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Biomedical subjects

E F Stange

Publications and source records attributed to E F Stange.

At least 127 records · Page 7Linked to original sources
PubMed1991

Inhibition of HMG-CoA reductase in mononuclear cells during gemfibrozil treatment.

The effect of gemfibrozil treatment (900 mg/day) on serum levels of total cholesterol, HDL-cholesterol, triglyceride, apoproteins A-I, A-II and B as well as HMG-CoA reductase in mononuclear cells was studied in patients with hyperlipoproteinemia types IIa and IIb. After 4 weeks of treatment gemfibrozil reduced total serum cholesterol (IIa: -17%, IIb: -26%), triglyceride (IIa: -39%, IIb: -47%) and apoprotein B (IIa: -22%, IIb: -15%). HDL cholesterol was increased by 20-22% and apoproteins A-I and A-II by 4-11%. Concomitantly, HMG-CoA reductase activity in freshly isolated mononuclear cells was suppressed by 78% in type IIa and 51% in type IIb patients. Continuation of treatment for up to 16 weeks prompted a further decline to 8 and 5% of the initial values, respectively. However, gemfibrozil failed to affect HMG-CoA reductase directly in homogenized or cultured mononuclear cells and did not further promote the suppressive action of LDL when added to the culture medium. Similarly, preincubation with the drug did not significantly modulate the binding or degradation of LDL in the cultured cells. However, LDL from patients with hyperlipoproteinemia types IIa and IIb exhibited enhanced binding and more potent HMG-CoA reductase suppression when isolated after compared to before gemfibrozil treatment. It is suggested that the HMG-CoA reductase inhibition observed in mononuclear cells during gemfibrozil treatment is due to changes in LDL structure affecting LDL receptor binding rather than direct effects of the drug on cellular cholesterol metabolism.

Adult↗
PubMed1991

In vitro effects of arachidonic acid on the prostaglandin synthesizing system in gastric mucosa.

Self-destruction of the prostaglandin cyclooxygenase has been suggested to be an important factor in the regulation of endogenous prostaglandin synthesis. The present study was done in order to define the role of this substrate-induced inactivation in the regulation of prostaglandin synthesis in gastric mucosa. In tissue homogenate, the prostaglandin synthesizing capacity is rapidly inactivated at 37 degrees C, even in the absence of exogenous arachidonic acid. It was shown that this inactivation can be prevented both by EDTA as a chelator of calcium-ions and by tetracaine, a specific inhibitor of the phospholipase A2. Additional exogenous arachidonic acid again inactivated prostaglandin synthesis in a dose dependent manner. In contrast, the prostaglandin synthesizing capacity in organ cultured mucosal biopsies is well preserved, although the release of endogenous substrate was activated by extracellular calcium and Ca-ionophore A23187. Furthermore, even at high concentrations of exogenous arachidonic acid present in the culture medium, the synthesizing capacity in intact biopsies was only slightly and reversibly reduced. These large differences between intact biopsies and cell free tissue preparations point to very efficient mechanisms controlling the substrate availability for the cyclooxygenase system both from endogenous and exogenous sources in intact gastric mucosa.

Animals↗
PubMed1991

The quality of gastroenterological reports based on free text dictation: an evaluation in endoscopy and ultrasonography.

The majority of physicians consider the use of free dictation for medical reports to be essential in many domains. One of the main criticisms of structured data entry is the possible lack of flexibility and completeness. Electronic documentation systems exist for endoscopy and ultrasonography examinations which are based on structured input as well as on free dictation. Endoscopy and ultrasonography reports based on free dictation were evaluated for omissive errors. The data evaluated was drawn from a database of 18,239 gastroscopy and 3,340 colonoscopy reports dictated by 28 physicians over 74 months, and 18,834 ultrasonography reports dictated by 37 physicians over 42 months. The error rates varied from 0% to 41.8% depending upon the particular feature and the particular examination, but were usually below 15%. The results were independent of the experience of the examiner. This study provides baseline measurements of omissive error rates for selected findings in gastrointestinal endoscopy and abdominal ultrasonography which can be used as standards for the development and evaluation of systems for collection of clinical data.

Database Management Systems↗
PubMed1991

Modulation of arachidonic acid metabolism by olsalazine and other aminosalicylates in leukocytes.

