Abr Thomson

The effect of feeding a diet supplemented with lipids and containing 2% cholesterol on the endothelium-dependent relaxation of rabbit aorta to acetylcholine was assessed. The effect of feeding a standard rabbit diet after an initial period of 2% cholesterol feeding was assessed also. Age-matched male, New Zealand white rabbits were fed either a 2% cholesterol diet or a standard rabbit diet. The animals were anesthetized with pentobarbitone sodium (25 mg/kg) and killed either at the beginning of the study (0 weeks) or at 4, 8, or 10 weeks. The animals in the reversal study were fed the 2% cholesterol diet for 6 weeks and killed after an additional 14 and 32 weeks on standard diet. The extent of atherosclerosis in the aorta was assessed by Sudan Red staining, estimation of tissue cholesterol, and light and electron microscopy. The relaxation response to acetylcholine was measured in rings of the thoracic aorta following precontraction with norepinephrine (-6.0 log mol/l). The relaxation was significantly impaired in aortas from rabbits fed the 2% cholesterol diet compared to aortas from animals fed the standard diet. The impairment of relaxation was apparent as early as 4 weeks after the start of the 2% cholesterol diet and remained impaired over the next 6 weeks. No improvement in endothelium-dependent relaxation was seen in rabbits on the reversal diet for 14 and 32 weeks. Thus, endothelium-dependent relaxation is attenuated in animals fed a 2% cholesterol diet, and the loss of relaxation persists for at least 32 weeks after the animals are returned to a standard diet.

The first Canadian Helicobacter pylori Consensus Conference took place in April 1997. The initial recommendations of the conference were published in early 1998. An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations. Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it was decided that the urea breath test (not serology) should be used for routine diagnosis of H pylori infection unless endoscopy is indicated for another reason; and recommended therapies were a twice daily, seven-day regimen of a proton pump inhibitor (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg) or ranitidine bismuth citrate 400 mg, plus clarithromycin 500 mg and amoxicillin 1000 mg, or plus clarithromycin 500 or 250 mg and metronidazole 500 mg. The need was reiterated to have funding for readily accessible, accurate testing for H pylori infection with the urea breath test. It was strongly recommended that regional centres be established to monitor the prevalence of antibiotic-resistant H pylori infections. The initial consensus document referred to pediatric issues that were not addressed in this update but were the subject of a subsequent Canadian Helicobacter Study Group meeting, and will be published later in 1999.

ARTICLESIntestinal uptake of iron, cobalt, and manganese in the iron-deficient ratAB Thomson, and LS ValbergAB Thomson, and LS ValbergPublished Online:01 Dec 1972https://doi.org/10.1152/ajplegacy.1972.223.6.1327MoreSectionsPDF (721 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySex differences in the link between blood cobalt concentrations and insulin resistance in adults without diabetes27 March 2021 | Environmental Health and Preventive Medicine, Vol. 26, No. 1Preliminary report on osteochondrosis in cattle in the north-western parts of South Africa9 March 2016 | Onderstepoort J Vet Res, Vol. 83, No. 1Review of cobalt toxicokinetics following oral dosing: Implications for health risk assessments and metal-on-metal hip implant patients28 January 2015 | Critical Reviews in Toxicology, Vol. 45, No. 5Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d,,The American Journal of Clinical Nutrition, Vol. 99, No. 3Kinetics of manganese transport and gene expressions of manganese transport carriers in Caco-2 cell monolayers31 August 2013 | BioMetals, Vol. 26, No. 6A review of the health hazards posed by cobalt8 May 2013 | Critical Reviews in Toxicology, Vol. 43, No. 4Kinetics of Manganese Absorption in Ligated Small Intestinal Segments of BroilersPoultry Science, Vol. 87, No. 12Cobalt7 January 2008Iron Absorption30 May 2013Transferrin is required for normal distribution of 59Fe and 54Mn in mouse brainJournal of the Neurological Sciences, Vol. 170, No. 2The Nramp1 Protein and Its Role in Resistance to Infection and Macrophage FunctionProceedings of the Association of American Physicians, Vol. 111, No. 4Existing and emerging mechanisms for transport of iron and manganese to the brain11 March 2011 | Journal of Neuroscience Research, Vol. 56, No. 2Nramp1Black tea, green tea, and tea polyphenolsBiological Trace Element Research, Vol. 53, No. 1-3Manganese bioavailabilityFerrous iron uptake by rat duodenal brush border membrane vesicles: Effects of dietary iron level and competing minerals (Zn+2, Mn+2, and Ca+2)The Journal of Nutritional Biochemistry, Vol. 5, No. 12Effects of calcium and sugars on intestinal manganese absorptionBiological Trace Element Research, Vol. 39, No. 2-3Effekte einer steigenden alimentären Fe-Zufuhr auf die scheinbare Verdaulichkeit von Fe, Cu, Zn und Mn sowie auf die Gehalte dieser Elemente in Leber und GanzkörperJournal of Animal Physiology and Animal Nutrition, Vol. 67, No. 1-5Biliäre Fe-, Cu-, Mn-Exkretion und Galleflußrate bei enteralen oder bei parenteralen Fe-ZulagenJournal of Animal Physiology and Animal Nutrition, Vol. 65, No. 1-5Manganese and Iron Interrelationship in the ChickPoultry Science, Vol. 70, No. 1The binding of manganese to the brush-border membrane vesicles of rat small intestineNutrition Research, Vol. 9, No. 7Higher retention of manganese in suckling than in adult rats is not due to maturational differences in manganese uptake by rat small intestineJournal of Toxicology and Environmental Health, Vol. 26, No. 4Mechanisms of Intestinal Brush Border Iron TransportThe relative bioavailability of iron from feedstuffs of plant and animal origin to the chickNutrition Research, Vol. 8, No. 2Effect of Added Dietary Cobalt on Metabolism and Distribution of Radioactive Selenium and Stable MineralsJournal of Dairy Science, Vol. 70, No. 3Mechanism of the Tissue Manganese-Lowering Effect of Corn, Soybean Meal, Fish Meal, Wheat Bran, and Rice BranPoultry Science, Vol. 66, No. 2ManganeseCharacterization of non-transferrin-bound iron clearance by rat liver.Journal of Biological Chemistry, Vol. 261, No. 23MAMMALIAN MANGANESE METABOLISM AND MANGANESE UPTAKE AND DISTRIBUTION IN RAT HEPATOCYTESBinding of Iron by Lignin in the Presence of Various Concentrations of Calcium, Magnesium, and ZincJournal of Food Science, Vol. 50, No. 5The oral assimilation of radiomanganese by the mouseBiological Trace Element Research, Vol. 7, No. 2Fe-, Cu- und Mn-Konzentration in ausgewählten Organen und Geweben von Ratten nach unterschiedlicher Zn- und Ni-Versorgung9 October 2009 | Zeitschrift für Tierphysiologie Tierernährung und Futtermittelkunde, Vol. 53, No. 1-5Role of iron in jejunal uptake of cadmium in the newborn rat20 October 2009 | Journal of Toxicology and Environmental Health, Vol. 15, No. 5The influence of calcium and magnesium on manganese transport and utilization in MiceBiological Trace Element Research, Vol. 6, No. 6Effects of High but Nontoxic Dietary Manganese and Iron on Their Metabolism by CalvesJournal of Dairy Science, Vol. 67, No. 7Excess Manganese Ingestion in the ChickPoultry Science, Vol. 62, No. 4Neurological Consequences of Manganese ImbalanceEffects of chronic manganese (Mn 3 O 4 ) exposure on selected reproductive parameters in rats19 October 2009 | Journal of Toxicology and Environmental Health, Vol. 9, No. 4Chronic ingestion of MN 3 O 4 by rats: Tissue accumulation and distribution of manganese in two generations20 October 2009 | Journal of Toxicology and Environmental Health, Vol. 9, No. 2Factors affecting iron balanceAmerican Journal of Hematology, Vol. 10, No. 2IronDisorders of Iron MetabolismMedical Clinics of North America, Vol. 64, No. 4The effect of iron additive to milk on cadmium, mercury, and managanese absorption in ratsEnvironmental Research, Vol. 22, No. 1Dietary composition and the absorption of trace elements by ruminantsInterrelationships Between Iron and Lead Absorption in Iron-Deficient MiceGastroenterology, Vol. 77, No. 5Intestinal absorption of cobalt and iron: Mode of interaction and subcellular distributionBlut, Vol. 38, No. 5ManganeseIron Absorption: Present State of the ArtBritish Journal of Haematology, Vol. 31, No. s1Nutrition; Iron Undernutrition in Infancy2 July 2016 | Clinical Pediatrics, Vol. 13, No. 6 More from this issue > Volume 223Issue 6December 1972Pages 1327-1329 Copyright & PermissionsCopyright © 1972 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1972.223.6.1327PubMed4641623History Published online 1 December 1972 Published in print 1 December 1972 Metrics

