Physiology and biophysics in electrocardiography

Simultaneous esophageal and gastric manometry and intraesophageal pH monitoring were performed in 12 patients with gastroesophageal reflux diseases in order to compare the frequency and mechanism of reflux in upright and supine postures. It was found that there was no differences in the number of reflux episodes, acid clearance time and percentage time of pH below 4 (P > 0.05). Frequency of reflux associated with lower esophageal sphinter relaxation (LESR) and gastric press increase was similar in two postures (P > 0.05). The results suggest that upright reflux may be as important as supine reflux in the development of reflux esophagitis. The main machanism of reflux in the two postures is LESR. Increase of gastric press may be a factor leading to gastroesophageal reflux.     

Reflux esophagitis: manometry and Ph measurement

Manometry and pH-metry are essential in the examination of functional disturbances of the esophagus. Proven indications for manometry are dysphagia of unknown origin and noncardiac chest pain; in reflux esophagitis manometry is used for measuring pressure of the lower esophageal sphincter and detecting motility disorders of the esophageal body, pH-metry is used as long-term pH-metry to quantify gastroesophageal reflux during day and night; furthermore long-term pH-metry is important in the classification of atypical esophagitis. Recording gastroesophageal reflux and esophageal motility may influence planning of therapy and predict prognosis. Before antireflux surgery manometry and pH-metry are useful in judging the clearance mechanisms of the esophagus. Used critically, manometry and pH-metry can be very helpful as cost-effective diagnostic tools in the long-term therapy of reflux esophagitis.     

Omeprazole as a diagnostic tool in gastroesophageal reflux disease

OBJECTIVE: To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease (GERD). METHODS: Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring. Patients with reflux esophagitis grade 0 or 1 were included in the study and were randomized to double-blind treatment with either 40 mg omeprazole or placebo o.m. The effect of treatment was evaluated after 1 and 2 wk with a symptom questionnaire with a four-grade Likert scale, and symptomatic response outcome was compared with the results of 24-h pH-metry. RESULTS: Ninety-eight patients were included; however, 13 were excluded from the final analysis because of protocol violation. Of the remaining 85 patients, 54 had no signs of esophagitis at endoscopy, and 31 had esophagitis grade 1. The pH registration showed pathological gastroesophageal reflux in 47 patients (55%). Forty-one patients were randomized to treatment with omeprazole and 44 to placebo. There was a significant correlation between the pH registration result and response to omeprazole (p = 0.04, chi2), but not to placebo (p = 0.16). With pH-metry as the gold standard, the omeprazole test had positive and negative predictive values of 68% and 63%, respectively, for the diagnosis of GERD. When the omeprazole test was used as the gold standard, the positive and negative predictive values of pH monitoring were 68 % and 63 %, respectively. Similar sensitivity was found when the pH-metry was compared with presence of esophagitis. CONCLUSION: Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD, with a sensitivity and specificity comparable to 24-h pH monitoring.     

Evaluation of gastroesophageal reflux in patients with laryngotracheal stenosis

To report the incidence of pharyngeal acid reflux events in patients with laryngotracheal stenosis (LTS), we studied 12 patients with LTS and 34 healthy volunteers. All patients and controls underwent ambulatory 24-hour 3-site pH monitoring. In ambulatory pH monitoring, pH was recorded at manometrically determined sites of the pharynx, proximal esophagus, and distal esophagus. For all 3 sites, a pH value below 4 that was not related to the time of oral intake or belching was considered an acid reflux event. Eight of the 12 LTS patients exhibited pharyngeal acid reflux events. In the control group, pharyngeal acid reflux events were documented in 7 subjects. In between-group comparison, the number of reflux episodes and the percent acid exposure time in the pharynx were greater in LTS patients than in controls. Reflux parameters of the proximal and distal esophagus in LTS patients were similar to those of controls. The incidence of pharyngeal acid reflux events in LTS patients was higher than that in controls. It is suggested that identification and treatment of gastroesophageal reflux in patients will significantly simplify and improve the results of treatment for LTS.     

