PubMed Health⌕ Search

Biomedical subjects

W Scheppach

Publications and source records attributed to W Scheppach.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Acute liver failure after therapeutic hyperthermia].

HISTORY AND ADMISSION FINDINGS: A 49-year-old women with malignant neoplasia had undergone whole body hyperthermia under sedation to a rectal temperature of 42.5 to 42.7 degrees C for about one hour. She failed to awaken afterwards and was admitted in a coma and transferred to the intensive care unit (ICU). There was slight improvement in consciousness in the following 30 hours. INVESTIGATIONS: Clinical and laboratory findings gave a constellation indicating acute liver and renal failure (transaminases ca. 1400 U/l, bilirubin 7.27 mg/dl, serum creatinine 3.15 mg/dl, Quick thromboplastin time under 3.5%, antithrombin III 57%, partial thromboplastin time 70.7 s, platelets 23,000/microliter). Other causes of acute liver failure, especially drug effects, and septicaemia were excluded. TREATMENT AND COURSE: Treatment consisted of infusion of fresh plasma, neomycin and lactulose by mouth, medication to prevent stress ulcer, and total parenteral nutrition which included branched-chain amino acids. The patient regained full consciousness on the regimen and on the 6th day after admission was transferred to an ordinary ward. She was discharged after a further 3 weeks, by which time results of laboratory tests were practically normal. CONCLUSION: The course of the illness as well as the exclusion of any other cause of the acute liver failure in a patients who, 7 days before whole-body hyperthermia had been induced, had shown no signs of liver disease, makes a causal relationship between the hyperthermia and the described abnormalities highly probable. These serious, not previously reported, side effects of whole-body hyperthermia treatment underline the importance of undertaking this form of treatment only if strictest specific criteria are met.

Anti-Bacterial Agents↗
PubMed1999

Anti-proliferative activity of protein kinase C in apical compartments of human colonic crypts: evidence for a less activated protein kinase C in small adenomas.

The protein-kinase-C (PKC) family of iso-enzymes regulates mitogenic signal transduction in colorectal-cell lines. Its function in human colonic mucosal proliferation is controversial. Our study investigated the role of PKC with regard to proliferation and changes of PKC iso-enzyme expression in colonic biopsies compared with small adenomas. In short-term tissue-culture experiments of colonic mucosal biopsies, we found reduced S-phase labeling in the 2 apical compartments of longitudinally sectioned crypts when PKC was activated by 200 nM of the phorbol ester TPA (n = 8). Thus, PKC inhibited growth of differentiated colonocytes which may influence cell homeostasis in colonic crypts. Furthermore, we have determined the expression of PKC alpha, -beta1, -beta2, -delta and -epsilon in colonic adenomas smaller than 1 cm in diameter of 18 patients and found a significant increase of PKC alpha in the cytosolic fraction and decreased membrane levels of PKC beta2 in adenomas compared to normal, neighboring mucosa while protein levels of PKC beta1, -delta and -epsilon were not altered. Moreover PKC delta but not PKC alpha mRNA expression was significantly lowered in adenoma tissue in 7 patients, as determined by ribonuclease-protection analysis. Changes in the regulation patterns of PKC isoforms suggest a decreased activation state of PKC even in small adenomas. This is compatible with an anti-proliferative function of PKC serving to protect mucosa from expanding mutated cells.

Adenoma↗
PubMed1999

Pattern of epithelial cell proliferation in colorectal mucosa of patients with large bowel adenoma or cancer: an ECP case-control study. European cancer prevention.

