Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy with superior mesenteric-portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high-volume centre, and to examine trends in management and outcome over a decade for the latter procedure. METHODS: This retrospective observational study included all patients undergoing pancreatoduodenectomy with or without venous resection at Oslo University Hospital between January 2006 and December 2015. Trends were evaluated by assessing preoperative clinical and radiological characteristics, as well as perioperative outcomes in three time intervals (early, intermediate and late). RESULTS: A total of 784 patients had a pancreatoduodenectomy, of whom 127 (16·2 per cent) underwent venous resection. Venous resection resulted in a longer operating time (median 422 versus 312 min; P = 0·001) and greater estimated blood loss (EBL) (median 700 versus 500 ml; P = 0·004) than standard pancreatoduodenectomy. The rate of severe complications was significantly higher for pancreatoduodenectomy with venous resection (37·0 versus 26·3 per cent; P = 0·014). The overall burden of complications, evaluated using the Comprehensive Complication Index (CCI), did not differ (median score 8·7 versus 8·7; P = 0·175). Trends in venous resection over time showed a significant reduction in EBL (median 1050 versus 375 ml; P = 0·001) and duration of hospital stay (median 14 versus 9 days; P = 0·011) between the early and late periods. However, despite an improvement in the intermediate period, severe complication rates returned to baseline in the late period (18 of 43 versus 9 of 42 versus 20 of 42 patients in early, intermediate and late periods respectively; P = 0·032), as did CCI scores (median 20·9 versus 0 versus 20·9; P = 0·041). CONCLUSION: Despite an initial improvement in severe complications for venous resection during pancreatoduodenectomy, this was not maintained over time. Every fourth patient with venous resection needed relaparotomy, most frequently for bleeding.

Imatinib mesylate alleviates diarrhea in a mouse model of intestinal allergy.

BACKGROUND: When sensitized epicutaneously and challenged orally with ovalbumin, Balb/c mice develop allergen-induced diarrhea. As mast cells play important roles in diarrhea, we studied whether allergic diarrhea could be alleviated with imatinib mesylate. METHODS: Balb/c mice were sensitized and challenged with ovalbumin and treated orally with imatinib. Cytokine mRNA expressions were determined with quantitative RT-PCR and numbers of small intestinal mast cells determined by staining for chloroacetate esterase and mucosal mast cell protease-1. Immunofluorescence staining was used to assess the intestinal CCL1 expression. KEY RESULTS: Ovalbumin-sensitized and challenged Balb/c mice developed diarrhea, which was associated with increased number of mast cells and expression of interleukin (IL)-4 and -13, and chemokines CCL1 and CCL17 in the small intestine. Treatment with imatinib reduced the incidence of diarrhea, inhibited the development of mastocytosis and jejunal mRNA expression of IL-13, CCL1, CCL17 and CCL22. Mast cell-deficient W/W(-V) mice, and surprisingly, also their mast cell-competent control (+/+) littermates failed to develop diarrhea as a response to ovalbumin. This strain-dependent difference was associated with the inability of +/+ and W/W(-V) mice to increase the number of intestinal mast cells and expression of IL-4, IL-13, CCL1 and CCL17 after ovalbumin challenge. CONCLUSIONS & INFERENCES: Development of allergic diarrhea is associated with the ability of mice to develop intestinal mastocytosis. Imatinib inhibited the development of intestinal mastocytosis, reduced the incidence of diarrhea, and reduced the expression of IL-13, CCL1, and CCL17. Targeting intestinal mast cells could be a feasible approach to treat allergic diarrhea.

Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review.

