Gastroesophageal reflux disease (GERD) is a prevalent, chronic medical condition that affects 13% of the adult population globally at least once a week. Sleep disturbances are frequently encountered in up to 25% of the GERD patients, likely due to nocturnal gastroesophageal reflux (GER). With advance in diagnostic techniques allowing for an improved understanding of involved physiological mechanisms of nocturnal reflux, there is growing evidence of a bidirectional relationship between GERD and sleep disturbances. Furthermore, nocturnal GER is associated with more complicated GERD. Obstructive sleep apnea (OSA) and GERD also have been linked, but to what degree remains controversial. Treatment of nocturnal GER has been shown to improve both subjective and objective sleep measures. The therapeutic approach includes lifestyle modifications and medication individualization and optimization with proton-pump inhibitors serving as the mainstay of treatment. Antireflux surgery and newer endoscopic procedures have been demonstrated to control nocturnal GER.

pH monitoring has been established as the "gold standard" in the diagnosis of gastroesophageal reflux. Evaluation of experimental antireflux therapy should therefore also include this technique, but a suitable technique in an experimental model did not exist so far. The aim of our study was to establish a reliable method for the evaluation of an experimental reflux model in pigs.

A total of 33 German Landrace pigs with an average body weight of 56 (50.2-67.2) kg were included. pH monitoring was performed before and after open cardiomyotomy in each animal. All manipulations were performed under general anesthesia. After manometric localization of the gastroesophageal high-pressure zone, a standard pH probe was inserted into the pharynx through a small needle-punctured canal on the side of the animal's snout and placed under endoscopic guidance with the proximal sensor 3 cm above the lower esophageal sphincter (LES) and the distal sensor in the stomach for reference. The harness to carry the pH recorder on the animal's back consisted of a modified belly strap that enabled the animal to move around without limitation. For analysis the same threshold levels were defined as in humans. Gastroesophageal reflux was induced by cardiomyotomy.

The placement of the standard pH probe was possible in all cases. Inserting the probe on the side of the snout left the animals free to nuzzle, which complies with the normal habits of pigs, without breaking the probes and without being compromised in their natural behavior. Repeated punctures for multiple measurements were easily feasible. We performed up to three examinations in each individual animal. Recording was performed for 48 h. A mean number of 67.3 (+/-9.7) acidic refluxes were registered. The mean number of long acidic refluxes was 3.2 (+/-0.75). For an average total time of 75.5 (+/-14.3) min the pH was below 4 accounting for a fraction time pH below 4 of 3.5% (+/-0.68%). Following cardiomyotomy the number of acidic refluxes increased significantly to 166.1 (+/-21.8) and the number of long refluxes to 17.74 (+/-3.35). The total time of pH below 4 increased to 371.3 (+/-62) min so that the fraction time pH below 4 was 14.5% ( p = 0.0006).

pH monitoring should be mandatory in any investigation of antireflux therapy. Our method is easy and secure to perform. It is suitable for other gastrointestinal investigations (Bilitec, long-term manometry) that could be carried out using the same technique. The described data represent the basis for other investigations of experimental antireflux therapy.

This study investigates whether the results of 24-h pH-metry can be predicted from clinical information and whether they affect patient management.

A total of 200 consecutive patients referred for 24-h pH-metry underwent structured interviews as well as endoscopic and manometric investigations. The most recent 53 patients were prospectively followed to determine the impact of pH monitoring on long term management.

Among a variety of risk factors, the presence of lower esophageal sphincter hypotension (OR = 3.3) and erosive esophagitis (OR = 2.3) were highly predictive of a pathological pH test result. If both abnormalities were present, the risk for an abnormal 24-h pH study increased by a factor of seven. Twenty-four-hour pH monitoring led to an immediate change in management in 42% of all investigated patients. However, such alterations in therapy were maintained for prolonged periods in less than half of them and only 6% of all patients associated changes in management with an improvement of symptoms.

The results of "open access" 24-h pH-metry are often predictable, and only a minority of patients benefit from this procedure in terms of a change in therapy and an improvement of symptoms.

Twenty-four normal subjects and 64 symptomatic patients with various degrees of reflux disease (24 with reflux symptoms without esophagitis and 21 with mild and 19 with severe esophagitis) underwent quantitative 24-hr intraesophageal pH monitoring. Various reflux parameters during supine, interprandial, and postprandial periods were examined by binary logistic regression and by CART analysis to determine the sensitivity and specificity to separate the various groups of subjects and patients. The distinction was excellent between asymptomatic controls and patients with severe erosive esophagitis (sensitivity and specificity both 100% by logistic regression and 95% and 88%, respectively, by CART), but discrimination was poor when asymptomatic controls were compared to symptomatic patients without esophagitis (71% and 79% by logistic regression and 75% and 92% by CART), which is the most important indication for pH recording in clinical practice. A 3-hr postprandial pH recording was inadequate to distinguish the various groups. The acidity of the reflux episodes during the night appeared to be a crucial factor in the development of severe erosive esophagitis. The duration of esophageal acid exposure was another important factor in the development of reflux lesions.

