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 lower oesophageal high pressure zone (HPZ) was studied in 5 non-refluxing and 3 refluxing Rhesus monkeys. The changes in HPZ and reflux status in response to infusion of various doses of secretin, cholecystokinin and glucagon were measured in all animals, and, in the 5 non-refluxing monkeys, after oesophagogastrectomy with replacement of the lower oesophagus by a stomach tube. All three hormones consistently produced a transient decrease in the HPZ pressure. The only change in response following oesophagagastrectomy and gastric tube replacement was a significant delay in the response to each hormone. Neither hormone infusion nor operation altered gastro-oesophageal reflux status. It appears that lower oesophageal competence in primates is more dependent on the presence of narrow, muscular, intra-abdominal tube than on a specialized segment of the lower oesophagus.
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PMID:Effect of gastrointestinal hormone infusions of lower oesophageal competence of rhesus monkeys. 9 6

Fourteen patients with clinically obvious gastro-oesophageal reflux were examined by conventional barium meal radiology. Neither exogenous penta-gastrin nor cholecystokinin appeared to influence the radiological competence of the gastro-oesophageal junction in ten of thos patients. The remaining four patients were used as controls and normal saline was injected instead of the active preparation. Radiological competence was unaffected. The significance of these findings is discussed.
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PMID:The effect of penta-gastrin and cholecystokinin on radiological gastro-oesophageal competence. 120 44

Smooth muscle specimens were taken from the lower esophageal sphincter of patients suffering from achalasia or hiatus hernia with gastro-esophageal reflux. The specimens were analysed for neurohormonal peptides using immunochemistry and immunocytochemistry. Control specimens were obtained from patients subjected to esophageal resection because of esophageal cancer. The concentration of vasoactive intestinal polypeptide (VIP) was higher and the VIP nerve supply greater in patients with hiatus hernia than in control patients. The VIP nerve supply and the content of this peptide was lower in patients with achalasia than in controls. The same tendency was observed for substance P and enkephalin although the changes in their concentrations were not statistically significant. Enkephalin fibers were few, both in specimens from control patients and from patients with hiatus hernia; they could not be detected in specimens from patients with achalasia. Never fibers containing somatostatin or gastrin/cholecystokinin could not be detected in any of the groups and somatostatin and gastrin/cholecystokinin could not be measured in extracts of the lower esophageal sphincter. We propose that changes in the concentration of neuropeptides may at least contribute to manifestations of achalasia and of decreased lower esophageal sphincter pressure and gastro-esophageal reflux.
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PMID:Regulatory peptides in the lower esophageal sphincter of man. 258 Dec 86

Experimental achalasia dogs produced with Deloyer's method showed higher resting pressure at the gastroesophageal junction and the increase in LES pressure in response to tetragastrin and cholecystokinin. Dose-response curve of the LES to each dose of tetragastrin in achalasia dog shifted to the left. Resting LES pressure in 11 patients with achalasia was 42.73 +/- 23.31 cm H2O. It increased significantly after intramuscular injection of 5 micrograms/kg of tetragastrin and fluoroscopic observation showed the tonic contraction of the lower esophagus and cardia. After the performance of Jekler-Lhotka operation, LES pressure decreased to lower values sufficient to prevent the gastroesophageal reflux. Comparing 5 kinds of hiatal herniorrhaphies in dogs, LES pressure increased postoperatively in the following order: Nissen, Belsey Mark IV, Stensrud, Hill and Harrington methods. Responses to tetragastrin increased after Nissen and Belsey Mark IV methods. In 12 out of 21 clinical cases of sliding esophageal hiatal hernia who had undergone Nissen-Rossetti method adding fundopexy and posterior gastropexy, preoperative esophageal manometry showed HPZ of 24.98 +/- 8.87 cm H2O in peak value and 5.1 +/- 3.46 cm in length. Seven cases showed the biphasic pattern and 5 cases showed the negative response to tetragastrin. Postoperative manometry showed HPZ of 31.42 +/- 18.46 cm H2O in peak value and 4.5 +/- 1.73 cm in length. One case showed the biphasic pattern and 3 cases showed the negative response to tetragastrin.
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PMID:[Gastrointestinal hormones and operations for achalasia of the esophagus and sliding esophageal hiatal hernia: their surgical significance]. 408 31

