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UNLABELLED In a prospective study the frequency of anaemia and serum iron deficiency was investigated in 373 patients with Crohn's disease. Anaemia was present in 52% of patients, hyposiderinaemia in 37%. Involvement of the colon resulted in more pronounced anaemia and hyposiderinaemia than in pure ileitis. For further assessment of iron metabolism serum ferritin or iron binding capacity as well as intestinal iron absorption were determined in 34 patients both anaemic and hyposiderinaemic. In 22 patients sideroachrestic anaemia due to inflammation was found, 5 patients showed iron deficiency due to bleeding. In 6 patients simultaneously lowered serum iron and ferritin or increased latent iron binding capacity with non-increased iron absorption indicated relative iron absorption defects. In one case also the absolute intestinal iron absorption was decreased. However, in only one of these 7 patients typical microscopic changes of Crohn's disease were demonstrable in the upper intestine. CONSEQUENCES 1. Anaemia in Crohn's disease is most frequently caused by inflammation (sideroachrestic anaemia). 2. In colonic involvement the anaemia can be aggravated by iron deficiency due to bleeding. 3. In rare cases part of the anaemia can be due to iron absorption defects which need not necessarily be associated with macroscopic recognizable mucosal damage.

UNLABELLED Faecal excretion of bile acids was investigated using 75Se-homotaurocholic acid (75SeHCAT) in a total of 75 patients: 9 with irritable colon, 58 with Crohn's disease and 8 with small-bowel resection due to various indications but without Crohn's disease. Bile acid malabsorption, taken as a pathological bile acid retention of less than 19%, was found present in 43 patients with diseased terminal ileum or with more than 20 cm resection of this organ, except in one case (12 cm). On the other hand a normal bile acid retention (21 to 27%) was found in 29 of 72 patients (including 9 patients with irritable colon) who showed either no radiologically detectable lesion of the ileum (n = 21) or changes involving an extension of up to 30 cm (inflammation or resection) in the terminal ileum (n = 8), with the exception of one case (50 cm). Three patients had a raised bile acid excretion contrary to clinical expectation: they had colitis Crohn without radiologically detectable involvement of the small intestine. Thus using the 75SeHCAT-retention test it seems possible to recognize functional disorders in diseased segments of the bowel before the appearance of radiologically detectable changes. CONCLUSION 75SeHCAT is a suitable substance for investigations on the function of the lower small intestine.

The European Pancreatic Club (EPC) was founded during a first symposium on December 9 and 10, 1965 in London (President H.T. Howat). The nine founding members were one biochemist (Jean Christophe, Belgium), one physiologist (Alfred A. Harper, UK), two surgeons (Andre Delcourt, Belgium, Yngve Edlund, Norway) and five physicians with special interest in the pancreas (Werner Creutzfeldt, Germany, Oliver Fitzgerald, Ireland, Karel Herfort, Czechoslovakia, Henry T. Howat, UK, Henri Sarles, France). It was the first scientific society worldwide which was concerned with the study of the pancreas. The idea was to bring basic scientists and clinicians together in an informal atmosphere to promote friendship and communication on research between them. The 2nd symposium was held in Marseilles in1967 (President H. Sarles). Until now there have nearly always been annual meetings, the one in 2005 is the 37th. In 1973 the EPC decided to lay down ‘Internal Rules’ and in 1992 new statutes were introduced. It became a member of the United European Gastroenterology Federation (UEGF) and is coorganizer of the United European Gastroenterology Week (UEGW). The official journal has been Pancreatology since 2001; previously the abstracts had been printed in Digestion since 1982. The officers of the EPC are the President, the Past President, the President Elect, the Secretary, the Treasurer and six Councillors from different European countries, three from basic and three from clinical science. A selection committee (4 basic and 4 clinical scientists) decides on the acceptance of papers. Officers and Presidents are elected by the General Assembly. At the meetings on average 150 contributions are accepted for presentation; the abstracts are printed in Pancreatology. Papers came from nearly all European countries and from overseas. In numbers Germany, France, the UK, Italy and Sweden are at the top. In total 4,837 scientific presentations were made from 1971 to 2004. Fifty-nine symposia and 245 invited lectures informed about the state of the art. Since 1991 a Young Researchers Corner given by international experts is especially designed to give information on new techniques of research. The European Study Group of Pancreatic Cancer (ESPAC) and the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) are affiliated with the EPC. Since 1999 a Newsletter of the EPC has been published. The website of the EPC is www.e-p-c.org.

Objectives In acute pancreatitis, infection of necrosis is associated with a substantial mortality of 15% to >50% even if immediate necrosectomy, the recommended standard treatment, is performed, mainly because of the patients' critical systemic and unstable local conditions at the time of manifestation of infection. We investigated whether this dreaded complication can be managed conservatively. Methods We evaluated 88 consecutive patients with severe (APACHE II score, > or =11; Ranson score, > or =4) acute necrotizing pancreatitis who received ICU treatment including early antibiotic prophylaxis. Twenty-eight patients were included who developed infection of necroses, verified by fine needle aspiration, 19 +/- 6 days after admission. No patient received urgent surgery; rather, in all patients, nonsurgical therapy was continued after adapting the antibiotic regimen to bacteriology. In the further course, 12 patients were excluded due to refractory local complications eventually requiring surgical treatment 36 +/- 14 days after diagnosis of infection. Results Sixteen patients (APACHE II score: 18.1 [11-33]; Ranson score, 5.9 [4-10]) were managed with medical treatment alone. Six patients recovered without further complications; 10 patients (62%) developed single or multiple organ failure, and 2 died (mortality, 12%). Conclusion These data suggest that in patients with acute necrotizing pancreatitis and infected necroses, surgery can be avoided without compromising prognosis and outcome.

