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The performance of endoscopic retrograde cholangiopancreaticography (ERCP) in patients with post-surgically altered anatomy is technically ambitious. Our study aimed at comparing a cohort of patients having successfully undergone single-balloon enteroscopy (SBE)-assisted ERCP to those in whom SBE-ERCP failed.This trial is a prospective single center cohort study. Participants included 30 patients (median age 69.5 years, range 20-86 years) with previous pancreaticobiliary surgery. First, a conventional ERCP approach was attempted in all patients. Additionally, those patients in whom prior conventional ERCP had failed underwent SBE-ERCP (n = 26). Patients' baseline characteristics were retrieved and patient cohorts with and without successful SBE-ERCPs were compared and analyzed. Statistical analysis was applied. Univariate analysis was performed to detect possible risk factors of SBE-ERCP failure.The overall success rate of SBE-ERCP, including two patients with percutaneous transhepatic cholangiography- assisted rendezvous technique was 65.4% (17/26). Patients with malignant obstructive cholestasis had a significantly higher failure rate compared to those with benign strictures (84.2% vs. 14.2%, p0.001).SBE-ERCP is a promising tool for diagnostic and therapeutic procedures in the pancreaticobiliary system of selected, previously operated patients with failure of conventional ERCP. However, higher failure rates in malignant biliary obstruction should be taken into account.

High calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini, and whether dietary or intraperitoneal magnesium administration affects the onset and course of experimental pancreatitis.Pancreatic acini were incubated with up to 10 mM magnesium; [Ca(2+)](i) (fura-2AM) and intracellular protease activation (fluorogenic substrates) were determined over 60 min. Wistar rats received chow either supplemented or depleted for magnesium (300 ppm to 30 000 ppm) over two weeks before pancreatitis induction (intravenous caerulein 10 µg/kg/h/4 h); controls received 1 µg/kg/h caerulein or saline. C57BL6/J mice received four intraperitoneal doses of magnesium (NaCl, Mg(2+) 55 192 or 384 mg/kg bodyweight) over 72 h, then pancreatitis was induced by up to eight hourly supramaximal caerulein applications. Pancreatic enzyme activities, protease activation, morphological changes and the immune response were investigated.Increasing extracellular Mg(2+) concentration significantly reduced [Ca(2+)](i) peaks and frequency of [Ca(2+)](i) oscillations as well as intracellular trypsin and elastase activity. Magnesium administration reduced pancreatic enzyme activities, oedema, tissue necrosis and inflammation and somewhat increased Foxp3-positiv T-cells during experimental pancreatitis. Protease activation was found in animals fed magnesium-deficient chow-even with low caerulein concentrations that normally cause no damage.Magnesium supplementation significantly reduces premature protease activation and the severity of pancreatitis, and antagonises pathological [Ca(2+)](i) signals. Nutritional magnesium deficiency increases the susceptibility of the pancreas towards pathological stimuli. These data have prompted two clinical trials on the use of magnesium in patients at risk for pancreatitis.

Bile duct stones that cannot be removed endoscopically are still a challenge in interventional gastroenterology. Extracorporeal shockwave lithotripsy (ESWL) with subsequent endoscopic extraction of residual fragments is an established treatment option if other endoscopic means are not successful. Our study aimed to investigate the efficacy and safety of ESWL for clearance of refractory bile duct stones.A total of 73 consecutive patients treated for refractory choledocholithiasis with ESWL were retrospectively analyzed. Success and complication rates were calculated.Complete stone clearance was achieved in 66 cases (90%). Patients with complete clearance had a significantly lower body mass index or BMI (25.55 ± 5.01 kg/m² vs. 31.60 ± 6.26 kg/m², p = 0.035) and needed less ESWL treatments (3.61 ± 1.87 vs. 5.00 ± 1.63, p = 0.048). A relevant drop of hemoglobin occurred significantly more often in the group with partial clearance (43% vs. 6%, p = 0.005).ESWL proves to be an excellent clearing approach to refractory bile duct stones with high success rates. However, obesity is one risk factor for ESWL failure and higher procedural hazard.

Endoscopic ultrasound (EUS) is considered a gold standard in the initial staging of esophageal cancer. There is an ongoing debate whether EUS is useful for tumor staging after neoadjuvant chemotherapy (NAC). Ninety-five patients with esophageal cancer were retrospectively analyzed. In 45 patients, EUS was performed prior to and after NAC, while 50 patients had no induction therapy. Histological correlation through surgery was available. uT/uN classifications were compared to pT/pN stages. Statistical analysis included calculation of sensitivity, specificity, and accuracy rates. Agreement between endosonography and T staging was assessed with Cohen's kappa statistics. For those patients with prior NAC, overall accuracy of yuT and yuN classification was 29 and 62%, respectively. Sensitivity, specificity, and accuracy rates for local tumor extension after NAC were as follows (%): T1: –/97/84, T2: 13/76/53, T3:86/29/46, T4:20/100/91, T1/2: 27/83/56, T3/4: 89/31/56. Cohen's kappa indicated poor agreement (kappa = 0.129) between yuT classification and ypT stage. Relative to positive lymph node detection, sensitivity and specificity were 100 and 6%, respectively (kappa = 0.06). T stage was overstaged in 23 (51%) and understaged in seven (16%) patients. EUS is an unreliable tool for staging esophageal cancer after NAC. Overstaging of the T stage is common after NAC.

BACKGROUND AND STUDY AIMS: Acute pancreatitis is considered a relevant major complication following endoscopic retrograde cholangiopancreatography (ERCP); according to literature data, the incidence varies between 1.5 % and 17 %. In the present study, we aimed to identify potentially new, hitherto unknown risk factors for post-ERCP pancreatitis. PATIENTS AND METHODS: A total of 2364 ERCP procedures performed in 1275 patients during the years 2004 - 2008 were included in the study. Post-ERCP pancreatitis was defined as acute abdominal pain within 48 hours following ERCP with at least 3-fold elevated levels of serum lipase and a requirement for analgesic drugs for at least 24 hours. The severity of the pancreatitis was determined using the Imrie score. RESULTS: In our cohort study a total of 54 different patients (2.3 %) developed post-ERCP pancreatitis. In 50 of these patients (92.6 %) the pancreatitis was mild; in 54 (7.4 %) it was severe. Patients with post-ERCP pancreatitis had highly significantly lower bilirubin levels than patients who did not have post-ERCP pancreatitis ( P < 0.001). Length of hospital stay, duration of analgesics, and need for analgesic drugs were significantly higher in patients suffering from severe pancreatitis ( P ≤ 0.01). In multivariate analysis, among other, already well-described risk factors we identified intraductal ultrasonography as another risk factor for post-ERCP pancreatitis, with a hazard ratio of 2.41 ( P = 0.004). CONCLUSIONS: According to our retrospective data, intraductal ultrasonography seems to be another independent risk factor for developing post-ERCP pancreatitis, which needs to be further elucidated in prospective studies.