Gastric asthma? No change in respiratory impedance during intraesophageal acidification in adult asthmatics

BACKGROUND: In patients with asthma, gastroesophageal reflux (GER) has been shown to be a common finding, and a number of investigators have suggested that reflux may have a deleterious effect in asthma, either as a result of recurrent (micro)aspiration or by some form of a reflex mechanism. AIM OF THE STUDY: To measure changes in lung function in response to intraesophageal acid perfusion in asthmatics with GER. METHODS: In 12 patients with bronchial asthma and complaints suggesting GER with increased reflux scores during 24-h intraesophageal pH monitoring, impedance measurements of the respiratory system using the technique of forced oscillations and spirometry were performed after intraesophageal acidification. RESULTS: No statistically significant changes in FEV1 or in respiratory impedance were demonstrated after intraesophageal acid provocation. CONCLUSION: No direct effect of intraesophageal acidification on bronchomotor tone was demonstrated in asthmatics with GER.     

Effect of graded exercise on esophageal motility and gastroesophageal reflux in nontrained subjects

The effects of graded exercise on esophageal motility and gastroesophageal reflux were evaluated in nine nontrained subjects, using a catheter with three strain-gauge transducers connected to a solid-state datalogger and an ambulatory intraesophageal pH monitor. Subjects exercised on a stationary bike at 45%, 60%, 75%, and 90% of peak O2 uptake (VO2 max). Durations of exercise sessions and rest periods varied among subjects. Studies were performed after an overnight fast and subjects received only intravenous infusion of 5% glucose solution during the study. Plasma concentrations of gastrin, motilin, glucagon, pancreatic polypeptide (PP), and vasoactive intestinal peptide (VIP) were determined at rest and before and after each exercise session. The duration, amplitude, and frequency of esophageal contractions declined with increasing exercise intensity, and the differences were significant (P < or = 0.05) for all three variables at 90% VO2 max. The number of gastroesophageal reflux episodes and the duration of esophageal acid exposure were significantly (P < or = 0.05) increased during exercise at 90% VO2 max. Plasma regulatory peptide concentrations showed no significant changes between rest and the various exercise sessions. Thus, exercise has profound effects on esophageal contractions and gastroesophageal reflux, which are intensity dependent. These effects were not mediated by the hormones measured. The results were similar to those observed in highly trained athletes, suggesting that the effects of exercise on esophageal function are similar in trained and nontrained subjects performing at similar percentages of VO2 max, even though the absolute levels of exercise achieved in each group are different.     

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

OBJECTIVE: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis. METHODS: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy < or = 3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects. RESULTS: Patients with Barrett's esophagus had significantly increased acid reflux time (p < 0.01-0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01-0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis. CONCLUSION: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

Exclusion of the meal period improves the clinical reliability of esophageal pH monitoring

Meal period exclusion from 24-h pH testing allows better separation between controls and patients with gastroesophageal reflux disease. We reviewed the results of 24-h pH studies of 350 patients with reflux symptoms. They were divided into two groups based on the 95th percentile of the total percentage of time when pH was < 4 for healthy persons in our laboratory. Thus group A consisted of 212 patients with symptoms and normal acid exposure and group B consisted of 138 patients with symptoms and abnormal acid exposure. The change in upright reflux excluding the meal period was calculated for each patient. Meal period exclusion resulted in opposite effects for the two groups of patients, with a change in median upright reflux of -0.6% for group A and +0.5% for group B (p < 0.0001). After meal exclusion, five patients were reclassified as having reflux, with four (80%) of these responding to antireflux therapy. Nine other patients were recategorized as not having reflux after meal exclusion. Only one of seven patients (14%) for whom data were available responded to treatment (two patients were lost to follow-up). We recommend meal period exclusion from pH analysis because it improves the clinical reliability of esophageal pH monitoring.     

"Silent" gastroesophageal reflux and upper airway pathologies in childhood

In children, gastroesophageal reflux (GER) plays an important role in both acute and chronic upper airway disorders including stridor, chronic cough, recurrent upper respiratory infections, obstructive apnea, laryngospasm, and wheezing. Diagnosis may prove difficult unless there is reason to suspect GER and one is aware of the concept of "silent" GER. This paper presents our experience with chronic and/or recurrent respiratory disorders of uncertain origin and without gastrointestinal symptoms in children. Thirty-two pediatric patients with upper respiratory symptoms were evaluated. Out-patient 24-hour intraesophageal pH was monitored and 56% of the patients underwent pharyngo-laryngeal fibroscopy. The patients were divided into two subgroups: Group A (18 patients < 6 months of age) and Group B (14 patients > 6 months). All the patients tested positive for GER with a mean Reflux Index of 21.5. The most common symptoms in Group A were apnea-cianosis and stridor while they were chronic cough for group B. The present study confirms the association between GER and respiratory disease and between GER respiratory-related symptoms and patient age. Emphasis is placed on the importance of otolaryngological diagnostic procedures and 24-hour pH-gastroesophageal monitoring in evaluating patients with respiratory disorders related to silent GER.     