Background & Aims: Antibiotic prophylaxis in necrotizing pancreatitis remains controversial. Until now, there have been no double-blind studies dealing with this topic. Methods: A total sample size of 200 patients was calculated to demonstrate with a power of 90% that antibiotic prophylaxis reduces the proportion of patients with infected pancreatic necrosis from 40% placebo (PLA) to 20% ciprofloxacin/metronidazole (CIP/MET). One hundred fourteen patients with acute pancreatitis in combination with a serum C-reactive protein exceeding 150 mg/L and/or necrosis on contrast-enhanced CT scan were enrolled and received either intravenous CIP (2 × 400 mg/day) + MET (2 × 500 mg/day) or PLA. Study medication was discontinued and switched to open antibiotic treatment when infectious complications, multiple organ failure sepsis, or systemic inflammatory response syndrome (SIRS) occurred. After half of the planned sample size was recruited, an adaptive interim analysis was performed, and recruitment was stopped. Results: Fifty-eight patients received CIP/MET and 56 patients PLA. Twenty-eight percent in the CIP/MET group required open antibiotic treatment vs. 46% with PLA. Twelve percent of the CIP/MET group developed infected pancreatic necrosis compared with 9% of the PLA group ( P = 0.585). Mortality was 5% in the CIP/MET and 7% in the PLA group. In 76 patients with pancreatic necrosis on contrast-enhanced CT scan, no differences in the rate of infected pancreatic necrosis, systemic complications, or mortality were observed. Conclusions: This study detected no benefit of antibiotic prophylaxis with respect to the risk of developing infected pancreatic necrosis.

It has been postulated that high intakes of animal fat and protein and low intakes of fiber, calcium, and antioxidants increase the risk of colorectal cancer. Whether specific types of protein such as that from red meat are important, and whether vegetables might be key protective factors will also be considered in this study. Dietary intake over the past year was studied according to the diet history method by means of a case–control study in 184 cases and matched controls. After adjustment for energy, relative weight, and social class, no associations were found for fat or protein in comparison with either control group. Unexpectedly, carbohydrate intake was inversely related with adenoma risk, the RR being 0.29 (0.10–0.81) for quintile 5 versus 1 in comparison with hospital controls. None of the antioxidants showed a significant protective effect except β-carotene intake in comparison with hospital controls, the RR being 0.24 (0.11–0.50) for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile of intake being 3.6 (1.7–7.5) in comparison with hospital controls and 4.4 (1.6–12.1) in comparison with population controls. Our data support the protective role for carbohydrate intake and of β-carotene intake in the etiology of colorectal adenomas and show a strong increased risk for developing adenomas in those with high meat intake.

The relation between risk of colorectal adenoma and serum concentrations of vitamins A, C, E and carotene was examined in a population-based case-control study of 105 cases of colorectal adenoma and a similar number of hospital controls showing no polyps at colonoscopy and a second control group of population controls. There were no significant associations with serum concentrations of vitamins C and E and carotene. Serum concentrations of vitamin A were significantly inversely related to the risk of colorectal adenoma when cases were compared with both control groups. After adjustment for energy intake, smoking, alcohol, estrogen therapy, body-mass-index and social class the inverse association between vitamin A and colorectal adenoma was even more marked. For the highest versus the lowest quartile of serum levels the adjusted RR was 0.23 (0.07–0.73) in relation to hospital controls and 0.08 (0.02–0.25) in relation to population controls. These findings suggest that the risk of developing colorectal adenomas is reduced in those with high vitamin A levels.

Bone loss in inflammatory bowel disease (IBD) is presumed to be mediated by inflammation. Increased levels of the multifunctional cytokine IL-6 in inflammatory diseases have been proposed to be the link in such “inflammation-mediated osteopenia.” A recently described G/C polymorphism with an effect on transcription rate and plasma levels of IL-6 suggests a genetically determined difference in the degree of the IL-6 response to stressful stimuli between individuals. This study aimed to assess the frequency of genotypes and haplotypes of the G/C polymorphism of IL-6 in IBD patients. A further aim was to assess whether carriage of the potentially protective CC genotype is favorable with respect to the development of bone disease in IBD. The IL-6 polymorphism was typed in 105 IBD patients and 113 healthy controls. Bone mineral density was evaluated at baseline and after a prospective 2-year-follow-up. The favorable CC genotype with decreased IL-6 release was not underrepresented in IBD patients compared to healthy controls. Carriage of this genotype was not protective with respect to the development of bone disease, either for the bone mineral density at baseline or for the prospectively observed bone loss. Within the subgroup of patients who did not receive steroids during follow-up, the prospectively observed bone loss was even slightly higher in CC carriers, but differences did not reach significance. Genetically determined differences in the degree of the IL-6 response to stressful stimuli are no major predictors for the degree of bone disease in IBD patients.

Objective An increased mucosal expression of transforming growth factor-beta (TGF-β) and hepatocyte growth factor (HGF) has been reported in patients with active inflammatory bowel diseases (IBD) and in proximit to injured gastric and intestinal mucosal surfaces. The air of this study was to measure systemic concentrations of TGF-β and HGF and to assess their potential value to predict disease activity or severity of inflammation in patients with inflammatory bowel diseases. Design and methods Plasma HGF and TGF-β 1 peptide levels were determined in 29 patients with ulcerative colitis, 45 patients with Crohn's disease and 28 healthy controls using commercial ELISA assays. Peptide levels were correlated with disease activity indices and various laboratory parameters. Results HGF and TGF-β 1 plasma levels were detected in all control and IBD subjects. Although a tendency towards increased HGF and TGF-β 1 peptide levels in IBD patients was observed, differences between groups were not significant In ulcerative colitis patients HGF plasma level positively correlated with white blood cell counts and negatively correlated with serum albumin concentrations and haematocrit. In Crohn's disease patients, a positive correlation between TGF-β and platelet count was observed. Conclusions HGF and TGF-β 1 plasma concentrations are not significantly different in IBD and healthy control subjects. Stratification of IBD patients according to disease activity did not reveal any substantial differences, suggesting that HGF and TGF-β plasma levels have no value in the assessment of disease activity or severity of inflammation in patients with IBD.