Proliferative abnormalities of the normal colorectal mucosa have been proposed as a possible marker of enhanced susceptibility to colorectal cancer. A case-control study was conducted to compare the cell kinetics of normal colon mucosa through the different steps of the adenoma-carcinoma sequence. The number and position of labelled epithelial nuclei after in vitro incubation of tritiated thymidine were compared in patients with large bowel cancer (n = 39), large adenoma >1 cm (n = 47), small adenoma (n = 30) and in controls (n = 135). The distribution of tertiles between cases and controls was analysed using odds ratio (OR), comparing the second tertile (OR2) and the third tertile (OR3) to the first one. There was no significant difference in the overall cell proliferation rate when comparing cancer, large adenoma and small adenoma groups to the control group. The ratio number of labelled cells in the upper 40% of the crypt/total number of labelled cells (4h index) was found to be significantly higher only when the cancer group was compared to the control group: OR2 = 5.87 (1.33-25.90), OR3 = 9.48 (2.07-43.38), P for trend = 0.002. The upward shift of the proliferative compartment in the normal mucosa of patients with large bowel cancer suggests that this abnormality is related to cancer risk.

Adenoma↗
PubMed1999

Faecal neutral sterols and bile acids in patients with adenomas and large bowel cancer: an ECP case-control study. European cancer prevention.

It is unclear whether neutral steroids and bile acids are involved in large bowel carcinogenesis. This study was conducted to compare the concentration of these faecal constituents at the different stages of the adenoma-carcinoma sequence. Neutral sterols and free bile acid concentrations were determined from stool samples collected form patients with large bowel cancer (n = 47), large adenoma > or = 1 cm (n = 42), small adenoma (n = 24), and controls (n = 104). The distribution of tertiles between cases and controls was analysed using odds ratio (OR), with 95% confidence interval (CI), comparing (two-sided tests) the second tertile (OR2) and the third tertile (OR3) to the first one. Persistence of primary bile acids appeared as a protective factor against cancer: (OR = 0.09, 95% CI 0.02-0.54). High values of cholesterol were associated with cancer risk (OR2 = 5.8, 95% CI 1.3-26.6; OR3 6.4, 95% CI 1.3-31.4). High values of cholesterol were more frequently observed in patients with large adenomas than in controls (OR2 = 8.5, 95% CI 1.9-37.5; OR3 = 4.3, 95% CI 0.9-20.9). Neutral sterols, cholesterol especially, may play a role in adenoma growth and adenoma transformation into carcinoma. Persistence of primary bile acids may afford protection.

Adenocarcinoma↗
PubMed1998

Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention.

Recent evidence suggests that resistant starch (RS) is the single most important substrate for bacterial carbohydrate fermentation in the human colon. During two 4-wk periods. 12 healthy volunteers consumed a controlled basal diet enriched with either amylomaize starch (55.2 +/- 3.5 g RS/d; high-RS diet) or available cornstarch (7.7 +/- 0.3 g RS/d; low-RS diet). Approximately 90% of the RS consumed disappeared during intestinal passage; increased fermentation was verified by elevated breath-hydrogen excretion. During the high-RS diet, fecal wet and dry weight increased 49% and 56%, respectively (P < or = 0.005), whereas stool water content did not change significantly. Fecal concentrations and daily excretion of short-chain fatty acids were not different in the two study periods. During the high-RS diet, bacterial beta-glucosidase activity decreased by 26% (P < or = 0.05). Fecal concentrations of total and secondary bile acids were significantly lower during the high-RS than during the low-RS period [a decrease of 30% (P < or = 0.05) and 32% (P < or = 0.01), respectively, in total and secondary bile acids] whereas concentrations of primary bile acids were unaffected by RS consumption. During the high-RS diet, fecal concentrations of total neutral sterols decreased by 30% (P < or = 0.005) and fecal concentrations of 4-cholesten-3-one decreased by 36% (P < or = 0.05). These data suggest that RS has potentially important effects on bacterial metabolism in the human colon that may be relevant for cancer prevention.

Adult↗
PubMed1998

Effect of dietary fish oil on fecal bile acid and neutral sterol excretion in healthy volunteers.