Background and study aims Double-balloon enteroscopy (DBE) is the first choice endoscopic technique for small-bowel visualization. However, preparation and handling of the double-balloon enteroscope is complex. Recently, a single-balloon enteroscopy (SBE) system has been introduced as being a simplified, less-complex balloon-assisted enteroscopy system. Patients and methods This study was a randomized international multicenter trial comparing two balloon-assisted enteroscopy systems: DBE vs. SBE. Consecutive patients referred for balloon-assisted enteroscopy were randomized to either DBE or SBE. Patients were blinded with regard to the type of instrument used. The primary study outcome was oral insertion depth. Secondary outcomes included complete small-bowel visualization, anal insertion depth, patient discomfort, and adverse events. Patient discomfort during and after the procedure was scored using a visual analog scale. Results A total of 130 patients were included over 12 months: 65 with DBE and 65 with the SBE technique. Patient and procedure characteristics were comparable between the two groups. Mean oral intubation depth was 253 cm with DBE and 258 cm with SBE, showing noninferiority of SBE vs. DBE. Complete visualization of the small bowel was achieved in 18 % and 11 % of procedures in the DBE and SBE groups, respectively. Mean anal intubation depth was 107 cm in the DBE group and 118 cm in the SBE group. Diagnostic yield and mean pain scores during and after the procedures were similar in the two groups. No adverse events were observed during or after the examinations. Conclusions This head-to-head comparison study shows that DBE and SBE have a comparable performance and diagnostic yield for evaluation of the small bowel.

Cronkhite-Canada syndrome (CCS) is a rare non-familial disorder with multiple gastrointestinal polyps and ectodermal changes. Adenomatous and carcinomatous changes have been reported. Video capsule endoscopy is a useful non-invasive tool to reveal polypoid lesions of the gastrointestinal tract suspicious for malignancy. We report a case of a patient with CCS with excessively elongated intestinal villi resembling dense sea grass under water as well as multiple polyps of the intestinal mucosa revealed by video capsule endoscopy. This report presents for the first time small bowel video sequences of CCS qualifying video capsule endoscopy for screening purposes and early detection of malignancy.

Hepatocellular carcinoma (HCC) is the most common tumor in cirrhotic patients with a median survival of only 8-10 months if untreated. Supraselective transarterial chemoembolization (STACE) is supposed to be a well-established method for treating HCC patients. In the present study, we evaluated the effect of STACE on post-transplant survival in patients with HCC.The charts of 53 HCC patients were retrospectively analyzed. Twenty-seven patients had STACE as a bridging therapy while 26 patients were scheduled for liver transplantation (LTX) without prior STACE therapy. A total of 53% of the patients who underwent LTX preoperatively fulfilled the Milan criteria, while 70.6% fulfilled the expanded University of California, San Francisco (UCSF) transplant criteria. Primary endpoint was the post-transplant survival. Statistical analysis included Kaplan-Meier-method, log rank, and chi square tests.Between the LTX groups (STACE vs. non-STACE), there was no significant difference in terms of age, Child classification, Okuda stage, co-morbidities, underlying disease, and post-transplant survival (p0.05). Independent of prior STACE, however, disease-free survival after LTX was highly significantly prolonged if LTX was performed within 3 months after initial diagnosis of HCC (p0.01) or if patients met the expanded transplant UCSF criteria (p = 0.02). Post-transplant survival did not depend on tumor size.We conclude that STACE performed prior to LTX does not secure any post-transplant survival benefit, while early LTX, i.e. within 3 months after HCC diagnosis, does improve survival regardless of whether STACE was performed or not. Additionally, fulfillment of the expanded transplant UCSF criteria leads to a prolonged post-transplant survival.

Double balloon enteroscopy (DBE) has evolved as one of the most innovative and fast spreading endoscopic procedures in the last decade. With increasing experience of performing endoscopic procedures in the mid gut outside the operating room it is necessary to investigate the effectiveness of DBE regarding therapeutic consequences, long-term efficacy as well as safety.To address this we retrospectively analyzed all DBE performed over a period of 2 years at our department. Furthermore, in order to evaluate long-term effectiveness of DBE procedures we performed a follow-up analysis on all patients, whose DBE procedure was at least 6 months ago. In addition, 100 consecutive patients who underwent DBE were questioned regarding procedure associated complaints using a standardized questionnaire.Retrospective analysis of all DBE procedures performed in our department before November 2006 (n = 545) revealed an overall diagnostic yield of 39.7% and a therapeutic yield of 31.1%. The overall number of major complications accounted to 0.9%. Follow-up analysis revealed a long-term effect of endoscopic interventions in more than 50%, while in those patients with an initially negative DBE long-term follow-up only revealed symptom explaining findings in 17% with the majority of the other patients being asymptomatic during follow-up. Regarding patient related complaints the prospective analysis showed that DBE procedures in general are well tolerated with the most common complaint being meteorism.DBE showed to be a relatively safe and well tolerated procedure. However, more sensitive algorithms are needed to enhance the therapeutic results.