Whether alcohol and tobacco can be considered as risk factors for the occurrence of adenomas remains inconclusive. A case-control study was carried out to examine these factors while taking into account possible confounding factors. One hundred eighty-two patients with colorectal adenomas and similar numbers of hospital and population controls were compared as to intake of alcohol and various nutrients including smoking and drug intake. There was a positive association between cigarette smoking and adenoma risk compared with hospital controls, the RR being 2.3 (1.1-4.6). Overall alcohol intake was no risk factor in hospital controls, but drinking liquor was associated with an increased risk, the RR being 4.1 (1.3-13.4) and was especially marked in males [RR 10.2 (2.3-46.2)]. Compared with population controls, there was no increased RR associated with smoking or alcohol intake. None of the risk factors was positively associated with disease risk in those with small or large adenomas. These findings suggest that alcohol and tobacco play no major role in the formation or growth of adenomas.

Aims: Previous studies have suggested that the regular use of NSAIDs reduces the risk of colorectal adenomas. The aim of this study was to examine this association while taking possible confounding factors into account. Methods: The intake of drugs including NSAID intake during the last 20 years was assessed by means of a case-control study in 184 cases and matched hospital and community controls. Results: Overall, there were few individuals with a relevant drug intake for more than 5 years. NSAID intake for more than five years was associated with decreased risk in comparison with both control groups. The RR was 0.20 (0.04–1.04) compared with hospital and 0.21 (0.04–0.99) compared with population controls, the latter association being statistically significant. Subgroup analysis by type of drug revealed a significant protective effect only for long-term aspirin intake in relation to hospital controls, the RR being 0.09 (0.01–0.82). Conclusion: Our data support the hypothesis that there is a protective effect of NSAID intake of more than 5 years against the development of colorectal polyps.

Background & Aims: Lysophosphatidic acid (LPA) is assumed to play an important role in the modulation of injury and tissue repair in nonepithelial tissues. The effects of LPA on intestinal epithelial wound repair in vitro and in vivo were characterized. Methods: Effects of LPA on intestinal epithelial restitution and proliferation were assessed by using an in vitro wounding model with confluent intestinal epithelial cell line 6 (IEC-6) monolayers and colorimetric thiazolyl blue (MTT) assays. In addition, LPA signaling pathways were characterized. Effects of LPA on intestinal wound healing in vivo were studied by using the trinitrobenzene model of colitis in rats. Results: LPA significantly enhanced migration and inhibited cell proliferation of IEC-6 cells in vitro. The effects on intestinal epithelial cell migration and proliferation were mediated through transforming growth factor b (TGF-b)-independent pathways and binding to a G-protein receptor. In addition, LPA significantly ameliorated intestinal epithelial injury in the trinitrobenzene model of colitis in rats. Conclusions: These findings suggest that LPA enhances intestinal epithelial wound healing by modulation of intestinal epithelial cell migration and proliferation through TGFb‐independent pathways. Thus, exogenous administration of LPA may provide a new approach for modulating intestinal injury in vivo.

To determine the incidence and clinical pattern of Crohn's Disease in a defined area in Germany, a prospective, population-based study was carried out from 1980 to 1984 and again from 1991 to 1995. All patients newly diagnosed with Crohn's disease within the respective study period who were resident in the study area were included in the study. The results from both study periods were then compared to detect time trends. Altogether 288 (156 and 132, respectively) incident cases were identified yielding an almost unchanged incidence over the years (1980-84: 4.9/10(5); 1991-95 5.2/10(5)). While the peak of incidence is still in the 15-24-year-old group, 1 out of 5 incident patients is now age 50 years and older. Median age at onset of symptoms increased to 30 years (20 years in the former period). Time from onset of symptoms was reduced from a median of 20 months in the 1980s to 5 months. Symptoms did not change significantly, although there seems to be less complicated disease recently. Distal migration of the inflammation in the intestinal tract was observed with significantly more involvement of the sigmoid and rectum in the recent period.

Background Acute intestinal mucosal inflammation is associated with recruitment of peripheral blood mononuclear cells (PBMN) into the mucosa and migration across the epithelium. It has recently been shown that several PBMN-derived cytokines, including transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interferon-gamma (IFN-gamma) may modify intestinal epithelial cell function, resulting in rapid improvement of wound repair. Our aim was to characterize the modulating effects of PBMN on intestinal epithelial restitution, the initial step of wound healing. Methods PBMN were separated from whole blood, obtained from healthy volunteers, by using a density gradient. The effect of PBMN on intestinal epithelial restitution was assessed by using an in vitro coculture wounding model with non-transformed small-intestinal epithelial IEC-6 cells. Results Coculture of PBMN caused a significant enhancement of epithelial cell restitution in vitro. The modulatory effects of PBMN could be significantly blocked by adding immunoneutralizing anti-IL-2 or anti-IFN-gamma to the culture media, suggesting that PBMN may modulate intestinal epithelial migration through an IL-2- and IFN-gamma-dependent pathway. In contrast, PBMN-induced stimulation of intestinal epithelial restitution was not influenced by addition of anti-TGF-beta or anti-TNF-alpha, suggesting that these cytokines are not critical for the modulation of restitution by PBMN. Conclusions These findings suggest that PBMN may promote intestinal epithelial wound repair by enhancing restitution through secretion of various cytokines, among them IL-2 and IFN-gamma, which are abundantly expressed in the course of several inflammatory diseases of the gut.

