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Biomedical subjects

K Lauritsen

Publications and source records attributed to K Lauritsen.

At least 91 records · Page 5Linked to original sources
PubMed1987

Does vitamin E supplementation modulate in vivo arachidonate metabolism in human inflammation?

To determine whether supplementation with the physiological radical scavenger, vitamin E, would modulate arachidonate metabolism in human inflammation, we performed equilibrium dialysis of rectum in eight patients with active ulcerative colitis confined to the rectum. The patients, all off drug treatment, were supplemented with 1920 IU/day of alpha-tocopherol and had rectal dialysis done at entry and after three and 14 days. Luminal concentrations of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), determined by radioimmunoassay in purified dialysates, were significantly raised compared to healthy controls. Supplements caused no change in these levels either at day 4 or 15, although serum-tocopherol showed a 3-fold increase. Also disease activity was unaffected. This failure of vitamin E supplementation to suppress the mucosal release of PGE2 and LTB4 in active inflammation does not encourage controlled trials on the effect of oral vitamin E in ulcerative colitis.

Adult↗
PubMed1987

In vivo effects of orally administered prednisolone on prostaglandin and leucotriene production in ulcerative colitis.

It has been proposed that anti-inflammatory actions of corticosteroids rely on promotion of a natural peptide phospholipase A2 inhibitor, lipocortin, but in vivo effects on arachidonic acid metabolism have not been shown. Equilibrium dialysis of the rectum in patients with ulcerative colitis was used to determine whether cyclooxygenase and lipoxygenase products released from the inflamed rectal mucosa could be differentially inhibited by systemic treatment with prednisolone and indomethacin, respectively. In 10 patients with severe disease luminal concentrations of prostaglandin E2, prostaglandin F2 alpha, and leucotriene B4 were markedly raised (p less than 0.05) on comparison with 10 healthy controls, and they decreased significantly (p less than 0.05) within 72 hours after administration of prednisolone 1.5 mg/kg/day orally. In contrast prostaglandin, but not leucotriene B4 concentrations decreased (p less than 0.05) within 72 hours after administration of indomethacin 150 mg/day in another 10 patients with distal disease. These prompt reductions in concentrations of arachidonic acid metabolites more likely are caused by direct drug actions, rather than being secondary to decreased tissue damage. The data accord with the theory explaining anti-inflammatory effects of corticosteroids through lipocortin activity and support the belief that leucotrienes are more important than prostaglandins as mediators of inflammation in ulcerative colitis.

Adult↗
PubMed1987

5-Aminosalicylic acid in the treatment of Crohn's disease. A 16-week double-blind, placebo-controlled, multicentre study with Pentasa.

The response to 5-aminosalicylic acid (5-ASA) in mild and moderately active Crohn's disease localized in the small bowel was studied in a randomized, double-blind, placebo-controlled trial in four centres. Sixty-seven patients were included, of whom 30 were treated with 1500 mg slow-release 5-ASA/day (Pentasa) for a scheduled period of 16 weeks. In the 5-ASA group 40% of the patients improved, versus 30% of the placebo-treated group ('intent to treat' basis; p greater than 0.1). Four of the patients treated with 5-ASA left the study owing to disease deterioration, versus 10 of the placebo-treated patients (p greater than 0.2). Seventeen patients were secondarily excluded, and the remaining 50 patients (23 receiving 5-ASA) were reevaluated in greater detail. No statistically significant differences in outcome were shown. Three patients (one given 5-ASA) were withdrawn from the study because of presumed side effects, but no serious adverse reactions were recorded. The present results indicate that 5-ASA, at least in the dosage used, is not superior to placebo. Nevertheless, trends towards a beneficial effect in Crohn's disease in the small bowel justify further clinical trials with a larger dosage of 5-ASA.

Adolescent↗
PubMed1986

Enprostil and ranitidine in duodenal ulcer healing: double blind comparative trial.

