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Biomedical subjects

S A Riley

Publications and source records attributed to S A Riley.

At least 37 records · Page 2Linked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1995

Wrist pain in adult athletes.

As more and more adults become physically active, primary care physicians are seeing an increasing number of wrist injuries. Effective treatment is based on (1) accurate diagnosis, (2) maintenance of bone and joint-surface alignment until healing of bone, soft tissue, or both occurs, and (3) institution of an appropriate rehabilitation program. After symptoms have subsided, patients can gradually return to athletic participation. The long-term sequelae of wrist injuries are yet to be determined. If it is assumed that such injury causes a form of joint trauma, then analogies may be drawn to other types of musculoskeletal trauma, in which such factors as joint-surface and bone malalignment can lead to abnormal cartilage wear, predisposing patients to degenerative arthritis. Similarly, untreated ligament injuries may alter joint biomechanics, which can also lead to joint-surface trauma. Further clinical study should clarify the long-term effects of wrist injury.

Adult↗
PubMed1992

Absorption of polar drugs following caecal instillation in healthy volunteers.

We have investigated colonic drug absorption in man by the caecal instillation of a multi-component solution of atenolol, cimetidine, frusemide, hydrochlorothiazide and salicylic acid. We found that salicylic acid absorption from this solution was delayed but complete whereas the absorption of atenolol, cimetidine, frusemide and hydrochlorothiazide was four- to five-fold lower than expected from oral bioavailability studies.

Adult↗
PubMed1992

The influence of gastrointestinal transit on drug absorption in healthy volunteers.

1. The effect of variability of gastric emptying and oro-caecal transit on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorthiazide and salicylic acid has been studied in six healthy subjects. Each subject was studied on five separate occasions: three times under basal conditions, once following metoclopramide and once following codeine pretreatment in an attempt to speed and slow transit respectively. 2. Inter-subject variability of gastric emptying, oro-caecal transit and the rate and extent of drug absorption was considerable. 3. The absorption of salicylic acid appeared rate-limited by gastric emptying but the rate and extent of frusemide, atenolol and hydrochlorthiazide absorption were unrelated to measures of gastric emptying or oro-caecal transit. 4. Codeine phosphate caused a two-fold delay in oro-caecal transit but did not influence gastric emptying while metoclopramide had no significant effect on either function. 5. Metoclopramide and codeine had no significant effect on the rate or extent of absorption of any of the study drugs. 6. Within the limits of this experiment, oro-caecal transit time did not appear to be an important determinant of frusemide, atenolol, hydrochlorothiazide or salicylic acid absorption. Other factors must account for the observed variability in drug absorption.

Administration, Oral↗
PubMed1992

Effects of a non-absorbable osmotic load on drug absorption in healthy volunteers.

1. We have studied the effects of a non-absorbable osmotic load on the absorption of a multicomponent solution of frusemide, atenolol, hydrochlorothiazide and salicylic acid in six healthy volunteers. 2. Each subject was studied on up to four separate occasions. The drugs were administered in one of four solutions: a) a mannitol/electrolyte solution, b) a double-strength mannitol/electrolyte solution, c) a glucose/electrolyte solution and d) water. Lactulose or sulphasalazine were added as oro-caecal transit markers. Lactulose was included in the mannitol- and glucose-based solutions, adding a further non-absorbable osmotic load, and sulphasalazine was added to the water, adding little osmotic load. 3. The absorption of atenolol and hydrochlorothiazide was two- to three-times less from all lactulose-containing solutions than from the sulphasalazine-containing solution. The absorption of frusemide and salicylic acid was similar from all four solutions. 4. The largest non-absorbable osmotic load impaired the absorption of atenolol and hydrochlorothiazide most and the incorporation of glucose only partly restored absorption. 5. These results suggest that transmucosal water movement is an important determinant of atenolol and hydrochlorothiazide absorption but is less relevant for the absorption of frusemide and salicylic acid. Furthermore, these data demonstrate a previously unrecognised interaction between a commonly prescribed laxative--lactulose, and atenolol and hydrochlorothiazide.

Adult↗
PubMed1992

Tests of renal function in patients with quiescent colitis: effects of drug treatment.

Mesalazine has structural similarities to aspirin and phenacetin and is nephrotoxic when given intravenously in high doses to rats. A number of cases of nephrotoxicity has been reported recently in patients taking oral mesalazine. Sensitive indicators of renal function in a group of patients maintained on long term, delayed release mesalazine and a comparable group on sulphasalazine have been studied. Sixty two patients (32 men, aged 28-82 years) with quiescent colitis were studied. Thirty four had been maintained on delayed release mesalazine 1.6 (0.8-2.4) g/day for 2.9 (0.5-6.9) years and 28 on sulphasalazine 2 (2-3) g/day. Groups were comparable for age, sex, disease duration, and disease extent. Renal function was assessed by: urine microscopy; creatinine clearance; the urinary excretion of two markers of glomerular toxicity, albumin and transferrin; and the urinary excretion for two markers of tubular toxicity, N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin. There were no significant differences in renal function between the two treatment groups. Furthermore, no correlations were found between measures of renal function and either cumulative mesalazine dose or mesalazine treatment duration. In this study, long term maintenance treatment with delayed release mesalazine was no more nephrotoxic than continued treatment with sulphasalazine.