Aims: Previous studies have found a positive association between Helicobacter pylori infection and colorectal adenomas. The aim of the present study was to examine this association while taking possible confounding factors into account. Methods: 98 serum samples were available from 182 patients with colorectal adenomas who entered a case-control study of colorectal adenomas and diet. The H. pylori status in patients was compared with a hospital control group and a population control group. Results: H. pylori IgG antibodies were more common in colorectal polyp patients compared with either control group, the prevalence being 79% in cases compared with 62% in both control groups. The corresponding RR was 1.4 (0.76–2.6) compared with hospital controls and 2.1 (1.1–3.9) compared with population controls. After adjusting for possible confounding variables the association between H. pylori status and adenoma risk was even more marked. There was an RR of 1.6 (0.80–3.4) compared with hospital controls and an RR of 2.6 (1.3–5.4) compared with population controls, the latter association being statistically significant. Conclusion: These findings suggest a statistically significant association between H. pylori infection and colorectal polyps. A possible mechanism might be increased gastrin levels in H. pylori-infected subjects which exhibit a trophic effect on colonic mucosa.

Background: The relative potency of prokinetics in patients with gastroparesis has not been systematically studied. This study, therefore, aimed to assess the available data and to compare the effects of different prokinetics on symptoms and gastric emptying rates in patients with gastroparesis. Methods: A systematic search of the literature was performed, covering the period 1980 to March 1998. All identified studies were reviewed and the following data elements assessed: characteristics of study populations; sample sizes; treatment regimes; drug doses; study design; main outcome variables, and the validity of measurements. Results: In 36 studies, 514 patients were treated with prokinetics p.o. Most studies had methodological limitations (i.e. nonvalidated measurement of symptoms or unblinded treatment). The mean improvement in gastric emptying and the reduction in the symptom score was higher in the open trial group than in patients treated double-blind. Overall, erythromycin seems to have had the strongest effect on gastric emptying as compared to domperidone, cisapride or metoclopramide. Concerning gastrointestinal symptoms, the symptom scores appeared to improve more during treatment with erythromycin than with domperidone, metoclopramide or cisapride. Conclusions: Most of the available trials have methodological limitations; this limits the conclusions. However, the data suggest that the motilin-agonist erythromycin is superior with regard to the acceleration of gastric emptying, while both erythromycin and domperidone appear to be the most effective with regard to improvements in the symptom score. Additionally, there is a lack of association between changes in gastric emptying times and improvements in symptoms.

Die therapeutische Wirksamkeit von 5-Aminosalicylsaure bei chronisch entzundlichen Darmerkrankungen erfordert ausreichende intraluminale Wirkstoffkonzentrationen am Ort der Entzundung. Um die Freisetzung der Substanz in den am haufigsten betroffenen Darmabschnitten zu sichern, wurden verschiedene orale 5-Aminosalicylsaure-Praparationen mit verzogertem Freisetzungsmuster entwickelt. Die resultierenden Wirkstoffkonzentrationen im Dunndarmlumen sind jedoch unbekannt. Deshalb wurde die Freisetzung von 5-Aminosalicylsaure in verschiedenen Dunndarmabschnitten aus einem mit Eudragit L uberzogenen Praparat (Salofalk®) und aus mit Ethylcellulose uberzogenen Mikrogranula (Pentasa®) gemessen und verglichen. Zwolf gesunde Probanden wurden mit einer oroilealen Multilumensonde intubiert zur Markerperfusion, duodenalen, jejunalen und ilealen Chymusaspiration und intestinalen Manometrie. Jeder Proband erhielt 500 mg 5-Aminosalicylsaure (Salofalk®, n=6, oder Pentasa®, n=6) mit einer semiliquiden Testmahlzeit. Intestinale Aspirate, Blut- und Urinproben wurden uber sieben bis zehn Stunden in regelmasigen Intervallen gewonnen und in diesen Proben 5-Aminosalicylsaure- und Acetyl-5-Aminosalicylsaure-Konzentrationen mittels HPLC bestimmt. Nach Gabe von Salofalk® erfolgte die Magenentleerung der 5-Aminosalicylsaure nicht wahrend der digestiven, sondern erst wahrend der anschliesenden interdigestiven Periode. Die Freisetzung der Wirksubstanz im Dunndarmlumen nahm von proximal (3% der Dosis) nach distal (30% der Dosis) zu. 10% der verabreichten Gesamtmenge wurden mit dem Urin ausgeschieden, und etwa 90% erreichten das Kolon in gebundener oder geloster Form. Im Gegensatz dazu wurde 5-Aminosalicylsaure aus Pentasa® zusammen mit der Testmahlzeit aus dem Magen entleert und wahrend des Dunndarmtransits gleichmasig freigesetzt (etwa 20% der Dosis in Losung an allen intestinalen Aspirationsstellen). Nur 3,5% der Gesamtdosis wurden mit dem Urin ausgeschieden. Ahnliche Wirkstoffmengen wie bei Salofalk® erreichten das Kolon. Aus beiden Praparaten werden erhebliche Wirkstoffmengen bereits wahrend des Dunndarmtransits freigesetzt, was die therapeutische Wirksamkeit bei Morbus Crohn mit Dunndarmbefall erklaren konnte. Aufgrund des spezifischen Freisetzungsmusters eignet sich Salofalk® moglicherweise besonders bei vorwiegendem Befall des terminalen Ileums. Daruber hinaus konnte Pentasa® bei ausgepragtem Dunndarmbefall, der den proximalen Dunndarm einschliest, von Vorteil sein.

Background—Abnormal visceral mechanosensory and vagal function may play a role in the development of functional gastrointestinal disorders. Aims—To assess whether vagal eVerent and aVerent function is linked with small intestinal mechanosensory function. Methods—In seven patients with functional dyspepsia, six patients with a history of Billroth I gastrectomy and/or vagotomy, and seven healthy controls, intestinal perception thresholds were tested by a randomised ramp distension procedure performed with a barostat device. On a separate day, an insulin hypoglycaemia test was performed to assess the plasma levels of pancreatic polypeptide (PP) in response to hypoglycaemia,as a test of eVerent vagal function. Results—First perception of intestinal balloon distension occurred at significantly lower pressures in patients with functional dyspepsia (median 19.3, range 14.7‐25.3 mm Hg) compared with healthy controls (median 26.0, range 21.7‐43.7 mm Hg, p

Non-Hodgkin's lymphoma predominantly involving the pancreas is a rare tumor of the gastrointestinal tract. Diagnosis can be difficult, since lymphoma may mimic carcinoma or pancreatitis. Lymphoproliferative diseases induced by immunosuppressive therapy frequently occur in the gastrointestinal tract of posttransplant patients. However, pancreatic involvement of posttransplant lymphoma is an exceptional condition. We present the case of a cyclosporin-treated renal transplant recipient with pancreatic lymphoma mimicking carcinomatous or inflammatory tumors. The diagnostic difficulties and treatment options of pancreatic lymphoma as well as lymphoproliferative disorders in immunosuppressed renal recipients are discussed in light of the current literature.