Diet-induced increases in fecal excretion of secondary bile acids (deoxy- and lithocholic acid) and certain neutral sterols (4-cholesten-3-one and 5a-cholestan-3-one) play a role in colon cancer development, whereas dietary fish oil (FO) has been implicated as a protective agent. In the present study the effects of FO and corn oil (CO) on these fecal parameters were investigated in 12 healthy volunteers consuming a low fat (30% of energy) controlled basal diet. After 4 weeks of FO supplementation (4.4 g omega-3 fatty acids/day), daily excretion of lithocholic acid showed a trend to lower values compared to CO consumption (p = 0.2), whereas other bile acids were not different during both study periods. Daily excretion of the putative colon carcinogen 4-cholesten-3-one was significantly lower in the FO compared to the CO period. This may be another biochemical mechanism by which FO exerts its protective effect on colon cancer development.

Adult↗
PubMed1998

Effects of sodium selenite on deoxycholic acid-induced hyperproliferation of human colonic mucosa in short-term culture.

It has been shown that in vitro incubation of human colonic biopsies with the secondary bile acid deoxycholic acid (DCA) leads to the hyperproliferation of colonic crypt cells with an expansion of the proliferative zone, which is regarded as a biomarker of increased cancer risk. Sodium selenite (SSE), on the other hand, has been implicated as a protective agent in experimental studies, but toxic effects were reported as well, depending on the dose of SSE. To elucidate the effects of SSE on human colonic mucosa, biopsies from endoscopically normal sigmoid colon tissue of 30 subjects were incubated with 5 microM DCA or a combination of 5 microM DCA and SSE in concentrations of 5, 10, 20, 50, 80, and 100 microM, respectively. Equimolar NaCl incubations served as a control. Proliferating cells were labeled by bromodeoxyuridine immunohistochemistry, and the labeling index (LI) was computed. In the experiments using 5, 10, and 20 microM SSE, the whole crypt LI was significantly lower after DCA + SSE incubation (0.136, 0.118, and 0.110, respectively) compared to that after incubation with DCA alone (0.172, 0.157, and 0.165, respectively; P < 0.01). The corresponding LIs during DCA + SSE incubation were comparable to the LIs obtained after NaCl incubation (average LI = 0.14). Contrary to this finding, severe cell damage was observed in the biopsies that were incubated with the higher SSE concentrations of 50 microM and above. The antiproliferative effects of SSE may indicate a possible protective effect in the prevention of human colon cancer development. However, the observed toxic effects of higher SSE concentrations strongly suggest the need for additional studies before general recommendations for the use of SSE in colon cancer prevention can be made.

Adult↗
PubMed1997

Innovations in topical therapy.

Topical therapy can be considered the standard treatment for distal ulcerative colitis. The group of drugs of first choice are the aminosalicylates which are effective in inducing remission in acute disease as well as in preventing relapse. Corticosteroids appear to be slightly less effective and have no proven benefit in maintenance therapy. With new topical steroids, such as budesonide, systemic effects can be minimized. The major role of corticosteroids is to complement aminosalicylates, when necessary. The new topical compounds appear to be especially valuable when there is a long-term requirement for corticosteroids. With the vast majority of patients obtaining remission with standard treatment, it is difficult to make the case for alternative substances. Short-chain fatty acids, local anaesthetics and bismuth compounds seem to be the most promising innovations in topical therapy although their equivalence or even superiority to mesalazine has not been established.

Aminosalicylic Acids↗
PubMed1997

Metabolic consequences of total colectomy.

Colectomy is performed for inflammatory bowel disease, familial polyposis syndrome and colorectal carcinoma. Surgical procedures are ileostomy with or without pouch, ileorectal anastomosis or ileal pouch-anal anastomosis. One of the major functions of the intact large intestine is to absorb water and electrolytes. After colectomy, as much as 400-1000 ml of nearly isotonic ileostomy fluid may be excreted, resulting in a chronic salt and water depletion. This is compensated for by an activation of the renin-angiotensin-aldosterone system. Reduced urine volumes may cause kidney stones. Both dehydration and renal sodium retention are probably less frequent in patients with ileal pouch-anal anastomosis. Absorption of nutrients in general is not impaired by colectomy. The large intestine salvages energy from malabsorbed organic matter through absorption of the short-chain fatty acids produced in bacterial fermentation. In ileostomy patients, fermentation is negligible, which leads to a significant loss of energy in the ileostomy fluid. Pouches are colonized by a bacterial flora similar to colonic bacteria. In these patients conservation of energy from malabsorbed substrate may be similar to healthy subjects. Resection of ileum and bacterial colonization may lead to malabsorption of vitamin B12 and bile acids. The latter may cause increased incidence of biliary cholesterol stones. Pouchitis is a frequent problem which may be caused by a deficiency of short-chain fatty acids and glutamine in the pouch contents. It is concluded that although the colon is not essential as a digestive organ in man, colectomy results in a number of metabolic changes. The ileal pouch-anal anastomosis may in part substitute for the functions of the large intestine.