The definition of criteria relevant to disease severity assessments should be considered in parallel with the long-term aims of treatment in gastro-oesophageal reflux disease (GORD). There is no doubt that the resolution of symptoms is the major management aim. Heartburn and regurgitation are specific for GORD when they are the predominant symptoms, but prove to be insensitive when the diagnosis of GORD is based on the measurement of oesophageal acid exposure. A relationship between the frequency of heartburn and the degree of acid exposure has been reported in GORD patients both with and without oesophagitis. GORD may also, however, cause a wide spectrum of atypical symptoms (e.g. non-cardiac chest pain or respiratory symptoms). To the extent that a causal relationship between these symptoms and reflux episodes has been established, evaluation of symptom severity should also encompass these atypical presentations. The role of symptoms in the prediction of relapse of oesophagitis is controversial, but in several studies the presence of residual symptoms of GORD at the time of healing has indicated a greater probability of relapse. Endoscopy is a useful technique for the evaluation of disease severity. Indeed, even typical symptoms may not predict the presence and severity of oesophagitis in an individual patient. Despite the fact that the interpretation of therapeutic trials is often impeded by differences in the grading systems used, healing rates of oesophageal lesions are inversely proportional to the initial severity of oesophagitis when drugs such as H2-receptor antagonists are used. Differences are less evident with highly effective drugs such as omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

We performed 24-hr ambulatory esophageal pH monitoring in north Indian patients with gastroesophageal reflux disease (GERD) and correlated it with symptom severity and endoscopic abnormalities. Thirty-six consecutive patients with symptomatic GERD and 16 healthy volunteers underwent objective grading of clinical symptoms and endoscopic findings. Total, supine, and upright reflux periods as well as frequency and duration of reflux episodes were determined from the 24-h pH-metry record using standard software. This was abnormal in 32 patients, who could be categorized into upright refluxers (31.2%), supine refluxers (34.4%), and combined refluxers (34.4%). Supine reflux and upright reflux were distinct entities that did not correlate with each other (r = 0.22, P = NS). In upright refluxers, symptoms (P < 0.02) and endoscopic abnormalities (P < 0.005) were milder than in combined refluxers. Total duration of acid exposure correlated significantly with severity of symptoms (P < 0.001) and endoscopic esophagitis (P < 0.005). Patients with GERD had three distinct patterns of abnormal gastroesophageal reflux, with upright refluxers having milder disease and supine and combined refluxers having more severe disease. This may reflect differences in underlying mechanisms of reflux.

Scarce information is available on gastroesophageal reflux disease in elderly patients. In this study we investigated patterns of gastroesophageal reflux and esophageal lesions in 24 elderly patients with typical gastroesophageal reflux symptoms and a mean age of 69 years (range, 65-76 years), as compared with 147 symptomatic younger patients with a mean age of 45 years (range, 21-64 years). The results of 24-h pH-monitoring and endoscopy showed that the elderly patients had pathologic reflux and reflux esophagitis more frequently than the young patients. The percentage time with pH < 4 in elderly patients with reflux esophagitis was 32.5% in 24 h, as compared with 12.9% in the younger patients with reflux esophagitis (P < 0.05). The elderly patients with reflux esophagitis had more prolonged periods of acid reflux in both the upright and supine positions than the younger patients. Endoscopy showed that 20.8% of elderly patients had grade III/IV esophagitis, whereas only 3.4% of younger patients had grade III/IV esophagitis (p < 0.002). The percentages of grade I/II esophagitis in the two groups were 12.5% and 26.5%, respectively (p < 0.002). We concluded that, compared with younger subjects, elderly patients have more severe gastroesophageal reflux and esophageal lesions.

The relationship between gastroesophageal reflux and asthma has not been clearly defined. We measured the lower esophageal sphincter pressures and studied gastroesophageal reflux patterns over 24 hours using an ambulatory Gastroreflux Recorder (Del Mar Avionics, Irvine, CA) in 44 controls and 104 consecutive adult asthmatics. The presence or absence of reflux symptoms was not used as a selection criterion for asthmatics. All asthmatics had discrete episodes of diffuse wheezing and documented reversible airway obstruction of at least 20%. Patients underwent reflux testing while receiving, if any, their usual asthmatic medications: 71.2% required chronic bronchodilators and 28.8% required no bronchodilators. Compared with controls, asthmatics had significantly decreased lower esophageal sphincter pressures, greater esophageal acid exposure times, more frequent reflux episodes, and longer clearance times in both the upright and supine positions (P less than 0.0001 for all parameters tested). There were no differences in any of the measured reflux parameters between asthmatics who required bronchodilators and those who did not. Thus, the decreased lower esophageal sphincter pressures and increased levels of acid reflux in asthmatics were not entirely caused by the effects of bronchodilator therapy. Receiver-operating characteristic analysis generated reflux values that discriminated asthmatics from controls. More than 80% of adult asthmatics have abnormal gastroesophageal reflux. We conclude that most adult asthmatics, regardless of the use of bronchodilator therapy, have abnormal gastroesophageal reflux manifested by increased reflux frequency, delayed acid clearance during the day and night, and diminished lower esophageal sphincter pressures.

