Effect of omeprazole on lower oesophageal function in normal subjects.

In a double-blind crossover study, lower oesophageal sphincter pressure (LOSP) and distal oesophageal motility were studied in eight healthy volunteers following a single intravenous dose of omeprazole or placebo. Lower oesophageal sphincter pressure was determined before and at intervals up to 120 min after intravenous administration of 40 mg omeprazole or placebo. No effects on LOSP or distal oesophageal motility were observed.

Pharyngoesophageal dysmotility in globus sensation.

Ambulatory esophageal pH monitoring, radiologic examination, endoscopy, and manometry were undertaken in 142 patients with globus. The results demonstrate that abnormal gastroesophageal reflux occurred in 23% of patients, implying that, while reflux may be responsible for globus in some patients, it is not the cause of globus sensation in the majority of individuals with this symptom. Comparing patients with globus and control subjects, there were no differences in lower esophageal sphincter pressures, esophageal body motility, or tonic upper esophageal sphincter pressures, but patients with globus exhibited higher pharyngeal and upper esophageal sphincter after-contraction pressures during deglutition. The physiological significance of this pharyngeal and upper esophageal dysmotility is not clear and it may be no more than a secondary phenomenon. Alternatively, it may contribute to the generation of globus, perhaps in combination with other physical and psychological triggers.

Analysis of the pharyngoesophageal pressure profile in amyotrophic lateral sclerosis.

Treatment of dysphagia resulting from bulbar amyotrophic lateral sclerosis has included cricopharyngeal myotomy for many years but is successful in only a minority of cases. The purpose of this study was to explore the rationale for this procedure with modern manometric techniques. The results of pharyngoesophageal manometry in 13 patients with amyotrophic lateral sclerosis were compared with 13 age- and sex-matched healthy volunteers by Mann-Whitney analysis. There was no significant difference between patients and control subjects in distal esophageal or lower esophageal sphincter motility nor any pressure parameter of pharyngoesophageal motility. Separate analysis of the seven significantly dysphagic subjects showed a significantly reduced upper esophageal sphincter after-contraction amplitude during water and bread swallows in patients than in control subjects. These data suggest that the dysphagia of amyotrophic lateral sclerosis is not due to upper esophageal sphincter spasm and that treatment by cricopharyngeal myotomy may be inappropriate.

Cricopharyngeal dysfunction.

The aim of the study was to determine the manometric patterns in dysphagic patients with radiologic evidence of upper esophageal sphincter (UES) dysfunction. Nineteen patients with radiographic abnormalities of the UES underwent measurement of several parameters of UES tonic pressure and pharyngoesophageal water swallow dynamics. At least two UES tonic pressures were elevated in six subjects, compared with a control group of 67 healthy volunteers. No patients had UES achalasia. The cricopharyngeal impression in the remaining patients may represent muscular hypertrophy or deficiency of UES opening, despite manometric relaxation, but its relationship to the patient's symptoms remains unknown. Cricopharyngeal myotomy appears to be a reasonable treatment for patients with manometric UES hypertonicity.

Gastroesophageal reflux and posterior laryngitis.

Esophageal acid exposure was assessed by 23-hour ambulatory pH monitoring and compared with a biopsy of the posterior larynx and proximal esophagus in 97 patients with hoarseness, burning pharyngeal discomfort, or globus sensation. Patient results were compared with normal acid exposure times obtained in 54 control subjects. In 24 patients there were laryngeal abnormalities but both esophageal biopsy results and acid exposure times were normal. Laryngeal disease was found in association with prolonged acid exposure time or esophagitis in only 17 of the 97 patients (17.5%) studied. Recent reports appear to have overestimated the importance of acid reflux as a cause of posterior laryngitis.

The analysis of paraquat in urine by high-speed liquid chromatography.

The paraquat content of urine can be directly determined by high-speed liquid chromatography using ultraviolet spectrophotometric detection. The method separates paraquat (and diquat) from the ultraviolet-absorbing components of urine and no extraction or pre-treatment of the sample is required prior to analysis. Concentrations down to 100 mug/1 of paraquat in urine were determined. Quantitative results are in good agreement with those obtained by a colorimetric method. Diquat does not interfere with the analysis of paraquat, and it would also be possible to analyse diquat in paraquat-containing urine.

Oesophageal manometry during eating in the investigation of patients with chest pain or dysphagia.