In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and gamma GT activity were significantly lower after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1, 1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6 months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.

BACKGROUND & AIMS: Intraileal nutrients modulate gastrointestinal motility, but effects of maldigestion on postprandial motility are unknown. The aim of this study was to compare motor responses with ileal nutrient exposure in health and pancreatic insufficiency after a meal or intraluminal perfusion. METHODS: After oroileal multilumen intubation for duodeno-jejuno-ileal sampling, marker perfusion, and motility recording, 14 normal subjects and 12 patients with severe pancreatic insufficiency received a labeled liquid meal twice, either with placebo or pancreatin. Effects of intraileal nutrient perfusion on fed motility induced by duodenal amino acid perfusion were also investigated. RESULTS: Compared with normals, untreated patients had greater cumulative ileal nutrient delivery (69 +/- 21 vs. 487 +/- 232 kJ), shorter fed pattern (196 +/- 22 vs. 131 +/- 14 minutes), greater 90% gastric emptying (163 +/- 12 vs. 128 +/- 10 minutes), and faster small intestinal transit (86 +/- 9 vs. 44 +/- 6 minutes). Pancreatin reversed these changes. Ileal nutrient perfusion converted fed into interdigestive-like motility in normals (7 of 8) and patients (4 of 5). CONCLUSIONS: In subjects with pancreatic insufficiency, a low-energy liquid meal induces shorter fed motor pattern associated with accelerated gastric emptying and intestinal transit compared with healthy subjects. Because changes responded to enzyme treatment and could be reproduced by ileal nutrient perfusion, ileal delivery of malabsorbed chyme may be involved as a mechanism. (Gastroenterology 1997 May;112(5):1624-34)

Primary biliary cirrhosis (PBC) is a rare chronic cholestatic disorder of unknown origin that can now be treated effectively with ursodeoxycholic acid (UDCA). The clinical course of PBC is very variable, but a significant proportion of patients eventually die or undergo liver transplantation. In this single-center prospective long-term study, we analyzed the effect of UDCA therapy (10 mg/kg b.w./day) on conventional liver function tests and we also investigated whether serial quantitative liver function tests are useful in the clinical management of patients with PBC. Fifteen patients, most of them in an early disease stage, were followed up for either 4 (n = 7) or 5 (n = 8) years. In addition to regular conventional liver function tests, every 12 months quantitative liver function tests were performed. Thus we measured galactose elimination capacity, indocyanine green half-life and lidocaine half-life. Quantitative liver function tests were also performed once in healthy volunteers. Treatment with UDCA significantly improved conventional liver function tests, and this effect was maintained for several years (values in U/l before therapy and 4 years after therapy: AP = 1,346 +/- 317 vs. 516 +/- 93; gammaGT 378 +/- 80 vs. 144 +/- 30; LAP 122 +/- 10 vs. 71 +/- 9; AST 61 +/- 19 vs. 34 +/- 12; ALT 90 +/- 19 vs. 68 +/- 35; GLDH 14.3 +/- 1.9 vs. 8.2 +/- 1.9). Quantitative liver function tests were not significantly different between healthy volunteers and patients (GEC 6.8 +/- 0.3 vs. 7.0 +/- 0.3 mg/kg x min; ICG half-life 4.2 +/- 0.4 vs. 3.7 +/- 0.3 min; lidocaine half-life 75 +/- 8 vs. 79 +/- 6 min). In the patients, results of quantitative liver function tests (GEC, ICG and lidocaine half-lives) were not affected by UDCA therapy and remained constant over time. In the 1 patient who was transplanted, serial quantitative liver function tests did not indicate deteriorating liver function earlier than the patient's progressive symptoms or conventional liver function tests. Thus UDCA therapy markedly improved conventional liver function tests in patients with PBC, and this effect was maintained for at least 4-5 years. Possibly due to the fact that most of the patients were in an early disease stage, serial quantitative liver function tests provided little additional information that was relevant for planning therapy in the individual patient.

Alterations of small intestinal sensory thresholds and small intestinal dysmotility are associated with functional dyspepsia. Because gastric and duodenal afferents partly project to the same areas, we postulated that patients with functional dyspepsia and H. pylori infection would be characterized by lower duodenal sensory thresholds. We evaluated 16 patients with functional dyspepsia and 16 age- and sex-matched controls. All patients had undergone an extensive diagnostic work-up to exclude organic lesions. Mechanosensitive function was tested in the third portion of duodenum utilizing a barostat device, and small intestinal motility was assessed before and during duodenal nutrient infusion with a five-channel low-compliance perfusion system. H. pylori status was assessed by a validated serological test. Small intestinal sensory thresholds (first perception and maximal tolerated pressure) were significantly lower in patients (21.1 +/- 2.1 and 30.9 +/- 1.8 mm Hg) compared to controls (33.0 +/- 2.2 and 38.8 +/- 0.9 mm Hg, all P0.003). Nine of 16 patients compared with five of 16 controls were H. pylori positive (P = 0.15). Thresholds for H. pylori-negative (28.7 +/- 2.8 and 36.5 +/- 1.1 mm Hg) or -positive subjects (25.0 +/- 3.0 and 32.7 +/- 2.4 mm Hg) were overall not significantly different (P0.3). However, in patients with defined high H. pylori titers (50 units/ml) defined a priori, thresholds for first perception were significantly lower (14.7 +/- 2.9 mm Hg, N = 5) compared to patients with H. pylori titers below this threshold (24.3 +/- 2.9 mm Hg, N = 4) or without H. pylori infection (23.8 +/- 3.4 mm Hg, P0.05). During duodenal nutrient infusion, the duodenal motility index increased (P0.03). This increase was not significantly different in patients and controls or in H. pylori-negative or -positive subjects. Sensory abnormalities are present in patients with functional dyspepsia. In a small subgroup of patients with high H. pylori titers, sensory abnormalities may be linked to H. pylori infection.