The reproducibility of 24 hour oesophageal pH monitoring was studied in 30 infants and children including the proportions of the investigation time with a pH less than 4 (reflux index), the number of episodes with a pH less than 4 or lasting longer than five minutes, and the duration of the longest episodes with a pH less than 4. Twenty four hour pH monitoring was performed using identical equipment on two consecutive days under similar conditions. Pearson correlation coefficients range from 0.88 to 0.98. The results obtained on two consecutive days were similar. The reflux index and the number of reflux episodes greater than five minutes were the most reproducible parameters. Despite the many patient related factors influencing pH data, the reproducibility of 24 hour pH monitoring data are satisfactory for routine clinical application.

The role of serosal bicarbonate ions (HCO3-) in protection against acid injury was investigated in rabbit esophageal mucosa mounted in Ussing chambers. Luminal acidification reduced potential difference and resistance in tissues exposed serosally to HCO3- or (unbuffered) HCO3-free solution. Whereas resistance declined similarly in both groups, potential difference declined less in HCO3- solution. After washout, HCO3-bathed tissues also had a greater increase in resistance, lower permeability to mannitol, and less histologic damage. Furthermore, as protection by HCO3- was not blocked by pretreatment with either the anion exchange blocker, 4 acetamido-4'-isothiocyanatostilbene 2-2'-disulfonic acid, or the carbonic anhydrase inhibitor, acetazolamide, and replacement of HCO3- with N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid, a buffer impermeant to cells, was protective, an extracellular site for protection by HCO3- was likely. Where in the extracellular space HCO3- buffers H+ is unclear, but the absence of change in luminal pH and the inability to prevent the acid-induced increase in permeability in HCO3-bathed tissues argue against a luminal (preepithelial) site. Also, rapid repair was not demonstrated, indicating that a luminal site for protection after surface cell damage was unlikely. We conclude that serosal HCO3- is important in esophageal protection against acid damage by buffering H+ within the intercellular compartment of the extracellular space.

Twenty-two consecutive patients with gastroesophageal reflux and erosive or ulcerative esophagitis entered a double-blind, randomized study comparing the effect of 20 mg omeprazole once daily with that of 150 mg ranitidine twice daily on esophageal acidity. Ambulatory 24-h esophageal pH measurements were performed within 1 month before inclusion and after 3 weeks of medication. Omeprazole significantly (p less than 0.05) reduced the number of reflux (pH less than 4) episodes, the number of refluxes lasting greater than 5 min, and the total reflux time. In contrast, ranitidine significantly reduced only the total reflux time. When the two treatment groups were compared, a significant difference in favor of omeprazole was found for daytime and total reflux values, except for the longest reflux and the number of reflux episodes lasting greater than 5 min. Substantial differences, also in favor of omeprazole, were found with regard to the effect on endoscopic healing of the esophagitis.

The aims of the present study were to evaluate the accuracy of 24-hr intraesophageal pH monitoring in the diagnosis of gastroesophageal reflux in the hospital setting and to establish whether there were any differences in terms of reflux events between patients with and without endoscopic esophagitis. Fifteen control subjects and 47 patients with proven gastroesophageal reflux disease were studied. A composite score of reflux events (number of reflux episodes; total, upright, and supine reflux time; number of refluxes lasting more than 5 min; and duration of the longest reflux) provided the best discrimination between controls and patients (94% sensitivity and 100% specificity). Patients with esophagitis showed concurrently a longer total reflux time and supine reflux time, and more prolonged reflux episodes than those without esophagitis. On the other hand the severity of esophagitis was directly related to the duration of both total and supine reflux. The results indicate that inpatient 24-hr pH-metry is very accurate in the diagnosis of gastroesophageal reflux. They also suggest that prolonged esophageal exposure to acid, particularly at night, and slow esophageal acid clearing are factors that determine the appearance and/or perpetuation of esophagitis in patients with reflux.

To evaluate the reproducibility of ambulatory 24 hour intraoesophageal pH monitoring, 20 patients were randomly selected to undergo two consecutive investigations. Fifteen patients were classified as either abnormal, or normal on both test days. The amount of acid reflux, expressed as percentage of time with oesophageal pH below 4.0 during the two 24 hour periods, showed 77% concordance. The upright and recumbent periods of measurement showed different degrees of concordance: 83% and 62%, respectively. The reproducibility during time periods of different length was found to increase with increasing length of day time pH recording. A 16 hour period during evening and night had a reproducibility of only 58%, however. It is concluded that there is fairly good reproducibility when measuring gastro-oesophageal reflux over 24 hours, but that the reproducibility is poorer at night, during the postprandial period and when daytime monitoring is shorter than 10 hours.

In a randomized crossover study, we compared the effect on gastroesophageal reflux of three sleeping positions: elevation of the head of the bed on standard eight-inch bed blocks; elevation by a foam wedge; or a flat position. Fifteen subjects with moderate to severe reflux symptoms were studied in each position on consecutive nights using continuous intraesophageal pH monitoring. We found no difference in reflux frequency among the positions. The wedge caused a statistically significant decrease in the time that distal esophageal pH was less than 4 as compared to the flat position. The wedge also decreased the longest episode experienced by the subjects. Elevation on blocks caused a similar improvement in parameters but failed in this study to achieve statistical significance. Both elevation by a wedge and on blocks showed a trend towards a decrease in clearance time as compared to the flat position. The patients did not always prefer elevation on a wedge, but for some it is a valuable alternative to elevation by bed blocks.