We investigated the action of the new aminosalicylate olsalazine (disodium azodisalicylate) on arachidonic acid metabolism in comparison with 5-aminosalicylic acid (5-ASA) and sulphasalazine (SASP) by in vitro incubation of cellular homogenates from human polymorphonuclear (PMNL) and mononuclear (MNL) leukocytes with 14C-labelled arachidonic acid. Olsalazine reduced the synthesis of leukotriene B4 (LTB4), 5-hydroxyeicosatetraenoic acid (5-HETE), 11-HETE, 12-HETE, and 15-HETE in PMNL and MNL slightly less than SASP. 5-ASA was significantly less inhibitory than olsalazine and SASP on the formation of lipoxygenase products in PMNL and on LTB4 synthesis in MNL. In contrast, in MNL the formation of 5-HETE was unaffected, and the production of 11-HETE, 12-HETE, and 15-HETE was even slightly activated by 5-ASA. Total prostaglandin synthesis was dose-dependently reduced by the aminosalicylates (SASP greater than olsalazine greater than 5-ASA), but only SASP markedly altered the prostaglandin (PG) profile, with an increase in PGE2 and PGF2 alpha at the expense of other cyclooxygenase products. It may be concluded that olsalazine resembled SASP with regard to the inhibition of the lipoxygenase but had effects intermediate between the other salicylates on cyclooxygenase. Furthermore, the alteration of the prostaglandin profile by SASP points to an overlying cofactor effect of this drug.

Aminosalicylic Acids↗
PubMed1991

Bezafibrate fails to directly modulate HMG-CoA reductase or LDL catabolism in human mononuclear cells.

The effect of bezafibrate on HMG-CoA reductase, the key enzyme of cholesterol synthesis, and LDL metabolism was studied in human mononuclear cells. Bezafibrate at concentrations achieved during administration in patients did not suppress preformed reductase in mononuclear cells. Similarly, the drug was ineffective in regulating reductase when added to the medium of cultured cells. Also, the fibrate did not modulate the enzyme suppression mediated by LDL. At very high concentrations bezafibrate enhanced LDL binding, but both total cell association and degradation were unchanged. Thus, the previously observed decrease of HMG-CoA reductase activity in mononuclear cells of patients treated with fibrates is likely to be indirect and probably due to changes in LDL structure.

Bezafibrate↗
PubMed1990

[Regulation of intestinal cholesterol metabolism].

The small bowel epithelium is of major importance in the cholesterol homeostasis of the organism. The morphological and functional heterogeneity of the gut, complicates studies on intestinal cholesterol metabolism. Cholesterol from diet, de novo synthesis and lipoproteins is strictly compartmentalized intracellularly and supports different metabolic needs. Interactions of cholesterol and lipoproteins were studied in cultured intestinal cells (IEC-6, CaCo-2). Newly synthesized cholesterol is mainly utilized for local purposes like membrane synthesis and is essential for cell growth. In contrast to other cell systems it cannot be replaced by LDL cholesterol in case of blocked synthesis. LDL is specifically bound, internalized and degraded. HDL3 also displays specific binding, internalisation and retroendocytosis, but is not degraded. The observed induction of HMG-CoA reductase, suppression of ACAT, as well as cholesterol efflux after contact of HDL3 with lipid droplets argue for intracellular cholesterol transfer to intact HDL3 and finally resecretion into the medium. HDL3 therefore appears as a mediator of reverse cholesterol transport also in the small intestinal epithelial cell.

Carrier Proteins↗
PubMed1990

[Local lysis of peritoneovenous shunt thrombosis with rt-PA].

We report five instances of local lysis with rt-PA (recombinant tissue type plasminogen activator) in three patients with thrombotic occlusions of their peritoneovenous Denver shunts (PVS). In all cases liver cirrhosis was alcohol-induced and ascites was refractory to all medical measures. Because of rethrombosis two patients were treated again after 13 months. The occlusion had occurred 2-30 days before treatment. In four of the five instances the local lysis was successful. Complications were rare. This scintigraphic visualization of the catheter system allowed assessment of shunt patency under physiological flow conditions. The local lysis of a thrombotic shunt with rt-PA and scintigraphic monitoring is a low-risk alternative to reoperation. Possible benefits compared to other fibrinolytics must be confirmed by a greater patient collective.