Dysphagia is a frequent cause of referral for oesophageal manometry although the motor response to eating is not routinely studied. We examined symptoms and oesophageal motor patterns in response to eating bread in 30 patients with either gastro-oesophageal reflux (n = 20), or normal oesophageal function tests (n = 10). No patient experienced symptoms while swallowing water but one complained of heartburn and one developed symptomatic oesophageal 'spasm' during eating. In eight further patients, pain or dysphagia which occurred with swallowing bread was associated with aperistalsis. Comparing asymptomatic and symptomatic periods, there was a slight increase in mean swallow frequency from 7.5 (0.79) (SEM) to 9.0 (1.17) swallows per minute (NS; n = 10). The mean number of aperistalsis swallows increased from 4.5 (0.96) per minute to 6.2 (1.30) (p less than 0.01; n = 10). Aperistalsis during symptoms was mainly caused by non-conducted swallows rather than synchronous contractions (mean 5.8 (1.45) per minute compared with 1.2 (0.44]. Aperistalsis can be produced by rapid swallowing in the normal oesophagus through 'deglutitive inhibition'. These results suggest that some patients experience dysphagia associated with aperistalsis perhaps as a response to increased frequency of swallowing. Functional abnormalities of this nature will not be detected by conventional oesophageal manometry.

Coordinated motor activity of the human gastroduodenal region.

Using real-time ultrasonic imaging, and a test meal of 500 ml of dilute orange juice, we have studied the temporal relationships among contractions of the terminal antrum, pylorus, and proximal duodenum of 22 normal subjects. A total of 259 cyclical periods of motor activity were observed. Individual mean gastroduodenal cycle times ranged from 17.9 to 29.6 seconds (2.0-3.3 cycles/min). Terminal antral contractions (TACs) were observed in 98% of cycles and pyloric closure invariably occurred at the midpoint of these contractions. The pylorus then opened as the terminal antrum relaxed and remained open until the next TAC. Only 67% of TACs were associated with contractions of the proximal duodenum (DC), but 94% of these occurred about 1 sec (range 1 sec before to 2 sec after) after pyloric closure. Only 6% of DCs were ectopic, in that their occurrence was apparently uncoordinated with the TACs. Our observations demonstrate that after ingestion of a test meal, the human terminal antrum, pylorus, and proximal duodenum usually contract in a sequential coordinated manner, presumably under the control of the gastric slow wave. No evidence of independent pyloric closure was obtained.

Comparison of intravenous edrophonium and oesophageal acid perfusion during oesophageal manometry in patients with non-cardiac chest pain.

Sixty consecutive patients referred for evaluation of non-cardiac chest pain had oesophageal manometry. Motility was assessed basally, after edrophonium 80 micrograms/kg iv and during oesophageal perfusion with 0.1 N HCl at 6 and 14 ml/min for eight and seven minutes respectively. A positive response, defined as symptom reproduction with or without abnormal motility, was present in 21 patients (35%) after acid perfusion and 12 (20%) after edrophonium. Eleven of the 12 patients responding to edrophonium also responded to acid perfusion, including most of the patients with primary motility disorders. Significantly greater increases in peristaltic duration, but not amplitude, were recorded after edrophonium (p less than 0.01) and acid perfusion (p less than 0.05) in positive responders, compared with non-responders. Results indicate that acid perfusion during oesophageal manometry may be a more useful stress test than edrophonium and that the mechanism of symptom production may be similar.

Site and mechanism of pain perception with oesophageal balloon distension and intravenous edrophonium in patients with oesophageal chest pain.

Ten healthy volunteers and 13 patients with oesophageal motility disorders whose primary presenting complaint was chest pain were studied by distending an intraoesophageal balloon in 1 ml steps to the point of a sensation of discomfort. The net balloon pressure (intra-balloon pressure when inflated within the oesophagus minus the pressure recorded at the same volume outside the patient) was measured at each volume increment and the distension volume at the perception of discomfort was noted. The measurements were repeated after intravenous injection of edrophonium (80 micrograms/kg) and again after 1.2 mg intravenous atropine. Oesophageal wall compliance was similar in patients and controls, and the two groups showed a similar effect of decreased compliance with edrophonium and increased compliance after atropine. There were no significant differences between patients and controls of distending volume at perception of discomfort. Edrophonium, however, resulted in a significant reduction in distension threshold for pain (p less than 0.03) in patients. A similar though non-significant trend was seen in controls. In both controls and patients, distension volume for pain production after atropine was significantly (p less than 0.01) higher than after edrophonium. From these results and other published data, we suggest that the pain receptor for noxious stretch and after edrophonium challenge is likely to be an 'in series' mechanoreceptor located in oesophageal longitudinal muscle.

Lowered oesophageal sensory thresholds in patients with symptomatic but not excess gastro-oesophageal reflux: evidence for a spectrum of visceral sensitivity in GORD.

