Sex hormone receptor immunohistochemistry staining in Barrett's oesophagus and adenocarcinoma.
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Adenocarcinoma↗
Biomedical subjects
S A Riley
Publications and source records attributed to S A Riley.
Axillary vein thrombosis in a healthy donor following platelet apheresis.
Platelet donation is a common and usually safe procedure accounting for almost half of the platelets donated in the UK. We describe a previously healthy female donor who developed an axillary vein thrombosis following an apheresis platelet donation.
Adult↗
Once versus divided daily dosing with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters.
BACKGROUND: Delayed-release mesalazine is traditionally taken as three divided doses. However, it is well-recognized that dosing frequency has a significant impact on compliance and that once daily dosing is preferable. METHODS: We measured serum, urinary, faecal and rectal tissue concentrations of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid in 24 healthy volunteers following dosing with delayed-release mesalazine, 1.2 g or 2.4 g daily, given as either a single daily dose at 08:00 hours or in three divided doses at 08:00, 13:00 and 18:00 hours. RESULTS: Urinary and faecal excretion and rectal tissue concentrations of 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid were similar following single or divided daily dosing, at both doses studied. Peak serum concentrations were found at 06:00-09:00 following divided dosing and at 17:00-20:00 following once daily dosing. However, peak and trough serum levels and serum area under curve values (AUC) were similar with both regimens and at both doses. CONCLUSIONS: Urinary, faecal and rectal tissue concentrations are similar following single or divided daily dosing. Minor differences in serum levels were apparent but maximum, minimum and AUC values were similar. Clinical trials should examine the efficacy and toxicity of once daily dosing in patients with ulcerative colitis.
Adolescent↗
The effect of cholecystokinin antagonism on postprandial lower oesophageal sphincter function in asymptomatic volunteers and patients with reflux disease.
BACKGROUND: Postprandial acid reflux is thought to be mediated by the increase in transient lower oesophageal sphincter relaxations (TLOSR) frequency and fall in lower oesophageal sphincter (LOS) pressure seen after ingestion of a meal. Studies in animals and healthy volunteers suggest that cholecystokinin (CCK) may play a role. AIM: To study the role of CCK in postprandial LOS function using the CCK antagonist loxiglumide. SUBJECTS: 10 asymptomatic volunteers (7 male, 20-29 years) and 9 patients with symptomatic gastro-oesophageal reflux (4 male, 33-66 years). METHODS: Oesophageal, LOS and gastric pressure and oesophageal pH readings were recorded for 1 h before and 2 h after intragastric infusion of a 200 kCal, 300 mL long chain triglyceride meal. Each subject underwent two studies and received intravenous loxiglumide or placebo infusion in randomized order. RESULTS: During placebo infusion, postprandial LOS pressure fell [volunteers: 17 (9-31) to 7 (1-19) mmHg (P < 0.01), patients: 15 (6-26) to 9 (2-21) mmHg (P=0.02)] and TLOSR frequency increased [volunteers: 0 (0-1) to 2 (0-7) per hour (P=0.01), patients: 0 (0-3) to 2 (0-10) per hour (P=0.03)]. Loxiglumide infusion attenuated the postprandial fall in LOS pressure and the postprandial increase in TLOSR frequency [volunteers: 0 (0-3) per hour (P=0.04 vs. placebo), patients: 0 (0-2) per hour (P=0.03 vs. placebo)], but it had only modest effects on postprandial acid exposure [volunteers: placebo 45 (0-1725) vs. loxiglumide 0 (0-443) seconds (N.S.), patients: placebo 60 (0-3442) seconds vs. loxiglumide 31 (0-1472) seconds (N.S.)]. CONCLUSIONS: Loxiglumide inhibits TLOSR and attenuates the fall in LOS pressure following a meal, but has only modest effects on postprandial gastro-oesophageal acid reflux.
Adult↗
Transient lower esophageal sphincter relaxations are no more frequent in patients with gastroesophageal reflux disease than in asymptomatic volunteers.