The study of GER has been hindered by the lack of a good animal model and by the presence of some reflux in all normal individuals. By the painstaking process of studying normal infants, children, and adults, it is becoming evident that abnormalities of acid clearance, especially in the recumbent position (or during sleep), may be critical to an understanding of this disorder. As more is learned about the conditions surrounding "normal" reflux, it will be possible to refine the techniques of diagnosis and thereby identify the abnormal with more security.

The variations in gastroesophageal reflux over 24 h were analyzed in 220 patients with symptoms suggestive of gastroesophageal reflux disease and in 50 normal subjects by studying the results obtained by ambulatory 24-h esophageal pH-monitoring. Three time periods, differing in amount of reflux, were identified: daytime (0700-1700 h), evening (1700-2400 h), and night (2400-0700 h). The greatest amount of reflux was seen during the evening period. This pattern was not solely due to increase in reflux postprandially, since it persisted even after the elimination of postprandial reflux. The pattern was most pronounced in patients with esophagitis. The pressure of the distal esophageal high-pressure zone was measured at 0800 h, at noon, and at 1600 h during one day in another 10 patients. The pressure was significantly lower at 1600 h than at 0800 h and at noon, providing a possible explanation for the changes seen in gastroesophageal reflux. We have described a time pattern of gastroesophageal reflux that has important implications for the design of medical therapy in different groups of patients.

In vivo prostaglandin E2 (PGE2) levels were measured in esophageal mucosa excised from 9 normal subjects, 11 patients with gastroesophageal reflux without esophagitis (GER) and 8 patients with reflux esophagitis (RE). Severity of GER was quantified by postcibal pH monitoring. A manometric study was also performed. No difference was found in PGE2 levels between healthy mucosa in controls (41.7 +/- 9.3 ng/g of wet tissue, at 15 cm above the lower esophageal sphincter (LES)) and healthy mucosa in GER (37.8 +/- 11.2 ng/g) or in RE (34.3 +/- 9.0 ng/l). However, PGE2 levels were significantly enhanced within the inflammatory mucosa in RE (290.4 +/- 45.7 ng/g). No difference was found in basal LES pressure between the 3 groups. These results suggest that PGE2 in the esophagus may be involved in pathogenesis of inflammation. Therefore PGE2 might not have the same cytoprotective function as in stomach or duodenum. No correlation was found between PGE2 levels in the esophagitis lesion or basal LES pressure. These data are not consistent with a possible relationship between LES pressure and the PGE2 content of the distal esophagus.

The results of ambulatory 24 hour oesophageal pH monitoring in 20 patients with established gastro-oesophageal reflux disease were compared with those of 20 healthy individuals with normal endoscopy. Cut off limits of pH 3, 4, and 5 were superior to pH 2 with respect to the discrimination of patients from normal subjects, and for the detection of pathological reflux. Using pH 4 as a cut off limit, the ambulant and recumbent periods of pH monitoring were more discriminatory than the postprandial period. Furthermore, it was possible to get complete separation between patients and normal subjects using several combinations of two reflux variables. Another group of 30 patients and 30 controls were investigated. Using percentage time at pH less than 4 as a single determinant of gastro-oesophageal reflux, the sensitivity and specificity were 87% and 97%, respectively, with 3.4% as upper limit for normality. Twenty four hour oesophageal pH monitoring in an ambulatory outpatient environment afforded clinically useful diagnostic accuracy in separating patients with gastro-oesophageal reflux disease from asymptomatic controls.

Long-term esophageal pH-metry has become the preferred test to quantify acid gastroesophageal reflux, but its accuracy in separating physiologic from pathological reflux is not well defined. To establish optimal thresholds of 24-h pH-metry, we studied 45 patients with clinically proven gastroesophageal reflux disease and 42 healthy volunteers. Twenty-four-hour esophageal pH was measured while the subject was ambulatory, using a combined glass electrode connected to a portable recorder. Percentage of time with esophageal pH less than 4, the number and mean duration of reflux episodes, the number of episodes lasting longer than 5 min, and the duration of the longest episode were calculated for periods of upright and supine body position, respectively. Discriminant analysis and receiver-operating-characteristic analysis were used to define optimal thresholds. A maximum of sensitivity (93.3%) and specificity (92.9%) was obtained using receiver-operating-characteristic analysis with the following criteria. Only percentage of time with esophageal pH less than 4 is considered. A subject is classified as "normal" if both values for the upright and supine body position are below the thresholds, otherwise the subject is classified as "pathological." The thresholds are 10.5% of time with esophageal pH less than 4 for the upright position and 6.0% for the supine position. Within the limits of this retrospective study, it is concluded that rather simple criteria yield a high diagnostic accuracy in the evaluation of long-term esophageal pH-metry. Nevertheless, a prospective and independent confirmation of these criteria is needed.

