adult gut. There are at least three groups that have obtained them using different methodologies and have described them in vitro. There is a growing amount of knowledge on their biology, but many questions are yet unanswered. Among these questions is whether these cells are part of a permanent undifferentiated pool or are recruited in a regular basis; in addition, the factors and genes involved in their survival, proliferation, migration, and differentiation are largely unknown. Finally, with between 10 and 20% of adults suffering from diseases involving the enteric nervous system, most notably irritable bowel syndrome and gastroesophageal reflux, what is the possible role of enteric nervous stem cells in health and disease?
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PMID:Biology of the adult enteric neural stem cell. 1697 79

Endoluminal operations for reflux are currently limited by the inability to visualise and manipulate structures outside the wall of the gut. This may be possible using endoscopic ultrasound (EUS). The aim of this study was to define EUS-anatomy of structures outside the gut which influence reflux; to place stitches in the median arcuate ligament (MAL); to perform posterior gastropexy (Hill procedure) and test the feasibility of crural repair under EUS control in pigs. In survival experiments in 14 pigs, using linear array echo-endoscopes the MAL and part of the right crus were identified and punctured with a needle, which served as a carrier for a tag and thread. These were anchored into the muscle. An endoscopic sewing device was used allowing stitches to be placed through a 2.8 mm accessory channel to any predetermined depth. New methods allowed knot-tying and thread-cutting through the 2.8 mm channel of the echo-endoscope. Stitches were placed through the gastric wall into the MAL and one just beyond the wall of the lower esophageal sphincter (LES). They were tied together and locked against the gastric wall. Preoperative manometry showed a median LES pressure of 11 mm/Hg and 21 mm/Hg after stitch placement (p = 0.0028). The length of the LES increased from median 2.8 cm pre-procedure to 3.5 cm post-procedure. At post mortem, the force to pull the tags out of the MAL was 2.8 kg median. This study shows that transgastric gastro-esophageal reflux surgery using stitching under EUS control can significantly increase the lower oesophageal sphincter pressure in pigs.
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PMID:Endoluminal fundoplication--the Hill procedure. 1719 Jun 61


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