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Biomedical subjects

K Lauritsen

Publications and source records attributed to K Lauritsen.

At least 55 records · Page 3Linked to original sources
PubMed1992

[Chronic inflammatory bowel disease].

Chronic inflammatory bowel disease (IBD) encompasses the disease entities, ulcerative colitis (UC) and Crohn's disease (CD). An aetiologic agent has not yet been defined and the diagnosis is based, therefore, on the sum of clinical, paraclinical, radiologic, endoscopic and histopathologic features. In recent years pathogenetic studies have focused on immune mechanisms, transmissible infectious agents, the potential role of the normal intestinal flora, dietary factors, enzymatic alterations and genetic features, in addition to vascular, neuromotor, allergic and psychologic factors. The corner stones in medical therapy of IBD are still corticosteroids and sulphasalazine (SAZ). The new oral salicylates, which are analogues of SAZ or "slow release" preparations of 5-aminosalicylic acid (mesalazine), have provided a therapeutic progress, because they are tolerated better than SAZ. Immunosuppressive agents, such as azathioprine and 6-mercaptopurine, reduce the requirement for corticosteroids and are effective in refractory CD, but the effect is delayed up to several months. The therapeutic action of cyclosporine A is not sustained, but often associated with side effects. Metronidazole has a beneficial effect on perineal disease. The efficacy of antimycobacterial drugs, sodium-cromoglycate, lidocaine, clonidine and sucralfate has been reported only in optimistic case stories and small open trials. A diet, rich in omega-3-fatty acids, modifies leukotriene (LT) production, but its clinical efficacy is insufficient. The first anti-leukotriene-drug, zileuton, has recently been evaluated and a significant, although insufficient, clinical response was obtained by a 70 per cent inhibition of rectal LTB4 synthesis. Dietary therapy may be useful as an adjunct to treatment of local complications in CD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1991

[Laparoscopic cholecystectomy--minimally invasive surgery].

In 1987, Mouret devised a technique of performing cholecystectomy through a laparoscope. When performed correctly and on the right indications, this type of minimal invasive surgery has distinct advantages for the patients. Postoperative hospitalization is reduced to a few days and most of the patients can return to work or normal activities within a week or two. In this department, laparoscopic cholecystectomy was used for treatment of symptomatic gallbladder stones in 34 patients. In three patients the procedure was converted to an open laparotomy. No mortality and no ductal injuries were observed and no re-operations were necessary. The operating time averaged 102 minutes and the postoperative stay was 2.3 days. The average duration of sick-leave was 12 days. We are convinced, that this new technique will play a dominant role in the future treatment of symptomatic cholelithiasis.

Cholecystectomy↗
PubMed1991

Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse. Double-blind comparative trial.

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.

Adolescent↗
PubMed1991

Final report on a placebo-controlled, double-blind, randomized, multicentre trial of cyclosporin treatment in active chronic Crohn's disease.

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease.

Chi-Square Distribution↗
PubMed1990

Selective 5-lipoxygenase inhibition in ulcerative colitis.

Leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) concentrations were measured in rectal dialysis fluid from ten patients with active ulcerative colitis before and after oral administration of 800 mg of the 5-lipoxygenase inhibitor A-64077. The median LTB4 level fell significantly, from 4.9 (range 0.6-20.4) ng/ml before treatment to 1.6 (0.3-5.7) ng/ml after 4 h and 0.7 (0.1-8.0) ng/ml after 8 h; it had returned to pretreatment levels by 28 h. The concentration of PGE2 did not change significantly. The increased generation of 5-lipoxygenase products, such as LTB4, in ulcerative colitis and the potent proinflammatory actions of these products suggest that they have an important role in the amplification of the inflammatory response. A controlled trial to assess the clinical efficacy of A-64077 seems worth while.

Administration, Oral↗
PubMed1990

Disposition of 5-aminosalicylic acid by olsalazine and three mesalazine preparations in patients with ulcerative colitis: comparison of intraluminal colonic concentrations, serum values, and urinary excretion.