Abstract Open-ended loops of rat duodenum, jejunum, and ileum were perfused with labelled solutions containing 5 mM. of manganese (Mn). In iron overload (FeL), similar amounts of Mn were absorbed from the 3 sites, but in iron deficiency (FeD) Mn absorption was increased from both the duodenum and jejunum. When the proximal intestine was perfused for 5 to 90 minutes with 5 mM. Mn, absorption occurred at a constant rate in FeL, and at an increased but constant rate in FeD. In FeL absorption was closely dependent upon doses of 0.25 to 10 mM. Mn; in FeD, a greater proportion of the test dose was absorbed from the smaller than from the larger doses. In FeD, the addition of 5 mM. iron (Fe) to the Mn perfusate competitively inhibited Mn absorption; conversely Mn reduced Fe absorption. Greater amounts of Fe than Mn were absorbed from an equimolar mixture. In FeL, neither metal affected the absorption of the other except when given in large doses. The results suggest that in Fe 2 Mn is absorbed largely by diffusion, whereas in FeD, Mn absorption in the proximal intestine is increased by the enhanced activity of a system which is dose-saturable and can be competitively inhibited by Fe. Duodenal perfusion of Mn in patients with varying iron stores confirmed that the rate of absorption was increased in FeD and that the enhanced absorption can be inhibited by Fe. Measurements of Mn 54 excretion 10 days after an oral dose showed no difference between control and FeD patients indicating that the increased Mn absorbed in FeD is not retained in the body.

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.

Fabry's disease is a rare, sex-linked disorder of glycolipid metabolism. We describe a patient with watery diarrhea, early satiety, and asymptomatic cholelithiasis. The jejunal aspirate demonstrated bacterial overgrowth; sigmoidoscopy showed rectal angiokeratoma corpora diffusum. The gastric emptying rate measured with 99mTc-sulfur colloid was markedly prolonged and the fasting gastrin was elevated at 276 pg/ml. The (14C)glycocholate breath test demonstrated a markedly elevated peak at 4 h, associated with an increased fecal bile acid loss of 0.82 g/day. Oral cholecystogram showed a solitary radiolucent stone in a functioning gallbladder. The bile acid pool size and lithogenic index were normal. Light microscopy of small bowel and rectal biopsy specimens revealed normal surface epithelium, but enlarged and vacuolated ganglion cells in Meissner's plexus. Electron microscopy showed laminated and amorphous osmiophilic deposits within ganglion cells of the submucosal plexus, within smooth muscle cells of the muscularis mucosae, and within endothelial cells lining arterioles, venules, and capillaries, but not in autonomic nerve fibers or enterocytes. The diarrhea and early satiety responded promptly to metoclopramide and to tetracycline. The early satiety was likely on the basis of delayed gastric emptying due to deposition of sphingolipid within ganglion cells of the autonomic nervous system; the diarrhea was likely on the basis of intestinal stasis with bacterial overgrowth and bile salt wastage.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To examine the effectiveness of psychotherapies for adults with a primary diagnosis of hypochondriasis.

