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Biomedical subjects

R E Marshall

Publications and source records attributed to R E Marshall.

At least 19 recordsLinked to original sources

Reproducibility and intragastric variation of duodenogastric reflux using ambulatory gastric bilirubin monitoring.

Duodenogastric reflux has long been considered to be important in the pathogenesis of many gastric disorders that exhibit regional variation within the stomach. Ambulatory gastric bilirubin monitoring is a new technique and, although extensively validated, reproducibility and gastric regional variation have not been specifically addressed. Fourteen patients with symptoms of gastroesophageal reflux and 12 healthy subjects underwent 24-h ambulatory gastric bilirubin monitoring with the bilirubin sensor in the upper stomach. Gastric bilirubin monitoring with two simultaneous bilirubin probes, one in the upper stomach and the other in the antrum, was performed on a separate occasion. Gastric bilirubin exposure in the initial and repeat studies showed a good correlation (R = 0.60, P < 0.01). Gastric bilirubin exposure in the upper stomach and the antrum showed a high degree of correlation (R = 0.90, P < 0.01). In conclusion, reproducible results are obtained with ambulatory gastric bilirubin monitoring and duodenogastric reflux does not exhibit significant regional variation within the stomach.

Adult↗

The extent of duodenogastric reflux in gastro-oesophageal reflux disease.

BACKGROUND: It is known that duodenogastro-oesophageal reflux (DGOR) increases with worsening gastro-oesophageal reflux disease (GORD). It is unclear whether this is accompanied by increasing duodenogastric reflux (DGR). OBJECTIVE: To investigate the extent of DGR in a control group and 66 patients with GORD, using the technique of ambulatory gastric bilirubin monitoring. METHODS: Sixty-six patients with reflux symptoms (30 grade 0 or 1 oesophagitis (group 1), 16 grade 2 or 3 oesophagitis (group 2), 20 Barrett's oesophagus (group 3)) and 17 healthy controls were studied. All underwent oesophageal manometry followed by 24-h ambulatory oesophageal and gastric pH monitoring and gastric bilirubin monitoring. RESULTS: Median per cent total oesophageal acid exposure (pH < 4) was significantly less in the control group (0.6%) than in group 1 (2.8%, P< 0.05) and groups 2 and 3 (7.5% and 7.8% respectively, P< 0.001). There was no significant difference between any group in median per cent total time gastric pH was greater than 4. There was no significant difference in median per cent total gastric bilirubin exposure (absorbance > 0.14) between any group. However, in each group gastric bilirubin exposure was greater in the supine position than the upright position, being significantly greater in the control group (P< 0.05) and group 1 (P < 0.001). CONCLUSIONS: Gastric bilirubin exposure is similar across the spectrum of GORD severity. It is greater in the supine than in the upright position.

Adult↗

Pharyngogastric colonic interposition for total oesophageal occlusion in epidermolysis bullosa.

Epidermolysis bullosa comprises a group of rare heritable disorders, characterized by blistering of skin and other epithelial lined structures following minor trauma. In the oesophagus, trauma from food boluses leads to bullae, ulceration and scarring, with formation of strictures. Oesophageal strictures are usually managed with balloon dilatation. We describe a case of a 19-year-old woman whose oesophageal stricture did not respond to balloon dilatation. She underwent a substernal colon interposition between the pharynx and stomach. The surgery included cervical, thoracic and abdominal approaches, with involvement of three specialist surgeons. Three months after surgery, the patient reported to be swallowing with little difficulty. Because of the high risk of morbidity and mortality associated with this surgery, we recommended that the patient should be managed in a specialist centre, with availability of intensive care facilities and the possibility of providing a multidisciplinary approach during surgery.

Adult↗

Investigation of gastro-oesophageal reflux in patients with an intact stomach: is oesophageal bilirubin monitoring a useful addition to pH monitoring?

OBJECTIVES: Ambulatory bilirubin monitoring has helped to establish the role of duodenal contents in gastro-oesophageal reflux disease. This study aims to define the clinical role of oesophageal bilirubin monitoring in reflux patients with an intact stomach. METHODS: In total, 113 consecutive patients with reflux symptoms were prospectively studied using combined ambulatory oesophageal pH and bilirubin monitoring. Patients were categorized as follows: no pathological reflux, isolated acid reflux, isolated bilirubin reflux, combined acid and bilirubin reflux. RESULTS: Thirty-eight patients (33%) had no pathological reflux, 49 patients (44%) had combined pathological acid and bilirubin reflux, and 17 patients (15%) had isolated pathological acid reflux. Only nine patients (8%) had isolated pathological bilirubin reflux. In these nine, the extent of pathological bilirubin reflux was small (median total bilirubin exposure time 12.2%, range 6.5%-20.7%) and mucosal damage was minimal (five had grade 1 oesophagitis, four had a normal oesophagus). In one patient, symptoms were temporally related to acid reflux, and in none were symptoms temporally related to bilirubin reflux. CONCLUSIONS: Isolated oesophageal bilirubin reflux in patients with an intact stomach is uncommon. In these patients mucosal injury is minimal, and reflux symptoms are not related to bilirubin reflux episodes. Further work is needed to define the role for oesophageal bilirubin monitoring in the investigation of reflux disease in patients with an intact stomach.