B-cell-activating factor (BAFF) influences peripheral B-cell survival, maturation and immunoglobulin class-switch recombination and has a range of potential clinical implications. Biological functions of BAFF and its relevance in various clinical disorders including currently investigated BAFF-targeting therapies are reviewed and discussed based on PubMed search of relevant articles. Serum levels of BAFF are increased in autoimmune diseases including autoimmune hepatitis and primary biliary cirrhosis where BAFF concentrations are related to titres of autoantibodies and disease progression. Increased BAFF levels are found in synovial, bronchoalveolar and gut lavage fluids, suggesting local class switching and immunoglobulin production. Clinical relevance and diagnostic potential of BAFF are also noted in patients with allergic diseases, malignancies and infections including hepatitis C virus. BAFF antagonists are promising new therapeutic agents, currently being tried in B-cell-related autoimmune diseases. Serum level of BAFF may indicate disease mechanisms and the degree of activity. Determination of BAFF in different body compartments like synovium, airways and gut may also have clinical implications. Results of ongoing clinical trials with BAFF antagonists are eagerly awaited.

Intestinal B cell-activating factor: an indicator of non-IgE-mediated hypersensitivity reactions to food?

BACKGROUND: Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose. AIM: To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease. METHODS: Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid. RESULTS: B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE. CONCLUSIONS: The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions.

Magnetic resonance enteroclysis in the diagnosis of small-intestinal Crohn's disease: diagnostic accuracy and inter- and intra-observer agreement.

PURPOSE: To evaluate the diagnostic accuracy and inter- and intra-observer agreement of magnetic resonance enteroclysis (MRE) in patients with or without Crohn's disease of the small intestine. MATERIAL AND METHODS: 60 consecutive patients with or without Crohn's disease examined with MRE were included. Two observers independently reviewed the MRE examinations, searching for 12 pathological signs. The reference standard was ileoscopy or surgery of the terminal ileum performed in 41 patients. RESULTS: Crohn's disease of the small intestine was found in 24 (40%) patients. MRE findings of increased intestinal wall thickness, intestinal wall enhancement, intestinal wall ulcer, and inflammatory activity of the terminal ileum showed high sensitivity, specificity, and positive and negative predictive values. Intestinal stenosis had sensitivities ranging from 43% to 100%, depending on the cut-off value. Inter- and intra-observer agreement was good or excellent for most pathological signs. However, observer agreement of intestinal wall edema was only fair and moderate. CONCLUSION: MRE evaluated Crohn's disease with a high diagnostic accuracy in the terminal ileum. Most MRE variables were evaluated with good or excellent observer agreement, indicating that the method was highly reproducible. Our study supports the notion that MRE is an appropriate method for diagnosing Crohn's disease.

Effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage in patients with inflammatory bowel disease.

BACKGROUND: Iron deficiency is a common complication of inflammatory bowel disease. Oral iron therapy may reinforce intestinal tissue injury by catalyzing production of reactive oxygen species. AIM: To compare the effects of ferrous sulphate and non-ionic iron-polymaltose complex on markers of oxidative tissue damage and clinical disease activity in patients with inflammatory bowel disease. METHODS: Forty-one patients with inflammatory bowel disease and iron deficiency were randomized to treatment with ferrous sulphate 100 mg twice a day or iron-polymaltose complex 200 mg once a day for 14 days. RESULTS: Following ferrous sulphate, plasma malondialdehyde increased (P = 0.02), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not change significantly. Iron-polymaltose complex did not change plasma malondialdehyde, urine 8-isoprostaglandin F(2alpha) or plasma antioxidants. Comparing the two treatments, changes in plasma malondialdehyde tended to differ (P = 0.08), while urine 8-isoprostaglandin F(2alpha) and plasma antioxidants did not differ. Neither ferrous sulphate nor iron-polymaltose complex altered clinical disease activity indices. CONCLUSIONS: Ferrous sulphate increased plasma malondialdehyde, a marker of lipid peroxidation. Comparing treatment with ferrous sulphate and iron-polymaltose complex, changes in plasma malondialdehyde tended to differ. Clinical disease activity was unchanged after both treatments.

Reduced joint pain after short-term duodenal administration of seal oil in patients with inflammatory bowel disease: comparison with soy oil.