Adult↗
PubMed1990

[Exclusion diet in Crohn disease: a controlled, randomized study].

In a controlled study patients with Crohn's disease received an exclusion diet or an diet low in refined carbohydrates and rich in fiber. A total of 26 patients was observed for 1 year. The exclusion diet was not significantly superior to the standard diet with respect to the clinical course (Crohn's disease activity index according to Best or van Hees) or laboratory parameters of inflammatory activity. During dietary counselling relapses were infrequent and symptoms improved in both dietary groups.

Crohn Disease↗
PubMed1990

Size exclusion chromatography for extraction of serum bile acids.

A major problem in the measurement of serum bile acids is their quantitative extraction from the high molecular protein matrix. In our hands, the standard techniques of adsorption and reversed-phase chromatography have yielded incomplete recovery for different bile acids (33-93%) and poor reproducibility. In contrast, with the novel extraction procedure of size exclusion chromatography, recovery was nearly quantitative (75-104%) and reproducibility was satisfactory. The described method allowed for a reliable determination of serum bile acids in healthy subjects and patients with liver cirrhosis. We conclude that size exclusion chromatography for serum bile acid extraction is more reliable than alternative techniques, because the separation by size is independent of solubility, charge, and polarity.

Adult↗
PubMed1989

Effect of antacid treatment on endogenous prostaglandin synthesis in human antral and duodenal mucosa.

Using 14C-labeled arachidonic acid as precursor for in vitro prostaglandin synthesis, the effect of an antacid containing Al (OH)3, Mg(OH)2 and CaCO3 on endogenous prostaglandin synthesis was investigated in antral and duodenal mucosa of healthy volunteers. After three weeks of treatment with a high-dose antacid, there was no detectable change in the total capacity of the mucosa for prostaglandin synthesis, but the prostaglandin profile was markedly altered. The relative amounts of PGE2 and PGF2 alpha synthesized by antral and duodenal mucosa increased at the expense of the prostaglandins A2/B2, thromboxane A2, and prostacyclin. In a short-term study, this change was not observed following a single antacid dose within 1 hr after application. It is concluded that long-term antacid treatment may alter the prostaglandin pattern formed by gastroduodenal mucosa and this may be related to its therapeutic effect.

Adult↗
PubMed1989

Cyclosporin A treatment in inflammatory bowel disease.

The effect of cyclosporin A in acute and chronically active inflammatory bowel disease was tested in 11 patients with Crohn's disease and two with ulcerative colitis who had exhibited a poor response to at least eight weeks of conventional therapy. Trough levels of the drug in the therapeutic range were obtained in 12 of 13 patients. Cyclosporin A, which was usually added to the continued previous medication, including corticosteroids (11 of 13) or metronidazol (1 of 13), prompted an apparent clinical improvement in all but one patient. In six of the nine Crohn's disease patients with an initial Best index of greater than 150, a definite fall by at least 100 points was observed after 2-10 weeks of treatment, but the van Hees index declined only in two patients. All four patients with chronic perineal fistulation experienced symptomatic relief. Both patients with ulcerative colitis had a clinical remission. Erythrocyte sedimentation rate or serum albumin improved in eight of 13 patients. However, two of the nine responders with Crohn's disease relapsed during cyclosporin A therapy and three immediately after the medication was discontinued. Common side effects included hypertrichosis, tremor, and hyperesthesia; hypertension and epigastric pain each occurred only in one patient.

Adrenal Cortex Hormones↗
PubMed1989

Laser treatment of upper gastrointestinal tract carcinoma: determinants of survival.

Fifty-nine consecutive patients with stenosing carcinoma of the upper gastrointestinal tract were entered into a prospective study defining parameters of survival during laser treatment. A total of 322 laser sessions were performed, 56% of which on an outpatient basis. Life table analysis revealed that survival was poor in the presence of metastases, and in patients under 60 years of age. Survival was statistically independent of tumor histology, location, length or previous treatment of any kind. In contrast, the degree of stenosis both before and after laser treatment was related to survival in a significant fashion. The best separation into groups was achieved with the parameter dysphagia after laser treatment. Thus, the data are compatible with an important role of adequate enteral nutrition in these debilitated patients.

Adenocarcinoma↗
PubMed1989

Alimentary tract and pancreas. Stimulation of mucosal prostaglandin synthesis in human stomach and duodenum by antacid treatment.