Bile Acids and Salts↗
PubMed1997

Effects of short-chain fatty acids on the inflamed colonic mucosa.

Selected inflammatory conditions of the distal alimentary tract may respond to topical SCFA treatment. The rationale for using SCFA enemas is based on Roediger's (1980) observation that butyrate is the preferred fuel of colonocytes and that SCFA deficiency could lead, in the short term, to mucosal hypoplasia and, in the long term, to colitis. The absence of luminal nutrients is especially evident in the excluded rectum after complete diversion of the faecal stream. Harig et al. (1989) were the first to treat successfully diversion colitis with SCFA irrigation (acetate 60 mM, propionate 30 mM, n-butyrate 40 mM). However, subsequent studies could not reproduce the initial positive data. In distal ulcerative colitis an impaired mucosal oxidation of SCFAs has been described despite their luminal abundance. Pilot studies using either the SCFA mixture or butyrate monotherapy have yielded promising results. However, extended confirmatory studies with a larger sample size have not yet been performed. Preliminary data are also available for the use of SCFA in pouchitis and radiation proctitis. In summary, SCFA topical therapy seems to be a promising option in distinct forms of inflammatory bowel disease; however, the routine use of SCFAs cannot be recommended until their efficacy has been confirmed in larger trials.

Administration, Topical↗
PubMed1997

Histological changes in the colonic mucosa following irrigation with short-chain fatty acids.

OBJECTIVES: Short-chain fatty acids (SCFAs) derived from bacterial fermentation of complex carbohydrates are preferred luminal nutrients of the colonic mucosa. Starvation of colonocytes through lack or impaired metabolism of luminal SCFAs may be a cofactor in the pathogenesis of ulcerative colitis. DESIGN: A detailed histological evaluation of colonic biopsy specimens was performed in patients with active distal ulcerative colitis who were treated with rectal enemas containing a mixture of SCFAs, n-butyrate alone or saline placebo. Together with light microscopic parameters of mucosal inflammation, the pattern of crypt cell proliferation (proliferating cell nuclear antigen) and the mucosal activity of factor XIII were assessed. RESULTS: Butyrate reduced the density of polymorphonuclear leucocytes in the lamina propria (4 weeks: P = 0.063; 8 weeks: P = 0.091); other inflammatory parameters remained unchanged. Both butyrate and the SCFA mixture reduced significantly the number of proliferating cells in the upper 40% of crypts. Tissue factor XIII activity in active ulcerative colitis was significantly lower than in mucosa from normal colons; however, it was not affected by SCFA or butyrate irrigation. CONCLUSION: SCFAs and butyrate have a more marked effect on crypt cell proliferation than on parameters of inflammation in patients with active ulcerative colitis.

Adult↗
PubMed1997

Effects of calcium and deoxycholic acid on human colonic cell proliferation in vitro.

