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Biomedical subjects

C Scheurlen

Publications and source records attributed to C Scheurlen.

At least 37 records · Page 2Linked to original sources

Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase. A possible diarrhogenic factor?

Olsalazine (azodisalicylate) and mesalazine (5-aminosalicylic acid) have recently been developed as new treatment modalities for inflammatory bowel disease to avoid sulfasalazine-related side effects. However, there are reports regarding new and hitherto unexpected side effects in some patients receiving olsalazine or mesalazine, such as watery diarrhea. Since sodium pump activities play an important role in the pathogenesis of water and electrolyte disturbances, we investigated the influence of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase and its specific [3H]-ouabain binding. We found a concentration-dependent inhibition of ileal and colonic (Na+ + K+)-ATPase by olsalazine with an IC50 of 4.1 mM and 4.8 mM, respectively. Mesalazine inhibited this enzyme in the ileum with an IC50 of 4.0 mM and in the sigmoid colon with an IC50 3.5 mM. In addition, [3H]-ouabain binding was inhibited by mesalazine with an IC50 of 3.6 mM. The maximal inhibition, however, did not exceed 80% under any conditions (up to 10 mM drug concentration). Olsalazine and mesalazine induce inhibition of the ileal and colonic sodium pump activities that may (in addition to other possible mechanisms) mediate impaired water and electrolyte absorption. This is possibly of clinical relevance in patients with severely damaged mucosa. In patients with milder forms of mucosal inflammation, this inhibition most likely is of minor importance because of the great capacity of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.

Aminosalicylic Acids↗

Olsalazine-related diarrhoea: does rat intestine adapt in vivo?

Diarrhoea may occur in up to 10% of patients with ulcerative colitis treated with olsalazine, the azolinked dimer of 5-aminosalicylic acid. However, this symptom often disappears despite continued drug medication. To examine reversibility of and adaptation to olsalazine effects on intestinal absorption, rats were fed olsalazine (4 mg/100 g body weight/day) for 0 (controls), 12, 24, and 32 days. Jejunal, ileal, and colonic loops were perfused in situ with buffer or olsalazine (11.6 mM) in a pendular perfusion system. Water and electrolyte absorption was inhibited in all intestinal segments (p less than 0.001). In the proximal small intestine, however, sodium absorption was inhibited by 61%, whereas chloride and potassium absorptions were turned into net secretion. In contrast, in ileal and colonic segments sodium, chloride, and potassium absorptions were turned into a net secretion. All inhibitory effects were reversible within a short time. Intestinal absorption remained inhibitable compared with controls (p = not significant) after chronic administration of olsalazine even for 1 month. Jejunal monosaccharide absorption was not altered by acute olsalazine perfusion. In the ileum, glucose absorption was significantly inhibited, but the inhibitory capacity of acute olsalazine application decreased significantly (p less than 0.05) depending on duration of olsalazine pretreatment (51% (controls) versus 38% (32 days)). These results point to a complex, acute, but fully reversible effect of olsalazine on intestinal passive and chloride-coupled absorptive processes. Since a mucosal adaptation to these diarrheogenic effects does not occur, the resulting increase in fluid load on the diseased colon may be important in the pathogenesis of olsalazine-related diarrhoea.

Adaptation, Physiological↗

[Crohn disease in advanced age].

Crohn's disease of late onset (greater than 65 years) is rare condition. Typical features are the localisation in the distal gastrointestinal tract and the presence of associated diseases such as cardiovascular disorders and/or diverticulitis. In about 25% of the cases mild intestinal hemorrhage occurs. Delay in diagnosis is sometimes due to coexistent diverticulitis. Ischemia has been suggested to be responsible for the development of the histological changes which occur in Crohn's colitis. Therefore, we carried out a retrospective analysis of our patients treated between 1978-1988 to reevaluate the resected specimens. 10 patients (6.2% of all surgical patients with Crohn's disease) were at least 65 years old at the time of primary operation. In 5 cases hematochezia was one of the symptoms before operation, two patients presented with massive hemorrhage of the lower GI-tract. Granulomas were seen only in 5 patients, whereas in all specimens transmural inflammation was detected. In 8 out of 10 patients vascular lesions were seen, among those thickening of the intimal and medial layers, thrombosis or bleeding. Our findings support the thesis that ischemia might play a role in the pathogenesis of Crohn's disease of late onset.

