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)

The presence of esophageal lesions and gastroesophageal reflux disease (GERD) symptoms do not coincide in some patients: some individuals suffer from the symptoms of GERD but have no evidence of GERD at endoscopy; while conversely, some with endoscopic evidence of GERD do not experience symptoms. In order to combine both healing of esophageal lesions and the presence of symptoms when measuring treatment efficacy, the concept of complete remission has been redefined to include both parameters. Until recently, an effective means of measuring GERD symptoms and response to therapy had been lacking. The symptomatic reflux questionnaire ReQuest(TM) was therefore developed; it is a validated, self-administered, hierarchical, dimension-oriented scale to assess response of a broad range of symptoms to treatment. It measures the frequency and intensity of seven symptom dimensions: acid complaints; upper abdominal complaints; lower abdominal complaints; nausea; sleep disturbances; other complaints; and general well-being (intensity only). ReQuest(TM) has recently been combined with an adaptation of the Los Angeles classification for endoscopic measurement of GERD, thus linking the assessment of symptom relief and healing of esophageal lesions. The new ReQuest(TM)/ LA-classification enables the detailed clinical characterization of GERD patients at any stage and accurate assessment of treatment outcome by a single global measure.
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PMID:The complete remission concept. 1698 66

This study reviews current data regarding duodenogastric and gastroesophageal bile reflux-pathophysiology, clinical presentation, methods of diagnosis (namely, 24-hour intraluminal bile monitoring) and therapeutic management. Duodenogastric reflux (DGR) consists of retrograde passage of alkaline duodenal contents into the stomach; it may occur due to antroduodenal motility disorder (primary DGR) or may arise following surgical alteration of gastoduodenal anatomy or because of biliary pathology (secondary DGR). Pathologic DGR may generate symptoms of epigastric pain, nausea, and bilious vomiting. In patients with concomitant gastroesophageal reflux, the backwash of duodenal content into the lower esophagus can cause mixed (alkaline and acid) reflux esophagitis, and lead, in turn, to esophageal mucosal damage such as Barrett's metaplasia and adenocarcinoma. The treatment of DGR is difficult, non-specific, and relatively ineffective in controlling symptoms. Proton pump inhibitors decrease the upstream effects of DGR on the esophagus by decreasing the volume of secretions; promotility agents diminish gastric exposure to duodenal secretions by improving gastric emptying. In patients with severe reflux resistant to medical therapy, a duodenal diversion operation such as the duodenal switch procedure may be indicated.
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PMID:[Duodenogastric and gastroesophageal bile reflux]. 1728 81

ReQuest is a self-reported questionnaire developed to assess, during clinical trials investigating GERD with or without oesophagitis, not only heartburn and acid regurgitation, but the broad spectrum of GERD symptoms. ReQuest comprises 2 sub-scales: ReQuest-GI which covers the 4 dimensions related to gastrointestinal symptoms (acid complaints, upper abdominal/stomach complaints, lower abdominal/digestive complaints, and nausea) and ReQuest-WSO which analyses the three other dimensions (general well-being, sleep disturbances, and other complaints). This self-reported questionnaire, which is completed daily, is available in two forms: a short version quantifying the intensity (10-cm VAS) and frequency (7-point Likert scale) of each of the six main dimensions of the scale and the intensity only of the general well-being dimension, and a longer version which includes, in addition to a global evaluation, a detailed analysis of all the symptoms contributing to each dimension. ReQuest is a tool with proven metrological strengths, enabling the investigators to follow--on a daily, multidimensional and reliable basis--the evolution of GERD in the course of clinical trials. Both versions, the long and the short, have identical metrological qualities.
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PMID:ReQuest: a new questionnaire for the simultaneous evaluation of symptoms and well-being in patients with gastro-oesophageal reflux. 1748 36