Medical personnel and patient skill in the use of metered dose inhalers: a multicentric study. CESEA Group

Gastroesophageal reflux may be responsible for atypical extra-esophageal symptoms, such as chest pain, dyspnea, chronic cough, or hoarseness. Prospective studies of gastroesophageal reflux have indicated reflux as the cause for chronic cough in 10 to 20% of patients. The precise mechanism by which reflux causes cough remains uncertain, although the possibility that the cough is caused by stimulation of the esophageal mucosa receptors rather than aspiration is suggestive from some studies. Prolonged esophageal pH monitoring affords an opportunity to document objective gastroesophageal reflux. Furthermore, pH monitoring gives the opportunity to correlate temporally acid reflux events with the onset of certain symptoms.     

Acid esophago-pharyngeal reflux as etiology of hoarseness

BACKGROUND: Gastroesophageal reflux has been implicated in otolaryngologic problems, particularly chronic hoarseness that cannot be attributed to other causes. PATIENTS AND METHODS: To study this relationship between gastroesophageal reflux and chronic hoarseness we used 24-h dual-site ambulatory pH-recordings in 68 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation. RESULTS: Thirty-eight patients (56%) had evidence of at least one esophago-pharyngeal reflux episode. The mean number of esophago-pharyngeal episodes was 6.7 +/- 12 within 24 hours (range: 1-34 episodes). The mean duration of these episodes was 201 +/- 28 seconds (range: 6 seconds-19.6 minutes). Most patients with esophago-pharyngeal reflux had no evidence of pathologic gastroesophageal reflux. Only 28.9% of the patients with esophago-pharyngeal reflux episodes also had pathologic gastroesophageal phageal reflux, whereas 23.3% of the patients without esophago-pharyngeal reflux had no gastroesophageal reflux disease. The esophago-pharyngeal reflux occurred mainly in the upright position. CONCLUSIONS: Occult esophago-pharyngeal reflux, predominantly in the upright position, appears to be common and severe in patients with chronic hoarseness. Gastroesophageal reflux may be an important factor in the pathogenesis of chronic hoarseness. The causative mechanisms are not clear.     

Characteristic expression of 105-kDa heat shock protein (HSP105) in various tissues of nonstressed and heat-stressed rats

BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism permitting gastroesophageal reflux (GER). Little information is available on how anti-reflux surgery affects reflux mechanisms, especially TLESRs. We evaluated the effects of partial fundoplication (Belsey Mark IV) on reflux mechanisms. METHODS: Sixteen patients were prospectively studied before and after Belsey Mark-IV operation by endoscopy, 24-h esophageal pH-metry, and simultaneous recording of pH and lower esophageal sphincter (LES) characteristics by sleeve manometry. RESULTS: The operation was successful in 14 of 16 patients (87%). Fasting and postprandial reflux decreased significantly (P < 0.01) after the operation. Partial fundoplication significantly (P < 0.05) decreased the number of TLESRs per hour in the fasting and postprandial period from 3.2+/-0.4 and 5.6+/-0.5 to 1.7+/-0.3 and 2.8+/-0.4, respectively. The percentage of TLESRs associated with reflux also decreased significantly (P < 0.05). Basal LES pressure increased from 14.7+/-2.1 mmHg to 17.9+/-2.6 mmHg (not significant). CONCLUSIONS: Partial fundoplication controls GER through a reduction in the number of TLESRs and by decreasing the number of relaxations associated with reflux.     

Non-cardiac chest pain]

Non-cardiac chest pain is caused in 50% by esophageal disorders. About 30% of such esophageal chest pain is induced by gastroesophageal reflux. 2/3 of esophageal chest pain is related to various esophageal motility disorders, which can be differentiated by manometry. Diagnostic procedures for esophageal dysfunction (endoscopy, radiology, long-term pH-metry) have been evaluated. Therapy of gastroesophageal reflux disease has been proven effective; maintenance therapy should be evaluated in further controlled randomized trials. Treatment of esophageal motility disorders, unsatisfactory so far, needs to be improved and standardized.     

