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)

Albeit remaining a controversial issue, it has become increasingly recognised that psychological stress has a major impact on gut mucosal function and affects the course of gastrointestinal disorders. Research during the last decade has shown that stress causes barrier dysfunction of the gastrointestinal mucosa by mechanisms that mainly involve neuropeptides and mast cells. Moreover, accumulating evidence implicates increased permeability as a pathogenic factor in gastroesophageal reflux disease (GORD). Recent data demonstrating that psychological stress may induce a permeability defect in stratified epithelia, including the oesophagus, shed new light on the pathophysiological events leading to heartburn and GORD.
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PMID:Stress-related changes in oesophageal permeability: filling the gaps of GORD? 1744 34

Infant colic is a common but poorly defined and understood clinical entity and, while several causative factors have been suggested, a unifying theory of its pathogenesis is still required. Food hypersensitivity/allergy and gut dysmotility are the lead contenders for causative factors of infantile colic. Additional confounders and covariables include psychological and social factors. Although the available data fail to provide insight into the exact triggers of infantile colic, these do allow for the hypothesis that certain infants are predisposed to dietary protein intolerance and disturbed gut motility, such as visceral hypersensitivity/ hyperalgesia, in the first few weeks of life. These processes lead to distress and altered perceptions, where normal stimuli (ie, intestinal distension) are misinterpreted as painful events. This review discusses a number of interventions, including pharmacological agents, which are based on the perceived pathogenesis; however, it is likely that infants with colic will require a multifactorial management strategy. Healthcare providers must offer support, reassurance and empathy to the caregiver, and adopt a biopsychosocial approach to the infants and their families by considering any underlying medical diseases in addition to examining the family unit. In a small subset of infants with colicky behavior, a specific medical disorder such as gastroesophageal reflux or milk protein allergy may be identified. While the vast majority of infants with colic will recover uneventfully, some may be at risk for the later development of behavioral problems and atopy/allergy.
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PMID:Update on infantile colic and management options. 1797 25

The concept of the gut forming the centre of an integrated gut-brain-energy axis - modulating appetite, metabolism and digestion - opens up new paradigms for drugs that can tackle multiple symptoms in complex upper gastrointestinal disorders. These include eating disorders, nausea and vomiting, gastroesophageal reflux disease, gastroparesis, dyspepsia and irritable bowel syndrome. The hormones that modulate gastric motility represent targets for gastric prokinetic drugs, and peptides that modify eating behaviours may be targeted to develop drugs that reduce nausea, a currently poorly treated condition. The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders.
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PMID:Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. 1830 13

Although the concept of purinergic signalling arose from experiments designed to find the identity of the non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter in the gut, it has taken many years for the more general importance of the various roles of ATP as a physiological messenger in the gut to be recognized. Firstly, vasoactive intestitial polypeptide (VIP) and later nitric oxide (NO) were considered the NANC transmitter and it was only later, after the concept of cotransmission was established, that ATP, NO and VIP were recognized as cotransmitters in NANC nerves, although the proportions vary in different gut regions. Recently, many purinoceptor subtypes have been identified on myenteric, submucosal motor, sensory and interneurons involved in synaptic neurotransmission and neuromodulation and reflex activity of several kinds, including ascending excitatory and descending inhibitory reflex pathways. Nucleotide receptors have been shown to be expressed on enteric glial cells and interstitial cells of Cajal. Purinergic mechanosensory transduction, involving release of ATP from mucosal epithelial cells during distension to stimulate subepithelial nerve endings of intrinsic and extrinsic sensory nerves to modulate peristalsis and initiate nociception respectively, is attracting current attention. Exciting new areas of interest about purinergic signalling in the gut include: involvement of purines in development, ageing and regeneration, including the role of stem cells; studies of the involvement of nucleotides in the activity of the gut of invertebrates and lower vertebrates; and the pathophysiology of enteric purinergic signalling in diseases including irritable bowel syndrome, postoperative ileus, oesophageal reflux, constipation, diarrhoea, diabetes, Chaga's and Hirschprung's disease.
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PMID:The journey to establish purinergic signalling in the gut. 1840 38