It is still unclear, which receptor subtype, Y1 and/or Y2, mediates the inhibitory action of PYY on exocrine pancreatic secretion. The present study was undertaken to characterize functionally the Y receptor subtype that mediates the inhibition of exocrine pancreatic secretion by peptide YY (PYY). In eight conscious dogs with chronic gastric and pancreatic fistulas, we compared the action of intravenous infusion of 200 and 400 pmol/kg/h of the Y receptor agonists PYY 1-36, PYY 3-36, PYY 13-36, Pro 34 PYY 1-36, and NPY 1-36 on the pancreatic secretory response to secretin (20.5 pmol/kg/h) and cerulein (29.6 pmol/kg/h). PYY 13-36, Pro 34 PYY 1-36, and NPY 1-36 were also studied by giving a fivefold dose (1,000 and 2,000 pmol/kg/h). PYY 1-36 and the Y2 receptor agonist PYY 3-36 significantly inhibited pancreatic secretory responses to secretin and cerulein, whereas inhibition by NPY 1-36 and the Y2 receptor agonist PYY 13-36 was attainable only at doses of 1,000 and 2,000 pmol/kg/h. The Y1 receptor agonist Pro 34 PYY 1-36 was without effect on pancreatic secretion. We conclude that in dogs the inhibition of exocrine pancreatic secretion by PYY is mediated via Y2 receptors of a PYY-preferring subtype.

Objective : To examine the hypothesis that low social status in chronic pancreatitis is accounted for by high physical activity at work. Design : A case-control study comparing 50 patients with an established diagnosis of chronic pancreatitis with 100 age- and sex-matched community controls. Results : There was a significant association between a high level of physical activity and chronic pancreatitis risk, the relative risk being 3.9 (1.3-11.7). After controlling for age, sex, smoking and alcohol intake, a high amount of calorie expenditure during work was still significantly associated with chronic pancreatitis risk, the relative risk being 4.5 (1.2-17.7). When social class was controlled for physical activity the increased risk for low social class status disappeared. Conclusion : This study suggests that the social class gradient may be explained by the amount of manual labour.

Alpha 1-Antitrypsin deficiency predisposes to pulmonary emphysema, liver cirrhosis and hepatocellular carcinoma. Anecdotal evidence and a large autopsy study suggest that severe lung and liver disease rarely coexist in the same subject, but this has not been studied in patients. Therefore we investigated 27 patients with severe alpha 1-deficiency (Pi ZZ) and pulmonary emphysema for signs of liver disease and impaired hepatic function. A subgroup of 7 patients underwent quantitative liver function tests. On physical examination or ultrasonography, cirrhosis or tumor was not suspected in any patient. Conventional liver function tests were completely normal in 17 patients. Elevated serum activities of gamma-glutamyltranspeptidase and/or aminotransferases were seen in 10 patients. In some, the elevation was only marginal and in none more than twice normal. The serum bilirubin concentration and activity of alkaline phosphatase were increased in 1 patient. Serum protein, albumin, fibrinogen, antithrombin III, alpha 1-fetoprotein concentrations, serum activities of cholinesterase and glutamate dehydrogenase, activated partial thromboplastin time and prothrombin time were normal in all patients. The indocyanine green half-life was abnormal only in 1 of 6 patients, suggesting that hepatic blood flow was not impaired in the study group. However, the lidocaine half-life and galactose elimination capacity, parameters of hepatic metabolization, were impaired in 4 and 6 of 7 patients, respectively. We conclude that liver disease or impaired liver function is not a clinically relevant problem in most patients with pulmonary emphysema due to alpha 1-antitrypsin deficiency. But results of quantitative liver function tests, although performed in only a small group of patients, suggest that hepatic metabolization might be impaired even in those patients who present with pulmonary disease.

Gastric distension has been used to evaluate gastric sensory function in humans, but the methodology is poorly validated and studies in vivo comparing different distension protocols are lacking. We aimed to compare the influence of the mode of gastric distension on sensation and gastric compliance utilizing a barostat device. In seven healthy volunteers, we positioned a barostat bag in the proximal stomach and tested in random order (in triplicate) four different distension protocols: (1) standard ramp distension with 4 mm Hg pressure step increments of 20 sec duration; (2) slow ramp distension with 2 mm Hg pressure increments of 40 sec duration; (3) random distension using a pressure ramp consisting of 2 mm Hg increments of 40 sec duration with randomly interposed pressure steps 50% below the preceding pressure step; and (4) rapid random distension with 4 mm Hg pressure increments of 10 sec duration with randomly interposed pressure steps 50% below the preceding pressure step. The distension procedures yielded mean airflow rates during the different distension protocols between 2.4 ml/sec for standard ramp and 18.4 ml/sec for rapid random distension. First perception and maximal tolerable pressure were 10.9 +/- 1.1 mm Hg and 19.6 +/- 1.5 mm Hg, respectively. First perception and maximal tolerable pressures were significantly correlated (r = 0.93, P < 0.005). The gastric pressure at occurrence of perception and the maximal tolerated pressure were not significantly different for the different distension protocols but gastric compliance was significantly reduced during rapid ramp distension (P < 0.01 vs slow ramp and P < 0.05 vs random distension) but not during standard ramp distension. We conclude that gastric sensory pressure thresholds as assessed by isobaric distension are not influenced by the mode of distension. The high correlation of pressure thresholds at first perception and maximal tolerated distension suggest a single population of gastric mechanoreceptors that mediate first sensation at low intensity stimulation and pain at intense stimulation.