The purpose of this study was to characterize the action of exogenous PYY, an ileocolonic peptide released by fatty meal, and that released by Heal perfusion with oleate on intestinal and gallbladder motility patterns and the posssible role of the adrenergic pathway in this action. Dogs were equipped with chronic duodenal electrodes for recording myoelectric activity and with a cannula in the gallbladder fundus for measuring the gallbladders intraluminal pressure and volume and calculating its motility index (MI) and emptying rate. After intravenous infusion of PYY, there was a dose-dependent prolongation of the migrating motor complex (MMC) interval and almost complete abolition of the contractions and emptying of gallbladder during the duodenal activity front. After meat feeding or during intravenous infusion of cerulein, 50 pmol/(kg · h), the MMC was interrupted and replaced by irregular spike activity, accompanied by a marked increase in the gallbladder MI and about 80% to 90% reduction of its volume. PYY, 200 pmol/(kg · h), reduced significantly the meal- or cerulein-induced duodenal spike activity but failed to affect the MI and volume of the gallbladder. Similar changes in fasted and fed patterns of motility were observed after Heal oleate (16 mM/h), producing plasma PYY levels in a range similar to that observed after infusion of exogenous PYY. The inhibitory effects of PYY or Heal fat on intestinal myoelectric activity were reversed in part by α-adrenergic blockade (phentolamine). We conclude that exogenous PYY or endogenous hormone released by Heal oleate inhibits the interdigestive and postprandial motility pattern of the small bowel but does not affect gallbladder motility, and that the inhibition of intestinal motility involves, at least in part, the adrenergic pathway.

Manometric investigations of patients with irritable colon show an undisturbed cyclic course of interdigestive motility studies of the rectosigmoid in patients with irritable colon show a spectrum of variable frequency of slow membrane potential changes with predominance of a frequency of 3/min. In addition, after a 1000 calorie test meal, patients with irritable colon showed a significantly prolonged increase of motility. As functional disturbances of irritable colon are mainly diagnosed by exclusion of organic changes, further development and rational use of colonic myoelectric methods promises future possibilities for objective diagnosis and control of treatment.

Endoscopic examination of the colon was performed in 405 patients (125 without, 217 with benign, and 63 with malignant colorectal diseases), and the serum levels of the tumour-associated antigens CEA and CA 19-9 were determined. On comparing both markers, the specificity of CA 19-9 (96% correctly normal values) was found to be higher in benign colorectal diseases than that of CEA (92% with a cut-off limit of 5 ng/ml for CEA). On the other hand, the sensitivity of CA 19-9 in colorectal carcinomas was only about 25% and thus much lower than that of CEA (52% correctly pathological values). The sensitivity of both markers was particularly low in the initial stages of carcinoma (in Dukes A: CEA 20%, CA 19-9 0%). If the cut-off limit for CEA was raised to 10 ng/ml, the specificity was increased to 99%, whereas the sensitivity was markedly reduced to 25%. The diagnostic accuracy of CEA in colorectal carcinomas was not surpassed by CA 19-9. There was no obvious advantage in simultaneous determination of CEA and CA 19-9.

Tumour-associated antigens CA 50 and CA 19-9 were determined in serum of 208 patients. Specificity of both neo-antigens as tumour markers was equally good, at 100% and 95%, in patients without malignancy or gastrointestinal disease, respectively, using an upper limit of normal of 17 U/ml for CA 50 and 37 U/ml for CA 19-9. Benign diseases of the upper gastrointestinal tract, such as pancreatitis, cholestasis or cirrhosis of the liver, reduce the specificity of CA 50 more than of CA 19-9. For example, specificity of CA 50 is only 33% for choledocholithiasis, but 74% with CA 19-9. The sensitivity of both closely related sialogangliosides in malignancies of the upper GI tract is similar, with the usual normal limits: in pancreas carcinoma 77% for CA 50, 81% for CA 19-9; in biliary tract carcinoma 80% for CA 50, 90% for CA 19-9; in gastric carcinoma 40% for CA 50, 50% for CA 19-9. But if one equalizes the upper limits of normal for both markers to a common 95% specificity, the tumour-indicating sensitivity of CA 19-9 clearly surpasses that of CA 50. Malignant tumours not recognized by increased levels of CA 19-9 also escape serological diagnosis with CA 50.

Tumour-associated antigen CA 19-9 was determined in serum from 166 patients (30 without gastro-intestinal disease, 32 with liver cirrhosis, 9 with choledocholithiasis, 65 with acute or chronic pancreatitis and 30 with malignant tumors in the region of pancreas and bile passages). The specificity of CA-19-9 as tumour marker was 97% in patients without gastro-intestinal disease, but in those with liver cirrhosis or choledocholithiasis it was only 56% and 44%, respectively. In particular, cholestasis reduced specificity. Acute pancreatitis in its initial attack gave false-positive CA 19-9 values in 27% of cases, repeated bouts in chronic recurrent pancreatitis in as many as 50%. In chronic pancreatitis the specificity was 90%. Malignant tumours of pancreas and bile ducts were diagnosed with a sensitivity of 80%. Determination of CA 19-9 in pure pancreatic secretion failed to differentiate between the control group (30), chronic pancreatitis (21) and carcinoma of the pancreas (22).

In a randomized, endoscopically controlled double-blind trial the effectiveness of a single oral, morning dose of 40 mg omeprazole was compared with a twice daily oral dose of 150 mg ranitidine given to 334 ambulatory patients with duodenal ulcers. Under omeprazole 105 of 146 duodenal ulcers were demonstrated to have healed within 14 days (72%), compared with 95 of 160 (59%) on ranitidine. The difference is statistically significant (P = 0.0121). After 14 days smaller ulcers healed more quickly than large ones, regardless of the drug used: 80 of 110 with diameter 3-5 mm (73%); 48 of 90 with diameter more than 8 mm (53%). Smoking delayed healing [healing rate among non-smokers, 87 of 117 (74%); among smokers, 113 of 189 (60%)]. Healing rates among smokers receiving omeprazole and non-smokers receiving ranitidine were nearly identical. After 4 weeks, at 96 and 92% respectively, there was no difference in regard to healing rate. Both drugs had a similar influence on the symptoms. Thus, for the first time it has been demonstrated that omeprazole is superior to ranitidine after 14-day treatment of duodenal ulcer.