Rikkunshito (TJ-43), a herbal medicine consisting of eight herbs, is used to treat chronic dyspepsia. Studies have shown that TJ-43 improves human gastric emptying. This study investigated the effects of TJ-43 on the clinical symptoms and esophageal acid exposure in children with symptomatic gastroesophageal reflux (GER). Eight children, aged from 2 months to 15 years (median age 4 years), were studied. Six of them had neurological impairment. TJ-43 (0.3 g/kg/day) was given orally or via nasogastric tubes in three divided doses before meals for 7 days. Their symptoms were frequent emesis in four, nausea in two, and hematemesis and stridor in one each. Twenty-four-hour esophageal pH monitoring was conducted using multichannel pH electrodes located at the distal esophagus (P1) and 10 cm proximal to P1 (P2). The clinical symptoms and esophageal pH were compared before and after TJ-43 therapy for 1 week. The frequency of emesis decreased in three patients. Other symptoms, including nausea, hematemesis, and stridor, were relieved in the remaining patients. Measured at the distal pH electrode, the percentage time of esophageal pH < 4.0 and the mean duration of reflux decreased significantly (P < 0.05). However, the number of acid reflux per hour did not change significantly, and no pH parameters measured at the proximal electrode differed significantly. The short-term administration of TJ-43 relieved symptoms and reduced the distal esophageal acid exposure through improved esophageal acid clearance.
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PMID:Effects of rikkunshito on the clinical symptoms and esophageal acid exposure in children with symptomatic gastroesophageal reflux. 1766 23

Cannabinoid (CB1) receptor activation acts neuronally, reducing GI motility, diarrhoea, pain, transient lower oesophageal sphincter relaxations (TLESRs) and emesis, and promoting eating. CB2 receptor activation acts mostly via immune cells to reduce inflammation. What are the key questions which now need answering to further understand endocannabinoid pathophysiology? GPR55. Does this receptor have a GI role? Satiety, Nausea, Vomiting, Gastro-Oesophageal Reflux, Gastric Emptying. Endocannabinoids acting at CB1 receptors can increase food intake and body weight, exert anti-emetic activity, reduce gastric acid secretion and TLESRs; CB2 receptors may have a small role in emesis. Question 1: CB1 receptor activation reduces emesis and gastric emptying but the latter is associated with nausea. How is the paradox explained? Q2: Do non-CB receptor actions of endocannabinoids (for example TRPV1) also modulate emesis? Q3: Is pathology necessary (gastritis, gastro-oesophageal reflux) to observe CB2 receptor function? Intestinal Transit and Secretion. Reduced by endocannabinoids at CB1 receptors, but not by CB2 receptor agonists. Q1: Do the effects of endocannabinoids rapidly diminish with repeat-dosing? Q2: Do CB2 receptors need to be pathologically upregulated before they are active? Inflammation. CB1, CB2 and TRPV1 receptors may mediate an ability of endocannabinoids to reduce GI inflammation or its consequences. Q1: Are CB2 receptors upregulated by inflammatory or other pathology? Pain. Colonic bacterial flora may upregulate CB2 receptor expression and thereby increase intestinal sensitivity to noxious stimuli. Q1: Are CB2 receptors the interface between colonic bacteria and enteric- or extrinsic nerve sensitivity? Relevance of endocannabinoids to humans. Perhaps apart from appetite, this is largely unknown.
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PMID:Endocannabinoids and the gastrointestinal tract: what are the key questions? 1776 70

Functional dyspepsia is a highly prevalent disorder that accounts for 5% of visits to primary care clinicians. It frequently coexists with other gastrointestinal tract disorders, including irritable bowel syndrome and gastroesophageal reflux disease. Symptoms of functional dyspepsia, including epigastric pain, early satiety, and postprandial nausea, are nonspecific, making its diagnosis difficult. Functional dyspepsia is a heterogeneous disorder involving a number of different pathophysiologic processes, culminating in both gastrointestinal sensory and motor dysfunction. Although functional dyspepsia does not impart any increased risks to long-term health, it significantly affects both individuals and society. The economic burden of evaluating and treating functional dyspepsia is estimated to be at least $1 billion per year, and patients with functional dyspepsia experience a markedly reduced quality of life. Using the case of Ms C, we apply an evidence-based approach to highlight current knowledge in the diagnosis, evaluation, and treatment of functional dyspepsia.
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PMID:A 32-year-old woman with chronic abdominal pain. 1816 96