Gastric emptying as an etiopathogenic factor in gastroesophageal reflux disease

The aim of this study is to evaluate gastric emptying change in patients with gastroesophageal reflux (GER). To this purpose, 36 patients with GER diagnosis and 18 control subjects have been studied. GER diagnosis was achieved by means of endoscopy, biopsy and 24 h continuous pH monitoring. Gastric emptying studies were performed on a two day basis, similar labelling meals were provided to patients and control subjects. Those consisted in a one-egg omelette, chicken (110 gr) and orange juice (200 ml). On first day liquid phase was labelled with 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), and on second day, the solid phase was labelled with 99mTc-sulfur colloid in the omelette (Labelling efficiency was 85.3 +/- 3.2%). The studies were carried out by imaging static anterior and posterior views every 20 minutes for a total of 180 minutes. Images were quantified obtaining solid and liquid gastric emptying curves. No statistical significative difference between patients and control subjects gastric emptying results were found. We can conclude that gastric emptying is not a main factor in the pathogenesis of gastroesophageal reflux.     

Esophageal dysmotility elicited by acid perfusion in children with esophagitis

OBJECTIVE: To determine the importance of acid reflux-induced dysmotility in the genesis of noncardiac chest pain in children. METHOD: We performed esophageal manometries during intraesophageal perfusion with 0.9% NaCl or 0.1 N HCl in 19 children (age, 14.5 +/- 0.5 yr) with gastroesophageal reflux, biopsy-proven esophagitis, and complaints of at least one episode of chest pain per day. RESULTS: Baseline esophageal motilities were normal in all patients. Eight of 19 children (42%) complained of chest pain during intraesophageal acid perfusion. In three of these eight patients, complaints of chest pain during acid perfusion were temporally associated with "conversion" of previously normal motility patterns to manometric tracings, indicating esophageal dysmotility. Compared with findings during saline perfusion, esophageal acid exposure in these three children resulted in significant increases in both the duration (13.6 +/- 4.0 vs 3.2 +/- 0.2 s, p < 0.05) and amplitude (105.2 +/- 7.8 vs 61.2 +/- 2.1 mm Hg, p < 0.05) of esophageal contractions during wet swallows. Symptoms of chest pain resolved in all patients after therapy with H2-receptor antagonists. CONCLUSIONS: These data represent the first demonstration of acid-induced esophageal dysmotility in children with chest pain and suggest that reflux-induced motor abnormalities contribute to the onset and/or exacerbation of chest pain in pediatric patients with gastroesophageal reflux and esophagitis.     

Gastric electrical dysrhythmias and delayed gastric emptying in gastroesophageal reflux disease

OBJECTIVE: Deranged gastric motility and delayed gastric emptying are commonly implicated in the pathophysiology of gastroesophageal reflux disease. We measured gastric electrical activity and gastric emptying time of a solid-liquid meal by electrogastrography and antral ultrasound, respectively, in 42 patients with gastroesophageal reflux disease (age 7.4 +/- 1.6 yr). METHODS: Based on endoscopy and histology of the esophageal mucosa, reflux disease was moderate in 20 patients and severe in 22. Electrogastrography was measured by placing two Ag-AgCl electrodes on the epigastric skin, signals were digitized and fed into a personal computer, and data were obtained by running spectrum analysis. The electrogastrographic variables calculated were: 1) percent of electrical dysrhythmias and normal electrical rhythm (bradygastria or 0.5-2.0 cycles/min, tachygastria or 4.0-9.0 cycles/min; normal rhythm is 2.0-4.0 cycles/min); 2) fed:fasting ratio of dominant electrogastrographic power; 3) fed:fasting ratio of the dominant frequency instability coefficient. Gastric emptying time and electrical activity results were compared with those measured in 15 controls (7.1 +/- 1.7 yr). RESULTS: Dysrhythmic episodes were more common in both groups of patients than in controls (p < 0.01); furthermore, gastric emptying time was significantly more delayed in patients than in controls (p < 0.01). Children with severe gastroesophageal reflux were distinguished from those with moderate disease for post-feeding gastric electrical abnormalities consisting of reduced electrogastrographic dominant power and increased frequency variability (p < 0.01), as well as for a more prolonged gastric emptying time (p < 0.05). Prevalence of both normal electrical rhythm and dysrhythmias did not discriminate the two groups of patients. In patients and in controls, a significant inverse correlation between fed electrogastrographic power and gastric emptying time was found (r -0.88, p < 0.01). CONCLUSIONS: Fed gastric electrical abnormalities consisting of reduced dominant power and increased variability of the electrical dominant frequency are detected in patients with severe gastroesophageal reflux disease and are associated with delayed gastric emptying. Gastric electrical dysrhythmias may be included among the pathogenetic components of gastroesophageal reflux disease.     

