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Biomedical subjects

K Lauritsen

Publications and source records attributed to K Lauritsen.

At least 73 records · Page 4Linked to original sources
PubMed1989

Cytoprotection of gastroduodenal mucous membrane with analogues of prostaglandins.

Analogues of E-type prostaglandins, such as arbaprostil, enprostil, misoprostol, rioprostil, and trimoprostil, suppress gastric acid secretion and (like native E-type prostaglandins) the chemically modified analogues enhance a number of gastroduodenal mucosal defence factors. These include regulation of the thickness and the composition of the mucous layer at the epithelial surface; modulation of active bicarbonate secretion; hydrophobicity of the surface epithelium; rapid cell proliferation and differentiation after mucosal damage; maintenance of interstitial bicarbonate; and the integrity of the mucosal microcirculation. In theory, this bimodal action makes prostaglandin analogues ideal drugs for treating and preventing lesions of the gastroduodenal mucous membrane. In practice, however, these expectations remain unfulfilled. First, in doses lower than those required to decrease acid secretion, prostaglandin analogues retain cytoprotective properties but are no better than placebo in healing peptic ulcers. Second, in fully antisecretory doses some prostaglandin analogues accelerate ulcer healing compared with placebo and provide healing rates about as high cimetidine, but less than achieved with ranitidine. Third, despite the fact that high doses of some analogues are superior to placebo in alleviating pain associated with ulcer disease, these agents proved inferior to cimetidine and ranitidine in relieving pain in most comparative trials. Fourth, enprostil and misoprostol in doses which combine antisecretory with cytoprotective properties perform significantly poorer than ranitidine in preventing relapse of peptic ulcer disease. Fifth, although several uncontrolled observations have suggested a therapeutic benefit of prostaglandin analogues in gastroduodenal haemorrhage, placebo-controlled trials show no effect of arbaprostil in stopping bleeding and in preventing rebleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial.

One hundred and sixty two patients with endoscopically proved reflux oesophagitis stratified for severity, 66 with grade 1 disease (erythema and friability) and 96 with grade 2 or 3 disease (including erosions or ulcerations), were allocated at random to double blind treatment with omeprazole 40 mg in the morning or ranitidine 150 mg twice daily for up to 12 weeks. A patient could be evaluated sooner if symptomatic relief and endoscopically normal mucosa (grade 0) were noted after four to eight weeks' treatment. Patients treated with omeprazole responded significantly more rapidly than those treated with ranitidine (p less than 0.0001), cumulative healing rates at four, eight, and 12 weeks being 90%, 100%, and 100% respectively for those with grade 1 disease and 70%, 85%, and 91% respectively for those with grade 2 or 3 disease in the omeprazole group. Corresponding rates in the ranitidine group were 55%, 79%, and 88% (grade 1) and 26%, 44%, and 54% (grade 2 or 3). Relief of the major symptoms of heartburn, regurgitation, and dysphagia and improvements in the histological appearance of the mucosa occurred earlier and were again more pronounced during treatment with omeprazole than with ranitidine. This observed superiority of omeprazole 40 mg in the morning over ranitidine 150 mg twice daily in the short term treatment of reflux oesophagitis was obtained without major clinical or biochemical side effects, but further research is needed into longer term use of omeprazole and the effects of the acid inhibition it induces.

Adolescent↗
PubMed1988

In vivo profiles of eicosanoids in ulcerative colitis, Crohn's colitis, and Clostridium difficile colitis.

To compare the local release of arachidonic acid metabolites in inflammatory diarrheal disease, in vivo equilibrium dialysis of the rectum was done in consecutive untreated patients with ulcerative colitis (n = 20), Crohn's colitis (n = 10), and Clostridium difficile colitis (n = 7). All patients had endoscopically proven rectal inflammation. Eicosanoid profiles were determined in rectal dialysates by radioimmunoassay after preliminary purification. Concentrations of prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2, but not 6-keto-prostaglandin F1 alpha, were raised in all groups and compared with healthy controls. The highest levels within each group were obtained in patients with widespread epithelial damage, as judged by endoscopy. In patients with ulcerative colitis, an extreme rise in prostaglandin E2 and thromboxane B2 were observed. Similarly, concentrations of leukotriene B4 were substantially increased in ulcerative colitis, but in Crohn's colitis and Clostridium difficile colitis only those patients with rectal ulcerations showed elevations. These findings probably reflect more severe tissue damages in ulcerative colitis, but differences between disease groups in cell-to-cell interaction may also contribute. The data suggest, therefore, that therapeutic inhibition of lipoxygenase pathways may prove more effective in ulcerative colitis than in Crohn's disease.

Adolescent↗
PubMed1988

Use of colonic eicosanoid concentrations as predictors of relapse in ulcerative colitis: double blind placebo controlled study on sulphasalazine maintenance treatment.

To establish whether concentrations of eicosanoids determined by equilibrium in vivo dialysis of faeces and equilibrium in vivo dialysis of rectum might predict a relapse in ulcerative colitis, 23 patients with completely inactive disease, maintained on sulphasalazine, stopped treatment and entered a prospective study. Concentrations of prostaglandin E2 were determined by radioimmunoassay on purified faecal and rectal dialysates at entry, at two weeks, and at two, six, and 12 months. If the above concentrations exceeded control concentrations (0.5 ng/ml and 1.0 ng/ml in faecal and rectal fluid, respectively) at any study day, the patient was allocated at random to double blind treatment with sulphasalazine 2 g/day, or placebo for six months. A relapse, defined as recurrence of symptoms accompanied by endoscopic inflammation occurred in none of six and in four of five patients allocated to sulphasalazine and placebo, respectively (p less than 0.05). In no case a normal rectal prostaglandin E2 concentration was associated with a relapse in the short term, but only two of 12 patients observed passively remained in remission. In retrospect, leukotriene B4 was a less sensitive predictor of relapse than prostaglandin E2. We conclude that raised concentrations of prostaglandin E2 in rectal dialysis fluid identify patients with a substantial risk of relapse.