OBJECTIVES: Studies of the relative frequency of transient lower esophageal sphincter relaxations (TLESRs) in patients with gastroesophageal reflux disease and asymptomatic controls have revealed conflicting data. We have therefore studied the frequency of TLESRs and the frequency and mechanisms of acid reflux episodes in patients with gastroesophageal reflux disease and age- and sex-matched asymptomatic controls using standardized criteria. METHODS: Ten patients with symptomatic gastroesophageal reflux disease (four male, aged 50 [30-59] yr) and 10 asymptomatic matched volunteers (four male, aged 50 [32-59] yr) were studied. Esophageal, lower esophageal sphincter, and gastric manometric and esophageal pH readings were recorded for 1 h before and 1 h after a 200-kcal, 150 ml long-chain triglyceride meal. RESULTS: TLESR frequency increased after the meal in both volunteers (median 0 [range = 0-3] to 3 [0-8] per hour,p < 0.01) and patients (1 [0-6] to 2.5 [0-9] per hour, p = 0.08). There was no significant difference in the frequency of TLESRs between volunteers and patients. TLESRs were more likely to be associated with acid reflux in patients (65% vs 37%, p = 0.03), whereas volunteers were more likely to reflux gas or liquid without acid (30% vs 3.0%, p = 0.01). CONCLUSIONS: TLESRs are no more frequent in patients with gastroesophageal reflux disease than age- and sex-matched asymptomatic volunteers. However, when TLESRs occur in patients, they are twice as likely to be associated with acid reflux.
Adult↗
Magnetic resonance imaging of electroconvection in a polar organic solvent.
Molecular motion in the polar organic solvent nitrobenzene induced by an electric field is studied by magnetic resonance imaging. Rf pulse sequences that correlate images obtained at two different times under conditions of both continuous and pulsed electric fields are introduced. The resultant image correlation spectra indicate that the time scale of motion in a 9.6 kV/cm electric field is tens of milliseconds. Comparison of the results to an analytic solution for the Fokker-Planck probability function for one-dimensional bounded diffusion yields an electric field dependent effective diffusion coefficient for perdeuterated nitrobenzene of D = 1.08 x 10(-5) cm(2)/s + (3.33 x 10(-3) cm(4)/kV(2)s) E(2) at room temperature. Characteristics of this electroconvection and its consequences for combining multidimensional nuclear magnetic resonance with electrical orientation are also discussed.
Artifacts↗
Dose loading with delayed-release mesalazine: a study of tissue drug concentrations and standard pharmacokinetic parameters.
AIMS: Tissue concentrations of 5-aminosalicylic acid (5ASA) and its metabolites may influence the clinical course of inflammatory bowel disease. Since the factors that determine tissue drug concentrations are unknown we have studied the relationships between the oral dose of delayed-release mesalazine, rectal tissue drug concentrations and standard pharmacokinetic parameters. METHODS: Twelve healthy volunteers were studied following 7 days treatment with 1.2, 2.4 and 4.8 g of delayed-release mesalazine daily. 5-aminosalicylic acid and N-acetyl 5-aminosalicylic acid concentrations were measured in serum, urine, stool and rectal tissue biopsies. RESULTS: Serum concentrations and 24 h urinary excretion of 5ASA and N-acetyl 5ASA increased as the oral dose of mesalazine was increased from 1.2 g through 2.4 g to 4.8 g daily (serum area under curve (AUC):5ASA = 3. 9, 15.4 and 46.8 microg ml-1 h, P < 0.0001; N-acetyl 5ASA = 17.2, 30. 9 and 57.8 microg ml-1 h, P < 0.0001: urinary excretion: 5ASA = 1.8, 85.5 and 445 mg, P < 0.0001; N-acetyl 5ASA = 250, 524 and 1468 mg, P < 0.0001, respectively). Faecal 5ASA excretion increased as the oral dose increased from 1.2 g to 2.4 g but did not increase further with 4.8 g daily dosing whereas faecal N-acetyl 5ASA excretion was similar at all three doses. Rectal tissue concentrations of 5ASA increased markedly, and N-acetyl 5ASA increased modestly, as the dose of oral mesalazine increased from 1.2 g to 2.4 g daily but neither increased further with 4.8 g daily dosing. CONCLUSIONS: The relationship between the ingested dose of delayed-release mesalazine and rectal tissue drug concentrations is complex. Factors other than dose are likely to be important determinants of rectal tissue drug concentrations.
Adolescent↗
Evaluation of omeprazole as a cost-effective diagnostic test for gastro-oesophageal reflux disease.
