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Biomedical subjects

T N Walsh

Publications and source records attributed to T N Walsh.

At least 37 records · Page 2Linked to original sources

Upper oesophageal sphincter function during general anaesthesia.

The effect of anaesthesia on the upper oesophageal sphincter response to acid in the distal oesophagus and hypopharynx, and the effect of atracurium besylate on acid migration into the hypopharynx, was studied in 102 patients undergoing elective varicose vein surgery. Group 1 (n = 48) received a general anaesthetic and the muscle relaxant atracurium besylate whereas group 2 (n = 54) received a general anaesthetic without relaxation. Upper oesophageal sphincter tone was significantly lower in patients receiving muscle relaxants ('sphinctometer output', eight versus 14, P < 0.05). Sixteen patients (16 per cent) had reflux into the distal oesophagus during anaesthesia (nine in group 1 and seven in group 2, P not significant), of whom seven had reflux to the hypopharynx. There was no difference in incidence of hypopharyngeal acid exposure between groups. Upper oesophageal sphincter tone did not alter in response to reflux into the distal oesophagus or hypopharynx in either group. The upper oesophageal sphincter fails to protect the hypopharynx under general anaesthesia even if patients do not receive a muscle relaxant.

Adult↗

Gastric motility following oesophagectomy.

The motility of the vagally denervated transposed stomach after oesophagectomy was examined by ambulatory gastric manometry and videofluoroscopy. Two groups of subjects were studied. Group 1 comprised ten patients who had undergone oesophagectomy 6-12 months previously and group 2 consisted of six normal control subjects. Studies were performed on fasting and fed subjects, and following injection of erythromycin 8 mg/kg. No distinguishable manometric wave activity was seen in either group while fasting. Feeding generated a measurable wave pattern in the patient group only. A significant increase in the mean (s.e.m.) distal wave amplitude was identified after infusion of erythromycin in both patients (34.0(15.1) versus 12.2(3.1) mmHg, P < 0.05) and controls (15.1(3.4) versus 5.0(0.0) mmHg, P = 0.05). The response to erythromycin was more rapid in patients than in controls (mean(s.e.m.) 113(16) versus 377(133) s, P < 0.05) and the effect persisted for longer (more than 1 h) in those who had undergone oesophagectomy. Videofluoroscopy confirmed purposeful motility in both the normal and vagally denervated stomach. It is concluded that the transposed stomach is a dynamic conduit. Enhancement of motility was greatest in the denervated stomach, indicative of denervation supersensitivity.

Erythromycin↗

Ambulatory oesophageal bile reflux monitoring in Barrett's oesophagus.

Bile reflux has been implicated in the pathogenesis of Barrett's oesophagus but evaluation remains difficult. Bilitec 2000 is an ambulatory system that detects bilirubin based on its spectrophotometric properties. Oesophageal bile exposure was evaluated in three groups of patients. Group 1 (n = 11) were normal controls, group 2 (n = 13) were patients with uncomplicated gastro-oesophageal reflux and group 3 (n = 12) were patients with Barrett's oesophagus. Bile reflux was greater in patients with Barrett's mucosa than in controls or those with uncomplicated reflux. This difference was seen in the supine and interdigestive periods. The percentage of time at which gastric pH was greater than 4 and oesophageal pH was above 7 did not differ between the groups. Bilitec 2000 detects greater bile reflux in patients with Barrett's oesophagus. No corresponding gastric or oesophageal alkaline shift is found. This ambulatory bile reflux monitoring system may be a useful tool in clinical practice.

Adolescent↗

Cardiac ischaemia induces vagally mediated lower oesophageal sphincter relaxation.

Gastro-oesophageal reflux and coronary artery disease frequently coexist. Direct stimulation of myocardial vagal receptors impairs lower oesophageal sphincter (LOS) function but the effect of cardiac ischaemia has not been examined. Eight adult mongrel dogs were studied under general anaesthesia. Each underwent occlusion of the left circumflex coronary artery before and after bilateral cervical vagotomy. Blood pressure, heart rate and LOS responses were measured. Median (range) LOS tone was significantly reduced by coronary artery occlusion, from 9 (6-14) to 6 (3-8) sphinctometer units (P < 0.01). This was accompanied by a reduction in heart rate (P < 0.05) and blood pressure (P < 0.01). After bilateral cervical vagotomy the same ischaemic insult produced no significant alteration in LOS tone or heart rate. These data suggest a direct vagal reflex to explain the high incidence of gastro-oesophageal reflux in patients with coronary artery disease.