BACKGROUND: Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease (IBD). Because the high ratio of n-6 to n-3 fatty acids (FAs) of the Western diet might promote rheumatic disorders, we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain. METHODS: Nineteen patients with IBD-related joint pain were included in the study; 9 had Crohn disease and 10 had ulcerative colitis. Ten millilitres seal oil (n = 10) or soy oil (n = 9) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days. RESULTS: Compared with soy oil treatment, seal oil significantly reduced the duration of morning stiffness (P = 0.024), number of tender joints (P = 0.035), intensity of pain (P = 0.025) and the doctor's scoring of rheumatic disease activity (P = 0.025) at the end of the 10-day treatment period. Analysis of the effects as area under the curve (area between the curve and baseline, zero) for the entire period from start of treatment until 6 months' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain, whereas soy oil tended (not significantly) to aggravate the condition. Consistently, the serum ratios of n-6 to n-3 FAs (P < 0.01) and arachidonic acid to eicosapentaenoic acid (P < 0.01) were reduced after treatment with seal oil. CONCLUSION: The results suggest distinctive, differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil (significant improvement) and n-6-rich soy oil (tendency to exacerbation).

Ferrous fumarate deteriorated plasma antioxidant status in patients with Crohn disease.

BACKGROUND: Iron deficiency anaemia is a frequent complication of Crohn disease. Treatment with ferrous iron (Fe2-) compounds is often unsatisfactory and is associated with gastrointestinal side effects. Theoretically, oral iron supplementation may even be harmful, because iron may reinforce intestinal inflammation by catalysing production of reactive oxygen species. We investigated the effect of ferrous iron on disease activity and plasma antioxidant status in patients with active Crohn disease. METHODS: Ten patients with Crohn disease and iron deficiency and 10 healthy controls were given ferrous fumarate 120 mg for 7 days. The Crohn Disease Activity Index, gastrointestinal complaints and blood samples for antioxidant status, anaemia, inflammation and iron absorption were investigated on day 1 and day 8. RESULTS: During 1 week of ferrous fumarate supplementation, the Crohn Disease Activity Index tended to increase (P = 0.071). Patients experienced aggravation of diarrhoea, abdominal pain and nausea. Plasma-reduced cysteine was lower (P = 0.038) in patients than it was in controls. One week of ferrous iron supplementation further decreased reduced cysteine (P < 0.001) and significantly decreased plasma-reduced glutathione (P = 0.004) in the patients. Serum iron increased significantly in patients after an oral iron load test (from 5.8 +/- 3.2 micromol/L to 30.9 +/- 13.1 micromol/L). CONCLUSIONS: Treatment of iron deficiency with ferrous fumarate deteriorated plasma antioxidant status and increased specific clinical symptoms in patients with active Crohn disease. Plasma reduced cysteine may be a sensitive indicator for oxidative stress in the intestine.

Changes in food tolerance and lifestyle after eradication of Helicobacter pylori.

BACKGROUND: It is known that patients with peptic ulcer disease (PUD) often have an unhealthy lifestyle that results in increased mortality because of smoking-related diseases. No thorough study has been done to see what changes, if any, the patient makes to lifestyle after eradication of Helicobacter pylori. METHODS: One-hundred-and-eighty-three patients were enrolled in an open-endoscopy setting; 58% had PUD and 42% gastritis and/or duodenitis (G/D). They filled out a lifestyle questionnaire before the start of anti-Helicobacter therapy and again 1 year later. RESULTS: The prevalence of food intolerance decreased from 71% to 44% among patients with PUD (P < 0.0001) and from 76% to 63% among patients with G/D (P = 0.09). Tolerance improved for coffee, orange juice, fried foods, spicy foods and fruits. There was no significant change in smoking or alcohol consumption after eradication. Coffee and tea consumption was unchanged. Milk consumption decreased from 4.2 dL/day to 3.3 (P = 0.01). The number of meals decreased from 3.5/day to 3.4 (P = 0.005) and snacking from 1.3 snacks/day to 1.1 (P = 0.02). Consumption of fruit increased from 4.0 to 4.3 times/week (P = 0.04), but the frequency of meat, fish, vegetables, spicy foods, salty foods, sweets and cakes did not change. The time spent on each meal was unchanged. There was no change in the time spent exercising. There were few significant differences between PUD and G/D patients. CONCLUSIONS: Food was better tolerated, but there were no major changes in lifestyle after eradication of H. pylori. Patients therefore do not abuse the privilege of a more tolerant digestion by indulging in a more unhealthy lifestyle.