BACKGROUND: There is a need for a simple, therapeutic test that is of diagnostic value and can also provide rapid symptom relief in patients who present with classic, mild symptoms suggestive of gastro-oesophageal reflux disease (GERD), when the diagnosis is based on symptom assessment alone. AIM: To assess the diagnostic value of a therapeutic trial of omeprazole 40 mg in a dyspeptic population. METHODS: A total of 90 patients with symptoms suggestive of GERD entered the study. Patients underwent endoscopy and ambulatory oesophageal pH monitoring for 18-24 h. Patients then received omeprazole 40 mg o.m. for 2 weeks. RESULTS: There was a significant correlation between the diagnoses obtained from a trial of omeprazole and the diagnoses obtained from pH monitoring (P < 0. 05). There was no significant correlation between the diagnoses obtained from endoscopy and those obtained from pH monitoring. Both omeprazole and endoscopy were compared to pH monitoring as the 'gold standard' for the diagnosis of GERD and the cost per correct diagnosis with omeprazole was pound47 (95% CI: pound40- pound59) compared to pound480 (95% CI: pound396- pound608) with endoscopy. There was a complete absence of acid-related symptoms in the majority (59%) of patients after 3 days of omeprazole 40 mg therapy and, after 2 weeks, 82% of patients had experienced an improvement in overall symptoms ( 1 grade). CONCLUSIONS: We conclude that omeprazole can be used as a clinically effective tool in the initial management of GERD and that it is of diagnostic value in patients who present with typical symptoms, such as heartburn, when the diagnosis is based on symptom assessment alone.
Adolescent↗
Monitoring the lower oesophageal sphincter: sphinctometer or sleeve?
Two methods have been used to study lower oesophageal sphincter (LOS) function in gastro-oesophageal reflux disease: the sleeve sensor and the sphinctometer. Our aim was to directly compare the sleeve and sphinctometer in vivo. Ten asymptomatic volunteers were intubated with a perfused assembly incorporating a sleeve sensor, a solid-state assembly incorporating a sphinctometer and a pH probe. LOS function was recorded pre- and post-prandially. During basal periods sleeve and sphinctometer readings correlated well both within and between subjects (r2 = 0.89 (P < 0.0001)). However, the sphinctometer relaxed less during swallows (median 42 (interquartile range 27-55)% vs 73 (62-81)% (P < 0.001)), transient LOS relaxations (TLOSR) (50 (40-70)% vs 94 (88-100)% (P < 0.001)) and reflux episodes (67 (59-75)% vs 97 (91-100)% (P = 0.02)). Using criteria derived from 10 dry swallows, the expected relaxation of the sphinctometer during TLOSR was defined. The sphinctometer had an overall sensitivity ranging from 43 to 71% for the detection of TLOSR with 11-22 false positive relaxations, depending on the criteria employed. Sensitivity was particularly poor in those with low basal LOS pressure. The sphinctometer has a lower capacity to register LOS relaxations than the sleeve sensor, which limits its value in studying the pathophysiology of reflux disease.
Adult↗
Studies of autonomic function in patients with achalasia and nutcracker oesophagus.
BACKGROUND: Post-mortem studies in patients with achalasia reveal degenerative changes in the vagus and its dorsal motor nuclei suggesting the possibility of widespread autonomic dysfunction. AIMS: To study a broad range of autonomic function in patients with achalasia and nutcracker oesophagus and in asymptomatic volunteers. SUBJECTS: Patients with a manometric diagnosis of achalasia and nutcracker oesophagus and age- and sex-matched asymptomatic volunteers. METHODS: Subjects underwent measurement of: (1) pupil cycle time estimation; (2) heart rate response to the Valsalva manoeuvre, standing and deep breathing; (3) systolic blood pressure response to standing; (4) diastolic response to sustained handgrip; (5) spectral analysis of heart rate variability; and (6) heart rate and blood pressure during the Valsalva manoeuvre. RESULTS: No significant differences were found between patients with achalasia and asymptomatic volunteers. Patients with nutcracker oesophagus, however, had longer pupil cycle times (1.2 (0.9-1.4) s versus 0.9 (0.8-1.2) s, P= 0.02) and had attenuation of both the rise in the low frequency peak of heart rate variability and the fall in the high frequency peak on standing (rise in low frequency peak - patients 26.6 (10.4-52.3)% to 42.2 (15.5-54.0)%, P = 0.46, volunteers 16.9 (8.4-37.2)% to 47.4 (21.1-66.3)%, P = 0.03; fall in high frequency peak - patients 18.1 (0.9-43.3)% to 10.1 (0.5-26.6)%, P= 0.46, volunteers 24.8 (8.5-44.4)% to 9.3 (2.6-35.6)%, P= 0.03). The rise in blood pressure during the Valsalva manoeuvre was also attenuated in patients with nutcracker oesophagus compared with asymptomatic volunteers (6.9 (1.0-9.3) mmHg versus 12.9 (11 -23.0) mmHg, P < 0.01). CONCLUSIONS: Whereas tests of cardiovascular and pupillary autonomic function are normal in patients with achalasia, patients with nutcracker oesophagus show defects in both parasympathetic and sympathetic function.