A B S T R A C T Doseand time-response studies were performed in iron-loaded and iron-deficient rats in order to define, (a) the kinetics of absorption of cobalt and iron, (b) the nature of the inhibitory effect of one metal on the absorption of the other, and (c) the effect of variations in body iron stores on these processes.The duodenum was perfused for 5-90 min with labeled solu- tions containing 5.0 mm iron or 5.0 mm cobalt.In iron- loaded rats, the rate of cobalt absorption was constant for 90 min whereas the rate of iron absorption fell after 30 min.In comparison to these results, the rate of ab- sorption of both metals was increased in iron deficiency, and was more rapid in the first 30 min than in the 30-90 min period.To determine the response to varying doses of metal, we perfused duodenal loops for 30 min with 0.1-10.0mm solutions of either iron or cobalt.In both iron-loaded and iron-deficient groups, a greater propor- tion of the metals was absorbed from smaller than from larger doses.When iron and cobalt were perfused to- gether in iron-deficient animals, cobalt competitively in- hibited iron absorption, and conversely, iron reduced cobalt absorption.The apparent maximum transport ve- locity was similar for both metals, but the affinity for cobalt was greater than iron.The results suggest that the absorption of cobalt and iron is mediated by a transport system in which two processes operate simultaneously; the first is limited largely by the concentration of available metal in the lumen of the intestine, whereas the second process de- pends upon the activity of a mechanism which displays saturation kinetics and competitive inhibition.The for- mer process prevails when iron stores are replete, whereas the latter predominates when there is a need for iron, such as in iron deficiency.

The objective of this study was to determine whether soy fiber supplementation of total enteral nutrition formulas affected small intestinal recovery of nitrogen, amino acids, and carbohydrates or mucin output in eight human subjects (four males, four females) with ileostomies. The subjects ingested five test diets to provide 1.0–16.5 g soy fiber/L for 2 consecutive days each. The five test diets, each with a different soy fiber content were formulated by varying the relative proportion (1:0, 0.75:0.25, 0.5:0.5, 0.25:0.75, and 0:1) of two commercially available formulas. Effluent dry matter increased with soy fiber intake as a result of the quantitative recovery of soy fiber nonstarch polysaccharide. Nitrogen and amino acid digestibilities were unchanged by the ingestion of soy fiber. Nutrients from the total enteral nutrition formulas were well digested in the small intestine with true nitrogen and amino acid digestibilities in excess of 90% and starch digestibilities approaching 100%. Ileal mucin output was higher in male subjects and was unaffected by soy fiber intake. In summary, soy fiber supplementation does not compromise protein and carbohydrate absorption from the small intestine of humans.

SUMMARY Investigators : This multicentre study was conducted by 29 principal investigators in 11 countries. Aims : To compare the safety and efficacy of oral mesalazine (Mesasal/Claversal, 5‐ASA) 1.5 g b.d. in comparison with placebo in the maintenance of remission in 286 patients with Crohn's disease. Materials and Methods : Patients had to score less than 150 in their Crohn's Disease Activity Index (CDAI), and had to have had one period of clinical activity (CDAI > 150) within 18 months of the study start. Patients were randomized to receive 5‐ASA 1.5 g b.d. daily or matching placebo for 12 months. Study visits were scheduled for months 1, 3, 6, 9 and 12, or when symptoms suggested a relapse of the disease. Relapse was defined as a CDAI score greater than 150, with at least a 60‐point increase from the baseline index score. None of the patients used glucocorticoids or immunosuppressants during the trial. Results : In the first group, 207 patients with Crohn's colitis or ileocolitis were randomized: there were 101 females and 106 males, in age range 18–71 years. A total of 106 patients (51 in the 5‐ASA group and 55 in the placebo group) were withdrawn from the study due to adverse events, insufficient therapeutic effect, or for other reasons. This left 101 patients (51 in the 5‐ASA group and 50 in the placebo group) who completed the 12‐month trial. In the second group, 79 patients with Crohn's ileitis were randomized to treatment. There were 53 females and 26 males, age range 18–66 years. A. total of 41 patients (19 in the 5‐ASA group and 22 in the placebo group) were withdrawn from the study. This left 38 patients (17 in the 5‐ASA group and 21 in the placebo group) who completed the 12‐month trial. the primary efficacy variable was the CDAI. A protocol‐eligible analysis and an intent‐to‐treat analysis were performed. No statistical differences were noted Between the two analyses. In patients with Crohn's colitis or ileocolitis, or in those with ileitis, no statistically significant differences were noted with: espect to the relapse rates between the 5‐ASA and the, placebo treatment groups. Adverse events in the gastrointestinal system were the most frequently, eported in both treatment groups. Many of the events such as diarrhoea or abdominal pain are symptoms of crohn's disease. The majority of the events reported were mild or moderate in severity. In neither study was he prevalence of adverse events or the proportion of drop‐outs different between patients in the treatment or in the placebo groups. The site of the Crohn's disease had no effect on the frequency of adverse events. conclusion : The relapse rates of Crohn's disease were similar for up to 12 months in both the 5‐ASA 1.5 g b.d. and the placebo treatment groups.

Cisapride is a substituted benzamide with gastrointestinal prokinetic effects presumed to be due to the enhancement of the physiological release of acetylcholine at the myenteric plexus. In a multicentre study, 189 patients with nonulcer dyspepsia (NUD) received single-blind placebo treatment for two weeks. A total of 123 patients with no or minimal response to placebo and epigastric pain of at least moderate severity and frequency were randomly assigned to one of the three parallel double-blind treatments for six weeks: cisapride 10 mg tid, cisapride 20 mg tid or placebo. The severity and frequency of individual symptoms (epigastric pain, heartburn, nausea, vomiting anorexia, postprandial discomfort, regurgitation, lower abdominal pain, bloating and constipation) were assessed on a four- and five-point categorical scale, respectively, by the investigator at three on treatment visits and by patients in a daily diary. Analysis of investigator and patient assessments for differences in symptom severity x frequency composite scores among the three treatment groups showed no statistically significant differences for individual symptoms or symptom clusters. As assessed by the investigator, and compared with baseline, cisapride 20 mg tid significantly (P < 0.05) improved epigastric pain, bloating and early satiety as well as improved the total symptom cluster. Investigator evaluation of the five most severe and frequent symptoms for each patient showed statistically significant improvement in each treatment group. For patient diary assessments, statistically significant within-treatment improvement of the total symptom cluster, the five most severe symptoms cluster, bloating and early satiety was observed for both cisapride 20 mg and placebo, whereas epigastric pain significantly (P < 0.05) improved in all three treatment groups. Investigator evaluation of global response (good+excellent) rate at the end of the six week treatment period was 38% for cisapride 20 mg, 47% for cisapride 10 mg and 33% for placebo. No statistically significant difference in this parameter among treatments was noted. Cisapride was well tolerated at both doses with a side effect profile comparable with that of placebo. It is concluded that in this double-blind multicentre study with a single-blind two-week placebo run in phase, cisapride 10 mg tid and 20 mg tid were not effective compared with placebo in improving symptoms in NUD patients. This study re-emphasizes the good prognosis of patients with NUD, with 14% of patients improving in the two-week placebo run-in phase and a further 33% improving in the next six weeks while on placebo. Within-treatment analysis of investigator assessments showed improvement for cisapride 20 mg tid suggesting a trend of efficacy at this dose.

