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Biomedical subjects

M Kristensen

Publications and source records attributed to M Kristensen.

14 recordsLinked to original sources
PubMed1992

The effect of second-line antirheumatic drugs on interleukin-8 mRNA synthesis and protein secretion in human endothelial cells.

Interactions between interleukin 8 (IL-8) and endothelial cells play an important role in the emigration of mononuclear cells from the blood into areas of inflammation. We examined the ability of specific second-line antirheumatic drugs to regulate (IL-8) gene expression and protein secretion in interleukin 1 (IL-1) stimulated human umbilical vein endothelial cells and peripheral blood mononuclear cells. The drugs sodium aurothiomalate, D-penicillamine and sulphasalazine were all able to modulate IL-8 mRNA synthesis in and protein secretion from endothelial cells. A bimodal effect was observed: at low concentrations IL-8 was suppressed, whereas higher concentrations resulted in an increased IL-8 production. In endothelial cells, treatment with hydrocortisone led to a linear suppression of IL-8 production in concentrations ranging from 0.5 micrograms/ml up to 500 micrograms/ml. Sulphapyridine, auranofin, hydroxychloroquine and methotrexate, had no effect on IL-8 secretion in endothelial cells. By contrast, 5-aminosalicylic acid induced a threefold increase in the IL-8 release. In peripheral blood mononuclear cells it was only possible to suppress the IL-8 production by hydrocortisone treatment. These results indicate that suppression of IL-8 production in endothelial cells could be an important factor in the mode of action for a number of second-line antirheumatic drugs.

Anti-Inflammatory Agents↗
PubMed1979

The relapse-preventing effect of methyl-salazosulphapyridine compared to salazosulphapyridine during long-term treatment of ulcerative colitis. A double-blind controlled trial.

In an attempt to improve the relapse-preventing effect of salazosulphapyridine (SASP) and to encircle the part of the molecule essential for therapeutic actin, methyl-SASP was compared to SASP in a controlled double-blind trial without cross-over. The patient group comprised 33 patients with ulcerative colitis who had been symptom-free for 1--6 months on continuous treatment with SASP (on an average 2 g daily). The daily doses were SASP 1 g X 3 and methyl-SASP 125 mg x 3. Thirty patients completed the trial, 14 on SASP and 16 on methyl-SASP. Applying clinical criteria, the relapse rate after 6 months was 0.14 in the SASP group and 0.69 in the methyl-SASP group. The difference is highly significant. The blood concentrations of SASP, methyl-SASP, sulphapyridine (SP), and methyl-sulphapyridine (methyl-SP) were measured after 3 and 6 months. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-SP on an average 1/10 of SP (the differences are significant). It is concluded that whereas SASP showed a relapse-preventing effect in ulcerative colitis in this study comparable to that previously reported, the effect of methyl-SASP was only comparable to that of placebo, and the active substance in SASP does not seem to be unsplit SASP.

Adult↗
PubMed1979

The therapeutic effect of methyl-salazosulphapyridine versus salazosulphapyridine in active ulcerative colitis. A double-blind controlled trial.

In an attempt to improve the ratio between therapeutic effect and side effects of salazosulphapyridine (SASP), methyl-salazosulphapyridine (methyl-SASP) was compared with SASP in a randomized controlled double-blind trial, without cross-over, in patients with active ulcerative colitis. The patient group comprised 53 patients. The daily doses were 1 g SASP x 3 and 125 mg methyl-SASP x 3. The methyl-SASP group comprised 26 patients, the SASP group 27 patients. The treatment period was 4 weeks. Applying clinical symptoms (bowel movements, registered by the patients on special charts), clinical condition (assessed by the patient), proctoscopic signs, and registration of side effects, it is concluded that methyl-SASP had an effect on ulcerative colitis indistinguishable from that of SASP. The rate of side effects was significantly less in the methyl-SASP group. The blood concentrations of SASP, methyl-SASP, sulphapyridine, and methyl-sulphapyridine were estimated at start during, and at the end of the trial. The methyl-SASP concentration was on an average twice as high as that of SASP, and the methyl-sulphapyridine on an average 1/13 of sulphapyridine, the differences being significant. It is concluded that methyl-SASP presents an improvement in the effect/side effect ratio when dealing with symptomatic ulcerative colitis. The discrepancy between the outcome of the present trial and the lack of effect in a controlled trial on the relapse-preventing effect of methyl-SASP is at present unexplained. A type II error in the present trial (or a type I error in the prophylactic one) is a possibility, or the patient-group selected for the present trial had a spontaneously benign course, cases demanding prednisone or colectomy having been excluded.

Adult↗
PubMed1977

Choreoathetosis during phenytoin treatment.