Measurements of pH in the microclimate on gastric and duodenal mucosa were made during gastrointestinal endoscopy in 21 normal subjects and 9 duodenal ulcer patients. In controls luminal and juxtamucosal mean pH (+/- SEM) of 3.29 +/- 0.3 and 4.48 +/- 0.25 were recorded respectively in distal esophagus, 2.01 +/- 0.17 and 4.84 +/- 0.37 in gastric fundus, 1.82 +/- 0.12 and 5.5 +/- 0.15 in body, 3.52 +/- 0.34 and 5.42 +/- 0.29 in antrum, 6.89 +/- 0.21 and 7.16 +/- 0.13 in duodenal cap, and 6.84 +/- 0.19 and 7.03 +/- 0.19 in proximal duodenal loop. When the lumen of esophagus and duodenum were perfused with acid (pH 2) luminal and mucosal pH values were 2.18 +/- 0.11 and 4.08 +/- 0.41 in esophagus, 2.57 +/- 0.15 and 6.74 +/- 0.13 in duodenal bulb, and 2.44 +/- 0.14 and 6.39 +/- 0.2 in duodenal loop. Juxtamucosal pH in fundus, body, and duodenum remained near neutral when luminal pH was 1.5, but in distal esophagus and antrum it fell sharply at luminal pH values below 3. In duodenal ulcer patients juxtamucosal pH in the cap was significantly lower than that in normals at luminal pH values below 3. These studies support the hypothesis that a "mucus-bicarbonate" barrier inhibits mucosal acidification in humans and that duodenal mucosa in ulcer patients is less able to maintain a neutral zone adjacent to it in the face of luminal acid.

The effect of cigarette smoking on gastroesophageal reflux and the effect of the pH electrode on salivary secretion and swallowing frequency were studied in 30 healthy volunteers (15 habitual smokers, 15 non-smokers) and in 10 smoking patients with proven gastroesophageal reflux disease. Twenty-four-hour pH profiles were measured while the subjects were ambulatory using a combined glass electrode connected to a portable recorder. In 8 of the smoking volunteers, swallowing frequency and salivary secretion were measured, both when smoking and when not. Smokers had more reflux episodes than nonsmokers [median per hour 2.8 (range 0.4-7.1) for the upright body position and 0.5 (range 0.0-1.7) for the supine body position vs. 1.4 (range 0.0-2.1) upright and 0.0 (range 0.0-0.7) supine, p less than 0.01], but the total time of exposure of the esophageal mucosa to acid was affected neither by the status of being a smoker nor by actual smoking. Nasopharyngeal intubation with the pH electrode did not affect the swallowing frequency, but it increased salivary secretion two-to threefold for a period of 4 h. Six hours after introduction of the pH electrode and later, salivary flow was similar to baseline. It is concluded that smoking and nasopharyngeal intubation does not adversely affect the results of 24-h pH-metry.

Fifty two patients were studied to investigate the patterns of gastro-oesophageal reflux during ambulatory pH monitoring and the relationship of reflux to presence and severity of oesophagitis. Twenty nine had evidence of oesophagitis which was graded according to severity. Acid exposure (pH less than 4) was calculated in each case for the total study period, the recumbent and upright periods, and the three hour period after the evening meal. Exposure in the upright period correlated closet (r=0.92: p less than 0.001) with that during the total period. Recumbent exposure correlated with both upright and postprandial exposure (p less than 0.001). Acid exposure during all four periods correlated significantly with the severity of oesophagitis, but postprandial acid exposure correlated best and recumbent acid exposure least well. Although acid clearance in the total, recumbent and upright periods correlated with oesophagitis, postprandial clearance showed the closest relationship. Thus the magnitude of daytime reflux, especially postprandial reflux and acid clearance, is more closely related than nocturnal reflux to oesophagitis. The results do not support the contention that night time reflux is inherently more injurious than daytime reflux to the oesophageal mucosa.

Of 53 patients with scleroderma (43 women and 10 men) evaluated by esophagoscopy and biopsy, 32 (60%) had erosive esophagitis. Symptoms of heartburn and dysphagia were significantly more frequent in the patients who had erosive esophagitis but often were present in those without this condition. Abnormal motility characterized by loss of peristalsis in the distal esophagus was present in all patients with erosive esophagitis, including the 5 who were asymptomatic. No patient with normal esophageal motility had erosive esophagitis at endoscopy. The patients with erosive esophagitis also had significantly diminished lower esophageal sphincter pressures and increased frequency and duration of gastroesophageal reflux episodes. Stricture was present in 13 of 32 patients with erosive esophagitis and was absent in the other 21 patients. The duration of disease, rate of gastric emptying, and fungal smear and culture were not significantly different in those with or without esophagitis. Treatment of fungal infection for a month had little beneficial effect. The pattern of esophageal motility in scleroderma identifies high and low risk groups for esophagitis and stricture, and can be used to select those who require further investigation, irrespective of symptoms.