Eradication of Helicobacter pylori does not increase acid reflux in patients with mild to moderate reflux oesophagitis.

BACKGROUND: A substantial minority of patients with gastro-oesophageal reflux disease (GERD) are infected with Helicobacter pylori, but there is controversy as to whether these patients should be treated for their infection. We hypothesized that H. pylori eradication increases gastro-oesophageal acid reflux in such patients with time. METHODS: Thirty-five consecutive H. pylori-infected patients (16 M and 19 F) with mild or moderate reflux oesophagitis were enrolled. Twenty-four-hour intra-oesophageal (n = 35) and intragastric (n = 12) pH-metry was recorded before and 15 months after H. pylori eradication. Gastric biopsy specimens from the antrum and corpus were obtained from 10 consecutive patients before and 15 months after H. pylori eradication. RESULTS: Fifteen months after eradication of H. pylori there was a significant decrease in percentage time oesophageal pH < 4 in the recumbent position only (P = 0.04). Despite a marked reduction in the severity of gastritis, there was no significant change in gastric acidity, total intra-oesophageal acid exposure or symptom score. Heartburn improved in 12, worsened in 7. and remained unchanged in 16 patients (P = 0.36) without any significant relationship to individual changes in acid exposure (P = 0.60). CONCLUSIONS: H. pylori eradication does not increase gastric acidity or gastro-oesophageal acid reflux in patients with mild to moderate reflux oesophagitis over the first 15 months.

Cerebrotendinous xanthomatosis: molecular characterization of two Scandinavian sisters.

Cerebrotendinous xanthomatosis (CTX) is a hereditary disorder, which is inherited as an autosomally recessive disease, causing production of cholesterol and cholestanol xanthomas and mental retardation. The disease is caused by mutations in the gene for sterol 27-hydroxylase (CYP27A1). The only CTX patients diagnosed in Scandinavia are two Norwegian sisters from a consanguineous marriage. Here we have characterized the mutation and its functional consequences for the enzyme. Analysis of genomic DNA from cultured fibroblasts identified a base exchange C > T in position 1441, causing arginine at amino acid position 441 to be replaced by tryptophan. The same mutation was introduced by mutagenesis in the complimentary DNA (cDNA) for CYP27, ligated into the expression vector pcDNA4/HisMax and transfected into HEK293 cells. The mutated enzyme had less than 5% of the enzyme activity compared with the native enzyme. No abnormal catalytic products could be identified in the cell culture medium. Probably the mutation affects the haem binding within the holoenzyme. The mutation has also previously been reported in a Japanese family. This is the second example of a CTX-causing mutation that has been recognized in more than one population.

Controversies in dyspepsia.

Even in the absence of visible lesions like an ulcer, cancer or oesophagitis, patients with functional dyspepsia may complain of severe dyspeptic symptoms and have a poor quality of life. Characteristically, these patients also often have a low estimate of their own health and have complaints from several organ systems. The cause of the disease is not known. Both central nervous system and gastric disturbances appear to be involved, and their relative importance is controversial. There is no clear beneficial effect of acid suppression or H. pylori eradication although effects of such therapy may be seen in minor subgroups. New findings emphasise the importance of distinguishing between functional dyspepsia and gastro-oesophageal reflux disease, which exhibit completely different gastric accommodation patterns to a meal and have very different therapeutic potential. The effect of drugs like glyceryl trinitrate, glucagon, sumatriptan and buspirone which all concomitantly improve symptoms and gastric accommodation support the important role of abnormal gastric accommodation to meals in patients with functional dyspepsia. A hypothetical model for the pathogenesis of functional dyspepsia is presented. It incorporates four established abnormalities: various psychological abnormalities, low vagal tone, impaired gastric relaxation, and visceral hypersensitivity, in a logical interplay along the brain-gut axis.

