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Biomedical subjects

S A Riley

Publications and source records attributed to S A Riley.

At least 19 recordsLinked to original sources
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↗
PubMed1990

Why do patients with ulcerative colitis relapse?

To determine the factors responsible for ulcerative colitis relapse a cohort of 92 patients (18 to 78 years, 50 men) with clinically inactive disease have been followed for over 48 weeks. At 12 weekly intervals patients were asked, by means of standardised questionnaires, about infections, compliance with maintenance medication, new drug treatment, dietary changes, episodes of non-bloody diarrhoea, life stresses, and feelings of anxiety and depression. Thirty five patients (38%) relapsed (median interval 17 weeks, range three to 46 weeks). Patients who relapsed had a higher previous relapse rate than non-relapsers (p less than 0.001) and a shorter time from previous relapse to trial entry (p less than 0.05). Other clinical characteristics were equally matched in the two groups. Between and within group comparisons revealed that upper respiratory tract symptoms, antibiotic ingestion, analgesic intake, diarrhoeal episodes and stressful life events were no more common in the four weeks before relapse than before routine attendance. Anxiety and depression ratings were also similar in the two groups. The timing of ulcerative colitis relapse showed a clear seasonal pattern with 26 patients relapsing from August to January and only nine from January to July (p less than 0.001). In addition, a retrospective case note analysis revealed significant seasonality of onset of ulcerative colitis. We conclude that seasonal factors may contribute to both onset and relapse of ulcerative colitis.

Adolescent↗
PubMed1989

A comparison of sucralfate and prednisolone enemas in the treatment of active distal ulcerative colitis.

Sucralfate is well established in the treatment of upper gastrointestinal inflammation and ulceration, and preliminary evidence suggests it may be of benefit in active colitis. We have therefore undertaken a clinical trial to compare enemas of sucralfate (4 g) and prednisolone metasulphobenzoate (20 mg) in the treatment of active distal ulcerative colitis. Forty-four patients were entered into a 4-week study. Two patients were withdrawn because of non-compliance, and five were unable to complete the study: two developed constipation (both allocated to sucralfate) and three were unable to retain the enemas (two prednisolone and one sucralfate). Intention-to-treat analysis showed significant within-treatment improvement in rectal bleeding, sigmoidoscopic grade, and histologic grade in the prednisolone-treated group, and in stool frequency, rectal bleeding, and sigmoidoscopic grade in the sucralfate-treated group. Between-treatment comparisons, however, showed greater resolution of rectal bleeding and more marked improvements in histologic grade in patients treated with prednisolone metasulphobenzoate enemas. Further studies using higher doses of sucralfate would be useful.

Adult↗
PubMed1989

Radiation exposure from fluoroscopy during orthopedic surgical procedures.

The use of fluoroscopy has enabled orthopedic surgeons to become technically more proficient. In addition, these surgical procedures tend to have less associated patient morbidity by decreasing operative time and minimizing the area of the operative field. The trade-off, however, may be an increased risk of radiation exposure to the surgeon on an annual or lifetime basis. The current study was designed to determine the amount of radiation received by the primary surgeon and the first assistant during selected surgical procedures involving the use of fluoroscopy. Five body sites exposed to radiation were monitored for dosage. The results of this study indicate that with appropriate usage, (1) radiation exposure from fluoroscopy is relatively low; (2) the surgeon's dominant hand receives the most exposure per case; and (3) proper maintenance and calibration of fluoroscopic machines are important factors in reducing exposure risks. Therefore, with proper precautions, the use of fluoroscopy in orthopedic procedures can remain a safe practice.

Fluoroscopy↗
PubMed1988

Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis.

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.6% (95% confidence limits, 24%-54%) and mesalazine 37.5% (95% confidence limits, 24%-53%), chi 2 = 0.01, p greater than 0.90. Mean time to relapse, cumulative relapse rate, and relapse severity were similar in the two groups. Headaches and upper gastrointestinal symptoms--common at trial entry--improved to a greater extent in patients receiving mesalazine. Delayed-release mesalazine is an effective treatment for maintaining ulcerative colitis remission and is associated with fewer side effects than equivalent doses of enteric-coated sulfasalazine.

Adult↗
PubMed1988

Delayed-release mesalazine (5-aminosalicylic acid): coat dissolution and excretion in ileostomy subjects.

1. Delayed-release mesalazine has been formulated to deliver 5-aminosalicylic acid to the colon. We have therefore studied the ileostomy excretion and coat dissolution of this preparation. 2. Following ingestion of a single tablet 88% (range 69-114%) of the 400 mg dose appeared unchanged in the ileosomy effluent over the subsequent 12 h. 3. Ileostomy effluent pH appeared to be a major determinant of 5-aminosalicylic acid release. 4. In vitro studies revealed rapid coat dissolution above pH 7.0, slow dissolution between pH 6.0 and 7.0 and non-dissolution at pH 2.0 and 4.0.

Adult↗
PubMed1988

Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse.

Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.4 g daily in a double blind, double dummy, four week trial. Groups were comparable for age, sex, extent of disease, and pretrial sulphasalazine intake. Four patients were unable to complete the study because of treatment failure (two taking sulphasalazine and two high dose mesalazine). A further two patients taking sulphasalazine developed side effects necessitating withdrawal. Within treatment comparisons revealed significant improvement of: sigmoidoscopic grade in the sulphasalazine group; rectal bleeding, sigmoidoscopic and histological grade in the low dose mesalazine group; stool frequency, rectal bleeding and sigmoidoscopic grade in the high dose mesalazine group. Greater improvement in rectal bleeding (p less than 0.05) and sigmoidoscopic appearances (p less than 0.05) occurred in patients taking high dose mesalazine than in those taking sulphasalazine. In two patients taking high dose mesalazine minor rises of plasma creatinine concentrations occurred, suggesting the need to monitor renal function.

Adult↗