Aged↗

[Changes in fecal composition, intestinal transit, bile acid metabolism and intestinal fermentation in long-term nutrition with high molecular weight formula diet].

Treatment with formula diets becomes more and more popular in many patients. The influence of those diets on gut functions is as yet poorly known. We studied in ten healthy volunteers the effects of a high molecular liquid diet. Despite of a sufficient energy supply the volunteers lost significantly weight which may be related to an acceleration of small bowel transit (60 +/- 9 min vs. 31 +/- 5 min; control vs. diet period). Whole gut transit did not change significantly (52 +/- 3 h vs. 56 +/- 3 h). The fecal excretion of bile acids decreased significantly (293 +/- 35 mg/24 h vs. 151 +/- 10 mg/24 h) which was particularly due to a decrease of primary bile acids. The serum bile acid concentrations behaved in a similar way (total bile acids: 3.19 +/- 0.66 mumol/l vs. 1.71 +/- 0.21 mumol/l). Neither the determination of unconjugated serum bile acids nor hydrogen breath testing did indicate increase of bacterial growth. In conclusion, chronic nutrition with formula diets causes significant changes of gut functions.

Adult↗

Effect of diets low and high in refined sugars on gut transit, bile acid metabolism, and bacterial fermentation.

Increasing consumption of refined sugar has been implicated in many gastrointestinal disorders on epidemiological grounds. Nine volunteers agreed to participate in a study comparing the effects of a diet containing 165 g refined sugar/day with a diet of only 60 g/day on gut transit, bile acid metabolism, and fermentative activity of the intestinal flora. The wet and dry weight, pH, and water content of the stools were similar on the two diets. On the high sugar diet mouth-to-anus transit time was significantly prolonged, despite a shortened mouth-to-caecum transit time. The faecal concentration of total bile acids and the faecal concentration of secondary bile acids increased significantly. Diet affected neither the serum bile acid pattern nor the concentration. Breath hydrogen tests showed significantly enhanced H2 production on the high sugar diet. We conclude that the quantity of refined sugar in the diet can significantly influence gut function and the composition of bowel contents.

Adult↗

Small intestinal transit, bacterial growth, and bowel habits in diabetes mellitus.

To investigate diabetic alterations of small intestinal transit and bacterial growth, we performed hydrogen breath tests (10 g lactulose via duodenal tube at the ligament of Treitz), bacterial cultures, and determinations of unconjugated serum bile acids in 19 patients with long-standing diabetes and 7 healthy controls. Asymptomatic diabetics had a late rise in breath hydrogen, indicating prolonged jejunal-cecal transit (86 +/- 10 min, p less than 0.05) as an early pathogenic event. Rise in breath hydrogen in symptomatic diabetics (constipation: 50 +/- 6 min; diarrhea: 41 +/- 11 min) was not significantly different from controls (57 +/- 8 min). Bacterial studies and increased unconjugated serum bile acids suggest bacterial overgrowth in some symptomatic diabetics. Bacterial overgrowth was associated more frequently (p less than 0.05) with a rise in breath hydrogen before 45 min or after 75 min. Changes in the hydrogen breath test, bacterial growth, or unconjugated serum bile acids did not correlate with gastrointestinal symptoms of diabetes.

Adult↗

[Risk factors for the development of fistulas in Crohn disease].

The pathophysiology of fistula formation in Crohn's disease is as yet poorly known. We, therefore, studied in 111 patients with Crohn's disease factors which may be associated with the development of fistulas. Male patients, patients with exclusively involved colon or extended disease of the colon and ileum as well as patients treated with prednisone demonstrated an increased relative risk to develop fistulas. In patients with ileitis alone and after laparatomy in combination with resection of the bowel the relative risk was less than 1. Furthermore, in 71% of the patients fistulas developed during active disease. In 65% the patients had underweight at the time of fistula formation. We conclude, that the localization of the disease, a factor which can not be influenced, as well as active disease and malnutrition, both factors which can be influenced, may be involved in the formation of fistulas in Crohn's disease.

Adolescent↗

[Exchange transfusion and (or) plasmapheresis: effective measures in severe tropical malaria?].