The effectiveness of omeprazole (20 mg orally each morning) or ranitidine (150 mg orally twice daily) in the treatment of gastric ulcer was compared in 184 out-patient in a randomized, endoscopically controlled multi-centre double-blind ("double dummy") trial. Healing rates with omeprazole after two, four and eight weeks were 43, 81 and 95%, respectively, those with ranitidine were 45, 80 and 90%, a statistically not significant difference. Independently of medication, small ulcers (less than 8 mm diameter) healed more quickly than larger ones. Ulcers in the body of the stomach responded poorest to both drugs. Smoking had no statistically significant effect on healing rate. Omeprazole and ranitidine had similarly favourable effects on symptoms. Neither side effects nor changes in biochemical parameters could be ascribed to omeprazole. Both drugs had equivalent effects on the healing of gastric ulcers in the stated dosages.

Background: Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (α-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide α-MSH(11–13) (KPV) and its mode of action in 2 models of intestinal inflammation. Methods: The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RBhi transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity. Results: In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis. Conclusions: The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD. (Inflamm Bowel Dis 2007)

Members of the interleukin (IL)-12 family constitute subunits of IL-12, -23, and -27. These ILs represent pivotal mediators in the regulation of cell-mediated immune responses and in animal models of human inflammatory bowel disease. Recent work has suggested that intestinal endothelial cells might serve as a second line of defense in bacterial sensing of invading pathogens. The purpose of this study was to examine the production of IL-12 family members in intestinal endothelial cells (HIMEC). HIMEC were stimulated with proinflammatory agents (TNF-alpha, IFN-gamma, IL-1beta) and microbial antigens [LPS, lipoteichoic acid, peptidoglycan, CpG-DNA, flagellin, poly(I:C)]. Expression of IL-12 family members and of Toll-like receptor (TLR)3 in HIMEC was assessed by real-time RT-PCR, immunostaining, flow cytometry, and immunoblot analysis. HIMEC display an induction of Epstein-Barr virus-induced gene 3 (EBI3), IL-12p35, and IL-23p19, whereas no expression of IL-12p40 and IL-27p28 was detectable. The strongest induction was induced by proinflammatory factors known to utilize the NF-kappaB pathway, and expression of EBI3 and IL-23p19 was diminished by an NF-kappaB inhibitor. HIMEC display regulated expression of TLR3. Adhesion and transmigration assays showed proinflammatory responses after HIMEC stimulation. HIMEC are capable of producing IL-12 family members as a response to microbial stimuli. The TLR3 agonist, poly(I:C), was shown to enhance leukocyte adhesion in vitro in HIMEC. Our data suggest that the intestinal microvasculature is responsive to ligands of TLR3 expressed on intestinal endothelial cells, thereby adding to the regulation of adaptive immunity and leukocyte recruitment.

Background: Exposure to bacterial antigens and other environmental factors in combination with a genetic susceptibility have been implicated in the etiology of inflammatory bowel disease (IBD). As certain perinatal circumstances, e.g., delivery by cesarean section, predispose to a different intestinal colonizations the aim of this analysis was to define a potential influence on the development of IBD in later life. Methods: In a case-control study design, birth data were recorded from patients diagnosed with IBD (Crohn's disease [CD], n = 1096; ulcerative colitis [UC], n = 763) and healthy controls ([C], n = 878) by a self-administered questionnaire. Results: Preterm birth (CD: odds ratio [OR] 1.5 [95% confidence interval 1.1–2.0], UC: OR 1.3 [0.9–1.9]), mother's disease during pregnancy (CD: OR 1.9 [1.3–2.9], UC: OR 1.6 [1.0–2.4]), and disease in the first year of life (CD: OR 2.2 [1.6–2.9], UC: OR 1.7 [1.3–2.3]) are associated with the development of IBD in later life. No significant associations were found for the mode of delivery and breast feeding. In a logistic regression analysis female sex, smoking, appendectomy, maternal IBD, and disease in the first year of life were independently associated with CD. Female sex, appendectomy, and disease in the first year of life were independently associated with UC. Conclusions: Preterm birth and other perinatal circumstances are associated with the development of IBD, of which disease in the first year of life is an independent risk factor in multivariate analysis. (Inflamm Bowel Dis 2007)

In the present in-vitro study we investigated the possible role of the calmodulin-antagonistic drugs loperamide and calmidazolium in the regulation of transepithelial Ca2+ transport of human duodenum. Brush border membrane vesicles and basolateral membrane vesicles were simultaneously prepared from surgically resected pieces of morphologically intact human duodenum with a modified Percoll-gradient centrifugation method. Brush border and basolateral membrane vesicles were characterized using enzyme marker analysis and electron microscopy: alkaline phosphatase was enriched 20-fold in brush border membrane vesicles, whereas [Na+ + K+]-stimulated adenosine triphosphatase was enriched 15-fold in basolateral membrane vesicles. Calmodulin activity was determined by a specific radioimmunoassay after solubilizing brush border and basolateral membrane vesicles in 1% Triton X-100. In basolateral membrane vesicles, we found no calmodulin activity. In brush border membrane vesicles calmodulin activity was impaired by 50% after pre-incubation with loperamide or calmidazolium. We measured calcium, sodium, D-glucose and D-mannitol uptake with a rapid filtration technique. Before the transport experiments, brush border and basolateral membrane vesicles were pre-incubated with 5 microM loperamide or 5 microM calmidazolium for 60 min at 5 degrees C. In drug-pretreated, brush border membrane vesicles calcium uptake was significantly reduced after 1 min incubation (-25% +/- 5%, P less than 0.05); this effect was completely reversed in the presence of 5 microM calmodulin. In basolateral membrane vesicles, we found two Ca2+ transport systems: (1) Na+/Ca2+ exchange and (2) ATP-dependent Ca2+ transport. In basolateral membrane vesicles loperamide had no effect. Calmidazolium had no effect on Na+/Ca2+ exchange, but significantly inhibited ATP-dependent Ca2+ transport. This effect could not be reversed by calmodulin.

