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)

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathogenesis of chronic persistent cough associated with gastroesophageal reflux. 811 76

Using our newly developed model of esophageal perfusion in humans, we were able to study the esophagosalivary reflex in 20 healthy volunteers (12M, 8F; mean age 40 yr). The placement of the intraesophageal catheter resulted in a 6.3-fold increase in the salivation rate over the baseline value (2.27 +/- 0.28 vs. 0.36 +/- 0.06 ml/min; p = 0.02), whereas inflation of the catheter balloons evoked a 6.9-fold increase (2.52 +/- 0.21; p < 0.001) in the rate of salivation. A stepwise and significant decline of salivation (p = 0.02), observed during subsequent perfusion with NaCl was prevented when perfusion with HCl and HCl/pepsin solutions was implemented. The placement of the intraesophageal catheter resulted in a significant increase of salivary pH over its basal value (7.77 +/- 0.05 vs. 6.89 +/- 0.11; p < 0.001). A gradual decline of salivary pH during subsequent perfusion with NaCl was eliminated when saline was replaced with HCl or HCl/pepsin (7.76 +/- 0.04 vs. 7.46 +/- 0.09; p < 0.01). Intraesophageal tubing enormously potentiated the viscosity of saliva (44.50 +/- 9.0 vs. 9.3 +/- 1.0 mPa.s; p < 0.001). A subsequent decline of viscosity during continuous perfusion with saline was also prevented when HCl was substituted for NaCl (29.95 +/- 4.5 vs. 19.50 +/- 3.30; p < 0.05). A significant potentiation of salivary volume, viscosity, and pH during esophageal stimulation of mechano- and chemoreceptors may suggest a contributing role of the esophagosalivary reflex in the maintenance of the esophageal mucosal integrity under the impact gastroesophageal reflux.
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PMID:Interrelationship between esophageal challenge with mechanical and chemical stimuli and salivary protective mechanisms. 814 62

Gastro-oesophageal reflux disease (GORD) is a multifactorial disease. Although it is primarily a motility disorder, several other disturbances can interfere and contribute to determine the severity of symptoms and the degree of lesions. In normal subjects, as in patients with pathological reflux, nearly all the episodes of reflux obey one of the following three mechanisms: (a) a transient complete relaxation of the lower oesophageal sphincter (TLOSR), (b) a transient increase in intra-abdominal pressure which overcomes the resistance of the antireflux barrier ('stress reflux') and, (c) a spontaneous reflux through a permanently hypotonic sphincter. Gastric distension is the major factor that can induce TLOSRs. Whereas, at rest, the diaphragm probably plays little role in cardial competence, diaphragmatic contraction may help prevent reflux in conditions resulting in increased abdominal pressure such as during physical activity and abdominal staining. The presence of a hiatal hernia increases susceptibility to reflux. A delayed gastric emptying may also facilitate reflux and represents a factor of resistance to antireflux therapy. Most studies in humans have shown that motor abnormalities remain unchanged after healing of oesophagitis. Acid and pepsin are the most noxious agents of the upper gastrointestinal secretions that can participate in the pathogenesis of oesophagitis. However, there is no evidence that patients with reflux have greater acid secretion than subjects without reflux. The clearance function is a two-stage phenomenon requiring first a reduction in volume by peristalsis and then chemical neutralization by saliva. Primary peristalsis is mainly responsible for the clearance of acid in both the upright and the supine positions. It takes longer to clear acid in patients with non-reducing hiatal hernia. The layer of mucus which carpets the mucosa comes from the saliva and also from the submucosal glands of the oesophagus. The paracellular pathway is the major route by which mucosal HCl enters and then damages the oesophageal epithelium. Only a minority of acid reflux episodes are accompanied by symptoms. The acid exposure during the time period that precedes a reflux episode (i.e. the acid burden) is a key factor determining whether that reflux episode will be symptomatic or asymptomatic.
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PMID:The pathophysiology of gastro-oesophageal reflux disease: an overview. 854 32

Gastroesophageal reflux has been indicated as an etiopathological factor in disorders of the upper airway. Upper airway collapsing pressure stimulates pressure-responsive laryngeal receptors that reflexly increase the activity of upper airway abductor muscles. We studied, in anesthetized dogs, the effects of repeated laryngeal instillations of HCl-pepsin (HCl-P; pH = 2) on the response of laryngeal afferent endings and the posterior cricoarytenoid muscle (PCA) to negative pressure. The effect of negative pressure on receptor discharge or PCA activity was evaluated by comparing their response to upper airway (UAO) and tracheal occlusions (TO). It is only during UAO, but not during TO, that the larynx is subjected to negative transmural pressure. HCl-P instillation decreased the rate of discharge during UAO of the 10 laryngeal receptors studied from 56.4 +/- 10.9 (SE) to 38.2 +/- 9.2 impulses/s (P < 0.05). With UAO, the peak PCA moving time average, normalized by dividing it by the peak values of esophageal pressure, decreased after six HCl-P trials from 4.29 +/- 0.31 to 2.23 +/- 0.18 (n = 6; P < 0.05). The responses to TO of either receptors or PCA remained unaltered. We conclude that exposure of the laryngeal mucosa to HCl-P solutions, as it may occur with gastroesophageal reflux, impairs the patency-maintaining mechanisms provided by laryngeal sensory feedback. Inflammatory and necrotic alterations of the laryngeal mucosa are likely responsible for these effects.
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PMID:Effects of HCl-pepsin laryngeal instillations on upper airway patency-maintaining mechanisms. 951 96