Summary Background : Adult Helicobacter pylori ‐positive patients by 13 C‐urea breath test with uninvestigated dyspepsia symptoms were randomized to 1‐week eradication treatment with omeprazole, metronidazole and clarithromycin (OMC) vs. omeprazole and placebo antimicrobials (OPP) in the Canadian Adult Dyspepsia Empiric Treatment— H. pylori ‐positive (CADET‐ Hp ) study. Aim : To perform an economic evaluation of this 1‐year study. Methods : Following blind eradication treatment, family practitioners managed patients according to their usual practices. Health resource utilization information was collected prospectively. From the mean costs of the health resources consumed and the treatment outcomes, the incremental cost‐effectiveness ratios and incremental net benefits of eradication treatment vs. OPP were determined. Results : Eradication therapy significantly improved dyspepsia symptoms (treatment success: OMC, 50%; OPP, 36%; P = 0.02). The incremental cost‐effectiveness ratio of OMC vs. OPP was − 387 Canadian dollars (CAD$) per treatment success (90% CI, – CAD$1707, CAD$607), indicating a lower cost with treatment success. The incremental net benefit analysis showed that H. pylori eradication was cost‐effective if the willingness‐to‐pay value exceeded a nominal figure of CAD$100 from a health service perspective or CAD$607 from the societal perspective. Conclusion : In uninvestigated patients presenting with dyspepsia at the primary care level, eradication of H. pylori in those who are H. pylori positive leads to a cost‐effective improvement in dyspepsia symptoms compared with a strategy of not eradicating H. pylori in these patients.

ARTICLESEffect of varying iron stores on site of intestinal absorption of cobalt and ironAB Thomson, C Shaver, DJ Lee, BL Jones, and LS ValbergAB Thomson, C Shaver, DJ Lee, BL Jones, and LS ValbergPublished Online:01 Mar 1971https://doi.org/10.1152/ajplegacy.1971.220.3.674MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByDietary intake of trace elements from commercially important fish and shellfish of Thoothukudi along the southeast coast of India and implications for human health risk assessmentMarine Pollution Bulletin, Vol. 173Annex D: absorption and retention of radionuclides17 May 2016 | Annals of the ICRP, Vol. 36, No. 1-2Annex F17 May 2016 | Annals of the ICRP, Vol. 36, No. 1-2Iron status influences trace element levels in human blood and serumEnvironmental Research, Vol. 98, No. 2Trace Elements in Blood and Serum of Swedish Adolescents: Relation to Gender, Age, Residential Area, and Socioeconomic StatusEnvironmental Research, Vol. 89, No. 1Endogenous excretion and true absorption of cobalt as affected by the oral supply of cobaltBiological Trace Element Research, Vol. 41, No. 1-2Problems in Diagnosis of Iron Deficiency AnemiaPediatric Annals, Vol. 14, No. 9The Effect of Methionine or Cysteine on Cobalt Toxicity in the ChickPoultry Science, Vol. 60, No. 6Transferrin, biochemistry, physiology and clinical significanceMolecular Aspects of Medicine, Vol. 4, No. 1Intestinal iron absorption in chickensBiological Trace Element Research, Vol. 2, No. 4Interrelationships Between Iron and Lead Absorption in Iron-Deficient MiceGastroenterology, Vol. 77, No. 5Intestinal absorption of cobalt and iron: Mode of interaction and subcellular distributionBlut, Vol. 38, No. 5Cobalt induced changes in immune response and adenosine triphosphatase activities in rats21 November 2008 | Journal of Environmental Science and Health, Part B, Vol. 14, No. 5Interrelationships of lead and iron retention in iron-deficient miceToxicology and Applied Pharmacology, Vol. 46, No. 3Effect of iron absorption on plasma membrane proteins of small intestinal mucosal cells from iron-deficient ratsBiochemical and Biophysical Research Communications, Vol. 73, No. 4Comparison of chemical and microbiological methods in the estimation of methionine in cowpea (Vigna unguiculata) seeds9 March 2007 | British Journal of Nutrition, Vol. 36, No. 02Kinetics of the subcellular distribution of iron and cobalt in the intestinal mucosa of the ratThe American Journal of Digestive Diseases, Vol. 21, No. 4Excessive vitamin D content of a standard iron-deficient diet for rats25 March 2008 | British Journal of Nutrition, Vol. 35, No. 2Integrity of the Iron Transport Process in Mice with X-Linked Anaemia24 April 2009 | Scandinavian Journal of Haematology, Vol. 14, No. 5Cobalt absorption in sex-linked anemic miceThe American Journal of Clinical Nutrition, Vol. 26, No. 4Iron Transport by Rat Small Intestine in Vitro: Effect of Body Iron StatusBritish Journal of Haematology, Vol. 23, No. 5Pharmaceutical Sciences—1971: Literature Review of PharmaceuticsJournal of Pharmaceutical Sciences, Vol. 61, No. 7 More from this issue > Volume 220Issue 3March 1971Pages 674-678 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.3.674PubMed5545674History Published online 1 March 1971 Published in print 1 March 1971 Metrics

