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Biomedical subjects

A Ireland

Publications and source records attributed to A Ireland.

At least 37 records · Page 2Linked to original sources

Acetylation of 5-aminosalicylic acid by isolated human colonic epithelial cells.

1. This study investigates the acetylation of 5-aminosalicylic acid by isolated human colonic epithelial cells. 2. After incubation of intact cells with 0.1 mmol/l 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid was detected in a concentration of 141 (+/- 23.8 SEM) nmol/g dry weight in the incubation medium, and 34.8 (+/- 5.5 SEM) nmol/g dry weight intracellularly. No unchanged 5-aminosalicylic acid was detected inside the cell. 3. Acetylation of 5-aminosalicylic acid by a cell homogenate was very poor, but the addition of 1 mmol/l acetyl-CoA resulted in complete conversion of 0.1 mmol/l 5-aminosalicylic acid to N-acetyl-5-aminosalicylic acid. 4. N-Acetyltransferase activity was detected in the cytosol, with a mean of 3.3 nmol min-1 mg-1 of protein. There was no N-acetyltransferase activity in the brush border. There was no difference in enzyme activity between epithelial cells derived from normal, Crohn's disease or ulcerative colitis patients. 5. Preliminary characterization of the N-acetyltransferase enzyme suggests a molecular weight of 150,000.

Acetylation↗

Mechanism of action of 5-aminosalicylic acid and its derivatives.

The mechanism of action of 5-ASA and its derivatives remains obscure. The most likely mechanisms would appear to be an interrelationship between local production of eicosanoids and reactive oxygen metabolites, in conjunction with activated neutrophils, though the nature of the initial triggering factor/s remains to be determined. The possibility that bacterial-derived chemotactic peptides, such as FMLP, might be a triggering factor is an attractive possibility, made possible by an underlying defect in mucosal permeability.

Aminosalicylic Acids↗

High-dose methylprednisolone in the treatment of active ulcerative colitis.

Twenty patients with severe active ulcerative colitis were entered into a pilot study to test the efficacy of pulsed high-dose methylprednisolone in inducing remission. Of 20 patients, 12 improved, but 8 of 20 patients (40%) who did not went for urgent colectomy. The group proceeding to surgery tended to have more extensive disease. These results contrast unfavorably with historical control data from this unit.

Acute Disease↗

Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis.

One hundred and sixty four patients with ulcerative colitis in remission were entered into a double blind, double dummy trial comparing olsalazine 500 mg bd and sulphasalazine 1 g bd. Clinical examination, sigmoidoscopy and rectal biopsy were performed at 0, three, and six months. Sixteen of 82 (19.5%) patients relapsed on olsalazine and 10/82 (12.2%) relapsed on sulphasalazine. The difference was not statistically significant (p = 0.1632). Adverse events were minor and were similar in both groups. No haematological or biochemical abnormalities were detected. Thus, olsalazine is as effective as sulphasalazine for preventing a relapse of ulcerative colitis.

Adolescent↗

Controlled trial comparing olsalazine and sulphasalazine for maintenance treatment of ulcerative colitis.

Olsalazine and sulphasalazine were compared in a double-blind, double-dummy trial in the prevention of relapse of ulcerative colitis over 6 months. The majority were taking sulphasalazine. They were randomized to receive either olsalazine, 500 mg b.d., or sulphasalazine, 1 g b.d. Of 82 patients, 16 relapsed on olsalazine compared with 10 of 82 on sulphasalazine. This difference was not statistically significant (p = 0.16). Twenty-one patients reported adverse events in the olsalazine group, of whom 16 were withdrawn, while 20 patients reported adverse events in the sulphasalazine group, with 9 of them being withdrawn. The differences were not statistically significant. No major haematological or biochemical abnormalities occurred. Thus, olsalazine is similar to sulphasalazine for the prevention of relapse of ulcerative colitis.

Aminosalicylic Acids↗

Olsalazine in patients intolerant of sulphasalazine.

Fifty patients with ulcerative colitis, intolerant of sulphasalazine, were treated with 500 mg olsalazine twice daily for a 3-month trial period. Thirty-eight of the patients (76%) tolerated the drug well, and all continued to take it beyond the 3-month period. Twelve (24%) were withdrawn because of side effects, the commonest being diarrhoea. There were no haematologic or biochemical abnormalities. Thus, olsalazine is a useful drug for patients who are intolerant of sulphasalazine.

Adult↗

Clinical importance of Campylobacter pyloridis and associated serum IgG and IgA antibody responses in patients undergoing upper gastrointestinal endoscopy.

Campylobacter pyloridis was isolated from 77% of 220 (35%) unselected adults undergoing gastroscopy. Isolation was significantly associated with histological gastritis (p less than 0.0001), duodenal ulcer (p less than 0.0001), and to a much lesser extent, with gastric ulcer (p less than 0.05). The relation between the isolation of C pyloridis and peptic ulcer seemed to be independent of coexisting gastritis. In those with no endoscopic or histological evidence of disease there was no relation between isolation and increasing age. Antibody responses to a whole cell sonicate of a strain of C pyloridis were measured by means of an enzyme linked immunosorbent assay (ELISA). Increased IgA (p less than 0.0001) and IgG (p less than 0.0001) antibody titres were found in patients with C pyloridis. Peptic ulceration or gastritis were present in 78% and 100% of patients with a high concentration of IgG and IgA, respectively, but in only 9% and 18% of those with low titres. These results provide further evidence for a possible pathogenic role of these organisms in gastric disease and suggest that immunological markers of their presence might be useful non-invasive indicators of disease.

