[Revised-OPS numbers 2004 and proposals for new DRGs in 2004 by the DGVS (German Society of Digestive and Metabolic Diseases)].
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Diagnosis-Related Groups↗
Biomedical subjects
W F Caspary
Publications and source records attributed to W F Caspary.
Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation.
BACKGROUND: Deoxycholic acid has long been attributed as a tumour promoter in the colon. It exerts its growth-related actions in a phorbol ester-like manner, by stimulating protein kinase C. The aim of this study was to investigate the effect of deoxycholic acid on proliferation and apoptosis in the colon, by exposing colon cancer cells to it in increasing concentrations. METHODS: Human colon cancer cells (Caco-2 and HT-29) were treated with deoxycholate or its two structural isomers, 3-beta-12-alpha-dihydroxy-5-beta-cholan-24-oic acid and 3-alpha-12-beta-dihydroxy-5-beta-cholan-24-oic acid. Proliferation was evaluated by cell counting, and apoptosis by estimating percentage cell survival and assessment of nuclear morphology. RESULTS: Within the concentration range of up to 20 microM, deoxycholate stimulated growth of both human colon cancer cell lines. Its growth-promoting effect was abolished after inhibition of protein kinase C. At concentrations above 100 microM, deoxycholate induced apoptosis in both cell lines. Epimers of deoxycholate were significantly less potent in stimulating growth. CONCLUSION: Low-dose deoxycholate stimulates colon cancer cell proliferation while > 100 micromol L(-1) of this secondary bile acid induces apoptosis in colon cancer cells. Deoxycholate might promote the likelihood of malignant transformation by increasing epithelial cell turnover in the colon.
Apoptosis↗
Long-term cisapride treatment improves diabetic gastroparesis but not glycaemic control.
BACKGROUND: In patients with diabetic gastroparesis, delayed food delivery to the intestine may become a major obstacle to post-prandial glycaemic control. AIM: To investigate whether cisapride accelerates gastric emptying in the long term or improves diabetes control in patients with diabetic gastroparesis. METHODS: Eighty-five patients with long-standing insulin-dependent diabetes mellitus (glycosylated haemoglobin (HbA1c) > 7.0%), dyspepsia and diabetic neuropathy were tested for impaired gastric emptying of solids by the 13C-octanoate breath test. Nineteen of these patients with severe diabetic gastroparesis (i.e. t1/2 > 170 min) were randomly treated with 10 mg cisapride t.d.s. (n=9) or placebo (n=10) for 12 months. Thereafter, the breath test, dyspeptic symptoms and HbA1c values were reassessed. RESULTS: Half emptying times in nine patients with diabetic gastroparesis were significantly shortened by cisapride (175 +/- 46 min vs. 227 +/- 40 min; P < 0.03). Half emptying times in the 10 patients taking placebo did not change (205 +/- 37 min vs. 211 +/- 36 min, P=0.54). Cisapride significantly reduced dyspepsia (score: 4.1 +/- 1.6 vs. 2.0 +/- 0.5, P=0.002). HbA1c values after 12 months of treatment were not different (cisapride: 7.7 +/- 0.4% vs. 7.6 +/- 0.9%, P=0.76; placebo: 7.5 +/- 0.6% vs. 7.6 +/- 1.5%, P=0.89). CONCLUSIONS: Prokinetic treatment with cisapride accelerates gastric emptying of solids and improves dyspeptic symptoms in diabetic gastroparesis. Glycaemic control, however, is not affected by cisapride.
Aged↗
[Doppler imaging of hepatic vessels - review].
Hepatic blood flow has been investigated using color Doppler ultrasonography in patients with liver disease, especially in patients with portal hypertension (e. g. liver cirrhosis, portal vein thrombosis, Budd-Chiari-syndrome). Duplex examination protocols, however, differ considerably because no standard technique has been established so far. Whereas there is an agreement about the angle of the ultrasound application (< 60 degrees ), neither the exact location nor the relevant examination parameters have been standardized. Based on a search of the relevant literature, published examination techniques and results were analyzed. These findings are to serve as a basis for a prospective multicenter study for the determination of standard values.
Blood Flow Velocity↗
The value of routinely performed ultrasonography in patients with Crohn disease.
BACKGROUND: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. METHODS: 255 consecutive patients with chronic CD (117 M, 138 F, mean age (+/-s) 38 +/- 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. RESULTS: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI > 150) and 17/46 (37%) as inactive disease (CDAI < or = 150). Of the 17 patients with a TMR and CDAI < or = 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. CONCLUSION: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.
Abdomen↗
Hydroxylamine-containing inhibitors of polyamine biosynthesis and impairment of colon cancer cell growth.