In den letzten Jahrzehnten ist den bildgebenden Verfahren mit zunehmender Inzidenz von kolorektalen Karzinomen eine immer wichtigere Rolle zugekommen, da insbesondere ein fruhzeitiger Nachweis maligner Prozesse entscheidend fur die Prognose sein kann. In einer prospektiven Studie wurde die virtuelle Kolographie mittels Mehrzeilen-CT (MSCT) mit der konventionellen Koloskopie bei Nachweis und Differenzierung von kolorektalen Lasionen verglichen. 78 Patienten (36 Frauen, 42 Manner, Durchschnittsalter 60,7 Jahre) aus einem Mischkollektiv wurden prospektiv an einem MSCT (Somatom Volume Zoom, Siemens, Forchheim) untersucht. Die Bilddaten wurden durch zwei geblindete Radiologen in Volume-Rendering-Technik ausgewertet. Als Goldstandard erfolgte die konventionelle Koloskopie in etablierter Technik im Anschluss an die MSCT-Kolographie. Bei der Auswertung ergab sich fur die MSCT-Kolographie eine Sensitivitat von 80% und eine Spezifitat von 86% fur alle polypoiden Lasionen unabhangig von ihrer Grose. In der Subgruppenanalyse wurden 7/7 Polypen groser als 10mm (100%), 13/16 Polypen zwischen 6 und 9mm (81%) und 19/26 Polypen kleiner oder gleich 5mm (73%) detektiert. Insgesamt wurden mit der MSCT-Kolographie 14 falsch positive Polypen nachgewiesen. Bei der Kostenanalyse zeigte sich, dass die MSCT-Kolographie mit · 335 aktuell noch zu teuer ist; erst ab Kosten von etwa · 160 ware die MSCT-Kolographie aus gesundheitsokonomischer Sicht sinnvoll. Die MSCT-Kolographie erlaubt eine sichere Detektion von Polypen uber 10mm Durchmesser; kleinere Befunde werden mit einer hoheren Sensitivitat nachgewiesen als bisher fur die Einschicht-Spiral-CT angegeben. Nachteilig bleiben weiterhin die hohe Anzahl falsch positiver Befunde, die hohe Strahlenbelastung fur den Patienten sowie das Fehlen der Moglichkeit einer histologischen Gewebesicherung. Neuere Studien zeigen allerdings, dass durch Reduzierung der Strahlenbelastung von 140 mAs auf 10 mAs ebenfalls eine verlassliche Aussage getroffen werden kann. Die Kosten fur eine MSCT-Kolographie bleiben aus gesundheitsokonomischer Sicht zu hoch, da bei computertomographischem Verdacht auf eine Neoplasie eine zusatzliche Koloskopie zur weiteren histologischen Abklarung erfolgen muss.

BACKGROUND: Biliary obstruction with its wide range of potential causes is a common disorder in gastroenterology. Infections of the biliary tract with Candida and other fungal species leading to obstructive jaundice have increasingly been recognized in the last few years. Besides a few case reports, there are few data in the literature giving us an idea how to diagnose and treat these patients. METHODS: We report on a series of seven patients suffering from biliary tract candidiasis who were diagnosed and treated at our institution. Predisposition factors, reliability of various diagnostic modalities, and treatment options based on our own experience are presented and discussed. RESULTS: Besides the general diagnostic modalities such as laboratory findings or ultrasonography, we often observed mycelia in the bile duct system endoscopically. Typical morphological changes in peripheral bile ducts could be detected during endoscopic retrograde cholangiopancreatography (ERCP). Aspiration of bile and subsequent microbiological analysis in combination with ERCP findings revealed diagnosis of bile duct candidiasis in all cases. Treatment included both antiinfectious drugs and endoscopic therapy such as bile duct drainage, lavage, or debridement. With respect to fungal eradication, therapy was successful in 71% of cases as proven by microbiological analysis of bile aspirates. Since many of these patients suffer not only from biliary mycosis but also from disease necessitating immunosuppression, the prognosis was poor in some cases. CONCLUSION: Biliary tract candidiasis because of immunosuppression is an increasingly recognized disease and remains a major clinical challenge. Besides laboratory analysis and ultrasonography, diagnostic modalities should include aspiration of bile during ERCP and microbiological analysis. Antiinfectious drug treatment as the main therapeutic column for biliary candidiasis should be complemented by endoscopic intervention.

Joint involvement is the most frequent extra-intestinal manifestation of chronic inflammatory bowel disease (IBD). Arthralgias are common and spondylarthropathy may affect peripheral joints, the spine as well as tendons. Clinical assessment has the greatest impact on diagnostics and therapy. In particular, a history of "inflammatory back pain" should lead to further investigations. HLA-B27 may be indicative of ankylosing spondylitis in IBD. Ultrasound and magnetic resonance imaging are preferred diagnostic modalities for the assessment of inflammation. Arthralgia often improves during treatment of IBD. In contrast, polyarticular arthritis, sacroiliitis, ankylosing spondylitis and enthesitis often require additional continuous therapy. Baseline therapy includes analgesics, intra-articular corticosteroid administration, and physiotherapy. Disease-modifying antirheumatic drugs such as sulfasalazine and methotrexate are used in polyarticular arthritis. Sulfasalazine may be effective in patients with early axial disease as well. Tumor necrosis factor (TNF) blocking agents may be employed in patients with active disease not responding to conventional treatment. For patients who fail to respond to TNF blockade, the emergence of other targets of the inflammatory cascade may provide more treatment choices in the future.

Background: We have previously shown that cell contacts between pancreatic acinar cells dissociate early in pancreatitis and that this is a prerequisite for the development of pancreatic oedema. Here we studied the underlying mechanism. Methods: Employing experimental caerulein induced pancreatitis in vivo and isolated pancreatic acini ex vivo, in conjunction with protein chemistry, morphology, and electron microscopy, we determined whether cell contact regulation in the pancreas requires or involves: (1) changes in cadherin-catenin protein expression, (2) tyrosine phosphorylation of adhesion proteins, or (3) alterations in the actin cytoskeleton. Results: During initial cell-cell contact dissociation at adherens junctions, expression of adhesion proteins remained stable. At time points of dissociated adherens junctions, the cadherin-catenin complex was found to be tyrosine phosphorylated and internalised. The receptor type protein tyrosine phosphatase (PTP)κ was constitutively associated with the cadherin-catenin complex at intact cell contacts whereas following the dissociation of adherens junctions, the internalised components of the cadherin-catenin complex were tyrosine phosphorylated and associated with the cytosolic PTP SHP-1. In isolated acini, inhibition of endogenous protein tyrosine phosphatases alone was sufficient to induce dissociation of adherens junctions analogous to that found with supramaximal caerulein stimulation. Dissociation of actin microfilaments had no effect on adherens junction integrity. Conclusions: These data identify tyrosine phosphorylation as the key regulator for cell contacts at adherens junctions and suggest a definitive role for the protein tyrosine phosphatases PTPκ and SHP-1 in the regulation, maintenance, and restitution of cell adhesions in a complex epithelial organ such as the pancreas.