Adult↗
PubMed1991

Active hexose transport across cultured human Caco-2 cells: characterisation and influence of culture conditions.

Human Caco-2 cells (passage 80 to 100) were seeded onto collagen-coated Millipore filter assemblies and these were maintained in culture either (a) floated on the surface of the medium or (b) submerged within the body of the medium. Structural and functional assessments were made over a 30-day period. After seeding, all cells assumed a flattened, squamous configuration and rapidly became confluent. Cells submerged within the medium formed polarised monolayers with well developed junctional complexes, abundant apical microvilli and increasing levels of alkaline phosphatase activity. Cells grown floated on the surface of the medium formed complex multilayers in which polarisation was confined to the surface layer. Junctional complexes and apical microvilli were similar to those seen in submerged monolayers but alkaline phosphatase activities were higher. Transepithelial electrical resistance increased rapidly from day 1, as the layers became confluent. Electrical resistance was higher and short-circuit current and potential differences were lower across monolayers than across multilayers. After 10 days in culture, the addition of D-glucose to the apical bathing solution, of all cell layers, caused a rapid rise in short-circuit current and potential difference. These changes were sodium-dependent and phlorizin-sensitive. Galactose and 3-O-methylglucose induced similar changes and the affinity constants for these hexoses ranked in the order reported for rat jejunum (Km glucose 2.44 +/- 0.52 mM; Km galactose 8.05 +/- 1.33 mM; Km 3-O-methylglucose 22.0 +/- 5.2 mM). Culture conditions had a marked effect on hexose maximum transport rates (glucose Vmax: submerged 2.94 +/- 0.20 microA/cm2; floated 9.94 +/- 0.82 microA/cm2, P less than 0.05) but affinity constants were unchanged. Apical to basolateral mannitol fluxes, used as an index of paracellular permeability, decreased from day 1 to day 5 and then remained steady. Fluxes across monolayers and multilayers were not significantly different. We conclude that sodium-dependent hexose transport occurs in cultured Caco-2 cell layers grown on permeable supports. Culture conditions, however, have a marked effect on both cell layer structure and function, and should be an important factor when considering Caco-2 cells as an in vitro model of enterocyte function.

Adenocarcinoma↗
PubMed1991

Mesalazine release from coated tablets: effect of dietary fibre.

Delayed-release mesalazine formulations relay on pH-dependent coat dissolution to ensure delivery of 5-aminosalicylic acid (5-ASA) to the colon. As dietary fibre acidifies the colonic lumen we have studied the effect of fibre supplementation in 10 patients with quiescent colitis. Greater intake of dietary fibre was associated with a decrease in stool pH and an increase in stool frequency and faecal mass. However, the 24 h faecal and urinary excretion of 5-ASA and N-acetyl-5-ASA was unchanged. The percentage of total faecal ASA excreted as N-acetyl-5-ASA correlated with whole-gut transit time, suggesting that prolonged transit may be disadvantageous to patients with colitis as N-acetyl-5-ASA appears to be inactive.

Adult↗
PubMed1991

Microscopic activity in ulcerative colitis: what does it mean?

To determine the prognostic importance of microscopic rectal inflammation we followed up 82 patients (aged 21 to 78 years, 44 men) with chronic quiescent ulcerative colitis over 12 months. At trial entry each patient underwent a rectal biopsy and sections were graded independently by two histopathologists. A chronic inflammatory cell infiltrate of varying severity was present in all biopsy specimens, and 58% had crypt architectural irregularities. In addition, 32% had evidence of acute inflammatory activity: 28% acute inflammatory cell infiltrate, 11% crypt abscesses, and 22% mucin depletion. Agreement between the two histopathologists for the presence of each of these features was 94% (90-98%). During the 12 month follow up 27 patients (33%) relapsed after a mean interval of 18 weeks (range 3-44 weeks). Relapse rates were unrelated to duration or extent of disease or to the type of maintenance drug treatment. In patients with an acute inflammatory cell infiltrate 52% relapsed, whereas in the absence of such an infiltrate only 25% relapsed (p = 0.02). Similarly, relapse rates were higher in the presence of crypt abscesses (78% v 27%, p less than 0.005), mucin depletion (56% v p less than 0.02), and breaches in the surface epithelium (75% v 31%, p = 0.1). The presence of a chronic inflammatory cell infiltrate or crypt architectural irregularities, however, bore no relation to the frequency of colitis relapse.

Adult↗