Barrett's esophagus, a squamous-to-columnar cell metaplasia that develops as a result of chronic gastroesophageal reflux disease (GERD), is a risk factor for esophageal adenocarcinoma. The molecular events underlying the pathogenesis of Barrett's metaplasia are poorly understood, but recent studies suggest that interactions among developmental signaling pathways, morphogenetic factors, and Caudal homeobox (Cdx) genes play key roles. Strong expression of Cdx genes normally is found in the intestine but not in the esophagus and stomach. When mice are genetically engineered so that their gastric cells express Cdx, the stomach develops a metaplastic, intestinal-type epithelium similar to that of Barrett's esophagus. Exposure to acid and bile has been shown to activate the Cdx promoter in certain esophageal cell lines, and Cdx expression has been found in inflamed esophageal squamous epithelium and in the specialized intestinal metaplasia of Barrett's esophagus. Barrett's metaplasia must be sustained by stem cells, which might be identified by putative, intestinal stem cell markers like leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and doublecortin and CaM kinase-like-1 (DCAMKL-1). Emerging concepts in tumor biology suggest that Barrett's cancers may develop from growth-promoting mutations in metaplastic stem cells or their progenitor cell progeny. This report reviews the roles of developmental signaling pathways and the Cdx genes in the development of normal gut epithelia and the potential mechanisms whereby GERD may induce the esophageal expression of Cdx genes and other morphogenetic factors that mediate the development of Barrett's metaplasia. The role of stem cells in the development of metaplasia and in carcinogenesis and the potential for therapies directed at those stem cells also is addressed.
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PMID:Acid, bile, and CDX: the ABCs of making Barrett's metaplasia. 1855 17

Non-erosive reflux disease (NERD) is a relatively new entity, the definition of which has been evolving and involves the use of symptoms, endoscopy, and objective evidence of reflux or reflux-related damage. The closest entity to NERD that is examined by available epidemiologic studies is defined by the presence of gastroesophageal reflux disease (GERD) symptoms in the absence of esophageal erosions or Barrett's esophagus. In this review, I identified two population-based studies, one non-community study, and several endoscopy-based studies that provided information on several aspects of NERD. Most of GERD is NERD (50-85%), and therefore one can estimate 11-12% of the general population and considerably higher proportions of patients presenting to endoscopy (37-87%) may have NERD. Risk factors for NERD including absence of hiatus hernia, low BMI, and presence of Helicobacter pylori indicate that it is a 'milder' part of the GERD spectrum. Other associations of NERD include younger age, female sex, and psychological comorbidities that resemble those of functional gut disorders. The temporal trends in NERD are unclear, and are probably increasing because GERD symptom prevalence has increased.
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PMID:Epidemiology of non-erosive reflux disease. 1883 34

Eosinophilic esophagitis (EE) is a chronic inflammatory, immunoallergic disease of the esophagus that represents the most common eosinophilic gut disease. Understanding and diagnosis regarding this condition have greatly increased in recent years, particularly in Europe and North America, in parallel with other allergic disorders. It consists of dense esophageal infiltration with eosinophils in the absence of gastro-esophageal reflux (GER). It involves individuals at all ages, and is particularly common in males during childhood and up to the 5th decade of life. It manifests with chronic, intermittent esophageal symptoms that predominantly include dysphagia, food impaction episodes, and GER-attributable complaints that do not respond to antisecretory therapy. Endoscopically, EE is a polymorphous disease that presents with various changes in esophageal caliber, and subtle changes in mucosal appearance, which lead to biopsy collection as a key procedure for diagnosis. Management must be multidisciplinary, including gastroenterologists, pathologists, allergologists, and also nutrition specialists in pediatric cases. Regarding therapy, dietary food restrictions are especially useful in the management of pediatric EE, but effectiveness is lower in the adult, maybe because of a greater involvement of air allergens. Drug use is standard, particularly involving topical steroids, which may revert manifestations and histological lesions, even though recurrence following discontinuation is common.
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PMID:Eosinophilic esophagitis -- clinical manifestations, diagnosis, and treatment. 1933 33