We present the case of a primary malignant esophageal melanoma arising in a 75-year-old male, initially diagnosed as anaplastic squamous cell carcinoma. After resection of the tumor, histological work-up was indicative of a marked morphological heterogeneity, resembling a focally amelanotic primary malignant melanoma. Primary malignant melanomas of the esophagus are exceptionally rare. An exact preoperative diagnosis is critical with respect to the appropriate therapeutic strategy. Clinicopathological features of this entity with a brief review of the literature are presented.

Tumors of the small intestine are rare as compared to malignant tumors of the pancreas. Here we report on the case of a 61-year-old man suffering from chronic pancreatitis presenting with a lesion projecting into the pancreatic head shown by both computed tomography and transabdominal ultrasound. Pancreatic cancer was suspected, but endoscopic ultrasound revealed this lesion to be situated in the submucosal layer of the duodenal wall. Surgery was performed since biopsy of this lesion was not diagnostic and a malignant leiomyosarcoma could therefore not be excluded. Limited surgery comprised resection of the duodenal lesion, whereas based on computed tomography alone, exploration of the pancreas would have been performed. Thus, in the present case endoscopic ultrasound leads to a more appropriate, less invasive therapeutic measure.

The discrepancy between high rates of sensitivity, specificity, and accuracy for intraductal ultrasonography (IDUS) in extrahepatic bile duct carcinoma and the failure to depict different wall layers as defined by the TNM classification have not yet been elucidated sufficiently.In a prospective study, endosonographic images were correlated with histomorphology including immunohistochemistry. Using IDUS, we examined fresh resection specimens of patients who had undergone pancreato-duodenectomy. For histological analysis, the formalin-fixed and paraffin-embedded specimens were stained by hematoxylin-eosin, elastica-van-Gieson, and immunohistochemically by smooth muscle-actin. To confirm our hypothesis, further cases from the archives were analyzed histopathologically and immunohistochemically.The various wall layers of the extrahepatic bile duct as described by the International Union Against Cancer are neither histomorphologically nor immunohistochemically consistently demonstrable. Especially, a clear differentiation between tumor invasion beyond the wall of the bile duct (T2) and invasion of the pancreas (T3) by histopathological means is often not possible. Endosonographic images using high-resolution miniprobes similarly confirm the difficulty in imaging various layers in the bile duct wall.Most adaptations made by the sixth edition of the TNM classification accommodate to the endosonographic and most of the histopathological findings as demonstrated in our study. In contrast to the new edition, however, our findings suggest to combine T2- and T3-staged tumors into one single class leading to clarification, and improved reproducibility of histopathological staging.

Aims/hypothesis Symptoms of gastroparesis possess a heavy impact on the quality of life; delayed gastric emptying may result in poor metabolic control in diabetics. Gastric electrical stimulation (GES) has recently been introduced as a treatment option in patients with drug refractory gastroparesis to increase the quality of life by alleviating nausea and vomiting frequencies. However, the effect of GES on metabolic control has not been assessed yet. Methods We performed a prospective single center study on the long-term effect (12 months) of continuous high-frequency/low-energy GES on symptoms, gastric emptying (measured scintigraphically), and metabolic control (HbA1c) in insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis for more than one year. Results Seventeen (12 female, 5 male) patients entered the study; all were available for analysis at all time points. No therapy-associated adverse events occurred. Weekly vomiting and nausea frequencies decreased significantly at 6 and 12 months. Gastric retention rates improved significantly from 83 % (2 h) and 38 % (4 h) to 35 % (2 h)/14 % (4 h) and 25 % (2 h)/17 % (4 h) at 6 and 12 months, respectively. HbA1c values were lowered in all 17 subjects; initially, all HbA1c values were above 7.5 %; at 6 and 12 months, mean values had significantly decreased from 8.6 % to 6.2 % and 6.5 %, respectively. Conclusions/interpretation Gastric electrical stimulation offers symptom control in diabetics with drug-refractory gastroparesis and decreases gastric retention. This study, for the first time, documents a positive effect of this therapy on metabolic control as indicated by HbA1c, a surrogate marker of the risk of diabetic complications.

A variety of imaging techniques are available to diagnose bile duct strictures; the most effective imaging technique, however, has not been established yet. In the present study, we compared the impact of endoscopic retrograde cholangiopancreatography (ERCP), intraductal ultrasonography (IDUS), and magnetic resonance cholangiopancreatography (MRCP) with regard to diagnosing bile duct strictures.We prospectively examined 33 patients with jaundice due to bile duct strictures by ERCP plus IDUS and MRCP. The objectives were to assess diagnostic quality of imaging, complete presentation of the bile duct, and differentiation of malignant from benign lesions. Surgical and histopathological correlations, which were used as the gold standard, were available in all cases since all included patients underwent laparotomy.Diagnostic image quality for ERCP was 88% and 76% for MRCP (p0.05). Comparing ERCP and MRCP, complete presentation of the biliary tract was achieved in 94% and 82%, respectively (p0.05). ERCP and MRCP allowed correct differentiation of malignant from benign lesions in 76% and 58% (p= 0.057), respectively. By supplementing ERCP with IDUS, the accuracy of correct differentiation of malignant from benign lesions increased significantly to 88% (p= 0.0047).Comparing ERCP with MRCP, we found adequate presentation of bile duct strictures in high imaging quality for both techniques. ERCP supplemented by IDUS gives more reliable and precise information about differentiation of malignant and benign lesions than MRCP alone without additional imaging sequences.