To compare the disposition of 5-aminosalicylic acid (5-ASA) and its acetylated metabolite during treatment with olsalazine and mesalazine, 14 patients with inactive ulcerative colitis were randomly assigned to olsalazine (1 g twice daily) and the mesalazines, Asacol (800 + 400 + 800 mg daily), Pentasa (750 + 500 + 750 mg daily), and Salofalk (750 + 500 + 750 mg daily) in a crossover design trial so that all received each drug for seven days. Intraluminal colonic concentrations of 5-ASA were estimated after five days by the method of equilibrium in vivo dialysis of faeces. A predose serum sample and a 24 hour urine collection were obtained on day seven. The 5-ASA and acetyl-5-aminosalicylic acid (Ac-5-ASA) values were determined by high performance liquid chromatography. Olsalazine almost doubled the colonic concentrations (mean 23.7 (SEM) (1.9) mmol/l) of its therapeutically active ingredient (5-ASA) compared with equimolar doses of Pentasa (12.6 (2.2) mmol/l; p less than 0.0003) and Salofalk (15.0 (2.0) mmol/l; p less than 0.003). At the same time, olsalazine treatment was associated with lower serum concentrations and urinary excretions (p less than 0.05) of 5-ASA and Ac-5-ASA compared with the mesalazine preparations. The low systemic load of 5-ASA provided by olsalazine reduces the potential risk of nephrotoxicity during long term treatment.

Adult↗
PubMed1990

Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part I).

Drug treatment of gastrointestinal diseases, which was previously limited to the use of antacids, anticholinergics, antispasmodics, cathartics and laxatives, has changed markedly over the past decade. Histamine H2-receptor antagonists (e.g. cimetidine, ranitidine and more recently famotidine and nizatidine) have revolutionised the treatment of peptic acid disorders, but their role is currently challenged by muscarinic-M1-receptor antagonists (e.g. pirenzepine), proton pump inhibitors (e.g. omeprazole), prostaglandin analogues and site-protective drugs (e.g. colloidal bismuth subcitrate and sucralfate). Newer antiemetics with prokinetic properties (e.g. metoclopramide, domperidone and cisapride) have also been introduced in the management of gastrointestinal motility disturbances, and new anti-inflammatory salicylates (e.g. olsalazine and mesalazine) have been developed for the treatment of chronic inflammatory bowel diseases. Finally, diphenoxylate and loperamide have gained wide clinical application as nonspecific antidiarrhoeal agents. The basic pharmacokinetic properties of the above agents are briefly reviewed with the main emphasis on the newer and more important drugs in current use. Furthermore, the effects of age and disease on pharmacokinetics, in addition to drug interaction potentials and pharmacokinetic-pharmacodynamic relationships, are discussed. The anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics will be dealt with in Part II.

Anti-Ulcer Agents↗
PubMed1990

Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part II).

Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth subcitrate, sucralfate); antacids and prostaglandin analogues; antiemetics and prokinetics (metoclopramide, domperidone, cisapride); and antispasmodics. In Part II, we consider the anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.

Administration, Oral↗
PubMed1989

[Prostaglandins and the resistance of the gastroduodenal mucosa].

The mechanisms responsible for maintaining the integrity of the gastroduodenal mucosa have been explored intensively in recent years. Prostaglandins seem to play a central role in mucosal defence. Important mechanisms by which prostaglandins may produce cytoprotection include regulation of the thickness and the composition of the mucus layer at the epithelial surface; modulation of active bicarbonate secretion by the surface epithelial cells; hydrophobicity of the surface epithelium; rapid cell proliferation and differentiation after mucosal damage; maintenance of interstitial bicarbonate; and the integrity of the microcirculation--in addition to synthesis of mucosal sulphhydryl groups. A defect mucosal defence is considered the most important pathogenetic factor in the majority of patients with peptic ulcer disease, but it is still unclear whether this is due to a deficiency in endogenous prostaglandins. Important risk factors for developing peptic ulcer disease, such as nonsteroidal antiinflammatory drugs and smoking, depress the formation of endogenous prostaglandins. The question of whether the use of direct cytoprotection may be relevant in ulcer therapy has yet not been solved and the rationale for substitution with prostaglandin analogues is to date empirical.

Animals↗
PubMed1989

[Prostaglandin analogues in the treatment of peptic ulcer disease].

The cytoprotective properties of native prostaglandins have been exploited for ulcer therapy through the development of analogous molecules, which are characterized by longer duration of action, more potent acid inhibitory effect and higher pharmacologic specificity. The therapeutic efficacy of prostaglandin analogues has been evaluated in a variety of controlled clinical trials, which are summarized briefly. The experience with arbaprostil, enprostil, misoprostol, rioprostil and trimoprostil shows that their effect on ulcer healing is superior to that of a placebo in acid inhibitory doses, which are also cytoprotective. Nevertheless, prostaglandin analogues are inferior to H2-receptor antagonists as regards their effects on ulcer healing, pain relief, and relapse prevention and less effective than expected from their acid inhibitory action. Placebo controlled trials of arbaprostil in acute upper gastrointestinal haemorrhage have failed to demonstrate any reduction in numbers of patients whose bleeding stopped, numbers with rebleeding or transfusion requirement. Diarrhoea occurs in 4%-34% of all patients and prostaglandin analogues are contraindicated in pregnant women. Although these drugs will probably not be marketed in Denmark for ulcer therapy, they may prove useful as replacement therapy in patients requiring nonsteroidal antiinflammatory drugs.