The effect of a low dose antacid treatment on mucosal prostaglandin metabolism was studied in 15 healthy volunteers. A daily dose of 46 mmol (= 138 mval) Al(OH)3 and 42 mmol (= 84 mval) Mg(OH)2 with a titrated in vitro neutralising capacity of 272 mval of H+ was given for three weeks. Total prostaglandin formation and the prostaglandin profile as well as the degradation of PGE2 were assayed by incubating homogenates of endoscopic biopsies from antral and duodenal mucosa with the precursor (14C)arachidonic acid. Total prostaglandin synthesis in antrum (623 (110) pmol/mg protein) and duodenum (432 (72) pmol/mg) was stimulated after three weeks administration of low dose antacids by 176% (p less than 0.05) and 154% (p less than 0.05), respectively. An untreated control group exhibited no significant changes. In contrast, the prostaglandin profile showed only a small increase of the prostacyclin metabolite 6-keto PGF1a (p less than 0.05) at the expense PGD2. PGE2 catabolism was unaffected. This enhanced activity of mucosal prostaglandin cyclooxygenase might represent one possible mechanism of action of a low dose antacid treatment.

Aluminum Hydroxide↗
PubMed1989

Role of primary and secondary bile acids as feedback inhibitors of bile acid synthesis in the rat in vivo.

The effect of various primary and secondary bile acids on the rates of synthesis of all major bile acids was studied in the live rat with an extracorporal bile duct. Bile acid synthesis was determined using HPLC based on mass or by isotope dilution. Derepressed rates of bile acid synthesis (30-54 h) were inhibited by an infusion of taurocholic acid only at a supraphysiological dose of 500 mumol/kg per h, but not at 300 mumol/kg per h, which approximates the initial bile acid secretion (250 mumol/kg per h). When administered together with taurocholic acid (200 mumol/kg per h) only a high dose of taurochenodeoxycholic acid (100 mumol/kg per h) decreased taurocholic but not tauromuricholic or taurochenodeoxycholic acid synthesis. The only bile acid suppressing taurocholic acid (36-71%) and taurochenodeoxycholic acid (up to 33%) formation at an infusion rate close to the normal portal flux was deoxy- or taurodeoxycholic acid at 15-50 mumol/kg per h. It may be concluded that deoxycholic acid and possibly other secondary bile acids are much more potent inhibitors than primary bile acids.

Alanine Transaminase↗
PubMed1988

Prospective, randomized, double-blind comparison of benzalazine and sulfasalazine in the treatment of active ulcerative colitis.

Benzalazine (salicylazobenzoic acid, SAB), a 5-azo derivative of 5-aminosalicylic acid, has been designed as a new therapeutic agent for the treatment of inflammatory bowel disease which might lack the frequent side effects caused by the sulfapyridine moiety of the sulfasalazine molecule (SASP). Here, we report on a prospective, randomized, double-blind comparison of SAB and SASP in patients with an acute relapse of ulcerative colitis. 43 patients with an acute relapse of ulcerative colitis proven by the pertinent endoscopic-macroscopic and histologic criteria were randomized to receive a 6-week course of either 1 g SASP (n = 21) or the equivalent dose of 0.72 g SAB (n = 22) three times a day. Both groups were comparable with respect to demographic data, previous duration and extension of the disease as well as clinical, endoscopic and histologic severity of the relapse. 1 patient on SASP had to be removed from the study due to side effects, while 3 patients on SAB were removed due to rapid worsening of the disease requiring either surgery (1 patient with toxic megacolon) or additional steroid treatment (2 patients). 2 SAB patients were lost to follow-up after substantial improvement had been observed within the first 3 weeks of treatment. In the remaining patients (20 SASP, 17 SAB), stool frequency, stool consistency and macroscopic appearance as well as histology of the diseased mucosa were improved within 6 weeks, with no significant difference between the two groups with respect to any of the parameters recorded. Side effects were recorded in 5 patients on SASP (3 with nausea, 1 with pruritus and 1 with a generalized exanthema) and in 3 patients on SAB (all nausea and vomiting; difference not statistically significant). We conclude that SAB and SASP in equivalent doses are of similar efficacy in the treatment of active ulcerative colitis.

Acute Disease↗