Animals↗

Helicobacter pylori infection increases following cholecystectomy.

Cholecystectomy is frequently linked with duodenogastric reflux and gastritis but its effect on Helicobacter Pylori (H pylori) infection has not been examined. In a prospective study, twenty two patients with documented cholelithiasis underwent upper gastrointestinal endoscopy and biopsy and 24hr dual channel pH monitoring prior to cholecystectomy and again at 3-6 months post-operatively. The antral biopsies were histologically assessed for H pylori and gastritis and awarded an alkaline reflux score. The number of patients with H pylori infection increased from 7 (32%) preoperatively to 15 (68%) post-cholecystectomy (p < 0.05). Cholecystectomy was also associated with an increase in the incidence of gastritis from 7 to 15 (p < 0.05). The increase in H pylori infection rate occurred in association with an increase in the percentage time gastric pH > 4 in the supine position, from 9.6 (2.2) to 22.2 (4.8) percent, (p < 0.01). The median chemical gastritis score, however, did not change significantly following surgery [8(3-11) vs 7(3-11)]. Seven patients remained symptomatic following cholecystectomy all of whom were H pylori positive and had gastritis. H pylori can survive in the alkaline environment which follows cholecystectomy and may contribute to the post-cholecystectomy syndrome.

Adult↗

Expression of epidermal growth factor receptor and proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to chemoradiotherapy.

BACKGROUND: Multimodality therapy with chemotherapy and radiotherapy followed by surgery may improve survival in patients with esophageal squamous cell carcinoma compared with each of the individual treatment options. Histologic assessment of resected tumors after chemoradiotherapy shows that some patients have a complete response with no residual tumor, whereas other patients derive no benefit. The ability to predict response to chemoradiotherapy would allow treatment to be planned accordingly. METHODS: Expression of the tumor growth and proliferation proteins epidermal growth factor receptor (EGFR) and proliferating cell nuclear antigen (PCNA) was determined using immunohistochemical staining of pretreatment endoscopic biopsies from patients with esophageal squamous cell carcinoma who were randomized to chemoradiotherapy before surgery. Response to chemoradiotherapy was assessed by histologic examination of the resected specimens. Response to chemoradiotherapy and survival were correlated with EGFR and PCNA expression individually and with both markers combined as EGFR/PCNA: RESULTS: Of 14 patients available for study, 6 had a complete histologic response (CR) to chemoradiotherapy with no residual tumor in the resected specimen, 3 had a partial response (PR) to chemoradiotherapy, and the remaining 5 had minimal response (MR). Of the nine patients with a CR or PR, tumors of eight patients were negative for one or both markers. Of the five patients with an MR, four tumors were positive for both EGFR and PCNA (P < 0.05, Fisher's exact test). Comparison of survival from the date of randomization shows that patients with tumors negative for one or both markers had a significant survival advantage (P = 0.0003, log-rank test). CONCLUSIONS: Evaluation of PCNA and EGFR status of pretreatment biopsies may identify a group of patients likely to derive the greatest benefit from chemoradiotherapy before surgery in terms of histologic response and long term survival.

Adult↗

Randomized controlled trial comparing Nissen fundoplication and the Angelchik prosthesis.

Sixty-one patients with gastro-oesophageal reflux refractory to medical therapy were entered into a prospective randomized trial comparing the Rossetti-Hell modification of the Nissen fundoplication (n = 31) with the Angelchik prosthesis (n = 30). Mean age, sex ratio, duration of symptoms, preoperative pH profiles and manometric findings were similar in the two groups. At a mean of 84 (range 64-105) months after closure of the trial 47 patients were available for review, eight had died from unrelated causes and six were lost to follow-up. Of the patients reviewed, 28 consented to endoscopy, 25 to oesophageal 24-h pH assessment and 20 to oesophageal manometry. Both fundoplication and the Angelchik prosthesis provided lasting control of gastro-oesophageal reflux, with 20 and 17 patients respectively maintaining a satisfactory outcome. There were no significant differences in pH profile between the groups but the Angelchik prosthesis had to be removed from three patients.

Esophagogastric Junction↗

Implications of upright gastro-oesophageal reflux.