Adult↗

N-acetyl-beta-D-glucosaminidase enzymuria in leukaemia and myelomatosis: effect of treatment in acute myeloblastic leukaemia and myelomatosis in adults.

The activity of the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase (NAG) was measured in the urine of patients with leukaemia or myeloma. Elevated pre-treatment enzymuria was noted in all patient groups with acute myeloblastic leukaemias (AML) FAB type M4 or 5 displaying higher activities than AML patients FAB types M1-3, which in turn were higher than those found in patients with myelomatosis and chronic lymphocytic leukaemia. The ratio of the major isoenzymes of NAG, A/B was reduced significantly only in patients with AML. Following treatment, AML patients who entered remission demonstrated NAG levels which approached normal values. In those AML patients who were either in relapse, in the terminal phase of their illness or treated with aminoglycoside antibiotics, NAG enzymuria was similar to pre-treatment values. A reduction in urinary NAG levels and both serum and urine beta 2 microglobulin concentrations was also observed following treatment in myeloma patients. The use of enzymuria both as a guide to progress towards remission in AML patients and for assessing prognosis and progress in myeloma patients is discussed.

Acetylglucosaminidase↗

Olsalazine in active ulcerative colitis.

Olsalazine (azodisalicylate) is a new drug in which two molecules of 5-aminosalicylic acid are linked by an azo bond. Its role in the treatment of mildly active, distal ulcerative colitis was investigated. Sixty patients were randomly allocated to receive olsalazine 1 g or a placebo as a retention enema nightly for two weeks. Clinical improvement was seen in 19 (66%) and sigmoidoscopic improvement in 17 (59%) of the 29 patients receiving olsalazine compared with 12 (43%) and 11 (39%), respectively, of the 28 in the control group. These differences were not significant. In a second trial 40 patients were randomised to receive oral olsalazine 2 g daily or a placebo capsule for two weeks. Significant clinical and sigmoidoscopic improvement was seen in the patients receiving oral olsalazine compared with the patients receiving placebo capsules. Oral olsalazine may be valuable in the treatment of mildly active ulcerative colitis. Its role in maintaining remission is yet to be determined.

Administration, Oral↗

Functional characteristics of the glomerular filter in the IgA-nephropathy.

The purpose of the present study was to compare the functional characteristics of the glomerular filter in patients having a well defined glomerulonephritis, the IgA nephropathy, with those of normal age-matched controls. A bolus intravenous injection of inulin (60 mg/kg), para-amino hippuric acid (36 mg/kg) and Rheomacrodex (130 mg/kg) was administered to each subject and followed by the timed collection of venous blood and urine samples. Compared to the controls, the nine patients with IgA nephropathy had no significant differences in renal plasma flow or glomerular filtration rate. The control group showed filtration of the neutral graded dextrans which diminished in a linear fashion with increasing molecular size. In contrast, the IgA patients showed two-phased glomerular sieving with a reduction in the filtration of dextrans sized 40 A or less and an increased filtration of those larger than 50 A. These changes in dextran filtration indicate the appearance of a population of larger than normal pores in the glomerular filter in the IgA nephropathy, although concomitant alterations in the electrostatic properties of the filter mechanism cannot be excluded.

Adolescent↗

Reducing overnight secretion of acid to heal duodenal ulcers. Comparison of standard divided dose of ranitidine with a single dose administered at night.

This study was undertaken to assess the clinical usefulness of a single nighttime dose of ranitidine in the short-term healing of duodenal ulcer. One hundred and nine patients with endoscopically diagnosed duodenal ulcer were randomly allocated to treatment with ranitidine, either 150 mg twice daily or 300 mg as a single nighttime dose for four weeks, in a prospective double-blind, double-placebo trial. Of the 102 patients who completed the study, 48 of 57 (84 percent) healed endoscopically on ranitidine 150 mg twice daily, and 43 of 45 (96 percent) healed on 300 mg at nighttime (Mantel-Haenszel test without continuity correction: X2 = 2.9, p = 0.09). One patient treated with ranitidine 150 mg twice daily had a transient episode of cholestatic hepatitis that did not necessitate stopping the drug; in this patient the ulcer healed after 28 days of treatment. There were no other unwanted effects in either group and no significant abnormal biochemical or hematologic changes. This study shows that ranitidine 300 mg given as one nighttime dose is as safe as 150 mg twice daily, and equally as effective. Three hundred milligrams at night appear to confer protection against the adverse effect of smoking in ulcer healing.

Adolescent↗

Ranitidine 150 mg twice daily vs 300 mg nightly in treatment of duodenal ulcers.

102 patients with endoscopically proven duodenal ulcers were randomly allocated to treatment with ranitidine either 150 mg twice a day or 300 mg every evening for 4 weeks in a prospective double-blind study. The two groups were similar. 48/57 (84%) healed on ranitidine 150 mg twice daily and 43/45 (96%) healed on 300 mg every evening (p = 0.9)--that is, ranitidine 300 mg as a single night time dose is as effective as 150 mg twice daily. The results also indicate the importance of overnight gastric acidity in the pathogenesis of duodenal ulcers.

Adolescent↗