While delayed gastric emptying of solid food has been reported in patients with symptoms of gastroesophageal reflux, the study populations were not defined by 24-h intraesophageal pH monitoring. Moreover, the influence that the gastric emptying rate may have on patterns of reflux during the day or night, as well as on esophagitis, is not known. In this study, we compared the gastric emptying rate of solid food (in vivo intracellular labeled chicken liver) observed in asymptomatic control volunteers (n = 15) with that of symptomatic patients with an abnormal 24-h pH record who had either the presence (n = 22) or absence (n = 11) of endoscopic esophagitis. We found no significant difference in the gastric emptying rate between the asymptomatic control volunteers and the symptomatic patients with and without esophagitis. Moreover, there was no significant correlation between the gastric emptying rate and the degree of daytime or nighttime distal esophageal acid exposure found during 24-h intraesophageal pH monitoring. Only 6% of the symptomatic patients had a gastric emptying rate that exceeded the mean value plus 2 SD of that found in the asymptomatic control volunteers. We believe these support a de-emphasis of the role that delayed gastric emptying of solid food may play in the pathophysiology of gastroesophageal reflux in most patients.

Thirty-six infants and children presenting with recurrent respiratory disorders (RRD) as the sole clinical symptom including bronchial asthma (6), recurrent obstructive bronchitis with or without wheezing (18), chronic nocturnal cough (3), recurrent episodes of pneumonia (3), recurrent pharyngitis (3) and recurrent laryngitis (3) were investigated for associated gastro-oesophageal reflux (GER) by oesophagram, endoscopy and continuous 24 h pH monitoring of the distal oesophagus. The pH monitoring criteria were selected on the basis of a preliminary study comparing statistically measurements of 32 variables recorded in 15 patients who all had clinical, radiological and endoscopic evidence of GER and in 8 asymptomatic controls. Although patients with symptomatic GER differed significantly from the asymptomatic ones for 27 variables examined, 6 variables emerged as having the highest value for discrimination (overlap score 0-1). Among these, the Euler-Byrne index (number of reflux pH less than 4 + 4 times the number of reflux episodes of more than 5 min), the percentage of total reflux time and the number of reflux episodes 1 h post-cibal scored 0 (no overlap). GER was considered to be present when at least five of these six parameters were abnormal. The overall incidence of GER in children with RRD was 41% (15) when detected by oesophagram and 61% (22) when diagnosed by pH monitoring criteria. In the children with bronchial asthma or with recurrent laryngitis, the percentage of reflux time during sleep was about 40 times higher than in asymptomatic controls and 2 times higher than in those with symptomatic GER.(ABSTRACT TRUNCATED AT 250 WORDS)

In a study comprising 100 patients referred to a surgical clinic with symptoms suggestive of gastro-oesophageal reflux disease the value of different diagnostic procedures was investigated. Positive acid perfusion and 24-h pH tests were the commonest findings. Forty-nine per cent showed a normal oesophageal mucosa or diffuse oesophagitis at endoscopy. The severity of heartburn and regurgitation did not differ between patients with normal oesophageal mucosa and oesophagitis of various severities. The severity of macroscopic oesophagitis was significantly correlated to the total reflux time, the presence of reflux or a hiatal hernia at radiology, an open cardia or reflux at endoscopy, pressure transmission or reflux and low lower oesophageal sphincter pressure at manometry. Gastric hypersecretion was found in 66% of the patients. Gastric acid secretion was not correlated to the severity of oesophagitis or to the findings at 24-h pH test. In patients with severe oesophagitis the sensitivity for radiologic, manometric, and endoscopic signs of incompetence of the gastro-oesophageal junction was 94%.

Gastro-oesophageal reflux is a common phenomenon in young infants. Normally it will disappear during the first months of life. The most important antireflux mechanism is the lower oesophageal sphincter (LOS). Another main factor to prevent reflux is an adequate oesophageal clearance. The significance of the upper oesophageal sphincter (UOS) and gastric emptying as antireflux barriers has yet to be clarified. Primary or secondary impairment of physiological antireflux factors may lead to a considerable number of clinical complications.

Prolonged oesophageal pH monitoring is being used increasingly to detect abnormal gastro-oesophageal reflux. To assess the influence of age on normal reflux patterns, a group of 13 young asymptomatic subjects (mean age 22 years) was compared with a group of 14 middle aged asymptomatic subjects (mean age 49 years). An ambulatory system using a radiotelemetry capsule and a portable receiving system was used, oesophageal pH being recorded for at least 16 hours during an overnight hospital stay under standardised conditions. There was no significant difference in the duration or frequency of reflux episodes as defined by pH less than 5, less than 4, less than 3, or as a fall in pH of more than two units. It is concluded that it is an acceptable practice to use young volunteers to establish normal values in reflux studies of young and middle aged patients.

A series of patients showing a previously unrecognized type of sliding hiatus hernia is presented and analyzed. This type of hernia is characterized by reflux of the mucous membrane of the Hiss angle into the lumen of the esophagus. The occurrence of mucosal prolapse is a secondary phase of gastroesophageal reflux. The mucous plug prevents further reflux of the acid contents of the stomach into the esophagus and mouth. After the appearance of mucosal prolapse, the symptoms and signs of esophagitis disappear. The most characteristic complaint of the patients is retrosternal pain on lying and bending down. Endoscopy with provocative tests reveals the mucosal prolapse. Tooth erosions due to previous acid reflux into the mouth are diagnostic. The symptoms of this new subtype of sliding hiatus hernia were cured by the Nissen fundoplication.