The function of the stomach includes initiation of digestion by exocrine secretions such as acid and pepsin, which are under the control of the endocrine secretion of hormones that also coordinate intestinal motility. The stomach also stores and mechanically disrupts ingested food. Various techniques have been developed to assess gastric physiology, the most important of which is assessment of acid secretion, as well as gastric motility and gastric emptying. The influence of drugs on gastric function and the effect of gastric secretion and mechanical actions on the bioavailability of novel compounds are of critical importance in drug development and hence to clinical pharmacologists. The control of acid secretion is essential in the treatment of peptic ulcer disease as well as gastrooesophageal reflux disease (GORD); pH-metry can be used to determine the necessary dose of an acid suppressant to heal mucosal damage. Disturbed gastric myoelectric activity leading to gastroparesis can cause delayed gastric emptying, often found in patients with diabetes mellitus. Electrogastrography (EGG) may be used to evaluate the influence of prokinetics and other drugs on this condition and aid in determining effective therapy.

Intestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC) is characterised by an influx of neutrophils into the intestinal mucosa. S100A12 is a calcium binding protein with proinflammatory properties. It is secreted by activated neutrophils and interacts with the multiligand receptor for advanced glycation end products (RAGE). Promising anti-inflammatory effects of blocking agents for RAGE have been reported in murine models of colitis.To investigate expression and serum concentrations of S100A12 in inflammatory bowel disease (IBD).We performed immunohistochemical studies and immunofluorescence microscopy in biopsies from patients with CD and UC. S100A12 serum concentrations were analysed using a sandwich ELISA.Immunohistochemical studies revealed profound expression of S100A12 in inflamed intestinal tissue from IBD patients whereas no expression was found in tissue from healthy controls. Staining for S100A12 during chronic active CD and UC was restricted to infiltrating neutrophils. Serum S100A12 levels were significantly elevated in patients with active CD (470 (125) ng/ml; p0.001, n=30) as well as those with active UC (400 (120) ng/ml; p0.01, n=15) compared with healthy controls (75 (15) ng/ml; n=30). Even in inactive disease, elevated serum concentrations were found, at least in CD. S100A12 levels were well correlated with disease activity in CD and UC.We demonstrated that neutrophil derived S100A12 is strongly upregulated during chronic active IBD, suggesting an important role during the pathogenesis of IBD. Serum S100A12 may serve as a useful marker for disease activity in patients with IBD.

Background Malignant mesothelioma of the peritoneum is a very rare neoplasm, commonly associated with asbestos exposure and often rapidly fatal. Well Differentiated Papillary Mesothelioma of the Peritoneum (WDPMP) is regarded as a less aggressive variety of the tumor. Progressive ascites is often the only clinical manifestation of the disease and differentiation of WDPMP from benign mesothelial hyperplasia or adenocarcinoma is difficult. Patients and methods Here we report the case of a 45-year-old patient who presented with ascites but without evidence of portal hypertension, liver disease or abdominal malignancy. On diagnostic laparoscopy small tumor nodules were found to cover the parietal peritoneum and the greater omentum and histopathologically corresponded to papillary mesothelial hyperplasia with minimal nuclear atypia. Histochemically biopsies were positive for Calretinin, Cytokeratins and Epithelial Membrane Antigen (EMA). Based on these findings the diagnosis of WDPMP was made and the patient was closely followed without primary cytostatic therapy. Conclusions Progressive ascites was the only clinical symptom in this patient, while liver disease, portal hypertension and gastrointestinal malignancies were ruled out by clinical, laboratory and imaging techniques. Laparoscopic biopsy revealed WDPMP to be the underlying disease. Immunocytochemistry is required to establish the diagnosis of this rare malignant disorder which is even more uncommon in the absence of a history of asbestos exposure. Due to the indolent course of WDPMP therapy should only be initiated when signs of rapid tumor progression become apparent.

Cell adhesion proteins have been implicated as tumor suppressors because they prevent malignant cells from dissociating their cell contacts. We have studied the role of p120(ctn), a recently discovered member of the cadherin/catenin family, in human pancreatic cancer.In 32 resection specimens of pancreatic adenocarcinoma and 10 control samples the expression of p120(ctn) was studied by Northern blot, immunocytochemistry, and immunogold electron microscopy. Patient survival data, tumor grading, and staging were correlated to the experimental results. In PaTu 8889 T pancreatic cancer cells, p120(ctn) expression was suppressed with 21-nucleotide small interfering RNA (siRNA) duplexes and proliferation was determined by bromodeoxyuridine (BrdU) incorporation.In pancreatic cancer p120(ctn) messenger RNA (mRNA) was increased 3- to 4-fold. Although p120(ctn) was localized exclusively at cell contacts in controls it was found in the cytosol and nucleus of pancreatic cancer cells. This redistribution correlated to the degree of tumor dedifferentiation but was independent of tumor stage. The mean survival of patients with predominant membrane localization of p120(ctn) was 24 +/- 7 (SEM) months vs. 9 +/- 2 months for patients with predominant cytoplasmic p120(ctn) expression (P0.05). Silencing of p120(ctn) with siRNA duplexes reduced pancreatic cancer cell growth by 40%.Up-regulation, cytoplasmic redistribution, and nuclear import of p120(ctn) are associated with a more malignant phenotype of pancreatic cancer. This study further represents conclusive evidence for a direct involvement of p120(ctn) in malignant tumor cell proliferation. Both p120(ctn)-defective tumor cell contacts and p120(ctn)-mediated growth signals appear to contribute to the aggressive spread of pancreatic cancer.

Background. Patients with extensive, long-standing ulcerative colitis have increased risk of colorectal cancer. Aims. To improve the detection of high-risk patients, using a combination of colonic cytology, histology, and DNA image cytometry after segmental colonic lavage. Patients. A series of 16 patients (8 high-risk patients) with ulcerative colitis were investigated. Methods. After segmental lavage step, biopsies were obtained. Gradient centrifugation of the colonic fluid was performed for isolation and purification of epithelial cells. The smears and biopsy specimens obtained were stained for routine interpretation and for DNA image cytometry. Results. Segmental lavage could be performed in all patients. Specimens from two high-risk patients showed low grade dysplasia and atypia by means of histology and cytology, respectively. In one patient, without increased colorectal cancer risk, atypia was detected. Three patients in the high-risk group, two of those diagnosed as positive for dysplasia and atypia, showed aneuploidy histologically and cytologically. DNA aneuploidy, in cytological material, was found exclusively in three low-risk patients, one of those had atypia cytologically. Conclusions. Isolation and purification of epithelial cells after segmental colonic lavage using density gradient centrifugation can be performed as part of routine endoscopy. It provides information about atypical cells and DNA aneuploidy as additional markers of malignant transformation. The combination of cytologic examination and DNA image cytometry might improve the detection of high-risk ulcerative colitis patients.