Humans↗
PubMed1989

Effect of 10 mg and 20 mg omeprazole daily on duodenal ulcer: double-blind comparative trial.

One-hundred and seventy-one patients with endoscopically proven duodenal ulcers were allocated at random to double-blind treatment with 10 or 20 mg of omeprazole in the morning for up to 4 weeks. Patients completed the study if ulcer healing and pain relief had occurred at 2 weeks. A total of 155 patients completed the trial. Patients treated with 20 mg of omeprazole daily responded significantly more rapidly than those treated with 10 mg of omeprazole daily (P less than 0.001; Cochran-Mantel-Haenszel test covering both time points), cumulative healing rates at 2 and 4 weeks were 74% (58/78) and 91% (71/78), respectively. The corresponding rates in the group treated with 10 mg daily were 48% (39/81) and 75% (58/77). Pain relief was again more pronounced during treatment with the larger dose (P less than 0.05; stratified Wilcoxon test). No major clinical or biochemical side effects were noted. An omeprazole dose of 20 mg daily is preferable to a lower dose for the treatment of duodenal ulcer disease in the short term.

Adolescent↗
PubMed1989

Low-dose cyclosporin for Crohn's disease: implications for clinical trials.

Cyclosporin is a potent immunosuppressant, which has gained recent interest as a possible treatment for Crohn's disease. Chronic nephrotoxicity, however, has recently been demonstrated as a result of early treatment with high initial cyclosporin doses. We report the effect of a 3-month treatment with low-dose cyclosporin (5-7.5 mg kg-1 day-1) in 11 chronically active, therapy-resistant Crohn's disease patients. Eight of the 11 patients (72%) improved according to a clinical grading score and the Dutch Activity Index whereas 9/11 (82%) improved according to the Crohn's Disease Activity Index (P less than 0.05) after 1 month. Three patients were withdrawn despite clinical improvement. One developed arterial hypertension, one dropped out and one required surgical treatment due to a small bowel stricture. Five patients (45%) completed the treatment period with improved clinical scores. After tapering-off, two patients (18%) were better at follow-up. No serious side-effects were encountered and it is concluded that low-dose cyclosporin treatment should be further investigated in Crohn's disease.

Adult↗
PubMed1989

Omeprazole in the treatment of prepyloric ulcer: review of the results of the Danish Omeprazole Study Group.

A Danish multicentre trial assessed the value of the more effective gastric acid inhibition provided by omeprazole, as compared with cimetidine, in promoting ulcer healing and pain relief in patients with prepyloric ulcers. A total of 176 patients were randomly allocated to 6 weeks of treatment with either cimetidine, 200 mg t.d.s. and 400 mg at bedtime, or omeprazole, 30 mg once daily. At 2, 4, and 6 weeks after entry, ulcers healed in a larger proportion of patients treated with omeprazole (54%, 81% and 86%) than in those treated with cimetidine (39%, 73% and 78%) ('intention-to-treat' cohort; p less than 0.05 at 2 weeks using Cochran-Mantel-Haenszel test). 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. A 6-month follow-up study revealed no significant difference between the recurrence rates after omeprazole or after cimetidine treatment.

Adult↗
PubMed1989

Rioprostil and ranitidine in the treatment of prepyloric gastric ulcer. A double-blind comparative trial.

Rioprostil, a synthetic 16-methylprostaglandin E1, combines antisecretory with cytoprotective properties, the latter being active even at doses below those required for acid inhibition. To test whether rioprostil given in antisecretory doses would heal prepyloric ulcers rapidly, we assigned patients with endoscopically proved ulcers randomly to double-blind treatment with 100 micrograms rioprostil twice daily or 150 mg ranitidine twice daily for up to 8 weeks. Recruitment was terminated at the time point of planned interim analysis because the total healing rate was markedly lower than expected. Thirty patients were allocated to each treatment group. The cumulative healing rates at 4 and 8 weeks were 40% and 60%, respectively, in the rioprostil group versus 70% and 90%, respectively, in the ranitidine group (p less than 0.01). Pain relief occurred simultaneously in the two groups. No major adverse effects were noted. These findings question the clinical relevance of using 'cytoprotection' by prostaglandin analogues as treatment for prepyloric ulcer disease in the short term.

Adolescent↗