ARTICLESKinetics of intestinal iron absorption in the rat: effect of cobaltAB Thomson, and LS ValbergAB Thomson, and LS ValbergPublished Online:01 Apr 1971https://doi.org/10.1152/ajplegacy.1971.220.4.1080MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByIntersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver14 September 2018Mechanisms and Regulation of Intestinal Iron TransportKinetics of iron absorption by in situ ligated small intestinal loops of broilers involved in iron transporters1Journal of Animal Science, Vol. 94, No. 12Molecular Mechanisms of Intestinal Iron TransportMorphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticityWorld Journal of Gastroenterology, Vol. 15, No. 7The Regulation of Cellular Iron Metabolism10 October 2008 | Critical Reviews in Clinical Laboratory Sciences, Vol. 44, No. 5-6Intestinal mucosal adaptationWorld Journal of Gastroenterology, Vol. 12, No. 29Manganese transport by caco-2 cellsBiological Trace Element Research, Vol. 67, No. 1Iron status alters the adsorption, uptake, and absorption capacities of rat duodenum for ferrous and ferric ironNutrition Research, Vol. 15, No. 8Iron speciation at physiological pH in media containing ascorbate and oxygen9 March 2007 | British Journal of Nutrition, Vol. 70, No. 1Iron Deficiency and Megaloblastic AnemiasContributions of heme and nonheme iron to human nutritionCritical Reviews in Food Science and Nutrition, Vol. 31, No. 4Mucosal iron in the control of iron absorption in a rat intestinal transplant modelGastroenterology, Vol. 100, No. 2Forms of soluble iron in mouse stomach and duodenal lumen: significance for mucosal uptake9 March 2007 | British Journal of Nutrition, Vol. 63, No. 1Trace Metal Interactions Involving the Intestinal Absorption Mechanisms of Iron and ZincIron Absorption and Iron OverloadClinics in Gastroenterology, Vol. 10, No. 3Intestinal iron absorption in chickensBiological Trace Element Research, Vol. 2, No. 4Interrelationships Between Iron and Lead Absorption in Iron-Deficient MiceGastroenterology, Vol. 77, No. 5Intestinal absorption of cobalt and iron: Mode of interaction and subcellular distributionBlut, Vol. 38, No. 5Capacity of the mucosal transfer system and absorption of iron after oral administration in ratsBlut, Vol. 38, No. 2Kinetics of the subcellular distribution of iron and cobalt in the intestinal mucosa of the ratThe American Journal of Digestive Diseases, Vol. 21, No. 4Integrity of the Iron Transport Process in Mice with X-Linked Anaemia24 April 2009 | Scandinavian Journal of Haematology, Vol. 14, No. 5Effect of Various Factors on Iron Absorption in Mice with X-linked AnaemiaBritish Journal of Haematology, Vol. 27, No. 4Iron Transport by Rat Small Intestine in Vitro: Effect of Body Iron StatusBritish Journal of Haematology, Vol. 23, No. 5Pharmaceutical Sciences—1971: Literature Review of PharmaceuticsJournal of Pharmaceutical Sciences, Vol. 61, No. 7 More from this issue > Volume 220Issue 4April 1971Pages 1080-1085 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.4.1080PubMed5551134History Published online 1 April 1971 Published in print 1 April 1971 Metrics

Cholestasis complicates total parenteral nutrition (TPN) in preterm infants. Ursodeoxycholic acid (UDCA) is used for several cholestatic problems. The hypothesis of this study was that intravenous UDCA prevents TPN-induced cholestasis by (1) maintaining normal basal and stimulated bile flow, (2) altering bile composition, and (3) changing hepatocyte membrane composition and Na+,K(+)-adenosine triphosphatase (ATPase) activity.Three groups of piglets were studied: group 1 received sow's milk, groups 2 and 3 received TPN, and group 3 also received 100 mumol.kg-1.day-1 UDCA intravenously. After 3 weeks, basal and stimulated bile flow were measured. Cholesterol, bile acids, phospholipids, and phospholipid fatty acids were analyzed in bile, and fluidity, phospholipid fatty acid composition, and Na+,K(+)-ATPase were analyzed in hepatocyte membranes.Bile acid secretion and basal and stimulated bile flow were similar in control and UDCA-treated animals but reduced to < 50% in the TPN group. Bile acid-dependent and -independent bile flow were lower in the TPN group. UDCA did not normalize abnormalities in TPN-induced bile composition. Sinusoidal but not canalicular membrane fluidity was different in TPN than in control and UDCA-treated animals. UDCA also increased Na+,K(+)-ATPase activity. Bile and membrane phospholipid fatty acids reflected dietary fatty acids.Intravenous UDCA improves bile flow and reduces bilirubin levels in the serum and liver in piglets with TPN-induced cholestasis.

The effect of Trasylol® on serum and urine amylase activity and on the occurrence of clinical pancreatitis associated with ERCP was evaluated in 61 patients by a double-blind randomized study. The frequency of clinical and biochemical changes was unrelated to the duration of the procedure, the number of ducts cannulated, or abnormalities in the ducts. The administration of Trasylol® before and after ERCP failed to prevent or signif ica nt ly reduce the frequency or magnitude of elevations in serum or urine amyiase activity or to prevent postexamination abdominal pain. The effect of Trasylol® on serum and urine amylase activity and on the occurrence of clinical pancreatitis associated with ERCP was evaluated in 61 patients by a double-blind randomized study. The frequency of clinical and biochemical changes was unrelated to the duration of the procedure, the number of ducts cannulated, or abnormalities in the ducts. The administration of Trasylol® before and after ERCP failed to prevent or signif ica nt ly reduce the frequency or magnitude of elevations in serum or urine amyiase activity or to prevent postexamination abdominal pain.

The utility of endoscopy in the management of patients with symptoms of gastroesophageal reflux disease (GERD) is unclear. The purpose of this prospective study was to assess the impact of endoscopy on the subsequent management of patients with uncomplicated reflux symptoms.A total of 742 patients underwent endoscopy for symptoms of GERD. Endoscopists recorded the therapy before endoscopy, the findings of endoscopy, and the treatment recommendations after endoscopy.There was no difference in pre-endoscopy therapy or grade of esophagitis in subjects undergoing endoscopy for failed therapy versus GERD symptoms alone. After endoscopy, the most common strategy for patients taking omeprazole was to maintain or increase the dose. For those taking an H2 blocker before endoscopy, the most common outcome was to switch the patient to omeprazole, independent of the grade of esophagitis.Most patients undergoing endoscopy for symptoms of GERD were switched to omeprazole regardless of the endoscopic findings. No esophageal cancer was identified and the incidence of Barrett's esophagus was low. It appears that endoscopy itself did not change the management of patients receiving H2-blocker therapy. A trial of a proton pump inhibitor before endoscopy should be considered.

Systemic steroids have been used in gastrointestinal disorders, such as ulcerative colitis and Crohn's disease. However, glucocorticosteroids are associated with potentially serious adverse effects. For that reason there is a search for a steroid which would have rapid first‐pass metabolism in the intestine and liver, low systemic bioavailability, high topical activity and rapid excretion. This review will consider the absorption, transport, metabolism, mechanisms of action, general effects and effects of steroids on the intestine, and the new steroids in particular.