Bilirubin↗

Effect of omeprazole on antral duodenogastric reflux in Barrett oesophagus.

BACKGROUND: The effect of long-term acid suppression therapy in Barrett oesophagus remains unknown, but the high intragastric pH generated has been shown to increase the cytotoxicity of duodenal refluxate on foregut mucosa. However, recent work suggests that duodenogastric reflux (DGR) may be reduced by omeprazole. AIM: To investigate the effect of omeprazole on the reflux of duodenal contents into the gastric antrum in Barrett patients and healthy subjects. METHOD: Fifteen patients with Barrett oesophagus and 14 healthy subjects underwent oesophageal manometry followed by 24-h ambulatory oesophageal and gastric pH and gastric bilirubin monitoring. The bilirubin sensor (modified by the addition of a weighted tip to facilitate manoeuvrability) was sited in the gastric antrum under fluoroscopic control. Combined ambulatory pH and bilirubin monitoring was repeated after 2 weeks on omeprazole 20 mg b.d. RESULTS: Changes in oesophageal acid reflux and gastric alkaline shift due to omeprazole were as expected (P < 0.001). There was no difference in total antral DGR between the Barrett and control groups (P = 0.56), and omeprazole had no significant effect on DGR in either group (P = 0.77 and 0.27, respectively). CONCLUSIONS: DGR into the antrum is of a similar level in Barrett patients and healthy controls. Omeprazole does not reduce the reflux of duodenal contents across the pylorus. Further work is required on the increased cytotoxic potential of continuing DGR in those on long-term acid suppression.

Adolescent↗

Investigation of oesophageal reflux symptoms after gastric surgery with combined pH and bilirubin monitoring.

BACKGROUND: Little is known about the role of bile in gastro-oesophageal reflux disease in patients with previous gastric surgery. This has partly been due to a lack of suitable techniques for identifying bile reflux objectively. METHODS: Some 28 patients with reflux symptoms and previous gastric surgery underwent oesophageal manometry, and 24-h ambulatory oesophageal pH and bilirubin monitoring. RESULTS: A wide variety of operations had been performed, most commonly Pólya gastrectomy (seven patients), vagotomy and pyloroplasty (six) and vagotomy and gastrojejunostomy (four). Three patients had isolated acid reflux, eight had isolated bile reflux, six had combined acid and bile reflux, and 11 patients had no reflux. Two-thirds of heartburn symptoms were not associated with reflux. However, one-quarter were associated with acid reflux and only 7 per cent with bile reflux. Erosive oesophagitis was present in five patients: two with combined acid and bile reflux, and three with isolated bile reflux. CONCLUSION: Acid and/or bile reflux can be present after a wide variety of gastric operations. Symptoms are more frequently associated with acid reflux than with bile reflux. Erosive oesophagitis can occur in the presence of isolated bile reflux. Combined pH and bilirubin monitoring determines the nature of the refluxate, and may help in the management of these patients.

Adult↗

Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation.

AIMS: Changes in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barrett's metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential. METHODS AND RESULTS: Tissue sections from 51 patients with Barrett's intestinal metaplasia, nine with dysplasia (three indefinite) and 28 resected adenocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a period of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's metaplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or MUC2 were expressed in the dysplastic epithelium whether in its pure form (6/6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies which were initially classified as high-grade dysplasia expressed MUC1 and these turned out to be carcinomas on further investigations. MUC1 was also expressed in 12/28 (43%) of the adenocarcinomas and majority of these were poorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin-secreting carcinomas (4/28; 14%) irrespective of the tumour stage. CONCLUSION: Despite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Barrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intestinal mucin) in Barrett's metaplasia and this expression is lost when the cells become dysplastic. The lack of MUC1 in dysplastic epithelium and its expression in carcinoma could be utilized as a marker which could differentiate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression of MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.

Adenocarcinoma↗

Esophageal body length, lower esophageal sphincter length, position and pressure in health and disease.