[Gastrointestinal disease with elevated plasma homocysteine level]. / Gastrointestinal sykdom ved forhøyet plasma-homocysteinnivå.

Elevated plasma homocystein (tHcy) is a marker for functional deficiency of folate and/or cobalamin. Malabsorption of these vitamins occurs in various gastroenterologic diseases. A frequent mutation (C677T) in the gene coding for the enzyme methyltetrahydrofolate reductase (MTHFR) is often associated with elevated values of tHcy. We have investigated 24 patients with tHcy > 40 mumol/l for gastrointestinal disease that can contribute to such elevation. Of these, 19 were homozygous for mutated MTHFR, four were heterozygous and one was normal. We found two cases of probable celiac disease, one case of Crohn's disease and one case of ulcerative colitis. These four were homozygous for the C667T mutation. Furthermore, we found eight persons who were anacidic; four homozygous, three heterozygous and one normal. All had gastritis histologically, six had serum gastrin > 50 pmol/l, and four were already on treatment with cobalamin injections. Helicobacter pylori-infection was found in nine out of 22 persons. Gastrointestinal disease occurs frequently in patients with tHcy > 40 mumol/l, but with the exception of conditions resulting in serious deficiency of cobalamin, these diseases alone do not seem sufficient to cause such high levels. We suggest that a reasonable approach to patients with homocystein values above 40 mumol/l is to exclude cobalamin deficiency, and that further investigations should be based upon thorough anamnesis and symptoms.

Therapy and diagnostic tests used for Helicobacter pylori infection in the Scandinavian countries in 1998.

BACKGROUND: We wanted to ascertain how Helicobacter pylori infection is managed in Scandinavia. METHODS: A one-page questionnaire with seven questions was mailed in April 1998 to 1718 gastroenterologists in Finland, Denmark, Norway, and Sweden (excluding Swedish surgeons). RESULTS: The questionnaire was returned by 36%. Antimicrobials were used by 99% for peptic ulcer associated with H. pylori, by 67% for mucosa-associated lymphoid tissue lymphoma, by 27% before long-term therapy with a proton-pump inhibitor (PPI), by 16% for non-ulcer dyspepsia, by 11% for reflux disease, and by 11% for other indications. In Finland several conditions other than ulcer were treated more frequently than in the other countries. The commonest primary therapy is PPI triple therapy (94%), followed by bismuth-based (11%), 'other' (2%), and PPI dual therapy (0.2%). Primary bismuth-based therapy was almost completely limited to Norway. The commonest secondary therapy for failures was also PPI triple therapy (71%), followed by bismuth-based (41%), 'other' (10%), and PPI dual therapy (1%). Clarithromycin for primary therapy was used much less frequently in Finland than in the other countries. Follow-up to ascertain whether eradication is successful was done always or often by 90% in Finland, 63% in Norway, 62% in Sweden, and 21% in Denmark and by 61% of the internists and 42% of the surgeons. The commonest method to confirm eradication was gastroscopy (69%), followed by the breath test (52%) and serology (11%). CONCLUSIONS: In Scandinavia H. pylori associated with peptic ulcer disease is treated with antimicrobials by virtually all gastroenterologists. PPI triple therapy is the commonest regimen for primary and secondary eradication. PPI dual therapy has essentially disappeared. Fifty-four per cent confirm eradication always or often, with gastroscopy being the commonest method.

Increased mucosal production of monomeric IgA1 but no IgA1 protease activity in Helicobacter pylori gastritis.