The presentation, oesophageal profile and management of 27 symptomatic patients with daytime (upright) gastro-oesophageal reflux only is reported. Oesophagitis was a presenting feature in 11 patients and its development was most closely correlated with postprandial reflux, which was characterized by cumulative acid exposure rather than by clearance abnormalities. Upright reflux was not associated with a hypotensive lower oesophageal sphincter or with oesophageal dysmotility. Antireflux surgery is indicated when conservative measures fail and was not associated with gas-bloat syndrome after operation.

Adult↗

Bradykinin, coronary artery disease and gastro-oesophageal reflux.

Gastro-oesophageal reflux and coronary artery disease frequently coexist. Stimulation of myocardial vagal receptors impairs lower oesophageal sphincter (LOS) function and may explain this link. This study examined the role of bradykinin, produced in increased quantities by the ischaemic myocardium, in activating this reflex. Thirteen dogs had patches soaked in bradykinin 100 micrograms/ml and saline applied sequentially to the left ventricular epicardium. Eleven of these animals were further divided into two subgroups: group 1 animals (six dogs) had the above sequence repeated after obliteration of sympathetic afferent fibres with phenol and those in group 2 (five animals) underwent sequential intravenous and intra-atrial injection of bradykinin 0.2 micrograms/kg. Epicardial bradykinin produced a fall in mean(s.e.m.) LOS tone from 13.3(1.3) to 6.0(0.5) sphinctometer units (P < 0.002), accompanied by a reduction in mean(s.e.m.) arterial pressure from 95(4) to 83(5) mmHg (P < 0.002). Destruction of sympathetic afferent fibres did not alter the LOS effect. Intra-atrial, but not intravenous, bradykinin reproduced the LOS effect; this suggests a cardiac origin. Myocardial release of bradykinin may play a role in producing transient LOS relaxation, predisposing to gastro-oesophageal reflux.

Animals↗

Hypotension induced by haemorrhage impairs lower oesophageal sphincter function.

The effect of haemorrhage-induced hypotension on lower oesophageal sphincter (LOS) tone was studied in 11 adult mongrel dogs. Mean(s.e.m.) blood loss of 760(66) ml, corresponding to 42 per cent of estimated blood volume, was associated with a significant fall in LOS tone (14.2(1.0) versus 7.2(0.6) sphinctometer units, P < 0.002). This was associated with a reduction in mean(s.e.m.) arterial blood pressure (99(7) versus 53(3) mmHg, P < 0.002) and heart rate (113(6) versus 106(5) beats per min, P = 0.06). Group 1 animals (n = 6) received autotransfusion, restoring LOS tone to prehaemorrhage values. Dogs in group 2 (n = 5) were given intravenous erythromycin 4 mg/kg, which also restored LOS tone. This effect was transient, lasting a mean(s.e.m.) of only 67(7) min. Infusion of an equivalent volume of 0.9 per cent saline following cessation of the erythromycin effect restored LOS tone to control values although the animals remained hypotensive. Reduction in LOS tone with haemorrhage may be part of a vagal reflex mediated by myocardial afferent C fibres and may explain the high incidence of pulmonary aspiration in shocked patients.

Animals↗

An ambulatory bile reflux monitoring system: an in vitro appraisal.

Assessment of duodenogastric bile reflux has hitherto been unsatisfactory. An ambulatory system which utilizes the optical properties of bilirubin is examined. Test readings are correlated with the laboratory values for bilirubin in each of a number of physiological solutions. For dilutions of pure bile there was a linear correlation between absorbance and bilirubin concentration (r = 0.93, p < 0.001). In the more acidic environment of gastric juice there was also a linear correlation between absorbance and bilirubin concentration (r = 0.65, p < 0.001), but absorbance values were significantly higher than those of pure bile solutions (F ratio = 130, p < 0.0001). Normal gastric secretions and saliva give low absorbance values (0.02-0.04). Common foodstuffs such as soups, tea and coffee give higher readings and may interfere with bile reflux assessment in a clinical setting. Bilitec 2000 has potential for use as an ambulatory bile reflux monitoring system but consideration should be given to a standard diet or attention must focus on the fasting period.

Ambulatory Care↗

Myocardial vagal stimulation impairs lower esophageal sphincter function.