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II, N = 6), and during endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Peptide YY (PYY) inhibits exocrine pancreatic secretion in several species. Two receptors, Y1 and Y2, are known to mediate PYY actions. While PYY 1-36 binds equally to both receptor subtypes, a second endogenous form of PYY, PYY 3-36, selectively activates Y2 receptors. The importance of Y receptor subtypes for inhibition of exocrine pancreatic secretion by PYY is unknown. We studied the effects of PYY 1-36 on cholecystokinin octapeptide (CCK-8)-stimulated amylase secretion in an isolated perfused rat pancreas model. To characterize functionally the receptors involved we determined the effects of a Y1-selective agonist, [Pro34]PYY; a Y2 selective agonist, PYY 3-36; and neuropeptide Y (NPY) in this model. PYY 1-36 significantly inhibited stimulated amylase secretion in the denervated rat pancreas. [Pro34]PYY and NPY both inhibited exocrine pancreatic secretion as potently as PYY 1-36. Contrary to that, the Y2 selective agonist, PYY 3-36, was inactive. We conclude that PYY inhibits exocrine pancreatic secretion in this extrinsically denervated rat pancreas model by Y1 receptors.

Objective: To study the incidence and prevalence of Crohn's disease in the Ruhr area of Germany. Participants: The population at risk comprised 1.6 million inhabitants in the four industrial cities of Essen, Oberhausen, Mulheim and Duisburg. All 35 hospitals in the area, including 79 in- and outpatient departments of internal medicine, surgery and paediatrics participated in the study. Methods: A prospective epidemiological study of the incidence and prevalence of Crohn's disease over 5 years from 1980 to the end of 1984. Results: Overall, 315 patients with Crohn's disease (181 women and 134 men) were newly diagnosed during the study period. The mean incidence was 4.0 new cases per 100000 inhabitants (range, 3.10–4.9) with no significant difference between the 5 years. Incidence figures were somewhat higher for women than for men (4.3 versus 3.6 per 100000 inhabitants, respectively), but this difference was significant only for those aged 20–29 years. The age- and sex-adjusted incidence was highest among those aged 20–29 years for both sexes with no second peak later in life. The prevalence of Crohn's disease on 31 December 1984 was calculated to be 36.0 per 100000 inhabitants (n = 556). Seventy-four per cent of cases living in the area were under 35 years of age and 44% were under 25 years; 30 were children under the age of 15 (5.4%). Conclusion: These figures for Crohn's disease range in the upper level of those reported for western industrial areas.

Two decades after Henderson put forward his hypothesis that the remarkable arrangement of the islets of Langerhans within the exocrine pancreas has a specific purpose(2), there is no doubt that insulin regulates both metabolism and secretion of pancreatic acinar cells. Teleologically this is only sensible, because digestion, absorption, and metabolism are not separate functions of the body, but closely related. Thus nutrients in the gastrointestinal tract will stimulate insulin secretion via nervous and hormonal pathways, summarized as the entero-insular axis(124), and the insulin released will not only regulate blood glucose, but will also potentiate exocrine pancreatic secretion. In addition, insulin also stimulates other acinar cell functions, such as transport of amino acids or glucose, as well as protein and enzyme synthesis. Thus, insulin has both short-term and long-term effects on the exocrine pancreas.

Background Patients with active Crohn's disease are often treated with corticosteroids, but the treatment has many side effects. Budesonide is a potent, well-absorbed corticosteroid, but because of a high rate of first-pass metabolism in the liver, its systemic bioavailability is low. Methods We conducted a randomized, double-blind, 10-week trial comparing the efficacy and safety of an oral controlled-release form of budesonide with the efficacy and safety of prednisolone in 176 patients with active ileal or ileocecal Crohn's disease (88 patients in each treatment group). The dose of budesonide was 9 mg per day for eight weeks and then 6 mg per day for two weeks. The dose of prednisolone was 40 mg per day for two weeks, after which it was gradually reduced to 5 mg per day during the last week. Results At 10 weeks, 53 percent of the patients treated with budesonide were in remission (defined as a score ≤ 150 on the Crohn's disease activity index), as compared with 66 percent of those treated with prednisol...

In a prospective study of the risk factors for duodenal ulcer relapse during maintenance (150 mg daily) ranitidine therapy, 1899 patients with chronic ulcer disease were recruited to a multicenter, German trial. Healing of all ulcers was confirmed endoscopically; endoscopy was also obligatory after one and two years or if the patients presented in the interim with symptoms of ulcer relapse. By the end of the first year, 247 patients had experienced at least one relapse and, by the end of the second year, 432 patients had relapsed at least once. The crude one- and two-year relapse rates were 13.0% (95% CI 11.5–14.5) and 22.7% (20.9–24.6%), respectively. Univariate analysis indicated that all seven prospectively defined risk factors were associated with an increased two-year relapse rate; of these, duodenal erosions distant from the healed ulcer [odds ratio (95% CI): 2.23 (1.59–3.15);P

Two endogenous forms of PYY are abundant in man and dog, PYY 1-36 (PYY-I) and PYY 3-36 (PYY-II). PYY-II is a major molecular form of PYY in human colon, but it is not known, whether PYY-II is also released into the circulating blood. Several radioimmunoassays for measuring PYY-I in plasma have been developed, but it has not been reported, whether they equally detect PYY-II. We characterize a radioimmunoassay for measuring PYY in human plasma which equally recognizes PYY-I and PYY-II. Using this radioimmunoassay and reversed phase HPLC we demonstrate the existence of two forms of PYY in human blood, coeluting with synthetic PYY-I and PYY-II.