Immunoglobulin A and IgM are subjected to epithelial transport only when they are produced as polymers with incorporated J chain. Immunocytes containing various Ig isotypes and associated J chain in gastric mucosa, as well as IgA-degrading protease activity in Helicobacter pylori cultures, were examined. Gastric body specimens from 15 H. pylori-positive and 14 H. pylori-negative patients were studied by paired immunofluorescence for IgA, IgA1, IgA2, IgG, or IgM and concurrent cellular J chain. H. pylori isolates were incubated with IgA1 or secretory IgA and examined by immunoelectrophoresis for cleavage products. A substantial increase of Ig-producing cells occurred in chronic gastritis, particularly in the IgA1 isotype, but H. pylori was shown to possess neither IgA1-specific nor nonspecific IgA-degrading protease activity. Regardless of infection status, reduced J chain expression was observed for all immunocyte isotypes (except for IgM) in inflamed compared with normal gastric body mucosa, the median positivity for IgA1 cells being reduced to 58.7% versus 87.9% (P = 0.0002), and for IgA2 cells to 48.9% versus 87.8% (P = 0.0002). This down-regulation of the J chain suggested that a large fraction of IgA monomers is produced in gastritis.

[Barrett esophagus--an increasing problem]. / Barretts oesophagus--et økende problem.

There has been a considerable increase in the incidence of adenocarsinoma in the proximal stomach (cancer of the cardia) and distal oesophagus (Barrett's cancer) for the past 20 years. There is probably also a parallel increase in the pathogenetically related conditions reflux oesophagitis and Barrett's oesophagus. In patients with classical Barrett's oesophagus, i.e., metaplastic changes in the mucosa more than 3 cm up from the gastro-oesophageal junction, a follow-up programme with endoscopy and adequate biopsies is recommended in cases where a finding of premalignant changes or malignancy will have therapeutic consequences. In "short segment" Barrett's oesophagus it is still not clear how extensive the biopsy and follow-up programme should be. It is also not clear whether other tests should be performed. Screening for malignancy, possibly by means of cancer-markers, and local treatment modalities of (pre-) malignant changes, are interesting possibilities that are being investigated.

Timing of postprandial dyspeptic symptoms and transpyloric passage of gastric contents.

BACKGROUND: Patients with functional dyspepsia often experience early satiety and discomfort after a meal. The role of early gastric emptying in symptom generation is not known. Our aim was to relate timing of symptoms and early postprandial emptying in functional dyspepsia. METHODS: Twelve patients with functional dyspepsia were investigated during 3 min of fasting, during 3 min of ingesting 500 ml of a meat soup, and during the first 10 min postprandially by means of duplex sonography. RESULTS: Gastric emptying commenced on average 52 sec after the start of ingestion. Transpyloric movements of gastric contents unrelated to peristalsis (that is, alternating transpyloric emptying and reflux within a common chamber created by the terminal antrum, the pylorus, and the duodenal bulb) appeared before peristaltic-related emptying, which commenced after on average 116 sec. In all patients epigastric, meal-related discomfort was experienced after the commencement of transpyloric emptying, on average after 143 sec. A negative correlation was found between intensity of fullness and duration of presymptomatic transpyloric movements of gastric contents (that is, the duodenal 'tasting' period). CONCLUSIONS: The early occurrence of meal-related symptoms suggests that gastric distension is the main factor in symptom generation. However, the onset of symptoms after the commencement of gastric emptying suggests that intestinal tasting receptors are involved in symptom generation. The inverse relationship between the duration of the tasting period and symptom intensity suggests that the time allowed for duodenal tasting might be too short in patients with FD.

Gastric meal accommodation and symptoms in diabetes. A placebo-controlled study of glyceryl trinitrate.