Gastroesophageal reflux disease (GERD) is a disease with serious consequences that may result in significant impairment in quality of life and disease morbidity. Across all grades of severity of symptoms and severity of underlying esophageal disease, proton pump inhibitors (PPIs) provide therapeutic gains over prokinetics (PKs) or H 2 receptor antagonists (H 2 RAs). The potential cost effectiveness of using medications with higher acquisition costs that may lower health care costs overall is often disregarded when conducting cost comparisons with medications having lower 'up-front' costs. Limiting therapy to less effective agents condemns many patients to protracted suffering, repeated physician visits and needless reinvestigation of symptoms that could have been resolved by appropriate initial therapy. Based on current data, use of any classification of symptom severity as a basis for selecting one class of therapeutic agents over another for first line therapy (ie PKs, H 2 RAs for 'mild' GERD, versus a PPI for 'severe' disease) is unwarranted.

A prospective study was undertaken to establish the role of individualized diet counselling in the management of 137 outpatients with Crohn’s disease. Individualized dietary counselling for 6 months was associated with a significant decrease in the Crohn’s disease activity index, an increased incidence of disease remission, a decreased need for prednisone and Salazopyrin® therapy, a reduction in the number of days spent in hospital, and a reduction in the amount of time lost from work due to Crohn’s disease, when compared with control patients who did not receive dietary counselling but who were seen regularly in follow-up under similar circumstances. Improvement with diet counselling was more likely to occur in patients who had not previously been subjected to small bowel resection, and occurred in patients with active or inactive disease. The effect of counselling 58 patients was assessed over a further 6 months (for a total 12-month period); there was a persistently reduced Crohn’s disease activity index and a continued decreased number of lost days of work. The mechanism for these beneficial effects of diet counselling was not established. It is suggested that individualized diet counselling, aimed at optimizing the patient’s nutritional status, may play a role in the management of patients with Crohn’s disease.

Nutrient uptake (Jd) is enhanced in diabetes mellitus (DM) in the rat; these studies were undertaken to determine the effect of 2 wk dietary modification on the Jd of fatty acids, fatty alcohols, and glucose. In control (C) rats, fatty acid Jd was lowest with the low essential fatty acid diet, but the incremental change in free energy (integral of delta Fw leads to l) was not affected by the other diets; in DM integral of delta Fw leads to l was lower with the low cholesterol or high carbohydrate diets, and higher with the high cholesterol diet. The effective resistance of the intestinal unstirred layer was assessed from the Jd of lauryl alcohol. In C intestinal unstirred layer was lowest in the high carbohydrate group and highest in the low cholesterol group; intestinal unstirred layer was less in DM than in C only in the rats fed the low cholesterol diet. In C, varying the protein content of the diet was associated with a rise in the value of the maximal transport rate and the Michaelis constant, but a decline in the passive permeability coefficient for glucose. Glucose Jd was increased in DM rats fed a high carbohydrate or a high cholesterol diet; the values of the Kms were similar in DM and C, but the maximal transport rates were higher in the DM than in the C and these values were influenced by dietary modifications. Thus short-term dietary modification influences intestinal unstirred layer, integral of delta Fw leads to l, and the kinetic constants for Jd of glucose in control and diabetic rats.

Thirty-five anemic patients with rheumatoid arthritis were studied to determine the relationship between serum ferritin levels and body iron status, as assessed by the grading of bone marrow iron stores. The incidence of greatly reduced or absent marrow iron stores was 60%. Peripheral blood smear, RBC indices, serum iron, and iron binding capacity correlated poorly with stainable marrow iron. Serum ferritin levels only correlated approximately with iron stores, and in iron deficient rheumatoid patients the levels were higher than would be expected in patients with uncomplicated iron deficiency. The study shows that reduced marrow iron stores is common in patients with rheumatoid arthritis, and that the serum ferritin concentration may provide a useful indication of reduced body iron stores in these subjects, but only if a range of normal values can be established for this disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used.Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation.There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.

Serum retinol and serum carotene concentrations were determined over a 6-month period in 137 outpatients with Crohn's disease. Serum retinol measurements were within the reference range for all patients at each assessment period, while serum carotene levels were low in about one quarter of the patients. Of the 56 patients who completed 48-hour stool collections, 41% had stool fat values exceeding the reference value. Serum retinol concentrations were not significantly correlated with the serum carotene concentrations, with the 48-hour stool fat content, or with the Crohn's disease activity. In contrast serum retinol concentrations were correlated with the dietary levels of vitamin A. Serum carotene concentrations were inversely correlated with the stool fat content but were not related to Crohn's disease activity or dietary levels of carotene or total vitamin A. Thus: (1) serum retinol concentrations were normal in this moderately large group of patients with Crohn's disease and did not reflect a low dietary vitamin A intake by 34% of the population; (2) serum carotene levels were frequently low in patients with Crohn's disease, possibly due to the presence of steatorrhea, but were not related to low dietary intakes of carotene or to active Crohn's disease, and (3) a low serum level of carotene does not indicate that the patient is at risk of developing vitamin A deficiency.

We wished to test the hypothesis that variations in the luminal content of bile acid produced by feeding chenodeoxycholic acid (CDC), ursodeoxycholic acid (UDC) or cholestyramine (C) alter intestinal transport properties and morphology. Rats were fed standard chow pellets containing 0.5% CDC, 0.5% UDC or 2 % C for a period of 2 weeks, and the in vitro uptake of glucose, cholesterol, bile acids and a homologous series of fatty acids was assessed. The food consumption was similar in animals fed chow, CDC, UDC and C, yet rats fed CDC or UDC gained less weight, and the weight of the jejunal and ileal mucosa was lower in animals fed CDC or C than in those fed chow or UDC. Ileal but not jejunal uptake of glucose was reduced in animals fed UDC, CDC or C. The active ileal uptake of bile acids was enhanced by UDC, CDC or C, whereas the jejunal passive permeability to bile acids was reduced by feeding C. Feeding C inhibited the jejunal and ileal uptake of cholesterol; C, UDC and CDC had a variable effect on the intestinal uptake of the fatty acids 10:0–18:0. The jejunal mucosal surface area was lower in groups fed CDC or UDC as compared with rats fed chow or C, and the ileal mucosal surface area was lower in rats fed CDC. However, the altered intestinal transport could not be explained by the altered morphology. Thus, (1) chronic variations in the intestinal luminal content of bile acids produced by the feeding of CDC, UDC or C resulted in alterations in the active and passive transport properties of the intestine, and (2) these changes differed between the jejunum and the ileum and were not explained simply by alterations in the animals’ food intake or mucosal morphology. These studies suggest that chronic variations in the bile acids in the intestinal lumen may be one of the factors independently influencing the transport properties and mucosal surface area of the intestine. The long-term effect of changes in luminal bile acid content on intestinal function in man remains to be established.