We compared esophageal dimensions in control subjects and patients with differing motility disorders and severities of reflux disease. Patients (1108) and healthy controls (36) underwent manometry and 24-h pH monitoring. Subjects were grouped according to pH and manometry data into seven groups. Mean (s.e.m.) esophageal body length is greatest in achalasia [22.41 (0.27) cm] and least in reflux disease [20.06 (0.13) cm, p < 0.05]. Lower esophageal sphincter (LES) pressure is greatest in achalasia [17.46 (1.06) mmHg] and least in reflux disease [6.57 (0.24) mmHg, p < 0.05]. LES length is least in achalasia patients and control subjects. The ratio of intra-abdominal to intrathoracic LES is greatest in achalasia (1.29), no reflux and normal motility group, and controls and least in reflux disease (1.04, p < 0.05). In conclusion, esophageal body length is greatest in achalasia and least in reflux disease. This is associated with caudal movement of the LES in achalasia and cranial movement of the LES in reflux disease, relative to the diaphragm.

Adolescent↗

What is normal oesophageal motility? An ambulatory study.

BACKGROUND: Our aim was to establish normal values for wave characteristics and patterns in long-term ambulatory oesophageal body motility. METHODS: A pressure sensor was positioned in the pharynx or cricopharyngeus for swallow detection. Oesophageal body pressures were recorded 5, 10, and 15 cm above the lower oesophageal sphincter. Contraction patterns and wave characteristics from eating, drinking, and postprandial, fasting, and supine periods in 16 healthy subjects were studied. RESULTS: Contraction patterns were similar during eating and drinking periods or fasting and postprandial periods (P > 0.05). Wave characteristics during each period differed significantly in amplitude, duration, area under the curve, or peristaltic velocity (P < 0.05). During the eating period the amplitude and area under the curve were greatest, and peristaltic velocity was slowest compared with all other periods. CONCLUSIONS: Data from the eating and drinking periods or the fasting and postprandial periods can be combined for contraction pattern analysis but not for wave characteristic analysis, for which data from different periods should be analysed separately.

Adult↗

The temporal relationship between oesophageal bile reflux and pH in gastro-oesophageal reflux disease.

OBJECTIVE: Damage caused to oesophageal mucosa by bile constituents is pH dependent. The aim of this study was to evaluate the relationship between pH and duodeno-gastro-oesophageal reflux in gastro-oesophageal reflux disease at night in the supine position. DESIGN: A prospective study of 113 patients with reflux symptoms [63 without erosive oesophagitis (group 1), 23 with erosive oesophagitis (group 2), 27 Barrett's oesophagus (group 3)] and 15 controls. METHODS: All subjects underwent 24 h ambulatory oesophageal pH and bilirubin and gastric pH monitoring. For the supine period, oesophageal pH during episodes of bile reflux was calculated, and the temporal relationship between individual oesophageal and gastric alkaline shift and oesophageal bile reflux episodes was established. The supine period was divided into four equal segments and the temporal patterns of acid and bile reflux and alkaline shift in each of the four supine time segments were investigated. RESULTS: Both acid and bile reflux are severe in Barrett's oesophagus, particularly at night. Nocturnal oesophageal bile reflux occurs mostly between pH 4 and 7 in all groups: 67.6%, 76.5% and 41.4% of the supine period for groups 1, 2 and 3 respectively (P < 0.001 vs. pH < 4 or > 7). Individual oesophageal bile reflux and oesophageal or gastric alkaline shift episodes rarely coincide. Acid reflux predominates in the first half of the night (P < 0.001), oesophageal bile reflux and alkaline shift continue throughout the night, gastric alkaline shift increases towards the end of the night (P < 0.001). CONCLUSION: Duodenal contents in the oesophagus exist at a wide pH range, and may have passed through an acid or an alkaline stomach. This has implications for the damage which individual constituents are able to cause.

Adolescent↗

Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett's oesophagus.

BACKGROUND: Both acid and duodenal contents are thought to be responsible for the mucosal damage in Barrett's oesophagus, a condition often treated medically. However, little is known about the effect of omeprazole on duodenogastric reflux (DGR) and duodenogastro-oesophageal reflux (DGOR). AIMS: To study the effect of omeprazole 20 mg twice daily on DGR and DGOR, using the technique of ambulatory bilirubin monitoring. METHODS: Twenty three patients with Barrett's oesophagus underwent manometry followed by 24 hour oesophageal and gastric pH monitoring. In conjunction with pH monitoring, 11 patients (group 1) underwent oesophageal bilirubin monitoring and 12 patients (group 2) underwent gastric bilirubin monitoring, both before and during treatment with omeprazole 20 mg twice daily. RESULTS: In both groups there was a significant reduction in oesophageal acid (pH<4) reflux (p<0.005) and a significant increase in the time gastric pH was above 4 (p<0.005). In group 1, median total oesophageal bilirubin exposure was significantly reduced from 28.9% to 2.4% (p<0.005). In group 2, median total gastric bilirubin exposure was significantly reduced from 24.9% to 7.2% (p<0.005). CONCLUSIONS: Treatment of Barrett's oesophagus with omeprazole 20 mg twice daily results in a notable reduction in the exposure of the oesophagus to both acid and duodenal contents. In addition, delivery of duodenal contents to the upper gastric body is reduced.