A 42-year-old man was admitted to hospital with, previously wrongly diagnosed, fulminant falciparum malaria, 14 days after a two-week trip to Kenya. He had a high fever and was jaundiced, with severe anaemia and thrombocytopenia. He was given quinine intravenously and pyrimethamine/sulfadoxine (Fansidar) by mouth. He developed acute renal failure and increasingly severe cerebral symptoms, at times coma. An exchange transfusion and several plasmaphereses were, therefore, performed. The cerebral symptoms quickly abated during the exchange transfusion, but renal function failed to improve. Because of continuing fever, mefloquin (Lariam) and doxy-cycline (Vibramycin) were also administered. After several dialysis periods the patient improved gradually and was discharged after three weeks in generally good condition with normal renal function.

Acute Disease↗

Crohn's disease is frequently complicated by giardiasis.

Giardiasis is a common infection, and many of its symptoms are similar to those of Crohn's disease. Despite a long discussion on the role of microbiologic agents in Crohn's disease, giardiasis has never been investigated. We studied giardiasis as assessed by the occurrence of cysts in 86 patients with Crohn's disease, in 82 patients with other gastrointestinal disease, and in 52 patients without gastrointestinal disease. In addition, in 20 patients with Crohn's disease the effects of metronidazole on giardiasis and disease activity were studied. Frequency of giardiasis was 61.6% in patients with Crohn's disease, 31.7% in patients with other gastrointestinal disease, and 5.8% in the control group (p less than 0.01). Stool frequency, disease activity, and humoral signs of inflammation in patients with Crohn's disease showed no relationship to giardiasis. All but two patients treated with metronidazole became free of cysts. Crohn's disease activity index decreased in 14 of 20 patients (p less than 0.05). In conclusion, giardiasis is a common finding in patients with Crohn's disease. Treatment of giardiasis can, in individual cases of Crohn's disease, result in a quick recovery from symptoms of high disease activity.

Adult↗

Accuracy of the whole body retention half-life of 75SeHCAT in the diagnosis of ileal dysfunction in patients with Crohn's disease.

The measurement of the whole body retention of the synthetic taurine conjugated trihydroxy bile acid 75SeHCAT has been suggested as a new clinical test for the function of the terminal ileum. Because of the frequent occurrence of ileal dysfunction in Crohn's disease (CD), the accuracy of the SeHCAT test was studied in 64 patients with CD in various clinical conditions. A positive test result (retention half-life less than 1.2 days) was seen in 48.4% of the patients with ileal involvement (true positive tests) whereas a negative test was seen in 33 of the 64 patients. In 21 of the 33 patients (63.6%) the test was false negative since ileal inflammation or resection was confirmed by radiology or endoscopy. In 14 of those 21 patients with false negative test results a stenosis of the intestinal lumen was diagnosed. At a specificity of 100% the sensitivity of the SeHCAT test was 59.6% and the efficiency was 67.2%. If patients with known stenosis were excluded sensitivity improved to 79.4%. In conclusion, calculation of the whole body retention half-life of SeHCAT does not seem to be a valuable screening test for the diagnosis of ileal dysfunction. In CD, a pathologic test result identifies ileal dysfunction with high accuracy.

Adult↗

Comparison of 75SeHCAT retention half-life and fecal content of individual bile acids in patients with chronic diarrheal disorders.

Measurement of the retention of 23-75Se-25-homotaurocholic acid (SeHCAT) has been suggested as a new test for ileal function. We investigated 31 patients with chronic diarrhea, 10 with ileal Crohn's disease and 21 with diarrhea but without ileal disease. The whole-body retention half-life of 1 mu Ci SeHCAT was determined and compared to the fecal content of total and individual bile acids. Patients with ileal disease had increased primary fecal bile acids (chenodeoxycholic acid: mean 6.95 mg/g dry weight, range 3.15-10.6 mg/g; cholic acid: mean 18.15 mg/g, range 10.3-33.9 mg/g) and a short SeHCAT retention (mean 11.9 h, range 2-24 h), whereas patients with intact ileum had normal fecal bile acids and a SeHCAT retention of 85.9 h (range 28-216 h). SeHCAT retention half-life differentiated well between patients with ileal disease and patients with normal ileum, thus indicating the SeHCAT test as a valid investigation method for detection of primary bile acid malabsorption in patients with chronic diarrhea and ileal dysfunction.

Adolescent↗