Olestra is a fat substitute made from sucrose and vegetable oil. Olestra is neither digested nor absorbed, and therefore adds no calories or fat to the diet. Because the gut is the only organ that is exposed to olestra, the potential for olestra to affect gastrointestinal structure and function, and the absorption of nutrients from the gut, has been investigated. Histological evaluations performed after long-term feeding studies have shown no indications that olestra causes injury to the gastrointestinal mucosa. Olestra is not metabolized by the colonic microflora, and has no meaningful effects on the metabolic function of these organisms. Studies of gastrointestinal transit have shown that the consumption of olestra with food does not affect gastric emptying, or small or large bowel transit times. Olestra does not affect the absorption of macronutrients, water-soluble vitamins or minerals. It causes a dose-responsive decrease in the availability of the fat-soluble vitamins A, D, E and K; however, this potentially adverse effect is offset by the addition of vitamins to olestra-containing foods. Olestra has no consistent effect on the amount of total bile acids excreted in the faeces, and therefore probably has no significant effect on bile acid absorption. The occurrence of gastrointestinal symptoms, including diarrhoea, loose stools, gas and abdominal cramping, after consumption of olestra under ordinary snacking conditions is comparable to that following consumption of triglyceride-containing snacks.

The symmetry of osmotic conductivity of the canine tracheal epithelial cells was examined in vitro. When an osmotic load of 100 mosM sucrose was added to the serosal bathing solution, no change in the transepithelial potential difference was observed in 15 tissue preparations. In contrast, when the same osmotic load was added to the mucosal bathing solution, there was a rapid decrease in the transepithelial potential difference of 3.9 +/- 0.5 mV (n = 23); ouabain (10(-4) M) eliminated this change. Tissues that had been exposed to the osmotic load added to either the mucosal or serosal side were compared with the control using light and electron microscopy. When the osmotic load was added to the mucosal fluid, there was no change in the nuclear-to-cytoplasmic area ratio of the cell types examined. However, when the same osmotic load was added to the serosal fluid, a marked increase in the nuclear-to-cytoplasmic area ratio of the ciliated cells was observed. This finding indicated cell shrinkage. Dilution potentials measured by substituting NaCl with mannitol also showed asymmetry. The morphological features are probably caused by differences in the osmotic conductivity (Lp) of the basolateral and apical cell membranes, with the Lp of the apical membrane being less than that of the basolateral membrane. The basis for osmotically induced potentials remained undetermined.

Vitamin C intake, and serum and leukocyte ascorbate levels were assessed serially over 6 months in 137 outpatients with Crohn's disease. Vitamin C intake was low in 18% of males and 37% of females. Serum ascorbate levels were suboptimal in 11% of males and 18% of females. Leukocyte ascorbate levels were low in 26% of males and 49% of females. Serum ascorbate levels were more frequently below the reference range in patients who smoked, but neither the serum nor the leukocyte ascorbate levels were affected by Crohn's disease activity, the use of an oral contraceptive agent, or by taking prednisone or sulfasalazine. Monthly diet counseling sessions significantly increased vitamin C intake, led to more patients consuming a normal ascorbate intake, and to a normalization of serum ascorbate values. We did not establish the importance of these ascorbate abnormalities on the clinical course of Crohn's disease. We conclude that low serum or leukocyte ascorbate levels are relatively common in patients with active or inactive Crohn's disease; these abnormalities are due in part to the reduced intake of dietary ascorbate; and the ascorbate status in patients with Crohn's disease may be normalized by improving the dietary intake of vitamin C.

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The objective of this study was to investigate the influence of food on the bioavailability of omeprazole (20 mg) given as an enteric-coated tablet under repeated dose conditions. This open randomized crossover study consisted of three seven-day treatment periods, each separated by a drug-free period. During each treatment period an enteric-coated tablet of omeprazole was taken once daily either under fasting conditions, or immediately before or after a standardized breakfast. On the last day of each treatment period, blood samples for the determination of plasma omeprazole concentrations were collected at baseline and at predetermined intervals over the 24 h period following drug administration. Fifty-seven male and female subjects, aged 18 to 52 years, completed the study according to the protocol. No statistically significant differences were found when comparing either the before breakfast or after breakfast treatment regimens with the fasting regimen for the estimated mean area under the plasma concentration-time curve (AUC). The maximum plasma concentration was not found to differ significantly among any of the treatment regimens. However, the lower limit of the CI for the comparison of fasting/before breakfast was not contained within the limits of bioequivalence. The time to reach maximum plasma concentration was significantly different when fasting and after breakfast regimens were compared. Thus, under repeated dose conditions, food has no influence on the bioavailability (expressed as AUC) of omeprazole given as the enteric-coated tablet formulation.

Incorporation of [1- 14 C]palmitic (16:0) and [1- 14 C]linoleic (18:2ω6) acids into microsomal membranes of proximal (jejunum) and distal (ileum) regions of rat small intestine was investigated, and the lipid composition, including fatty acid profiles of membrane phospholipids, was determined. Jejunal microsomes contained significantly higher amounts of total phospholipids, phosphatidylcholine, and phosphatidylinositol, and lower amounts of cholesterol and sphingomyelin when compared with ileal microsomes. Jejunal microsomal phospholipids contained higher levels of stearic (18:0), 18:2ω6, and eicosapentaenoic (20:5ω3) acids followed by reduced levels of oleic (18:1ω9), arachidonic (20:4ω6), and docosahexaenoic (22:6ω3) acids when compared with those from the ileum, except for phosphatidylinositol where no significant difference between 20:4ω6 content of each site was observed. In both jejunal and ileal microsomes, incorporation of [1- 14 C]18:2ω6 was significantly higher than that of [1- 14 C]16:0. Incorporation of both [1- 14 C]16:0 and [1- 14 C]18:2ω6 was significantly higher in jejunal microsomal lipid fractions (phospholipids, diacylglycerols, triacylglycerols) when compared with the ileal microsomal fraction. These data suggest that (1) jejunal and ileal microsomal membranes differ from each other in terms of lipid composition and lipid synthesis, (2) site variations in the specificity of acyltransferases for different fatty acids exist, and (3) higher Δ9-, Δ6-, Δ5-, and Δ4-desaturase activities exist in ileal compared with jejunal enterocytes.