Gastro-esophageal reflux (GER) is a common phenomenon, characterized by the regurgitation of the gastric contents into the esophagus. Gastro-esophageal reflux disease (GERD) is the term applied when GER is associated with sequelae or faltering growth. The main aims of treatment are to alleviate symptoms, promote normal growth, and prevent complications. Medical treatments for children include (i) altering the viscosity of the feeds with alginates; (ii) altering the gastric pH with antacids, histamine H(2) receptor antagonists, and proton pump inhibitors; and (iii) altering the motility of the gut with prokinetics, such as metoclopramide and domperidone. Our aim was to systematically review the evidence base for the medical treatment of gastro-oesophageal reflux in children. We searched PubMed, AdisOnline, MEDLINE, and EMBASE, and then manually searched reviews from the past 5 years using the key words 'gastro-esophageal' (or 'gastroesophageal'), 'reflux', 'esophagitis', and 'child$' (or 'infant') and 'drug$' or 'therapy'. Articles included were in English and had an abstract. We used the levels of evidence adopted by the Centre for Evidence-Based Medicine in Oxford to assess the studies for all reported outcomes that were meaningful to clinicians making decisions about treatment. This included the impact of clinical symptoms, pH study profile, and esophageal appearance at endoscopy. Five hundred and eight articles were reviewed, of which 56 papers were original, relevant clinical trials. These were assessed further. Many of the studies considered had significant methodological flaws, although based on available evidence the following statements can be made. For infant GERD, ranitidine and omeprazole and probably lansoprazole are safe and effective medications, which promote symptomatic relief, and endoscopic and histological healing of esophagitis. Gaviscon(R) Infant sachets are safe and can improve symptoms of reflux. There is less evidence to support the use of domperidone or metoclopramide. More evidence is needed before other anti-reflux medications can be recommended. For older children, acid suppression is the mainstay of treatment. The largest evidence base supports the early use of H(2) receptor antagonists or proton pump inhibitors.
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PMID:Current pharmacological management of gastro-esophageal reflux in children: an evidence-based systematic review. 1944 47

Gabapentin is a gamma-aminobutyric acid analog used for numerous neurologic conditions, including neuropathic pain and epilepsy. We describe a 39-week gestational age, male infant with hypotonicity, functional short gut, and microduplication of chromosome 22 who was treated with gabapentin to control pain and irritability. During his hospitalization, the infant experienced multiple complications including respiratory distress, persistent pulmonary hypertension of the newborn, hypocalcemia, hypoglycemia, hyperbilirubinemia, gastroesophageal reflux, necrotizing enterocolitis, and cholestatic jaundice. Pain associated with related invasive procedures and surgeries was treated with intermittent and scheduled morphine. In addition to postoperative and procedural pain, the infant continued to experience pain and irritability attributed to neurologic impairment, presumably secondary to his chromosomal abnormality. Trials of scheduled lorazepam along with intermittent morphine and phenobarbital were unsuccessful in managing these symptoms. After failure of nonpharmacologic treatment and continued trials of sedatives and analgesics, gabapentin 5 mg/kg at bedtime was started on day of life 98. Improvement in the infant's tone and disposition was noted by numerous health care professionals and the infant's mother. In addition, the infant's pain scores, using the Pain Assessment in Neonates Scale, showed marked improvement. The infant continued to receive gabapentin; the dosage was increased to 10 mg/kg at bedtime after 6 days, then to 5 mg/kg in the morning and 10 mg/kg at bedtime 10 days later. When the infant was 7 months old, his mother requested that gabapentin be discontinued. He was slowly weaned, and the drug was discontinued when he was 11 months old. The infant tolerated gabapentin well except for experiencing nystagmus, which was noted 31 days after starting the drug and resolved after drug discontinuation. Clinicians should be aware of gabapentin as an alternative treatment for pain and irritability in neurologically impaired infants. Further study is needed, however, to verify the drug's safety and efficacy in neonates and infants. Standardized pain scales along with close patient monitoring will help to guide clinicians in dosage titration to optimize therapy.
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PMID:Gabapentin therapy for pain and irritability in a neurologically impaired infant. 1963 54

Australian surgeons have been prominent in the introduction, development, and consolidation of laparoscopic surgery of the upper gut. In doing this, some of the very best principles of surgical innovation have been in evidence: preliminary animal work in which to test hypotheses and techniques, followed by careful application and documentation in the clinical setting, randomized clinical trials and finally academic reporting and ongoing development. This review documents the introduction of laparoscopic surgery for gastroesophageal reflux, hiatus hernia, achalasia, gastroesophageal malignancy, obesity, and a range of emergency conditions in Australia. Those involved are regarded as world leaders in their field. A vital component of this success has been the close cooperation between surgeons and gastroenterologists within the Gastroenterological Society of Australia.
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PMID:Laparoscopic upper gut surgery. 1979 92


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