Adult↗

The relationship between acid and bile reflux and symptoms in gastro-oesophageal reflux disease.

BACKGROUND: The role of bile in the genesis of oesophageal symptoms and disease is incompletely understood. A new method of ambulatory bile monitoring may help to define this role. AIMS: To establish the relationship between symptom events and acid and bile reflux episodes. PATIENTS: 59 consecutive patients presenting for further investigation of gastro-oesophageal reflux disease. METHODS: All patients underwent combined ambulatory pH and bile monitoring. For each patient, a symptom index (SI) was calculated in relation to both acid reflux and bile reflux episodes. RESULTS: Patients were divided into those without (group 1, n = 21) and those with (group 2, n = 38) acid reflux. A total of 394 symptoms were identified in 59 patients. In group 1, there were fewer symptom events per patient (mean 4.1) than group 2 (mean 8.1). Twenty three per cent of symptom events were associated with acid reflux in group 1 and 41% in group 2. Only 6% of symptom events in both groups were related to bile reflux. In group 1 both the acid and bile related SI score were low. In group 2 the bile related SI score was low, but the acid related SI score was high. CONCLUSIONS: Symptoms are much more often related to acid reflux than bile reflux. Bile reflux does not seem to be a major factor in producing oesophageal symptoms.

Adult↗

Oesophageal motor responses to gastro-oesophageal reflux in healthy controls and reflux patients.

AIMS: To compare oesophageal motor responses to gastro-oesophageal reflux (GOR) in 16 healthy controls (group 1) and 25 reflux patients, 15 without (group 2) and 10 with (group 3) oesophagitis. METHODS: All subjects underwent 24 hour ambulatory oesophageal pH measurements (5 cm above the lower oesophageal sphincter (LOS)) combined with pressure monitoring (5, 10, and 15 cm above the LOS for oesophageal body motility and 27 cm above the LOS for voluntary swallow detection). Contraction patterns (peristaltic, simultaneous, isolated, mixed type, and non-transmitted swallows) and peristaltic contraction wave characteristics (amplitude, duration, and velocity) during GOR were compared in the three groups. RESULTS: The average number of motor activities per minute was significantly higher in group 1 (p < 0.05). In all groups, the most common motor contraction pattern was peristaltic. The percentage of peristaltic activity per subject was significantly higher in group 1 (p < 0.05). There were no significant differences in other contraction patterns among the three groups (p > 0.05). Of the peristaltic contraction wave characteristics there were no significant differences in any parameters (amplitude, duration, and velocity) among the three groups (p > 0.05). The average pH increment in response to motor activities was significantly higher in group 1 (p < 0.05). CONCLUSIONS: Motor responses to GOR were found to be predominantly primary peristaltic in all groups. During GOR, reflux patients have less frequent activity, a smaller proportion of activity is peristaltic, and the average pH increment in response to motor activities is reduced compared with controls.

Adult↗

Bile in the oesophagus: clinical relevance and ambulatory detection.

BACKGROUND: Experimental work in animals has implicated a role for bile in the pathogenesis of several oesophageal mucosal diseases such as oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma. Recent descriptions of a high incidence of intestinal metaplasia at the gastro-oesophageal junction in patients without a classical 3-cm Barrett's columnar-lined segment, combined with a rising incidence in oesophageal and cardia adenocarcinoma, have stimulated interest in the causes of these conditions. METHODS AND RESULTS: Animal studies concerned with defining the role of the various gastroduodenal reflux constituents in oesophageal mucosal injury are summarized and evidence for bile in the pathogenesis of Barrett's oesophagus and oesophageal adenocarcinoma is reviewed. The results of various techniques for clinical measurement of oesophageal bile reflux, such as aspiration, scintigraphy and pH monitoring, are evaluated and the significance of recent studies employing ambulatory fibreoptic bilirubin monitoring is discussed. CONCLUSION: There seems little doubt that bile plays a significant role in oesophageal mucosal disease, in synergy with other constituents of reflux. Although ambulatory bilirubin monitoring is new, some intriguing findings have been reported and it is hoped that this technique will continue to shed light on the role of bile in the oesophagus.

Barrett Esophagus↗