One hundred and eighty patients with endoscopically proved duodenal ulcers were allocated at random to double blind treatment with the synthetic dehydroprostaglandin E2 enprostil 35 micrograms twice daily or ranitidine 150 mg twice daily for up to six weeks. Patients completed the study if ulcer healing and pain relief had occurred at two or four weeks. A total of 163 patients completed the trial. The duration of treatment was longer in the enprostil group (p less than 0.005) and the cumulative healing rates at two, four, and six weeks were 51%, 74%, and 85%, respectively. In the ranitidine group the corresponding figures were 65% (p less than 0.04), 89% (p less than 0.02), and 99% (p less than 0.002). More patients treated with ranitidine reported relief of pain (p less than 0.004 at weeks 5 and 6). The observed superiority of ranitidine 150 mg twice daily over enprostil 35 micrograms twice daily questions the clinical relevance of using so called "cytoprotection" as treatment for duodenal ulcer disease in the short term.

Adolescent↗
PubMed1986

Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis.

To determine the influence of inflammation and topical treatment with 5-aminosalicylic acid or prednisolone on arachidonic acid metabolism in vivo, we carried out a double-blind controlled study on the release of prostaglandin E2 and leukotriene B4 to the rectal lumen in 24 consecutive patients with proven distally located ulcerative colitis. Before and at days 15 and 29 a dialysis bag was placed in the emptied rectum for 4 h prior to assessing clinical, endoscopic, and histologic disease activity. A single enema was given daily at bedtime (1 g 5-aminosalicylic acid or 25 mg prednisolone) until complete remission or for a maximum of 4 wk. Clinical and endoscopic remission was obtained in 16 (7 on 5-aminosalicylic acid) and 11 (3 on 5-aminosalicylic acid) patients, respectively. Luminal concentrations of prostaglandin E2 and leukotriene B4 were positively correlated to disease activity and significantly decreased among the prednisolone-treated patients. In both treatment groups a decrease toward normal levels occurred in patients responding to therapy. In retrospect, the pretreatment prostaglandin E2 and leukotriene B4 levels were significantly higher in patients not responding to therapy than in those improving during treatment. In conclusion, luminal prostaglandin E2 and leukotriene B4 levels may prove more useful predictors of the outcome of treatment in relapsing ulcerative colitis than clinical indices of disease activity.

Adult↗
PubMed1986

Effect of azodisal sodium and sulphasalazine on ileostomy output of fluid and PGE2 and PGF2 alpha in subjects with a permanent ileostomy.

Azodisal sodium is a highly effective means of oral delivery of 5-amino-salicylic acid to the colonic mucosa. Administration of this drug to patients intolerant of sulphasalazine, however, occasionally results in liquid stools. In preliminary experiments, which comprised 10 healthy volunteers treated with colectomy for ulcerative colitis, ileostomy fluid output increased (p less than 0.001) during oral intake of azodisal sodium (1 g/day). In a double blind, placebo controlled crossover study, comprising eight similar volunteers, ileostomy fluid output increased (p less than 0.05) in a dose related manner during intake of azodisal sodium (1 g/day vs 2 g/day) compared with placebo or sulphasalazine (2 g/day). Concentrations of prostaglandin (PG)F2 alpha in free ileal water determined by equilibrium in vivo dialysis of ileostomy contents decreased (p less than 0.05) during intake of azodisal sodium (2 g/day), whereas concentrations of PGE2 and the output of PGE2, PGF2 alpha, and 'PGE2 + PGF2 alpha' remained unchanged. Thus increased formation of PGs is apparently not the cause of increased ileostomy fluid output associated with azodisalicylate intake.

Adult↗
PubMed1986

Symptomatic recurrence of healed duodenal and prepyloric ulcers after treatment with ranitidine or high-dose antacid. A 1-year follow-up study.

Eighty-seven patients with duodenal (n = 49) or prepyloric (n = 38) ulcers healed with ranitidine (n = 44) or a high-dose liquid antacid (n = 43) completed a 1-year double-blind comparative study of symptomatic relapse without treatment. Both duodenal ulcers and prepyloric ulcers tended to remain true to their type of recurrence. Age, sex, history of ulcer disease, duration of initial treatment, and smoking habits were all without influence on the relapse rates. The subgroup of patients with a duodenal ulcer who had healed on either treatment regimen had a symptomatic relapse significantly more frequently than those with prepyloric ulcer (64% +/- 13 versus 34% +/- 15; p less than 0.025), but the estimated probabilities of relapse were unaffected (p greater than 0.05) by the initial type of medication (ranitidine group, 56% +/- 15; antacid group, 51% +/- 15). Thus the present study could not confirm the hypothesis that patients treated with H2-receptor antagonists tend to relapse earlier than those treated with antacids during the following year without treatment.