Objective To test the efficacy and safety of zileuton 800 mg twice daily for up to 4 weeks against placebo. Design and setting A randomized double-blind, placebo-controlled multicentre trial including 76 outpatients with relapsing mild to moderately active ulcerative colitis from seven specialist gastroenterological departments in three countries. Main outcome measures 'Clinical response as defined by the dichotomous end points, CR25 and CR10, to combine improvement in both symptom and endoscopy scores [50% or more decrease in stool character and rectal bleeding scores, stable or improved scores of abdominal/rectal pain or urgency, and a 25% (CR25) or 10% (CR10) decrease in total sigmoidoscopy score] and leukotriene B4 concentrations in rectal dialysis fluid. Results Forty patients were randomized to zileuton and 36 to placebo; 45 patients received concurrent sulphasalazine, while 31 received no such medication. A clinical response occurred more often in the zileuton group and significantly so (P Conclusion More potent 5-lipoxygenase inhibition may reduce leukotriene B4 production further and improve clinical outcome. Hence, further studies of zileuton at higher doses and over a longer period of time seem worthwhile.

Objective: To study the course of chronic duodenal ulcer disease and the influence of risk factors on duodenal ulcer relapse after 2 years of maintenance treatment. Design: Prospective multicentre 1-year follow-up study in outpatients. Patients: Nine hundred and sixty-four patients with chronic duodenal ulcerations who had completed 2 years of maintenance treatment (ranitidine 150 mg daily). Main outcome measures: Duodenal ulcer relapse rate. Results: During the 1-year follow-up, 233 patients continued and 731 discontinued maintenance treatment. During this period, 27.7 relapses/100 patients per year [95% confidence interval (CI) 24.9-30.5] occurred compared with 169.4 relapses/100 patients per year (95% CI 144-196) before and 7.7 (95% CI 6.2-9.7) symptomatic and 2.2 (95% CI 1.3-3.3) asymptomatic relapses/100 patients per year during the 2 years of maintenance treatment

Objective: Previous studies have consistently found strong negative associations between smoking and ulcerative colitis [1-12]. Although earlier studies of sugar intake and ulcerative colitis found no association, it is possible that the relationship between sugar and ulcerative colitis could have been masked by the strong connection between this disease and non-smoking. Design: Case-control study examining the association between smoking and sugar intake in 82 patients and 111 controls. Results: Overall, there was no association between smoking and added sugar intake. After adjusting for smoking, there was no association between added sugar and ulcerative colitis, with the relative risk for no sugar compared with added sugar being 1.4 (0.70-2.9)

Cysteamine is known to deplete somatostatin from pancreatic D cells. In the isolated perfused rat pancreas we investigated its effects on somatostatin and insulin release as well as exocrine pancreatic secretion in the presence of 16.7 mM glucose and 180 pM CCK-8. At a concentration of 0.1 mM, cysteamine had no significant effect on pancreatic endocrine and exocrine functions. At 10 mM, however, cysteamine released somatostatin (380 +/- 70 vs 100 +/- 20 fmol/20 min), inhibited insulin output (890 +/- 120 vs 13210 +/- 3260 mu units/20 min) and reduced exocrine pancreatic secretion (volume: 12 +/- 2 vs 20 +/- 2 microliters/20 min; lipase: 31 +/- 3 vs 60 +/- 7 units/20 min). We conclude that the complex changes induced by cysteamine are consistent with a physiological role of endogenous somatostatin in the regulation of insulin release. The reduction of exocrine pancreatic secretion, however, was at least in part, if not completely, mediated via the insuloacinar axis rather than a direct effect of cysteamine-released somatostatin on pancreatic acinar cells.

A total of 2,109 outpatients with active duodenal ulcer (DU) entered an open, prospective study in order to investigate factors influencing healing and relapse during 2 years of ranitidine therapy (300 mg daily for healing, 150 mg as maintenance treatment). In a retrospective analysis, we evaluated the influence of age. Symptoms related to DU in 1,899 evaluable cases in patients over 65 years of age (n = 185) were identical to those of DU patients younger than 65 years old (n = 1,714). Rapid healing within 2 weeks of ranitidine therapy was less frequent in the elderly (32.5%) than in younger patients (40.7%) though identical healing rates (94.1%) in each group were achieved by continuation of ranitidine therapy for 8 weeks. Cumulative recurrence rates during the 2 years of long-term therapy were lower (17.3%) in old age than in patients under 65 years of age (23.3%). Adverse events were rare in both age groups. We conclude that DU healing during ranitidine is delayed in old age. Additional differences in relapse rates in favor of the elderly suggest that DU disease has a different course in the elderly.

The influence of the neuropeptide galanin, present in intrapancreatic nerve endings, on the endocrine pancreas is well known. The most potent effect of galanin is inhibition of insulin release. Little is known of its effect on the exocrine pancreas. Whether galanin plays a role in the regulation of exocrine pancreatic secretion and whether this effect is mediated directly on acinar cells or indirectly via the influence on insulin secretion is not clear. In the present study, we investigated these questions using the model of the isolated and arterially perfused rat pancreas with intact exocrine and endocrine secretion. In the presence of 15.8 mM glucose in a modified Krebs-Ringer buffer and during half-maximal stimulation of enzyme secretion with 100 pmol/ml cholecystokinin octapeptide (CCK-8), a dose-response study of 0.001-100 pmol/ml porcine galanin was performed. At concentrations of 0.001 and 0.01 pmol/ml, porcine galanin significantly stimulated insulin release (p < 0.05 and < 0.01, respectively) and also significantly enhanced CCK-8-stimulated amylase secretion (p < 0.05). Doses of 0.1 and 1 pmol/ml galanin resulted in a nonsignificant inhibition of insulin release, while 10 and 100 pmol/ml strongly inhibited the endocrine response (p < 0.001). However, concentration levels of 1-100 pmol/ml galanin did not affect CCK-8-stimulated amylase secretion. Rat galanin, tested at 0.01 and 10 pmol/ml, showed no significant difference from the effects of porcine galanin at the equipotent concentrations. It is concluded that the effect of galanin on exocrine pancreas, like the effect on endocrine functions, tends to be a direct one and that it could exert a modulatory influence on the level of neuronal transmission.