OBJECTIVE: To study mechanisms behind postprandial symptoms in patients with diabetes mellitus and the effect of nitric oxide (NO) on gastric accommodation and symptoms in these patients. DESIGN: A double-blind, placebo-controlled, randomized trial was designed in 20 patients with type 1 diabetes (10 male and 10 female, aged 35.3 +/- 7.6 years). METHODS: 0.5 mg sublingual glyceryl trinitrate (GTN), a donor of exogenous NO, or placebo was administered 5 min prior to a 500 ml soup meal. Gastric accommodation of the meal was assessed by abdominal ultrasound. Accommodation in proximal stomach was visualized in a sagittal area (Psa) and a frontal diameter (Pfd) and accommodation in distal stomach was visualized in a sagittal area of the antrum (Asa). Symptoms were assessed using visual analogue scales. RESULTS: Psa correlated significantly (r = 0.57, P = 0.015) with perception of fullness 5 min after the meal, whereas Pfd correlated significantly (r = 0.67, P = 0.004) with nausea at 15 and at 25 min after the meal. Asa correlated (r = 0.50, P = 0.05) with pain at 5 min, 10 min (r = 0.50, P = 0.05) and 25 min (r = 0.68, P = 0.007). GTN had no significant effect on Psa or Pfd, but reduced significantly (P = 0.05) Asa (1 3.5 +/- 4.5 cm2 with GTN vs 16.1 +/- 4.3 cm2 with placebo). GTN increased significantly (P = 0.04) the intragastric proximal/distal meal distribution ratio (proximal/distal sagittal area), but had no significant effect on symptom scores. CONCLUSION: In patients with diabetes, a large proximal stomach is associated with perception of fullness and a large antrum is associated with perception of pain after a meal. Sublingual administration of GTN prior to the meal decreases the antral area and improves the intragastric meal distribution, but fails to improve symptoms.

Flow across the human pylorus soon after ingestion of food, studied with duplex sonography. Effect of glyceryl trinitrate.

BACKGROUND: By means of duplex sonography, gastric emptying can be related to antral motor activity. The aim of this study was to examine gastric emptying in relation to antral contractions during and immediately after ingestion of a liquid meal in healthy subjects and to study the effect of glyceryl trinitrate (GTN) on this early phase of gastric emptying. METHODS: Ten healthy, non-smoking men (median age, 36 years; range, 29-41 years) were studied twice on separate days, once without drug administration and once after taking a 0.5-mg sublingual GTN tablet 3 min before ingesting 500 ml of a meat soup (20 kcal; Toro). The subjects were investigated during 3 min of fasting, during 3 min of drinking the soup, and during the first 10 min postprandially. RESULTS: Transpyloric forward flow commenced on average 80 sec and 95 sec after the start of drinking the soup without and with GTN, respectively (P = NS). Non-contractile, pulsatile transpyloric flow (that is, pendulating, transpyloric flow not associated with antral contractions) occurred during episodes of concurrent relaxation of the terminal antrum, the pylorus, and the duodenal bulb. This type of flow occurred mainly just before the start of contractile, pulsatile transpyloric flow (associated with propulsive antral contractions). Initial non-contractile, pulsatile transpyloric flow before commencement of contractile, pulsatile transpyloric flow lasted longer with GTN (188 sec) than without GTN (25 sec) (P < 0.05). Consequently, contractile, pulsatile transpyloric flow commenced later with GTN (302 sec) than without (102 sec) (P < 0.05). CONCLUSIONS: Non-contractile transpyloric flow seems to be a physiologic phenomenon during the early phase of gastric emptying. GTN prolongs the initial phase of non-contractile, and delays the onset of contractile, pulsatile transpyloric flow.

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract.

BACKGROUND/AIMS: Uncontrolled complement activation may be of immunopathological importance in inflammatory diseases of the gastrointestinal tract. Expression of membrane bound factors that regulate complement activation was therefore studied in situ. METHODS: Frozen tissue specimens were obtained from patients with Helicobacter pylori gastritis, coeliac disease, Crohn's disease, or ulcerative colitis, and from histologically normal controls. Sections were examined by immunofluorescence with monoclonal antibodies to protectin (CD59), decay accelerating factor (DAF), and membrane cofactor protein (MCP). RESULTS: Protectin and MCP were widely expressed in normal and diseased mucosae. MCP was generally observed basolaterally on all epithelial cells, whereas apical protectin expression was more intense on the epithelium of normal colonic mucosa than in the normal duodenum (p = 0.001). Epithelial DAF and to some extent protectin were upregulated in gastritis, coeliac disease, and inflammatory bowel disease. Areas of the stomach with intestinal metaplasia expressed DAF, unlike the adjacent gastric epithelium. Parietal cells of the gastric body expressed neither protectin nor DAF. CONCLUSION: Epithelial complement inhibitory molecules were expressed differently at various normal gastrointestinal sites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.