A high-fat and low-fiber diet is regarded as a major risk factor for colon cancer by increasing luminal contents of secondary bile acids. Calcium, on the other hand, has been implicated as a possible preventive agent in colon tumor development. In in vitro studies with human colonic epithelium, incubation with the secondary bile acid deoxycholic acid (DCA) induced hyperproliferation of colonic crypt cells which is regarded as a sign of preneoplastic transformation. In the present study the effects of calcium chloride (CaCl2) on DCA-induced hyperproliferation were tested at different stages of DCA-induced cell injury. Colonic biopsies from 36 patients (no tumors, polyps or IBD) were incubated with CaCl2 (1 and 10 mM) and 5 microM DCA which was added to the incubation medium either together with (experiment A), after (experiment B), or before CaCl2 (experiment C). Coincubation of the biopsies with DCA and 10 mM CaCl2 at the same time (experiment A) resulted in a significant reduction of whole crypt labeling index by 12% (p < 0.05), whereas in the other incubation experiments no significant growth-inhibitory effects could be demonstrated for CaCl2. These findings may best be explained by the formation of calcium-bound bile acid salts which lost most of their toxicity for the colonic cells.

Adult↗
PubMed1997

Bile acid metabolism by colonic bacteria in continuous culture: effects of starch and pH.

Secondary bile acids (BA) have been shown to be involved as a promoting agent in the adenoma-carcinoma sequence of colorectal cancer. In previous studies, fermentation of starch has been shown to inhibit the degradation of primary to secondary BA by the colonic microflora. This study was designed to investigate BA metabolism in continuous cultures of mixed fecal bacteria to get further insights into the mechanisms of this inhibition. Fermentation vessels were fed with media containing cholic (0.6 g/l) and chenodeoxycholic acid (0.4 g/l). Cultures were either starch-free or enriched with starch (10 g/l). pH was controlled and adjusted to 7.0 or 6.0. Total culture duration was 28 days and concentrations of BA, short-chain fatty acids (SCFA), and starch were measured periodically. At pH 6, significantly more primary BA remained in the media and less secondary BA were produced. Total BA concentrations were lower at pH7. SCFA concentrations were higher in the vessels supplemented with starch. Starch was completely fermented and not present in significant amounts in any fermentation vial after the first week. These data indicate that bacterial breakdown of primary to secondary BA is inhibited when starch is simultaneously fermented. This effect can be explained by the reduction of pH resulting from SCFA production. Considering these findings, resistant starch which escapes assimilation in the small bowel may be a protective factor against colorectal cancer.

Acetates↗
PubMed1997

[Massive hemorrhage from jejunal varices].

A 21-year-old male presented with melaena and signs of hemorrhagic shock. In the following days several episodes of hematochezia occurred requiring the transfusion of nine units of blood. Findings at gastroscopy were normal, at colonoscopy fresh blood was noted from the ileocecal valve. Angiography performed in a bleeding-free interval showed no abnormalities. At repeat angiography, bleeding (from a left lateral branch of the superior mesenteric artery) was provoked by instillation of plasminogen activator. Subsequently, hemostasis was achieved by superselective embolization using coils. At operation one week later, a polypoid tumor of 1 cm diameter was resected along with a 4 cm segment of adjacent jejunum (40 cm distal to the ligament of Treitz). Histologically, a jejunal varix with superficial ulceration was diagnosed.

Adult↗
PubMed1996

[Pneumatosis cystoides intestinalis].

HISTORY AND CLINICAL FINDINGS: A 56-year-old man was admitted to hospital for investigation of meteorism and severe flatulence for 10 months and irregular stools. He had no previous illness. On examination his abdomen was quite distended, with very active but low-pitched peristalsis. INVESTIGATION: Plain x-ray of the abdomen showed multiple round translucencies along the wall of the left hemicolon. Coloscopy revealed multiple firm-walled cysts in the descending and sigmoid colon which contained H2 in high concentration. Histologically there was slight inflammatory infiltration of the submucosa as well as some slit-like hollow spaces, pointing to the diagnosis of pneumatosis cystoides intestinalis. The H2 breath test, done to confirm the diagnosis, indicated increased H2-concentration, both on fasting and after lactulose. TREATMENT AND COURSE: A diet low in flatulence-producing carbohydrates satisfactorily controlled the symptoms, but the local findings remained unchanged over 4 years. CONCLUSION: Pneumatosis cystoides intestinalis should be included in the differential diagnosis of meteorism and flatulence. Diet can satisfactorily control the symptoms of this rare disease.

Breath Tests↗