Adult↗
Familial clustering of reflux symptoms.
OBJECTIVE: A number of case reports describe multiple family members with gastroesophageal reflux disease and Barrett' s esophagus. The wider importance of familial factors in gastroesophageal reflux disease has not been established. Therefore, we have studied the prevalence of reflux symptoms and medication use among relatives of patients with documented gastroesophageal reflux disease. METHODS: A postal questionnaire study of the first degree relatives of six groups of matched patients. The groups comprised patients with 1) no dyspeptic symptoms; 2) reflux symptoms and a normal pH study; 3) reflux symptoms, an abnormal pH study, and a lower esophageal sphincter (LOS) pressure more than 10 mm Hg; 4) reflux symptoms, an abnormal pH study, and a LOS pressure less than 10 mm Hg; 5) Barrett's esophagus; and 6) peptic stricture. RESULTS: Four hundred eighteen subjects replied (78% response). Infrequent reflux symptoms were equally common in all groups of relatives. Frequent reflux symptoms, however, were more common among relatives of patients with an abnormal pH study and normal (26%, p = 0.007) or low LOS pressure (27%, p = 0.01) or Barrett's esophagus (30%, p = 0.003), compared with relatives of nondyspeptic patients (9%). Frequent reflux symptoms were no more common among relatives of patients with a normal pH study (16%) or peptic stricture (18%). Reflux medication use showed a similar pattern. CONCLUSIONS: Familial clustering of reflux symptoms is seen in relatives of patients with reflux symptoms and increased esophageal acid exposure and in relatives of patients with Barrett's esophagus.
Adult↗
Simple method for the determination of 5-aminosalicylic and N-acetyl-5-aminosalicylic acid in rectal tissue biopsies.
We describe a sensitive high-performance liquid chromatographic method for the determination of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid in rectal tissue biopsies. Samples were derivatised using propionic anhydride and proteins were precipitated with methanol. A Supelcosil ABZ column (150x4.6 mm I.D., 5 microm silica particles) was used with a mobile phase comprising 0.1 M acetic acid, acetonitrile and triethylamine (1600:114:6, v/v/v). Fluorescence detection was employed and detection limits were 0.2 ng/mg tissue at a signal-to-noise ratio of three (measured concentration: 5-aminosalicylic acid, 0.254 (0.228-0.286) ng/mg, C.V. 10.7%; N-acetyl-5-aminosalicylic acid, 0.18 (0.154-0.198) ng/mg, C.V 9.8%). This assay was validated for use with serum, urine and faecal samples for which it proved to be both precise and accurate (C.V.<10%, measured concentration within 10%).
Aminosalicylic Acids↗
Mesalazine release from a pH dependent formulation: effects of omeprazole and lactulose co-administration.
AIMS: Delayed-release formulations of mesalazine often rely on the gastrointestinal luminal pH profile to deliver 5-aminosalicylic acid (5ASA) to the colon. The aim of this study was to examine the influence of luminal pH on mesalazine release. METHODS: We studied the effect of co-administration of omeprazole and lactulose on the steady-state pharmacokinetics of Eudragit S-coated mesalazine in healthy volunteers. RESULTS: No significant changes in urinary or faecal levels of 5ASA or its main metabolite, N-acetyl 5ASA, were apparent. CONCLUSIONS: This study suggests that co-administration of omeprazole and lactulose does not impair the release of delayed-release mesalazine.