Some patients undergoing ambulatory oesophageal pH monitoring to investigate symptoms suggestive of gastro-oesophageal reflux disease (GORD) are found to have oesophageal acid exposure within the physiological range but show a close correlation between their symptoms and individual reflux episodes. It is suggested that these patients might exhibit enhanced oesophageal sensation, akin to the heightened perception of both physiological and provocative stimuli in the gut that has been described in patients with functional gastrointestinal disorders. This study tested the hypothesis by measuring the sensory thresholds for oesophageal balloon distension and discomfort in 20 patients with symptoms of GORD, in whom ambulatory pH monitoring had shown normal acid exposure times, but in whom the symptom index for reflux events was 50% or greater, and compared these with 15 healthy volunteer controls, and with control groups with confirmed excess reflux. The study group showed lower thresholds both for initial perception of oesophageal distension, and for discomfort, compared with healthy controls (median ml (range)); 7.5 (2-19) v 12 (6-30) (p = 0.002) and 10 (5-20) v 16 (8-30) (p < 0.0001), respectively. Sensory thresholds in the study group were also significantly lower than in patients with excess reflux, and than patients with Barrett's oesophagus, who also exhibited significantly higher sensory thresholds than healthy controls. No differences in sensory thresholds for somatic nerve stimulation were found between the study group and health controls. The results show a spectrum of visceral sensitivity in GORD, with enhanced oesophageal sensation in patients with symptomatic but not excess gastro-oesophageal reflux, suggesting that their symptoms result from a heightened perception of normal reflux events.

Nucleotide sequence analysis of the serotype-specific epitope of infectious pancreatic necrosis virus.

The cDNA nucleotide sequences of the infectious pancreatic necrosis virus (IPNV) serotype-specific epitope of the major structural protein VP 2 were determined for a Scottish strain (Sp serotype), and an IPNV field isolate from Shetland. Comparison of the sequence data indicated that the field isolate was of the Sp serotype. The Scottish Sp strain and the field isolate showed less than 3% difference in nucleotide sequence over this region compared to the Norwegian N 1 strain, and all three European viruses differed by approximately 23% from the Canadian Jasper strain.

Transpyloric fluid movement and antroduodenal motility in patients with gastro-oesophageal reflux.

The pattern of transpyloric fluid movement and associated antroduodenal motility was compared in patients with gastro-oesophageal reflux (GOR) and healthy controls using real time ultrasonic imaging. A similar number of cyclical periods of antroduodenal motor activity (GOR 94 and control 91) was studied in each group. Mean antral cycle times and the frequency of occurrence of related proximal duodenal contractions (antroduodenal coordination) were similar. Transpyloric fluid movement occurred as a number of discrete episodes in each cycle. Gastroduodenal flow was more frequent in the GOR group (mean 2.7 +/- 0.4 episodes per cycle) than in controls (mean 1.7 +/- 0.3). The mean duration of these episodes in both groups was similar at around 2.5 seconds. Duodenogastric flow (reflux) was observed in many cycles (GOR 63%; controls 54%), but there was no difference in the mean number of episodes per cycle (GOR 0.79; control 0.74) or their mean duration (two seconds for both). Transpyloric fluid flow only occurs when a pressure gradient is created across the open pylorus. These observations indicate that in GOR the gastroduodenal pressure gradient is positive more frequently than in normal controls. Gastroduodenal liquid flow but not duodenogastric reflux differs in GOR patients and controls.

Effect of alterations in test meal composition on episodic transpyloric fluid movement in humans.

Using real-time ultrasonic imaging we have observed the effect of four different liquid test meals on transpyloric fluid movement and related gastroduodenal motor activity in 10 normal subjects. The mean interval between antral contractions (cycle times), and the frequency of occurrence of related proximal duodenal contractions were similar with all four meals (F = 0.3, for both). Forward (gastroduodenal) flow through the pylorus was observed in 95% of cycles and occurred as up to four brief episodes per cycle, each lasting 2-3 sec. The duration of these episodes with pH 2.8 and pH 7.0 meals was longer than with protein and glucose meals (P less than 0.05). There were, however, fewer episodes of forward flow in each cycle with the pH 2.8 and pH 7.0 meals with the protein and glucose meals (P less than 0.05). Retrograde (duodenogastric) flow was observed in 56% of cycles and occurred, on average, as less than one brief episode lasting about 2 sec each cycle. The pattern of retrograde flow was similar with all meals. Gastric emptying and duodenogastric fluid movement both occur in intermittent brief episodes lasting a few seconds only. Changes in the nature of the test meal cause subtle alterations in the basic pattern of transpyloric fluid movement, presumably reflecting the influence of the meal on control mechanisms governing gastric emptying.

Relationships of human antroduodenal motility and transpyloric fluid movement: non-invasive observations with real-time ultrasound.