Fifteen patients with intractable reflux or its complications were sequentially studied after the placement of the Angelchik antireflux prosthesis. In all, 16 devices were inserted. Parameters were measured before and 3, 12, 24, and 36 months after prosthesis placement and included symptom scoring, esophageal manometry with Tuttle test, endoscopy, suction biopsy, barium swallow, and gastroesophageal scintigraphy. In addition, a subset of patients underwent stimulation/inhibition of the lower esophageal sphincter (LES) with pentagastrin, metoclopramide, edrophonium, and atropine. At a mean time of 16 months postsurgery, 10 of 16 (63%) patients were reflux-free and there was significant improvement in endoscopic, biopsy, and symptom scoring. Post-insertion, there were statistically significant increments in LES pressure with intravenous boluses of pentagastrin, metoclopramide, and edrophonium, and a significant decrease with atropine. Two patients who developed prosthesis herniation into the chest required removal because of ongoing reflux and dysphagia. An additional patient had prosthesis disruption and migration, which also required removal. Four patients with previously failed antireflux procedures had five prostheses placed. All continued to reflux postoperatively. No patient who was initially reflux-free subsequently developed reflux, despite a tendency for LES pressure to decline with time. Although this procedure proved effective for up to 36 months in patients who had had no previous antireflux procedure, the displacement rate (3/16 = 19%), reoperation rate (3/16 = 19%), and the progressive decline in LES pressure over time should make one cautious about its routine use in the surgical treatment of reflux esophagitis.

There is much evidence to suggest that peristaltic function is defective in esophagitis patients and that this defect may contribute to prolonged acid exposure, promoting esophageal mucosal injury. Abnormal peristalsis may also be related to the generation of reflux symptoms. We evaluated primary peristalsis and its relationship to symptoms under basal conditions and during saline and HCl perfusion in 15 symptomatic reflux patients with gross esophagitis and 15 healthy controls. In the basal state, LES pressure (15.3 vs 25.1 mm Hg) and peristaltic amplitude (74.2 vs 104.8 mm Hg) were significantly lower in subjects with gastroesophageal reflux disease (GERD) (P less than 0.05). During HCl perfusion, peristaltic amplitude and duration increased slightly, and peristaltic velocity slightly decreased similarly in both groups. There was no difference in the incidence of nonpropagated, segmental, or swallow-initiated simultaneous contractions, or change in resting intraesophageal pressure during HCl perfusion in control and GERD groups. This study identified abnormal contractile amplitude as a specific defect in the primary peristaltic wave of esophagitis patients but does not support a role for acid-induced motility changes in the generation of symptoms in GERD.

Gastro-oesophageal reflux has been assessed in 10 symptomatic patients and 10 asymptomatic normal subjects during a study period of 24 hours at work and in the home using a newly developed pH sensitive radiotelemetry capsule and a portable receiving system. Oesophageal pH was continuously monitored by the tethered radiotelemetry capsule and recorded with a portable receiver and a 24-hour cassette recorder, allowing the patient complete freedom of movement so that ambulatory studies could be undertaken during a normal working day. The number and duration of reflux episodes was greater in symptomatic patients than normal subjects during 24-hour studies at home (p less than 0.002). In both groups, reflux occurred more during the day than at night (p less than 0.01). Patients refluxed significantly more at home than when they were in hospital (p less than 0.01). Ambulatory outpatient oesophageal pH monitoring may be useful in the management of patients with atypical symptoms and may demonstrate significant reflux when inpatient investigations and endoscopy findings show minimal abnormality.

This paper reviews progress in the use of 24-hour distal esophageal pH monitoring in the study of gastroesophageal reflux. This technique records acid exposure as numbers of reflux episodes and time required by the esophagus to return this acid juice to the stomach. These data afford an opportunity to conceptualize the pathophysiology of gastroesophageal reflux disease in relation to physiologic activities such as alimentation, sleep, and postural change. This knowledge will enable the clinician to critically focus attention on important issues of patient management and therapy as they relate to the pathophysiology of this disease.

The effect of eating on childhood gastroesophageal reflux (GER) is unclear. Twenty-eight asymptomatic children and 28 children with symptoms of GER were fed apple juice or milk-formula and observed for 3 hr postcibal. Distal esophageal pH was monitored continuously during this interval and used to quantitate the frequency and duration of GER. A period of frequent GER occurred for up to 2 hr after apple juice feedings in asymptomatic children, whereas symptomatic patients had frequent GER for longer periods. Compared to apple juice feedings, milk-formula feedings resulted in a decreased esophageal acidity for the first 2 hr. However, the type of feeding did not affect GER seen in asymptomatic children more than 2 hr postcibal. The frequency and duration of postcibal GER were not reduced by the upright position in either group. Effective medical treatment of symptomatic children did not eliminate the frequent GER within 2 hr of apple juice feedings, whereas the Nissen fundoplication usually eliminated all GER. The absence of GER episodes following apple juice correlated with the inability of most children to burp or vomit following antireflux surgery. Therefore, frequent GER for up to 2 hr after clear liquid meals is probably physiologic in children. The effective control of vomiting by medical or surgical therapy correlated best with a decrease in GER more than 2 hr postcibal.