Bronchoconstriction in asthmatic patients is frequently associated with gastroesophageal reflux. However, it is still unclear whether bronchoconstriction originates from the esophagus or from aspiration of the refluxate into the larynx and larger airway. We compared the effect of repeated esophageal and laryngeal instillations of HCl-pepsin (pH 1.0) on tracheal smooth muscle activity in eight anesthetized and artificially ventilated dogs. Saline was used as control. We used pressure in the cuff of an endotracheal tube (Pcuff) as a direct index of smooth muscle activity at the level of the larger airways controlled by vagal efferents. The Pcuff values of the first 60 s after instillations were averaged, and the difference from the baseline values was evaluated. Changes in Pcuff were significantly greater with laryngeal than with esophageal instillations (P = 0.0166). HCl-pepsin instillation into the larynx evoked greater responses than did saline (P = 0.00543), whereas no differences were detected with esophageal instillations. Repeated laryngeal exposure enhanced the responsiveness significantly (P < 0. 001). Our data indicate that the larynx is more important than the esophagus as a reflexogenic site for the elicitation of reflex bronchoconstriction in response to acidic solutions.
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PMID:Larynx vs. esophagus as reflexogenic sites for acid-induced bronchoconstriction in dogs. 1019 7

1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway protective mechanisms and cardiorespiratory reflexes following simulated gastro-oesophageal reflux (GER) to different levels in the oesophagus and pharynx. 2. Physiological and radiographic recordings were made in 21 naturally sleeping (controls) and 21 sedated (1.5 mg/kg, p.o., promethazine) piglets. On 3 consecutive days physiological recordings were made in all piglets during active sleep. Gastro-oesophageal reflux was simulated by the injection of boluses of 0.5 mL HCl, pH 2 or 3, or NaCl (0.9%) at 37 degrees C into the pharynx, upper or lower oesophagus. 3. In healthy neonatal piglets, minimal sedation with promethazine, which did not affect behaviour during wakefulness, revealed previously unreported findings during active sleep. 4. The most significant effects were observed following simulated GER to the pharynx, with no effect observed in the lower oesophagus. In sedated piglets, compared with naturally sleeping piglets, there was a significant reduction in swallowing (P < 0.01), delayed radiological clearance of fluid (P < 0.05), a reduction in breathing rate, oxygen saturation and heart rate and an increase in apnoea. 5. These findings are consistent with a low dose of promethazine producing a significant attenuation of airway protective mechanisms and, thus, stimulation of the laryngeal chemoreflex. The results suggest a mechanism for the association observed between promethazine use and the occurrence of ALTE and SIDS. The results support continued caution and suggest the need for greater regulation of promethazine-containing medications in infants.
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PMID:Airway protection following simulated gastro-oesophageal reflux in sedated and sleeping neonatal piglets during active sleep. 1142 20

The hypothesis that fat increases esophageal sensitivity to acid was tested in eight patients with gastroesophageal reflux disease and 11 healthy subjects. Protocol 1 included randomized intragastric infusions of saline or Lipofundin S 20% (306 kcal) on two separate days, followed after 30 and 90 min by an 8 ml/min intraesophageal infusion of 0.1 N HCl. The time to the onset of heartburn and the maximum heartburn score by visual analog scale during the acid infusion were similar after intragastric saline (2 min and 29.5 mm, medians) and fat (2 min and 20.5 mm). Protocol 2 included two 8 ml/min intraesophageal infusions of 0.2 N HCI diluted in an equal volume of saline or Lipofundin S 20% at a time interval of 10 min in randomized order. The time to the onset of heartburn and the maximum heartburn score were unaffected by the presence of fat in the esophageal infusate (2.5 min and 53 mm without vs 1.5 min and 49 mm with fat). We conclude that fat does not increase esophageal sensitivity to acid.
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PMID:Fat and esophageal sensitivity to acid. 1191 56