Adolescent↗
PubMed1988

Effect of omeprazole and cimetidine on prepyloric gastric ulcer: double blind comparative trial.

We conducted a six week double blind randomised study of 176 patients with prepyloric gastric ulcer to determine whether the proton pump inhibitor, omeprazole 30 mg daily would accelerate healing and pain relief, as compared with cimetidine 1 g daily. At two, four, and six weeks after entry ulcers healed in a larger percentage of patients treated with omeprazole (54, 81, and 86%) than of those treated with cimetidine (39, 73, and 78%) ('intention to treat' cohort; p less than 0.05 at two weeks). A higher proportion of patients on omeprazole became free of pain during the first week of treatment (p less than 0.05). No major clinical or biochemical side effects were noted. Omeprazole is an efficient treatment for patients with prepyloric gastric ulcers.

Adult↗
PubMed1988

Longterm olsalazine treatment: pharmacokinetics, tolerance and effects on local eicosanoid formation in ulcerative colitis and Crohn's colitis.

To examine pharmacokinetics and tolerance of long term administration of olsalazine (azodisalicylate), increasing doses of the drug were given for one year to 31 patients with ulcerative colitis (UC) and nine patients with Crohn's colitis (CC), refractory to, or intolerant of sulphasalazine, until sustained remission was obtained or a maximum of 4 g/day was reached. Colonic drug metabolism was studied by equilibrium in vivo dialysis of faeces. Complete azoreduction occurred in most cases. Concentrations of 5-aminosalicylic acid, but not N-acetyl-5-aminosalicylic acid, in faecal dialysates increased dose dependently. Serum concentrations disclosed no cumulation in the long term and olsalazine was well tolerated, although loose stools occurred transiently in some patients with extensive disease: this was associated with a larger proportion of unsplit olsalazine in the faecal dialysates. Patients with ulcerative colitis having a high prostaglandin E2 concentration (greater than ng/ml) determined by equilibrium dialysis of rectum, were less likely to benefit from treatment. Olsalazine is a very effective means of delivery of 5-aminosalicylic acid to the colonic mucosa in active disease. Use of the drug in controlled trials may be considered safe even in prolonged high dosage.

Adolescent↗
PubMed1988

Colonic prostaglandin E2 levels and olsalazine metabolism in relapsing ulcerative colitis: implications for controlled trials in the long term.

To examine the tolerance and pharmacokinetics of long-term olsalazine administration, increasing doses of the drug were given to 31 patients with ulcerative colitis. All patients were refractory to or intolerant of sulphasalazine. Complete azo-reduction occurred in most cases. Concentrations of 5-ASA, but not acetyl-5-ASA, in faecal dialysates increased dose-dependently. Estimates of efficacy were more favourable among those intolerant of sulphasalazine. Patients with high prostaglandin E2 levels determined by equilibrium in vivo dialysis of rectum were less likely to benefit from treatment. In conclusion, olsalazine is a highly effective means of delivering 5-ASA to the colonic mucosa. Long-term use of olsalazine in controlled trials may be considered safe, even in high doses.

Adult↗
PubMed1987

Enprostil and ranitidine in prevention of duodenal ulcer relapse: one year double blind comparative trial.

One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non-recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence.

Adult↗
PubMed1987

Effects of cisapride on gastroparesis in patients with insulin-dependent diabetes mellitus. A double-blind controlled trial.

Fourteen insulin-dependent diabetics with symptoms and signs of delayed gastric emptying were treated with a new prokinetic agent, cisapride. In a placebo-controlled cross-over trial no significant differences from placebo was found regarding overall symptomatic effects and effects on gastric emptying of a mixed solid/liquid isotope marked test meal. Solid emptying was most markedly delayed in diabetics compared with healthy controls, but the emptying rate was not correlated to the severity of symptoms as observed for liquid emptying. During active treatment with cisapride the amelioration of symptoms was correlated to increased emptying rates assessed by combined measure of liquid/solid gastric emptying.

Cisapride↗
PubMed1987

Review: clinical trials in peptic ulcer disease--problems of methodology and interpretation.

This review focuses on the methodology and interpretation of drug trials in peptic ulcer disease. The problems of planning and conduct that are discussed include the ethics of using placebo, eligibility criteria, estimations of sample size, stopping rules, randomization, blinding, and efficacy criteria, that is, ulcer healing and pain relief in the short term and prevention of relapse and complications in the long term. Statistical topics covered include confidence intervals, evaluation of survival type data, post-stratification, and sub-group analysis. The difference between clinical and statistical significance is discussed, major problems being overemphasis on P-value, type II errors, and post hoc power determinations. Explanatory and pragmatic questions are based on compliance-to-protocol and intention-to-treat cohorts, respectively, and involve problems of compliance testing, evaluation of withdrawals, and the use of fixed-dose regimens. The rather slow process for clinical trials to gain acceptance is described, and it is proposed to rely on disease-related and behavioural barriers, lack of knowledge of the inherent limitations of methodology, and overemphasis on the subject of peptic ulcer healing, in addition to some concern at the relevance of assessing long-term drug intervention by repeated endoscopies rather than by studying symptoms and the incidence of complications. We foresee an increased impact of clinical trials on ulcer research and therapeutic decision making, provided physicians are able to develop the proper methodology to answer the relevant questions.

Anti-Ulcer Agents↗