To ascertain how elevation of the head of the bed, bethanechol, and antacid foam tablets affect gastroesophageal reflux, we used prolonged intraesophageal pH monitoring in 55 symptomatic patients. Acid exposure was separated into reflux frequency and esophageal acid clearance time and recorded during the day in the upright posture and recumbent at night. Values before and during each therapy were compared to physiologic reflux in 15 asymptomatic controls. Ten patients slept with the head of the bed elevated and had a 67% improvement in the acid clearance time (P less than 0.025); however, the frequency of reflux episodes remained unchanged. Twelve patients given 25 mg of bethanechol 4 times a day had a 50% decrease in recumbent acid exposure only (P less than 0.05), due to a trend towards decreased reflux episodes and acid clearance in time. Bethanechol combined with head of bed elevation in 19 other patients decreased both reflux frequency (30%) and acid clearance time (53%, all P less than 0.05). Antacid foam tablets failed to significantly diminish acid exposure. Nocturnal reflux responded the best to those therapies tested.

Impaired esophageal clearing of refluxed gastric contents during sleep has been implicated in the pathogenesis of reflux esophagitis. To more directly evaluate this hypothesis, 13 symptomatic patients with esophagitis and 13 normal controls had 15 ml of 0.1 N HCl instilled into the esophagus in the recumbent position while awake and during polygraphically monitored sleep. When sleep was maintained for the majority of the acid-clearing duration, the clearance times for both patients and controls were significantly prolonged when compared to those while awake (P less than 0.01). However, when sleep was maintained for less than 50% of the acid-clearing interval, the patients showed significantly longer acid clearance times. The swallowing rate did not differentiate the two groups under any condition. These data show that sleep impairs esophageal acid clearance. Acid clearance occurred predominantly in association with arousals from sleep. The defective acid clearance found in patients with esophagitis probably plays a major role in the pathogenesis of this disorder.

Forty-seven patients with symptomatic gastro-oesophageal reflux were evaluated on the basis of symptoms, endoscopy, extended 18-h pH-monitoring of the lower oesophagus, and the pentagastrin test. The patients' acid secretion capacity did not correlate with symptoms or duration of acid reflux, but men with endoscopic oesophagitis had significantly higher BAO and MAO values than men without oesophagitis. In women this correlation was not found. The higher MAO values (in meq/h) in men than in women were abolished when the MAO was expressed as meq/h/FFB (fat-free body mass). The MAO values in all the men or all the women were not higher than the values obtained from a normal Finnish population. Both men and women with endoscopic oesophagitis had a significantly longer duration of oesophageal acid reflux than men and women with normal mucosa.

Seventeen infants under 2 years of age with documented gastroesophageal reflux were studied by continuous distal esophageal pH monitoring and were compared to six age-matched control. Records obtained from patients with GER differed significantly from controls in the percent of monitored time with pH below 4.0, the number of episodes of reflux per monitored hour, and the duration of the longest episode of reflux. The differences between the groups became highly significant when the two-hour period after a clear liquid feeding was evaluated separately. Continuous monitoring of distal esophageal pH is a more sensitive and specific means of diagnosing GER than the diagnostic tests available at present.

Twenty patients with reflux oesophagitis causing a tight peptic oesophageal stricture entered a randomised double-blind crossover trial in which they received cimetidine, 1.6 g daily, and matching placebo each for six months. The gross endoscopic appearances of oesophagitis, though not the grades of histopathological changes, showed significant improvement during treatment with cimetidine. The need for dilatation of the strictures, however, was not reduced.

Twelve-hour simultaneous registration of acid gastro-oesophageal reflux and peristaltic activity in the oesophagus was carried out on 30 healthy subjects. The intensity of the acid gastro-oesophageal reflux was determined by automatic integration of the pH variation. Acid gastro-oesophageal reflux to pH less than or equal to 4 occurs in normal subjects within a range of 0--2.4% of the total registration period. The intravariation was measured in 10 investigations on 1 subject, and lay within the intervariation. To maintain the pressure-measuring system intact, 3 ml H2O/h were fed to the proximal and distal pressure catheters, respectively; it has been shown that this small quantity of water has no influence on the pH variation. Peristaltic activity for the entire measuring period was recorded and related to the individual reflex episodes. The total activity was found to be dependent on the level of consciousness, with little activity occurring during sleep. A positive correlation was found between the lowest pH during a reflux episode and the peristaltic activity in the oesophagus (p less than 0.001), between the lowest pH during a reflux episode and the duration of the reflux episode (p less than 0.001), and between the peristaltic activity and the duration of the reflux episode (p less than 0.001). During long-term registration of oesophageal pH it appears that pH less than or equal to 4 is a usable parameter for distinguishing between pathological and non-pathological acid gastro-oesophageal reflux. Sudden falls in pH to below 4 release increased peristalsis in the oesophagus.