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

We have previously demonstrated that the prototypical GABA B receptor agonist baclofen inhibits transient lower esophageal sphincter relaxations (TLESRs), the most important mechanism for gastroesophageal reflux. Thus, GABA B agonists could be exploited for the treatment of gastroesophageal reflux disease. However, baclofen, which is used as an antispastic agent, and other previously known GABA B agonists can produce CNS side effects such as sedation, dizziness, nausea, and vomiting at higher doses. We now report the discovery of atypical GABA B agonists devoid of classical GABA B agonist related CNS side effects at therapeutic doses and the optimization of this type of compound for inhibition of TLESRs, which has resulted in a candidate drug ( R)- 7 (AZD3355) that is presently being evaluated in man.
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PMID:Synthesis and pharmacological evaluation of novel gamma-aminobutyric acid type B (GABAB) receptor agonists as gastroesophageal reflux inhibitors. 1857 71

Rabeprazole is a proton pump inhibitor that can be used in the treatment of acid-peptic-related disorders (gastroesophageal reflux disease [GERD], duodenal ulcer, gastric ulcer, gastric acid hypersecretory syndromes) and Helicobacter pylori. Pharmacodynamic data has demonstrated that rabeprazole, with a high pKa of approximately 5.0, can be activated at a higher pH than other proton pump inhibitors. This possibly results in faster onset of action. Owing to its non-enzymatic pathway of metabolism, rabeprazole is also less influenced by genetic polymorphisms of the CYP2C19, which others proton pump inhibitors are dependent on. In a 2-week, placebo-controlled trial, rabeprazole was both rapid and effective in relieving heartburn on day 1 of therapy and improved other GERD-related symptoms including regurgitation, belching, bloating, early satiety and nausea. For oesophageal reflux disease without erosions both 10 and 20 mg of rabeprazole are equivalent and better than placebo at 2 and 4 weeks. An on-demand approach to non-erosive reflux disease with 10 mg of rabeprazole has also been documented as superior to placebo. Some success in the treatment of extra-oesophageal manifestations of GERD, such as asthma and chronic laryngitis, has also been achieved with rabeprazole. Overall, rabeprazole with very few side effects is a safe and efficacious medication for acid suppression therapy.
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PMID:Rabeprazole: a pharmacologic and clinical review for acid-related disorders. 1923 23

Bariatric surgery dramatically alters the normal stomach anatomy resulting in a significant incidence of hiatal hernia and gastroesophageal reflux disease. Although the majority of patients remain asymptomatic, many complain of severe heartburn refractory to medical management and additional highly atypical symptoms. Here, we describe the diagnosis and treatment regarding four cases of symptomatic hiatal hernia following bariatric surgery presenting with atypical symptoms in the University Hospital, USA. Four patients presented following laparoscopic Roux-en-Y gastric bypass or duodenal switch/pancreaticobiliary bypass (DS) with disabling and intractable midepigastric abdominal pain characterized as severe and radiating to the jaw, left shoulder, and midscapular area. The pain in all cases was described as paroxysmal and not necessarily associated with eating. All four patients also experienced nausea, vomiting, and failure to thrive at various intervals following laparoscopic bariatric surgery. Routine workup failed to produce any clear mechanical cause of these symptoms. However, complimentary use of multidetector CT and upper gastrointestinal contrast studies eventually revealed the diagnosis of hiatal hernia. Exploration identified the presence of a type I hiatal hernia in all four patients, with the stomach staple lines densely adherent to the diaphragm and parietal peritoneum. Operative intervention led to immediate and complete resolution of symptoms. The presence of a hiatal hernia following bariatric surgery can present with highly atypical symptoms that do not resolve without operative intervention. Recognition of this problem should lead to the consideration of surgery in cases where patients are dependent on artificial nutritional support and whose symptoms are poorly controlled with medication alone.
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PMID:Diagnosis and treatment of atypical presentations of hiatal hernia following bariatric surgery. 1985 36


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