Oesophageal acid clearance in patients with severe reflux oesophagitis

Previous studies examining oesophageal acid clearance have employed a variety of techniques to induce or simulate acid reflux. Clearance abnormalities have been deduced from abnormal standard motility studies, barium radiology or from 24-h pH recordings. In this study a 24-h pH and oesophageal motility recording system was used to study naturally occurring acid reflux episodes in control subjects and in two groups of patients with severe acid reflux disease (erosive oesophagitis and oesophageal stricture). Acid clearance was compared between the subject groups. Patients with oesophageal stricture were found to have poor oesophageal peristaltic ability and particularly poor oesophageal acid clearance. Those with erosive oesophagitis had normal peristaltic swallowing but abnormal acid clearance. This study has characterized, for the first time, the abnormalities in acid clearance during naturally occurring acid reflux episodes in patients with severe reflux disease. A more complete understanding of these clearance abnormalities could influence future medical and surgical strategies in the management of severe gastro-oesophageal reflux disease.     

A personal experience of research

Apnea in the neonatal period frequently is associated with prematurity. Full-term infants who develop apnea usually have associated clinical conditions such as infection, shock, metabolic disorders, neonatal abstinence syndrome, intracranial pathology, and gastroesophageal reflux. Gastric ulcer also is a rare phenomenon in the neonatal period. We describe a full-term infant presenting with apnea. Upon investigation, a 6-channel pneumocardiogram revealed central apnea and multiple episodes of low esophageal pH (< 4), which is suggestive of gastroesophageal reflux. This was confirmed by an upper gastrointestinal series. A small antral ulcer crater also was demonstrated. When assessing the etiology of apnea in a full-term infant, gastroesophageal reflux and gastric ulcer should be considered.     

Effect of pneumatic dilation on gastroesophageal reflux in achalasia

The aims of this study were to assess the effect of pneumatic dilation on gastroesophageal reflux in achalasia, differentiate esophageal acid due to lactate from acid due to gastroesophageal reflux, and determine if chest pain and heartburn are reliable indicators of gastroesophageal reflux. Eight untreated achalasia patients underwent pre- and postdilation esophageal fluid/food residue lactate and pH analysis, esophageal manometry, 24-hr pH monitoring, and symptom assessment. All patients had a successful clinical outcome and a decrease in lower esophageal sphincter pressure from 29.1 +/- 12.7 to 14.7 +/- 3.8 mm Hg (mean +/- SD; P = 0.04). Abnormal acid exposure was present in two patients before and two patients after dilation. Postdilation acid exposure was mild. Lactate was detected before dilation in all patients. A lactate concentration >2 mmol/liter was associated with acidic residue and one abnormal 24-hr pH profile. There was no correlation between an abnormal 24-hr pH test and age, lower esophageal sphincter pressure, or duration of symptoms prior to treatment. Chest pain and heartburn were unrelated to drops in pH. Gastroesophageal reflux is rare in untreated achalasia and esophageal acidity may result from ingestion of acidic foods or production of lactate. Mild gastroesophageal reflux occurs after dilation but is of no clinical significance. Chest pain and heartburn are not indicators of acid reflux in achalasia.     

Variables influencing parental perception of inherited metabolic diseases before and after genetic counselling

BACKGROUND: Sixty percent of adults has typical symptoms of gastroesophageal reflux in Chile. AIM: To report the clinical and laboratory features of patients with gastroesophageal reflux. PATIENTS AND METHODS: Five hundred thirty-four patients (255 male) with gastroesophageal reflux were included in a prospective protocol that included clinical analysis, manometry and endoscopy in all patients, barium swallow in 427, scintigraphy in 195, acid reflux test in 359, 24 h pH in 175, and differential potential of gastroesophageal mucosa in 73 patients. RESULTS: There was no correlation between the severity of symptoms and the endoscopical severity. Patients with Barret esophagus were 12 years older, were male in a greater proportion and had a higher proportion of manometrically incompetent sphincters than patients with esophageal reflux but without esophagitis or with erosive esophagitis. Severity of acid reflux, measured with 24 h pH monitoring was proportional to the endoscopical damage of the mucosa. There was a close relationship between the mucosal change limit determined with differential potentials and with endoscopy. No short esophagi were found. CONCLUSIONS: Patients with symptoms of gastroesophageal reflux must be assessed using several objective measures to determine the severity of their pathological alterations.