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 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

It is anticipated that unraveling the human genome will have a direct impact on the management of specific diseases. Variations or mutations in genes involved in drug metabolism or disease pathophysiology in gastroenterology and hepatology are expected to have effect on response to therapy. The spectrum of diseases is vast. Thus, we focus this review on clinical pharmacogenetics of inflammatory bowel disease, Helicobacter pylori infections, gastroesophageal reflux disease, irritable bowel syndrome, liver transplantation, and colon cancer. Although only a few genotyping tests are used regularly in clinical practice, we anticipate that in the future there will be more routine use of many of the tests described in this review.
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PMID:Pharmacogenomics in gastrointestinal disorders. 1837 Feb 39

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

Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by symptoms originating from the gastroduodenal region in the absence of underlying organic disease that readily explains the symptoms. The Rome II consensus, which defined FD as the presence of unexplained pain or discomfort in the epigastrium, had a number of drawbacks, including an unjustified focus on pain, inclusion of a large number of nonspecific symptoms, and an unclear position on overlap with gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). The Rome III consensus redefined FD as the presence of epigastric pain or burning, postprandial fullness or early satiation in the absence of underlying organic disease. Frequent overlap with GERD and IBS is acknowledged but does not exclude a diagnosis of FD. A subgroup classification into postprandial distress syndrome and epigastric pain syndrome was proposed. Ongoing studies will clarify the impact of this subdivision on clinical management and treatment outcomes.
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PMID:Functional dyspepsia: past, present, and future. 1845 39

The enterochromaffin cells of the gastrointestinal (GI) tract secrete 400 times as much melatonin as the pineal gland; therefore, it is not surprising that research is finding that this indole plays an important role in GI functioning. In animal studies, it protects against GI ulcerations, and randomized clinical trials suggest its efficacy in treating functional dyspepsia and irritable bowel syndrome. Melatonin administration has been shown to protect against esophageal lesions in animals. Moreover, in a randomized, single-blind clinical trial of subjects with gastroesophageal reflux disease (GERD), the combination of melatonin with other natural supplements was found to be superior to omeprazole, a proton pump inhibitor (PPI). Its administration as a single treatment for GERD has not been previously reported. A 64-year-old Caucasian female who required treatment with a PPI for symptoms of GERD wished to substitute a natural treatment because of the risk of worsening her osteoporosis. She experienced a return of symptoms following each of three 20-day trials of a proprietary blend of D-limonene when attempts were made to discontinue the PPI. She then underwent a trial of a natural formula consisting of melatonin 6 mg, 5-hydroxytryptophan 100 mg, D,L-methionine 500 mg, betaine 100 mg, L-taurine 50 mg, riboflavin 1.7 mg, vitamin B6 0.8 mg, folic acid 400 microg, and calcium 50 mg. After 40 days, the PPI was withdrawn without a return of symptoms. Subsequently, an attempt to reduce melatonin to 3 mg resulted in symptoms, while all other ingredients were withdrawn with minimal symptoms during 10 months of follow-up.
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PMID:Melatonin for the treatment of gastroesophageal reflux disease. 1861 70

Population-based studies have shown that gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) coexist more commonly than expected by chance. We aimed to investigate the relationship between GERD and IBS in primary care. The General Practice Research Database was used to identify patients with a first diagnosis of GERD (n=6,421) or IBS (n=2,932). Patients were followed up for 12 months after diagnosis to investigate the incidence of IBS among GERD patients and GERD among IBS patients. The relative risk (RR) of developing IBS was 3.5 (95% CI: 2.3-5.4) in the GERD cohort compared with the comparison cohort. The RR of developing GERD was 2.8 (95% CI: 1.7-4.9) in the IBS cohort compared with the comparison cohort. A first diagnosis of either IBS or GERD significantly increases the risk of a subsequent diagnosis of the other condition.
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PMID:Irritable bowel syndrome and gastroesophageal reflux disease in primary care: is there a link? 1872 2