Summary Background : Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules. Aim : To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-α therapy vs. standard-dosage interferon-α therapy, in a triple therapy combination with ribavirin and amantadine. Methods : Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-α group (n = 15), receiving thrice weekly 6 MU interferon-α for 12 weeks, followed by 3 MU interferon-α for 36 weeks, or the high-dose interferon-α group (n = 15), receiving daily 9 MU interferon-α for 4 weeks, followed by 6 MU (weeks 5–8), 3 MU (weeks 9–12) and 1.5 MU (weeks 13–48) interferon-α. All patients were given ribavirin (1000–1200 mg) and amantadine (200 mg) daily for 48 weeks. Results : At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-α, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-α, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons. Conclusions : The findings suggest that, although the difference between the response rates of standard and high-dose interferon-α regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-α therapy and an equal safety profile.

Objective. To determine the impact of implant integrity on clinical symptoms and antibody status in women with silicone breast implants (SBIs). Methods. Ninety consecutive women were examined by means of magnetic resonance imaging (MRI) to assess the integrity of their silicone breast implants. The presence of silicone in the liver was estimated by 1 H localized stimulated echo acquisition mode (STEAM) magnetic resonance spectroscopy (MRS). Results were correlated with patients’ complaints, as evaluated by a standardized questionnaire, physical examination by a rheumatologist and antibody screening. Results. Breast MRI revealed defects in 24 patients (26.6%); in 13 (54.2%) of these women, silicone was detected in the liver by MRS. Of the 66 patients with MRI-estimated intact implants, 15 (22.7%) had apparent silicone in their liver, arguing for gel bleeding. Clinically, two patients had had rheumatoid arthritis before SBIs, whereas the other patients revealed no typical symptoms of arthritis or connective tissue disease (CTD). The patients with MRS evidence of silicone in the liver had no statistically significant differences in their complaints with the exception of the most frequent symptom, tinglingunumbness of the fingers (82.1 vs 51.6%, P= 0.006). A positive pattern of antinuclear antibodies (ANA) was obtained in 13 of the 28 MRS-positive patients (46.4%) and in 15 of the 62 MRS-negative patients (24.2%, P= 0.033). However, in only one of these 28 ANA-positive patients was a specific weak antibody titre against SS-A detected by ELISA. Conclusion. Implant integrity has no major impact on rheumatic symptoms of women with SBIs. This finding supports the standpoint that silicone does not cause either a specific CTD or any other distinct disease entity. However, the moderately increased incidences of ANA-positivity and neuropathy-associated symptoms require explanation.

Upper GI bleeding in patients without underlying systemic or liver disease is most commonly due to peptic ulcer disease, a mucosal tear, or esophageal erosions.1 This is a case of a young woman who presented with recurrent upper GI hemorrhage. On endoscopy, the source of bleeding appeared to be convoluted varices in the gastric fundus. The clinical course, however, as well as angiography, Doppler EUS, and surgical pathology identified a Dieulafoy’s lesion as the source of the recurrent bleeding. The underlying disorder that led to formation of the Dieulafoy’s lesion was identified as fibromuscular dysplasia of the celiac trunk and its branches.

Background: Holographic interferometry is based on the superimposition of the holograms of different motional states of an object on a single holographic storage medium. It has been used to detect structural changes in prosthetic heart valves. The combination of holographic interferometry and endoscopic imaging were applied to assess disturbances of porcine stomach wall elasticity. Methods: By connecting an electronic speckle pattern interferometry (ESPI) camera system (light source: continuous wave argon-ion laser, λ = 514.5 nm) to different types of endoscopes, ex vivo experiments were performed on porcine stomachs to detect areas characterized by altered tissue elasticity. With linkage of the endoscopic ESPI camera complex to a fast image processing system, the method of double pulse exposure image subtraction was applied at a video frame rate of 12.5 Hz. Results: The speckle correlation patterns resulting from gentle gastric wall deformation were analyzed in a series of experiments in 16 porcine stomachs. Interferograms of gastric wall areas without structural abnormalities exhibited concentric fringes, whereas fringe patterns corresponding to areas of reduced tissue elasticity were characterized by parallel lines. Conclusion: Applying the nondestructive method of dynamic holographic endoscopy, abnormalities of the gastric wall leading to diminished tissue elasticity can be distinguished reliably from surrounding healthy tissue.

Background: The roles of active oxygen metabolites and anti-oxidative defenses in aspirin (ASA)-induced gastric damage have been little studied. Aim: We determined the effects of aspirin (400 mg b.d.) with or without vitamin C (480 mg b.d.) for 3 days on gastric mucosa in human volunteers. Methods: Gastric injury was assessed endoscopically; gastric blood flow, reactive oxygen release (quantified by chemiluminescence), lipid peroxidation, myeloperoxidase, superoxide dismutase and glutathione peroxidase activity and intragastric vitamin C content were measured. Expression of superoxide dismutase and glutathione peroxidase mRNAs was assayed semi-quantitatively. Results: ASA produced erosions, a marked increase in chemiluminescence, lipid peroxidation, and myeloperoxidase activity. It also resulted in a suppression of gastric blood flow, intragastric vitamin C levels, superoxide dismutase and glutathione peroxidase activities. The addition of vitamin C significantly attenuated gastric damage and reversed the effects of ASA on these parameters. Superoxide dismutase and glutathione peroxidase mRNAs were decreased in ASA-treated subjects; the addition of vitamin C restored their regular levels. Conclusions: (i) free radical-induced lipid peroxidation and suppression of antioxidizing enzymes play an important role in gastric damage induced by aspirin; (ii) increased myeloperoxidase activity suggests activated neutrophils to be the major source of these radicals; (iii) vitamin C protects against ASA-induced damage due to its anti-oxidizing activity.