Barrett's oesophagus is a premalignant metaplastic change of the oesophageal mucosa. Due to its relationship with oesophageal reflux disease and the development of adenoma-carcinoma of the oesophagus the problem arouses increasing interest. In the wide pathogenesis of the disease most probably the composite effect of the refluxed HCl content and duodenal juices play a part. In the diagnosis in addition to fundamental methods--endoscopy and histology--increasingly chromoendoscopy and fluorescent endoscopy are involved. Dispensarization of patients is essential and depends on the degree of pathohistological epithelial changes. Treatment of Barrett's oesophagus can be divided into conservative, where the drug of choice are proton pump inhibitors, and surgical treatment. Promising is endoscopic ablation of the epithelium in combination with subsequent antisecretory therapy.
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PMID:[Barrett's esophagus]. 1213 67

Although symptoms arising from the esophagus such as heartburn and pain can at times become challenging clinical problems, esophageal viscerosensation, especially with regard to chemical stimulation in humans, is incompletely understood. Our aims were 1) to characterize and ascertain the reproducibility of cerebral cortical registration of heartburn and 2) to elucidate the differences between these findings and those of esophageal subliminal acid stimulation in asymptomatic controls. We studied 11 gastroesophageal reflux disease (GERD) patients (9 males, 30-55 yr) and 15 healthy controls (8 males, 21-49 yr). Cerebral cortical functional magnetic resonance imaging (fMRI) activity was recorded twice in each subject, during two 5-min intervals of 0.1 N HCl, separated by 5 min of NaCl perfusion. Time from onset of acid perfusion to instant of fMRI signal increase and first report of heartburn averaged 1.60 +/- 0.80 and 1.85 +/- 0.60 min, respectively. Average maximum percent signal increase in the GERD patients (16.3 +/- 3.5%) was significantly greater than that of healthy controls (3.8 +/- 0.9%; P < 0.01). Temporal fMRI signal characteristics during heartburn were significantly different from those of subliminal acid stimulation in controls (P < 0.01). Activated cortical regions included sensory/motor, parieto-occipital, cingulate and prefrontal regions, and the insula. There was 92% concordance between the activated Brodmann areas in repeated studies of GERD patients. Cortical activity associated with perceived and unperceived esophageal acid exposure in GERD patients and healthy controls, respectively, involves multiple brain regions but occurs more rapidly and with greater intensity in GERD patients than the activity in response to subliminal acid exposure in healthy controls. The cortical pain-processing pathway seems to be involved in perception of esophageal acid exposure and could explain the variations encountered in clinical practice defining this sensation.
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PMID:Characterization of the cerebral cortical representation of heartburn in GERD patients. 1451 87

Patients with nonerosive gastroesophageal reflux disease often have relatively low esophageal acid exposure and respond suboptimally to gastric acid suppression. In these patients, other constituents of gastric contents may induce esophageal symptoms. We have demonstrated that gastric contents can cause heartburn when the gastric pH >4. (Aliment Pharm Ther 14:129-134, 2000). The aim of this study was to determine relative sensitivities to chenodeoxycholic and ursodeoxycholic acids, and 0.1 N HCl, administered as provocative perfusion tests. Patients with functional heartburn and healthy control subjects were evaluated. Patients underwent a modified Bernstein acid infusion test and esophageal Barostat balloon distention. Time and volume to pain were recorded. Barostat balloon distention was performed using our standard protocol. Stepwise distentions were performed and pain was recorded. Sensitivity to chenodeoxycholic acid (Cheno) and Ursodeoxycholic acid (Urso) were assessed similarly to the Bernstein test using 2 mM concentrations of each, followed immediately by 5 mM if no pain was reported with 2 mM. Volume of bile acid infusion and length of time until pain was induced were assessed and compared to the same endpoints for acid sensitivity. "Total" time and "total" volume to induce pain were calculated for Cheno and Urso. Least-squares means were generated and two-tailed t-tests and regression analyses were performed (P < 0.05 level of significance). Ten functional heartburn patients and six healthy controls were evaluated (3 M, 13 F; age range, 19 to 56 years). Since five of six controls had pain with acid infusion (hypersensitive), all subjects were analyzed as one group. Only three subjects (all controls) had no pain with infusion of 2 mM Cheno and received the follow-up infusion of 5 mM. These same three subjects tolerated the maximum infusion (150 ml and 15 min) of 5 mM Cheno. Nine subjects did not have pain with 2 mM Urso and received the follow-up infusion of 5 mM Urso (five functional heartburn, four controls). Significantly more subjects tolerated the maximum bile acid infusion of 2 mM Urso vs 2 mM Cheno (nine vs three; P < 0.05, Chi-square test). The pain threshold (volume and time) for Urso was significantly higher than that for Cheno and acid (P < 0.05), and the pain threshold for Cheno was significantly higher than that for acid (P < 0.05). Conclusions are as follows: (1) Bile acids differ in their ability to induce pain. (2) Changing bile acid composition by treatment with Urso may change symptom presentation and symptom severity in patients with bile acid-induced esophageal pain.
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PMID:Esophageal visceral sensitivity to bile salts in patients with functional heartburn and in healthy control subjects. 1571 42


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