A patient with symptomatic epilepsy receiving only phenytoin developed choreoathetosis and orofacial dyskinesias. These movement disorders disappeared when the drug was stopped and reappeared when the patient was challenged. Throughout the period of treatment, concentrations of phenytoin in serum were consistently low within the therapeutic range. Interfering symptoms from the cardiovascular system and the absence of some classic symptoms of phenytoin intoxication (nystagmus and dysarthria) contributed to delay the diagnosis. The patient died in hospital and autopsy of the brain showed rather localized encephalomalacies of corpus striatum. The pathogenic action of phenytoin and the role of preexisting brain lesions are discussed. Phenytoin must be suspected as the cause, when patients on this drug present with uncontrolllable epilepsy or neurological or mental deterioration.

Aged↗
PubMed1976

The effect of different oral anticoagulants on diphenylhydantoin (DPH) and tolbutamide metabolism.

The effect of bishydroxycoumarin, phenprocoumon, warfarin and phenindione on the metabolism of diphenylhydantoin (DPH) and tolbutamide has been studied in 54 patients. The half-lives of DPH and tolbutamide in blood following i.v. injections were studied in 33 patients before and after one week of anticoagulant treatment. Bishydroxycoumarin increased the mean half-life values of DPH from 8.8 to 37.4 hours and of tolbutamide from 4.9 to 17.5. Phenprocoumon prolonged DPH half-life from a mean value of 9.9 to 14.0 hours but did not change the tolbutamide half-life. Warfarin and phenindione did not affect DPH or tolbutamide half-lives. Steady state concentration studies in 21 patients showed a rise in serum DPH during bishydroxycoumarin and phenprocoumon treatment but not during treatment with warfarin and phenindione. A rise in serum tolbutamide was noted during treatment with bishydroxycoumarin. These findings suggest that bishydroxycoumarin inhibits the betabolism of DPH and tolbutamide and that phenprocoumon inhibits DPH metabolism. No effect on DPH and tolbutamide metabolism could be demonstrated following administration of warfarin and phenindione.

Coumarins↗
PubMed1976

Postoperative mortality and complications after colectomy for ulcerative colitis.

During a 10-year period colectomy was performed on 101 patients. The postoperative mortality of 12 per cent was influenced decisively by duration and severity of the disease. Seventy-eight per cent of the patients were severly ill during the attack leading to colectomy, and 15 per cent of them died. One-third of the patients with toxic megacolon and general intoxication died. One-quarter of the patients with a history of less than 3 months died. The causes of death were peritonitis and pulmonary complications. Half of the patients developed postoperative complications of varying severity. Preoperative steroid medication did not influence the mortality or the postoperative complications. It is concluded that only close medical and surgical cooperation, careful selection of patients, and skillful timing of operations may reduce the mortality in ulcerative colitis. The paper supports that total colectomy in suitable cases may be performed without higher mortality than subtotal colectomy.

Acute Disease↗
PubMed1976

Serum orosomucoid in ulcerative colitis: its relation to clinical activity, protein loss, and turnover of albumin and IgG.

Serum orosomucoid was compared with clinical activity, routine laboratory tests, intestinal protein loss, and albumin and IgG turnover in 22 cases of ulcerative colitis. Serum orosomucoid was well correlated with clinical activity, haemoglobin and leucocyte counts were not. A significant correlation was present between serum orosomucoid and intestinal protein loss (gastro-intestinal 59Fe-iron dextran clearance), serum albumin, fractional catabolic rates of albumin, and IgG and IgG synthesis rate. No correlation was found between serum orosomucoid and albumin synthesis rate or serum IgG. It is concluded that serum orosomucoid is a highly reliable indicator of disease activity in ulcerative colitis.

Adolescent↗
PubMed1975

Toxic megacolon in ulcerative colitis.

During a 10-year period toxic megacolon occurred in 21 patients out of 296 with ulcerative colitis. The majority had a brief history, and half were over 40 years. A barium enema, which presumably may provoke dilatation of the colon, had been performed within the past week in 8 cases. The ulcerative colitis involved the entire colon in 85%, whereas the dilatation affected predominantly the transverse segment. Fourteen patients were on steroid medication when the dilatation developed. Operation was indicated in 20 patients (colectomy with ileostomy and preserved rectum). Six patients died postoperatively, half of pulmonary complications. Only one death occurred among 6 patients with perforation of the colon. Postoperative complications arose in 80%. Both complication rate and mortality were independent of steroid medication. Mortality was lowest among patients treated by a team of internists and surgeons specialized in gastroenterology. This was presumably due to an earlier recognition of the colonic dilatation, intensive medical treatment of severe attacks even before the dilatation had developed, and careful supervision for timing the operation, which should never be delayed in favour of attempts at steroid treatment.

Adult↗