Gastrointestinal problems account for a significant proportion of general practitioners' workload, and gastrointestinal cancers, taken together, make up the largest group of malignancies. Approximately 10% of consultations in general practice in the UK are for gastrointestinal symptoms or problems, split roughly equally between the upper and lower gastrointestinal tract. Gastroenterology represents about 10% of the work of hospital specialists and the prescribing costs involved in the management of gastrointestinal disorders in general practice are around 14% of the drug budget. These disorders range from relatively minor and self limiting conditions such as acute gastritis and acute gastroenteritis, through the more significant, chronic digestive disorders such as gastro-oesophageal reflux disease (GORD), irritable bowel syndrome (IBS) and coeliac disease, to much more serious problems including inflammatory bowel disease (IBD) and upper gastrointestinal and colorectal cancer.
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PMID:Primary care research and clinical practice: gastroenterology. 1894 Sep 46

The 12th Update in Gastroenterology and Hepatology for the Primary Care Practitioner is an annual course organized by the Division of Gastroenterology and Hepatology at the University of California, Davis, and held in beautiful Monterey, California. The course was geared towards primary care physicians, nurse practitioners and other allied health professionals. The goals of this symposium were to provide current information regarding the diagnosis and management of digestive diseases commonly seen in the primary care setting and to provide practical guidelines for disease management. Topics covered during this symposium included viral hepatitis, alcoholic liver disease, hepatocellular carcinoma, dysphagia, gastroesophageal reflux disease, chronic diarrhea, inflammatory bowel disease, irritable bowel syndrome, dyspepsia, gastroparesis and bariatric surgery. The course was organized into two sessions each morning, over 2 days, with three or four 30-min lectures. A brief question-and-answer session followed each lecture.
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PMID:12th Update in Gastroenterology and Hepatology for the Primary Care Practitioner. 1907 40

Up to 79% of IBS patients report gastroesophageal reflux disease (GERD) symptoms, and up to 71% of GERD patients report irritable bowel syndrome (IBS) symptoms. There are two principal hypotheses for the common presence of IBS symptoms in GERD patients. The first theory suggests that GERD and IBS overlap in a significant number of patients. The second theory suggests that IBS-like symptoms are part of the spectrum of GERD manifestation. The first theory is supported by genetic studies and similarities in gastrointestinal sensory-motor abnormalities potentially due to general gastrointestinal disorder of smooth muscle or sensory afferents. The other theory is primarily supported by studies demonstrating improvement of IBS-like symptoms in GERD patients receiving anti-reflux treatment. The close relationship between GERD and IBS could be explained by either GERD affecting different levels of the GI tract or a high overlap rate between GERD and IBS due to similar underlying GI dysfunction.
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PMID:Gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS)--is it one disease or an overlap of two disorders? 1908 21

Studies comparing pH-metrically well-characterized gastro-oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24-h pH-monitoring (pH+), defined as pH<4 > or = 6% of time. A symptom index (SI) > or = 50% was considered positive, as well as a symptom association probability (SAP) > or = 95%. We included 84 GORD patients with physiological acid exposure (pH-) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND-36 quality of life scale. pH- patients were younger (45 vs 50 years, P = 0.003), more often female (60%vs 39%, P = 0.001), smoked more (31%vs 19%, P = 0.021) and reported proton pump inhibition failure more often (47%vs 32%, P = 0.027). A hypotensive lower oesophageal sphincter was less common in pH- patients (18%vs 34%, P = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P = 0.045). pH- patients had hiatal hernia and oesophagitis less often (48%vs 73%, P < 0.0005; 36%vs 54%, P = 0.012 respectively). pH- patients less often reported no other symptoms besides GORD (20%vs 34%, P = 0.015). pH- patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P < 0.0005; dyspepsia 54 vs 38 out of 156, P < 0.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.
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PMID:Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum. 1923 23


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