The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the number of reflux episodes was investigated in six healthy subjects. LOS pressure was recorded on four separate occasions during continuous intravenous infusion of either saline or CCK-33 in doses of 0.25, 0.5, or 1.0 Ivy Dog units per kg body weight per hour (IDU.kg-1.h-1) for 90 minutes. Plasma CCK concentrations did not change during saline infusion, but increased significantly from 2.5 (0.3) pmol/l to steady state levels of 4.0 (0.4) pmol/l, 6.1 (0.4) pmol/l, and 9.3 (0.9) pmol/l respectively starting from 30 minutes. LOS pressure did not change significantly during infusion of saline or of CCK-33 at doses of 0.25 or 0.5 IDU.kg-1.h-1. However, a significant (p < 0.05) reduction in LOS pressure to a minimum level of 12 (4) mm Hg at 30 minutes compared with basal level (18 (4) mm Hg) and compared with saline was observed during infusion of CCK-33 at a dose of 1.0 IDU.kg-1.h-1. In addition, oesophageal motility and pH were recorded simultaneously in these six subjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) combined with continuous intravenous infusion of saline or CCK-33 at a dose of 1.0 IDU,kg-1.h-1. Plasma CCK concentrations did not change during the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infusion of CCK. The number of transient LOS relaxations increased significantly in the first hour during administration of the gastric load compared with fasting levels, both during saline infusion (fasting: 1.7 (0.6)/h, 1st hour: 4.3 (1.2)/h) and during CCK infusion (fasting: 1.7 (0.5)/h, 1st hour: 3.8 (0.7)/h). In the second and third hours the number of transient LOS relaxations fell to fasting levels in both experiments. No significant differences were observed in the number and type of transient LOS relaxations, mechanism of gastro-oesophageal reflux, or duration of acid exposure between the two experiments. It is concluded that in healthy subjects infusion of CCK-33 in a dose of 1.0 IDU.kg-1.h-1 significantly reduces LOS pressure but does not affect the frequency of transient LOS relaxations or acid exposure time during a continuous liquid gastric load.
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PMID:Effect of cholecystokinin on lower oesophageal sphincter pressure and transient lower oesophageal sphincter relaxations in humans. 755 91

Cholecystokinin (CCK) belongs to the group of substances known as brain-gut peptides: it functions both as a neuropeptide and a gut hormone. The peptide and its synthetic derivatives (like for instance CCK-8 and the amphibian counterpart caerulein) significantly delay emptying of gastric contents in both animals and humans. The fact that CCK, in doses mimicking postprandial plasma levels, strongly affects emptying rate suggests the peptide to be a physiologic regulator of gastric emptying. Unfortunately, clear definition of the role of CCK in the physiology of gastric motor activity has long been hampered by the lack of specific and potent non-peptide antagonists of CCK-receptors. The availability of such compounds has stimulated a broad array of investigations into the physiological actions of this hormone and examination of its putative role in certain diseases. This paper summarizes the available data concerning the effect of CCK and its antagonists on gastric emptying. The use of selective CCK-antagonists has allowed to establish that the gastric motor effect of the peptide is direct and mediated through the stimulation of CCK-A receptors. As a consequence, CCK-A antagonism results in acceleration of emptying rate under certain experimental and clinical conditions. This peculiar pharmacologic effect of CCK-A antagonists, which could be useful in the treatment of functional dyspepsia (idiopathic or diabetic), gastroparesis and gastro-esophageal reflux disease (where patients often display a delayed emptying rate of solid food) needs to be further investigated, in order to fully explore their potential as gastrokinetic drugs.
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PMID:Effect of CCK and its antagonists on gastric emptying. 829 6

Basal and postprandial levels of the foregut hormones gastrin, cholecystokinin (CCK), motilin, and pancreatic polypeptide, and the distal gut hormones neurotensin and peptide YY were measured in 20 patients with gastroesophageal reflux disease (GERD). GERD was defined by abnormal esophageal exposure to pH less than 4. Ten GERD patients had decreased lower esophageal sphincter (LES) pressure (mean: 4.5 mm Hg, range: 0.8 to 6.8 mm Hg), and 10 patients had normal LES pressures (mean: 14.1 mm Hg, range: 9.7 to 22.4 mm Hg). Eight age-matched healthy subjects were also studied. Basal levels of peptide YY were moderately decreased in GERD patients compared with controls irrespective of LES pressure. In patients with abnormal LES pressure, basal levels of motilin and the postprandial response of CCK were significantly decreased compared with controls; and basal levels of neurotensin and the postprandial response of gastrin were significantly increased compared with controls. Pancreatic polypeptide levels were similar in all groups. These gut hormone changes, which are more marked in patients with poor LES pressure, may reflect primary or secondary abnormalities in GERD.
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PMID:Gastroesophageal reflux disease is associated with enteric hormone abnormalities. 831 Nov 31