Polyamine synthesis (by the action of ornithine decarboxylase [ODC] and S-adenosylmethionine decarboxylase [SAMDC]) and polyamine content are high in colon cancer. In addition, colonic lumen is rich in polyamines synthesised by colonic microflora; for this reason, polyamine depletion in colon cancer may be a logical approach to impair growth of colon cancer cells. We evaluated highly specific and reportedly non-toxic hydroxylamine-containing inhibitors of ODC (1-aminooxy-3-aminopropane, APA) and SAMDC (S-(5'-deoxy-5'-adenosyl)-methylthioethyl-hydroxylamine, AMA) in human colon cancer cells (Caco-2 and HT-29) in culture. APA depleted ODC activity within 24 hr, more rapidly than did difluoromethylornithine. APA and AMA in combination (100 microM each) reduced ODC and SAMDC activities to undetectable levels within 24 hr and intracellular polyamines to 8-23% of control. The resulting growth arrest could be reversed only by twice as much spermidine as is physiologically present in the colonic lumen. In concentrations sufficient to deplete growth, APA and AMA were not toxic. Simultaneous treatment with APA, AMA, and 5-fluorouracil reduced colon cancer cell survival more potently than treatment with 5-fluorouracil alone. The hydroxylamine-containing ODC and SAMDC inhibitors APA and AMA are potent inhibitors of colon cancer cell proliferation and might be therapeutically promising in colon cancer.
Adenosylmethionine Decarboxylase↗
[Diagnosis of celiac disease and sprue. Recommendations of the German Society for Pathology Task Force on Gastroenterologic Pathology].
The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsy specimens. In recent years it has been seen that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes; at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density, and an increase in intraepithelial lymphocytes counts. Exact histological classification of the histological findings is required for diagnostic purposes and for monitoring of CD patients. This has become possible by using a modified Marsh classification. We present both the histological presentation of CD and the modified Marsh classification, and the most important differential diagnoses.
Biopsy↗
Permeability characteristics of polyamines across intestinal epithelium using the Caco-2 monolayer system: comparison between transepithelial flux and mitogen-stimulated uptake into epithelial cells.
The polyamines putrescine, spermidine, and spermine are present in foods in high amounts, and are used for cell growth throughout the body. Surprisingly little is known about the mechanisms of polyamine absorption in the gut. To elucidate the mechanisms, transepithelial transport of polyamines was studied in human enterocytelike Caco-2 cells, grown on permeable filter supports. Transport of all three polyamines across Caco-2 cell monolayers was linear; intraepithelial accumulation of polyamines was higher in confluent than in differentiated Caco-2 cells, but still negligible in comparison with the overall transport across the monolayers. Epidermal growth factor (EGF) enhanced polyamine accumulation in Caco-2 cells four-fold, and basolateral uptake was higher than apical uptake if the cells were stimulated to grow. The amounts of polyamines taken up by the cells were nevertheless negligible in comparison with the net polyamine flux across the monolayers. Basolateral excretion of polyamines was in the picomolar range, whereas their transepithelial transport, occurring presumably by passive diffusion through the paracellular pathway, contributed hundreds of micromoles of polyamines to the basolateral chamber. We conclude that transepithelial transport of polyamines occurs by passive diffusion, and that it is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.
Biological Transport↗
A new approach to evaluating intestinal acute graft-versus-host disease by transabdominal sonography and colour Doppler imaging.
An objective and non-invasive method to assess the extent, severity, course and prognosis of acute graft-versus-host disease (aGvHD) of the gastrointestinal tract would be of great importance. As high-resolution ultrasonography (HRU) and colour Doppler imaging (CDI) are used in inflammatory and ischaemic bowel diseases, we introduced these techniques to evaluate acute intestinal GvHD. In this study, 12 patients with suspected intestinal and/or severe cutaneous aGvHD were investigated by HRU and CDI. The structure and thickness of the bowel wall and the blood flow pattern in the superior mesenteric artery (SMA) as well as in the bowel wall were evaluated. All patients showed thickened bowel wall segments, especially in the ileocaecal region. Even in patients without any clinical signs of intestinal involvement (3/12), sonographic changes were observed. In six patients with severe diarrhoea, sonographic signs of secretory diarrhoea were observed. In 4/12 patients, an increased arterial blood flow in the bowel wall was demonstrated as a typical characteristic of an inflammatory bowel process. In contrast, in 4/12 patients, ischaemic bowel wall lesions with high-resistance flow pattern in the SMA were found. These patients did not respond to immunosuppressive therapy and died. In conclusion, HRU is a useful tool for detecting acute bowel GvHD even before clinical symptoms. Moreover, HRU and CDI can be applied to define the severity of aGvHD and to identify patients with a poor prognosis.