Adolescent↗
Mechanisms of gastro-oesophageal reflux in the lateral decubitus positions.
Gastro-oesophageal reflux is more common in the right than in the left lateral position but the reasons why are not well understood. We have therefore studied the mechanisms underlying reflux in the lateral decubitus positions in patients with reflux disease. Fifteen patients with symptomatic reflux and excessive oesophageal acid exposure were studied (nine male, age 25-63 years). Each was intubated with a perfused manometric assembly, incorporating a Dent sleeve, and a pH probe. Following a 30-min basal period, a 400-kCal meal was infused into the stomach and patients were studied for 60 min in each lateral position. Following infusion of the meal, lower oesophageal sphincter (LOS) pressure fell and transient LOS relaxation (TLOSR) frequency increased. Acid reflux episodes were more common in the postprandial period (fasting 0 (0-6) h, first postprandial hour 1 (0-9) h, P = 0.0002, second postprandial hour 1 (0-22) h, P = 0.02) and occurred more than twice as often in the right lateral position (right 3 (0-22) h, left 0 (0-10) h, P = 0.01). However, TLOSRs, swallow-related relaxations and low basal LOS pressures were equally common in both lateral positions. In patients with reflux disease, postprandial reflux is twice as common in the right lateral position. This does not relate to differences in gastro-oesophageal junctional pressure, suggesting that other aspects of barrier function or differences in the intragastric distribution of chyme may be important.
Adult↗
Impact of smoking cessation on salivary function in healthy volunteers.
BACKGROUND: Salivary bicarbonate and epidermal growth factor (EGF) have an important protective role in the oesophagus. The effect of smoking cessation on these aspects of salivary function is unknown. METHODS: Salivary bicarbonate secretion and EGF output were measured before and after attempted smoking cessation in 28 healthy volunteers. Urinary cotinine excretion was used to assess compliance. RESULTS: Negative correlations were found between salivary flow rate and age (rho = -0.34) and between cigarette consumption and salivary flow (rho = -0.27) and salivary bicarbonate concentrations (rho = -0.32). Smoking cessation was associated with a significant increase in salivary bicarbonate secretion (day 0, 1.7 (0.14-6.2); day 7, 3.6 (0.52-6.4); day 21, 3.3 (0.44-6.6) micromol min(-1); P < 0.01) but left salivary EGF output unchanged. CONCLUSION: Smoking cessation is associated with significant improvements in salivary bicarbonate secretion. This would benefit patients with reflux disease who stop smoking.
Adult↗
What dose of 5-aminosalicylic acid (mesalazine) in ulcerative colitis?
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Anti-Inflammatory Agents, Non-Steroidal↗
Intestinal metaplasia at the squamocolumnar junction in patients attending for diagnostic gastroscopy.
BACKGROUND: The incidence of adenocarcinoma of the oesophagus and gastric cardia is increasing rapidly. Barrett's oesophagus is the major risk factor. Intestinal metaplasia at the squamocolumnar junction in the absence of Barrett's oesophagus is common but its relation to adenocarcinoma and gastro-oesophageal reflux disease is unclear. AIMS: To study the prevalence and clinical, endoscopic, and histological associations of intestinal metaplasia at the squamocolumnar junction. METHODS: Biopsy specimens were taken from 120 randomly selected patients undergoing routine diagnostic endoscopy. Eight biopsy specimens, taken from above and below the squamocolumnar junction, gastric fundus, and gastric antrum, were stained with haematoxylin/eosin, alcian blue/periodic acid-Schiff, and Gimenez, and graded independently by one pathologist. RESULTS: Intestinal metaplasia at the squamocolumnar junction was found in 21 patients (18%). Metaplasia was associated with increasing age (p < 0.01) and antral intestinal metaplasia (p = 0.04). Logistic regression analysis revealed that age was the only independent predictor (p < 0.01). There was no association with symptomatic, endoscopic, or histological markers of gastro-oesophageal reflux disease. CONCLUSIONS: Intestinal metaplasia at the squamocolumnar junction is a common finding. It is associated with increasing age but not gastro-oesophageal reflux disease.
Adult↗
Japanese endoscopy: reflections of a British gastroenterologist.
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Endoscopy, Gastrointestinal↗