To study the relationships between gastric antral and proximal duodenal motor activity, and the movement of liquid across the pylorus, 10 healthy volunteers were given a test meal of dilute orange juice and bran, and events at the gastric outlet monitored by real-time ultrasound. A total of 116 complete gastric peristaltic cycles were observed and in 86% of these, associated proximal duodenal contractions were seen. Transpyloric fluid movement, as reflected by the movement of the bran particles, occurred as brief episodes during the time when the pylorus was open. Distal flow, in episodes lasting 2-4 seconds, was seen to occur in 81% of the 116 complete cycles and 75% of these episodes occurred just after the relaxation of the terminal antrum, pylorus, and proximal duodenum. The remainder occurred shortly before the terminal antral contraction. Retrograde flow, in episodes of up to 5 seconds, occurred in 78% of observed cycles with the majority occurring immediately before contraction of the terminal antrum. Our findings indicate that transpyloric fluid movement occurs in brief episodes lasting a few seconds only and that retrograde flow across the pylorus occurs in normal subjects. This pattern of fluid movement can bear no direct relationship to a steadily advancing antral peristaltic contraction, nor be wholly attributable to constant intragastric pressure.

Five year prospective study of the incidence, clinical features, and diagnosis of achalasia in Edinburgh.

With the increasing availability of manometry, patients with achalasia are often referred at an early stage when they lack the classic features of established disease. A prospective five year study of the presenting features of untreated achalasia referred to our department was undertaken. Twenty men and 18 women presented throughout adult life, with a mean age at the time of diagnosis of 44 years (range 17 to 76 years). The presenting symptoms were dysphagia: for solids (100%) and for liquids (97%), chest pain (74%), and weight loss (60%). Endoscopy was reported as normal in 15 patients and achalasia was suggested in only 21 of 33 barium examinations. Fourteen had been treated for gastrooesophageal reflux but none had been misdiagnosed as having cardiac or psychiatric disease. The annual incidence of achalasia in the Lothian region is 0.8/100,000 of population. Persistent dysphagia is the cardinal symptom of achalasia which presents throughout adult life. Nevertheless, recent onset achalasia is often misdiagnosed as gastrooesophageal reflux disease. Because endoscopy is frequently normal and the diagnosis is often not made by radiology, manometric investigation is necessary if the condition is to be recognised and treated at an early stage.

Immunoglobulin synthesis in the "resting" breast.

Nulliparous women have a greater risk of developing breast cancer than women who have borne children, but so far no functional differences in breast tissue have been reported between parous women and nulliparae. Macroscopically and histologically normal breast tissue was obtained from 74 women of reproductive age during biopsy of benign breast lesions and was examined for the presence of plasma cells by immunfluorescence. Immunoglobulin synthesis was detected by an in-vitro culture technique. Synthesis of IgA was detected in 81% of specimans of IgG in 45%, and of IgM in 3%. IgA synthesis much more intense than IgG or IgM synthesis. Plasma cells containing IgA were seen in 71% of the specimens examined, and 88% of specimens had deposits of IgA in the ductules. The findings were not significantly incluenced by the nature of the condition necessitating biopsy or by oral contraception. Nulliparous women showed no cyclical changes, but among parous women IgA synthesis was more intense during luteal phase of the menstrual cycle. This suggests that after the first pregnancy the breast is more sensitive to progesterone.

Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro-oesophageal reflux disease.

The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient's usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 'gastro-oesophageal reflux disease' are absent, or who do not have symptoms during pH monitoring.

Systematic comparison of conventional oesophageal manometry with oesophageal motility while eating bread.

Conventional oesophageal manometry is seldom accompanied by symptoms and may indeed be normal in patients with a history of dysphagia. We have recently shown that oesophageal manometry during eating may be helpful in the evaluation of patients with dysphagia but there has been little systematic comparison of fed oesophageal motor patterns with conventional clinical manometry. Oesophageal manometry in response to water swallows and during eating was therefore examined in 58 consecutive patients who had been referred for clinical oesophageal function studies. The patients were divided into three groups according to the percentage of peristaltic activity during conventional manometry: group 1 (n = 21) had 100% peristalsis; group 2 (n = 29) had 1-99% peristalsis and group 3 (n = 8) were aperistaltic. All the patients in group 3 had achalasia and remained aperistaltic during eating, however, was less than with water swallows in both group 1 (53% compared with 100%) and group 2 (49% compared with 82.3%) patients. Synchronous contractions and non-conducted swallows were correspondingly increased during eating. Although there was a significant correlation between the amplitude of peristaltic contractions with water and bread in groups 1 and 2, mean peristaltic amplitudes were less with bread than with water swallows. The data show that there are substantial differences in the distal oesophageal motility patterns produced by water swallows and by eating. Conventional manometry with water swallows does not allow prediction of the fed oesophageal motility pattern, except in patients with achalasia.