Acute Disease↗
The TCR-delta repertoire in normal human skin is restricted and distinct from the TCR-delta repertoire in the peripheral blood.
The skin and the intestinal mucosa form surfaces to external environments and share similarities in anatomic structure and immunologic defense. In healthy humans, intestinal gamma/delta T cells express a highly restricted gamma/delta T cell receptor repertoire whereas gamma/delta T cells of the skin were thought to express a polyclonal repertoire. Herein we report, using complementarity-determining region 3 size spectratyping and nucleotide sequencing of T cell receptor DV1 and DV2 rearrangements, that the human skin is also composed of clonally expanded gamma/delta T cells that are widely distributed. Identical complementarity-determining region 3 profiles and T cell receptor delta rearrangements were found in two separate skin samples that were obtained as far as 2-10 cm apart. Furthermore, analysis of peripheral blood mononuclear cells of these subjects clearly demonstrated that the skin harbors a unique population of gamma/delta T cells that is distinct from that in the peripheral blood. In addition comparable data were obtained irrespective of whether DNA or RNA was analyzed, indicating that the observed oligoclonality is not secondary to the expression of large amounts of mRNA from a few activated cells. Thus, gamma/delta T cells of the skin and the intestine both express an oligoclonal repertoire that enables them to respond to a variety of deleterious antigens without the need for diverse T cell receptors, possibly by recognition of stress-induced self-antigens or of conserved foreign antigens.
Clone Cells↗
[Diagnosis and therapy of ulcerative colitis--results of an evidence-based consensus conference of the German Society of Digestive and Metabolic Diseases].
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Colitis, Ulcerative↗
[Study Group of Gastroenterological Pathology of the German Society of Pathology. Recommendations for celiac disease/sprue diagnosis].
The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsies. In the past few years it has turned out that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes (IEL), at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density and an increase in IEL counts. For diagnostic purposes and for monitoring of CD patients an exact histological classification of the histological findings has to be given. This has become possible by using a modified Marsh classification. In the present paper the histological presentation of CD is presented as well as the modified Marsh classification and the most important differential diagnoses.
Biopsy↗
Topical application of nitrates onto the papilla of Vater: manometric and clinical results.
BACKGROUND AND STUDY AIMS: Systemic administration of nitrates inhibits motility of the sphincter of Oddi (SO) but is hampered by a decrease of the arterial blood pressure. We evaluate whether topical application of glyceril trinitrate (GTN) onto the papilla can facilitate cannulation of the common bile duct during routine endoscopic retrograde cholangiopancreatography (ERCP) and compare the effect of topical GTN with that of isosorbide dinitrate (ISDN) on SO motility. PATIENTS AND METHODS: A total of 80 patients undergoing routine ERCP for suspected biliary obstruction received topical application of either saline (n = 40) or 10 mg of GTN (n = 40) onto the papilla of Vater in a randomized, double-blind fashion. Thereafter, selective bile-duct cannulation was attempted with a 0.035" hydrophilic guide wire. In another trial, 16 biliary type III patients underwent endoscopic SO-manometry and received in a randomized fashion either 10 mg of GTN (n = 8) or 10 mg of ISDN (n = 8) which was infused topically onto the papilla via the manometric catheter. Thereafter, the manometric recording was continued for a further 5 minutes. RESULTS: A spontaneous opening of the papilla with concurrent transpapillary bile flow was observed in 24/40 patients after topical GTN, and in only 8/40 patients after topical saline (P < 0.01). However, neither the number of cannulation attempts nor the time until successful cannulation differed significantly between the groups. In addition, the pre-cut rate was nearly identical in the two groups. Topical GTN showed no significant influence on the mean arterial blood pressure. The SO-baseline pressure was significantly lowered by topical GTN (28.2+/-12.9 mm Hg before ISDN vs. 22.5+/-13.7 mmHg after P<0.01). The phasic SO motility was also strongly inhibited by both drugs. However, the effect of GTN completely wanes after 3 minutes, whereas ISDN inhibited SO motility for > 5 minutes in all patients. CONCLUSIONS: Both topically administered GTN and ISDN evoked a profound inhibition of SO motility, but the effect of ISDN was longer lasting than that of GTN. However, locally administered GTN did not facilitate selective bile-duct access during routine ERCP.
Administration, Topical↗
[Diagnosis related groups (DRG)--current significance in gastroenterology].
Prospective payment systems using the diagnosis related groups (DRG) payment mechanism have been introduced in many countries all over the world. In June 2000 the Australian Refined Diagnosis Related Groups System (AR-DRG) was chosen as the model which will be introduced in 2003 as the control instrument for the hospital dependent public health system in Germany. Background and possible implications for gastroenterologists and hepatologists are discussed.