Feeding problems, anorexia and vomiting are common in infants and children with chronic renal failure (CRF), and play a major role in the growth failure often found in this condition. However, the gastroenterological and nutritional aspects of CRF in children have received little attention, hence therapeutic interventions are usually empirical and often ineffective. Gastritis, duodenitis and peptic ulcer are often found in adults with CRF on regular haemodialysis and following renal transplantation. Despite persistent hypergastrinaemia, gastric acid secretion is decreased rather than increased in most of these patients, and active peptic disease appears to be promoted by the removal of the acid output inhibition (neutralisation of gastric acid by ammonia) that follows active treatment. Helicobacter pylori, on the other hand, does not seem to play a significant role in the pathogenesis of peptic disease in CRF. Gastro-oesophageal reflux has been found in about 70% of infants and children with CRF suffering from vomiting and feeding problems, and thus appears to be a major problem in these patients. In a number of symptomatic patients with CRF, gastric dysrhythmias and delayed gastric emptying have also been found; hence there appears to be a complex disorder of gastrointestinal motility in CRF. Serum levels of several polypeptide hormones involved in the modulation of gastrointestinal motility [e.g. gastrin, cholecystokinin (CCK), neurotensin] and the regulation of hunger and satiety (e.g. glucagon, CCK) are significantly raised as a consequence of renal insufficiency, and can be reverted to normal by renal transplantation. Furthermore, several other humoral abnormalities (e.g. hypercalcaemia, hypokalaemia, acidosis, etc.) are not uncommon in CRF. By directly affecting the smooth muscle of the gut or stimulating particular areas within the central nervous system, all these humoral alterations may well play a major role in the gastrointestinal dysmotility, anorexia, nausea and vomiting in patients with CRF. Specific pharmacological and nutritional interventions should thus be considered for the treatment of vomiting and feeding problems in CRF.
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PMID:Gastrointestinal function in chronic renal failure. 874 22

Esophageal peristalsis and lower esophageal sphincter(LES) function have an influence on gastroesophageal reflux disease(GERD). Incomplete contraction during primary and secondary peristalsis leads to poor clearance of refluxed gastric acid. Failure of LES function can result in a low basal LES pressure, absent or incomplete LES relaxation after swallowing, or an inadequate increase of LES pressure accompanying gastric activity. In addition, transient LES relaxation(TLESR) has been suggested as an important factor in GERD. Recent studies have indicated that TLESR has a relationship to nitric oxide(NO) and cholecystokinin(CCK).
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PMID:[Esophageal peristalsis, lower esophageal function, and the methods of their evaluation]. 1100 11

Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism of reflux in patients with gastroesophageal reflux disease. They are therefore attractive targets for pharmacotherapy. During the past 5 years, there has been a burgeoning interest in the neural pathways that control these events and in the pharmacologic receptors involved in these pathways. Several agents have been shown to reduce the rate of TLESRs, including cholecystokinin-A antagonists, anticholinergic agents, nitric oxide synthase inhibitors, morphine, somatostatin, serotonin type 3-receptor antagonists, and gamma-aminobutyric acid-B (GABA(B)) agonists. Their predominant site of action appears to be on either the afferent pathways and/or the central integrative mechanisms within the dorsal vagal complex in the brainstem. Most of the agents tested are unsuitable for clinical use either because of side effects or because of the lack of an orally effective formulation. The most promising agents identified to date are the GABA(B) agonists. Baclofen, the prototype GABA(B) agonist, inhibits the rate of TLESRs by more than 50%. Control of TLESRs is a major new approach to the treatment of reflux disease. It is likely to be applicable to the majority of patients, particularly those without macroscopic mucosal lesions or only mild erosive disease. Further development of more effective agents will depend both on a better understanding of the neural pathways and receptors involved in the control of TLESRs, as well as on investigation of other novel agents. At present, inhibition of TLESRs is at the threshold of transition from concept to practical use. Whether it makes the final leap into the mainstream of therapy will depend on the development of new, novel, and well-targeted pharmacologic agents.
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PMID:Systemic pharmacomodulation of transient lower esophageal sphincter relaxations. 1174 47


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