Antacids↗
PubMed1986

Prostaglandins and clinical experience in peptic ulcer disease.

Synthetic prostaglandin analogues of the E series offer a new approach to the medical treatment of peptic ulcer disease by combining antisecretory with cytoprotective properties, such as protection of the gastric mucosa against damage induced by aspirin. Controlled trials of prostaglandin analogues in peptic ulcer healing have failed to demonstrate any superiority to conventional treatment. Any beneficial effect is explicable by acid inhibition, and diarrhoea is a major and dose-limiting side effect. Non-antisecretory doses that are still said to be cytoprotective do not accelerate ulcer healing. Also, the prostaglandin analogues seem ineffective in the treatment of peptic ulcer haemorrhage. Thus the clinical relevance of cytoprotection by synthetic prostaglandins has not been established. Although antisecretory doses of some analogues may prove to be yet another approach to drug treatment, the present results do not forecast a new breakthrough in the management of peptic ulcer disease.

Duodenal Ulcer↗
PubMed1985

Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial.

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.

Adult↗
PubMed1985

Comparison of ranitidine and high-dose antacid in the treatment of prepyloric or duodenal ulcer. A double-blind controlled trial.

One hundred and nineteen patients with endoscopically confirmed prepyloric (n = 59) or duodenal (n = 60) ulcer were stratified for ulcer location before entering a randomized double-blind trial comparing ranitidine (150 mg twice daily) and a potent liquid antacid (Novaluzid; 10 ml seven times daily, with a neutralizing capacity of 600 mmol H+). Fifty-four patients with prepyloric (26 receiving ranitidine) and 53 patients with duodenal ulcer (28 receiving ranitidine) completed the trial in accordance with the protocol. The 4 and 6 weeks' healing rates for prepyloric ulcers were 54%, 68%, and 61%, versus 69%, 79%, and 74% for the ranitidine, the antacid, and whole groups, respectively. For duodenal ulcers these figures were 89%, 84%, and 87%, versus 100%, 96%, and 98% for the ranitidine, antacid, and whole groups, respectively. Differences in healing rates between treatments were statistically insignificant within strata for ulcer type, but healing rates for prepyloric ulcers were significantly lower than for duodenal ulcers (p less than 0.002). A significant early pain relief was found in all groups, and side effects, including diarrhoea, were rare. In conclusion, these two ulcer treatment modalities appear to be equally effective in the short term. In addition, the data emphasize the need for proper stratification of prepyloric and duodenal ulcers in clinical trials of ulcer healing.

Adult↗
PubMed1984

Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls.

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18,000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p less than 0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p less than 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE2 concentrations to values above normal levels (p less than 0.05) which returned to pretrial values (p less than 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.

Adult↗
PubMed1984

Colonic azodisalicylate metabolism determined by in vivo dialysis in healthy volunteers and patients with ulcerative colitis.

Azodisalicylate, a second generation drug of sulfasalazine, delivers twice the amount of 5-aminosalicylic acid to the colonic lumen on a molar basis when split by bacterial azoreductases. In 6 patients with inactive ulcerative colitis, the colonic metabolism of sulfasalazine and azodisalicylate was studied by equilibrium in vivo dialysis of feces to measure the therapeutically relevant concentrations of their metabolites (5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid) in free fecal water. After oral intake of sulfasalazine (2 g/day) the total luminal concentrations of 5-aminosalicylic acid and N-acetyl-5-aminosalicylic acid determined by high-performance liquid chromatography were higher (median 14 mmol/L) than previously reported and almost doubled (median 25 mmol/L, p less than 0.05) when sulfasalazine was replaced by the same dose of azodisalicylate. In contrast, the corresponding serum concentrations were negligible. After administration of azodisalicylate to 12 healthy volunteers, a similar distribution of the metabolites was found. In nearly all cases, the concentrations of azodisalicylate in fecal dialysates were below the detection limit (6 mumol/L). We conclude, therefore, that oral azodisalicylate is a highly effective means of delivery of 5-aminosalicylic acid to the colonic mucosa. In addition, determination of the active metabolites in free fecal water seems important for the interpretation of results obtained in vitro concerning the mode of drug action.

Adult↗