Cost Control↗
[Duplex sonography of visceral arteries].
Mesenterial bloodflow has been investigated routinely using colour Doppler ultrasound especially in patients with bowel disease. Examination protocols, however, differ considerably, because no standard technique has been established so far. Whereas there is agreement about the angle of ultrasonic application (< 60 degrees ), neither the exact location nor the relevant examination parameters have been standardized. Based on a search of the relevant literature, examination techniques and results were analysed. These findings are to serve as a basis for a prospective multi-center study for the determination of standard values.
Humans↗
[Hypertransaminasaemia and impaired liver function in a patient with oligosymptomatic celiac disease].
Hypertransaminasaemia and impaired liver function in a patient with oligosymptomatic celiac disease. We describe the case of a 45-year-old man who was referred for evaluation of elevated aminotransferases. One year before referral the patient developed an ischemic stroke followed by a subdural hematoma three months later. In our outpatient clinic the patient presented with a malabsorption syndrome including diminished vitamin-K-dependent clotting factors. Serologic testing was positive for IgA antigliadin antibodies and IgA antiendomysial antibodies. Celiac disease was confirmed by an upper endoscopy examination and biopsies obtained from the distal duodenum. Histological examination showed villous atrophy, crypt hyperplasia and an increase in intraepithelial lymphocyte count consistent with celiac disease. After initiation of a gluten-free diet the malabsorption syndrome as well as liver dysfunction improved. Serum aminotransferase levels normalized within 6 months. The clinical course demonstrates involvement of the liver in patients with celiac disease.
Alanine Transaminase↗
Qualitative and quantitative clinical evaluation of the laser-assisted ratio analyser for detection of Helicobacter pylori infection by (13)C-urea breath tests.
OBJECTIVES: Currently, the (13)C-urea breath test is the reference method for non-invasive diagnosis of Helicobacter pylori infection and therapy control. Therefore, new technologies have been developed to measure the ratio of (13)CO(2)/(12)CO(2) in breath. The laser-assisted ratio analyser (LARA) device is based on optogalvanic effects of the stimulated CO(2) molecules. DESIGN: In this study, the LARA system is prospectively compared to conventional isotope ratio mass spectrometry (IRMS) analysis of (13)C-urea breath tests. METHODS: The (13)C-urea breath test was used to screen 103 patients for H. pylori infection. Breath samples were analysed by LARA and IRMS techniques. RESULTS: Seven breath tests could not be analysed by the LARA system, one by IRMS. Out of the remaining 95 breath tests, 13 were positive for H. pylori infection (13.7%). In reference to IRMS analysis (with a cut-off of > 5 delta per thousand at 30 min), LARA produced one false positive and one false negative breath test result giving a sensitivity of 92.3% and a specificity of 98.8%. The mean difference in delta over baseline values between IRMS and LARA measurements was 2.02 delta per thousand +/- 5.48 delta per thousand. CONCLUSION: LARA allows the reliable qualitative evaluation of 13C-urea breath tests, but the quantitative results differ from IRMS findings.
Adolescent↗
Deoxycholic acid stimulates migration in colon cancer cells.
BACKGROUND: Deoxycholic acid and other secondary bile acids have long been considered tumour promoters in the colon. However, their effect on cell migration, known to play an important role in colon carcinogenesis, has not been studied so far. OBJECTIVE: To investigate the possible effects of deoxycholic acid on colon cancer-cell migration in culture. METHODS: Human colon carcinoma cells (Caco-2) were seeded on basement membrane matrix. To evaluate replication-blocked cell migration, we wounded confluent monolayers of cells with a sterile scalpel, and inhibited cell replication with mitomycin C. Immediately after wounding, the cells were exposed to 0-100 micromol/l deoxycholic acid. Migration over 72 h was monitored using a phase contrast microscope. RESULTS: Replication-blocked migration was stimulated by deoxycholic acid in a dose-dependent manner, with the maximum effect at 20 micromol/l deoxycholic acid. Enhancement of migration rate was unaffected by immunoneutralization of transforming growth factor beta (a known migration-promoting peptide). However, specific inhibition of protein kinase C markedly inhibited deoxycholic acid-induced Caco-2 cell migration. CONCLUSION: In addition to its well-established role in the enhancement of proliferation, deoxycholic acid also stimulates colon cancer-cell migration along the basement membrane matrix. The mechanism of this stimulation is likely to involve protein kinase C. Deoxycholic acid-stimulated migration might additionally contribute to the tumour-promoting effects of secondary bile acids in the colon.
Caco-2 Cells↗