BACKGROUND: Coronary artery disease and gastroesophageal reflux disease frequently coexist, but a direct pathophysiologic link has not been established. METHODS: This study examines the effect of myocardial vagal receptor stimulation on lower esophageal sphincter (LES) tone in eight adult mongrel dogs, each acting as its own control. Pharmacologic stimulation was carried out by the application of 1 cm gauze patches soaked in nicotine (200 micrograms/ml) to the epicardium. Epicardial vagal receptors were stimulated mechanically by digital friction. RESULTS: Pharmacologic stimulation produced a rapid fall in LES tone from a mean (SEM) of 12.6 (1.5) to 8.6 (0.9) sphinctometer units (p = 0.007). Mechanical stimulation also produced a rapid fall from 12.0 (1.5) sphinctometer units to 6.8 (0.7) (p = 0.007). Both were associated with a drop in mean arterial blood pressure and heart rate. Sham patches soaked in sterile water produced no effects. CONCLUSIONS: These data suggest a direct vagal reflex linking the myocardium and the LES that may explain the high incidence of gastroesophageal reflux in patients with heart disease.

Animals↗

[Carcinoma arising in Barrett's esophagus and report of 51 cases].

Fifty-one patients with carcinoma arising in Barrett's esophagus were treated surgically from 1971 to 1990. This represented 10.2% of all treated cases with esophageal carcinoma during the same period. The mean age was 63 years. The most common symptom was dysphagia. According to PTNM staging, 18 were stage II, 24 stage III and 4 stage IV. All patients were treated by surgery. The 30-day hospital mortality was 3.9%. The one, two and five-year survival rates were 45.9%, 25.0% and 13.6%, respectively. The 5-year survival rate was significant greater for stage II (25.0%) than for stage III + IV patients (4.5%), and for tumor length < 6 cm (21.0%) than for tumor length > 6 cm (0). The results indicate that the survival rate following resection is closely related to the clinical stage and tumor size.

Adenocarcinoma↗

Mechanisms of columnar metaplasia and squamous regeneration in experimental Barrett's esophagus.

BACKGROUND: This study examined the effect of the lower esophageal milieu on the healing of a mucosal defect. METHODS: With a canine model a mucosal defect was created in the lower esophagus, and acid reflux was promoted by a cardioplasty and pentagastrin injection in 10 animals. At 3 months the regenerated mucosa was excised and underwent histologic examination. Six of these animals underwent an antireflux procedure, had their acid secretion suppressed, and were followed up for a further 3 months, at which time they were killed and the entire esophagus underwent histologic examination. RESULTS: When reflux was stimulated, healing of the mucosal defect was by columnar epithelium alone in seven of 10 animals. After reflux control in six animals healing was again by columnar epithelium, but in all six cases islands of squamous epithelium occurred. Histologic examination showed both types of regenerating epithelium to be in continuity with the ducts of the esophageal glands, lined in their proximal two thirds by columnar and in their distal one third by squamous cells. CONCLUSIONS: It is suggested that the type of regenerating epithelium is determined by the depth of injury to mucosa or gland ducts. If both cell types survive, a mixed pattern of regeneration may occur, but columnar repair will usually predominate because of its more rapid turnover. If the squamous cells of the mucosa and ducts are destroyed, however, repair will be by columnar epithelium alone.

Animals↗

Cholecystectomy and oesophageal reflux: a prospective evaluation.

The effect of cholecystectomy on oesophageal function was examined prospectively. Of 37 patients studied, 17 (46 per cent) were still symptomatic 3-4 months after surgery. Thirteen patients (35 per cent) had abnormal oesophageal pH profiles before cholecystectomy, increasing to 27 (73 per cent) afterwards (P < 0.002). The mean (s.e.m.) DeMeester acid reflux score increased from 15.2(2.1) to 34.2(5.2) (P < 0.001) after operation. Lower oesophageal sphincter function, as measured by the sphincter function index, was significantly reduced in the patients with abnormal pH profiles after operation (P < 0.01). Mean(s.e.m.) supine gastric alkaline shift (proportion of time at pH > 4) increased from 9.2(2.0) to 17.7(3.7) per cent (P < 0.02) and the incidence of gastritis from eight patients (22 per cent) to 23 (62 per cent) (P < 0.001). These data suggest that cholecystectomy results in gastro-oesophageal reflux that appears to be related to compromised sphincter competence.

Adult↗