This paper attempts to estimate the cost of inflammatory bowel disease (IBO) to the health care system of Alberta. In the 1015 patients responding to a questionnaire, two types of direct costs were compared to provincial averages; physicians' fees and hospital costs. Costs were calculated using the Alberta Health Care Insurance Plan prescribed billing races. The 15-to 24-year-old age group exhibited the highest annual physician fees. This was probably due to the high incidence rate of IBD in this group. The mean cost per patient-year for Crohn's disease was estimated to be $4400 and the mean cost for ulcerative colitis was estimated to be $3020; this did not include outpatient laboratory or radiological investigations, and as such represents an underestimation of the total costs to the health care system. However, only a small minority of the patients were using a large majority of the resources: for example, for both Crohn's and ulcerative colitis, 7% of the patients accounted for 69% of hospital days. The average hospital and physician associated costs declined markedly with duration of the disease. It is estimated that the future cost of IBO to the provincial health care system (the percentage of the provincial health care budget used to diagnose and treat IBO) will double from 1985 to 2000. This underscores the need for continued and expanded research into the cause and treatment of IBO, and the importance of maintaining a health care system which can respond to the needs of these patients.

Recent evidence has suggested that transport of nutrients from the lumen to the interior of the gastrointestinal epithelium and exit of nutrients from the enterocyte to the circulation is governed by physicochemical properties of brush border and basolateral membranes, respectively. The main determinants of membrane properties are phospholipid, cholesterol, and fatty acyl chain composition (chain length and degree of unsaturation). Lipid synthesis occurs in enterocyte microsomes and the fine tuning of lipid composition is done at other subcellular sites by deacylation-reacylation or by changing the polar head group (e.g., by phosphatidylethanolamine methyltransferase). The present paper will focus on the mechanisms by which enterocyte membranes adapt functional properties in response to external stimuli. It is proposed that under the influence of internal or external stress, the enzymes of lipid metabolism in microsomes are modulated. These changes in lipid synthesis are reflected in other subcellular membranes, changing their physicochemical status and thus transport phenomena. One of the initial events appears to be alteration in desaturase enzyme activity. Our results suggest that desaturase activity and the fatty acyl profiles of the intestinal mucosal phospholipid rapidly respond to physiological conditions such as fasting and dietary fat treatment.

The bioelectric and barrier properties of the tracheal epithelium in nose-breathing dogs and in dogs that had been exposed for 75 min to compressed air or to two high concentrations of SO2 were measured and compared. We also studied tissues that had been treated with chloroform. Based on a model of restrictive diffusion we demonstrated heteropores (6 and 250 A) in the control tissues. Bioelectric changes due to 100-ppm SO2 were minimal. After exposure to 500 ppm SO2, adverse changes in the bioelectric properties were focal; they were marked in 8 out of 12 animals but were less striking in the other 4. Nonelectrolyte permeability increased with an increase in SO2 concentrations. Small pores were still present in the tissues severely affected by SO2 but they were absent in chloroform-treated tissues. Scanning electron microscopy of tissues from animals exposed to 500 ppm SO2 showed that in the same dog tissue appearance varied from normal to one of repair (normal bioelectric properties) or one of marked exfoliation of ciliated cells (abnormal bioelectric measurements).

Analysis of a modified 14C-glycocholate breath test on 165 consecutive in-patients being investigated for chronic diarrhea showed that the measurement of 14CO2 between 3 and 6 h after oral dosing of 5 microCi of 14C-glycocholic acid was of only limited use to distinguish between patients with Crohn's disease (CD), idiopathic bile salt wastage (IBW), or ileal resection (IR) from those with the irritable bowel syndrome (IBS). Continuing 14CO2 collections for up to 24 h was of little more help in establishing the presence of bacterial overgrowth syndrome (BOS) and in distinguishing between BOS and CD. Stool bile acid measurements were of use in differentiating between IBW and IBS, but did not distinguish between CD and BOS or between CD and IR. Since the range of normal values was defined by measurements in the IBS group, a positive test was specific for an organic cause of chronic diarrhea. Even so, the sensitivity of the test was relatively low: CD, 53%; IR, 23%; IBW, 14%; and BOS, 10%. We believe that the 24-h 14C-glycocholic breath test combined with the measurement of stool bile acids represents a screening test of only limited use for the identification of organic causes of chronic diarrhea.

A prospective controlled 6-month study was undertaken to compare the effect of Ensure, a defined formula dietary supplement, and diet counselling in 122 outpatients with Crohn's disease. The compliance to Ensure was poor due to a high incidence of side effects. Taking any amount of Ensure reduced the need for surgery and the amount of hospitalization. There was a trend for patients receiving Ensure to experience a decline in the value of their Crohn's disease activity index (p less than 0.10). No consistent effects of Ensure were seen on the amount of work missed due to Crohn's disease, in laboratory measurements, in the need for prednisone or Salazopyrin. The vitamin B12 intake was improved, but otherwise nutrient intake declined due to a decreased food intake. Thus, certain beneficial clinical trends were associated with taking Ensure, but larger numbers of compliant patients will need to be studied to better assess the long-term role of defined formula diets in the management of outpatients with Crohn's disease.

Eradication of Helicobacter pylori from the gastric and duodenal mucosa is an important clinical goal in the treatment of infected patients with peptic ulcer disease and other H pylori -associated conditions. Although several oral drug combination regimens are associated with eradication rates of approximately 85% in controlled trials, the success rate in patients infected with a resistant strain of H pylori is closer to 75%. Resistance to metronidazole and clarithromycin, which are common components of combination treatment regimens, is of greatest concern. Reported rates of H pylori resistance to various antibiotics vary considerably. In Canada, the data documenting H pylori susceptibility are limited but suggest that resistance to these antibiotics varies geographically and within specific treatment groups. Although susceptibility testing is not a prerequisite for initial treatment of individual patients infected with H pylori , formal efforts to identify and monitor both the causes and prevalence of antibiotic resistance across Canada are a much needed step in the ongoing management of this important infection. Recommended treatment regimens may be useful, even for treating apparently resistant H pylori strains. However, it is important to understand the mechanisms of the development of resistant strains to manage patients with treatment failure better.

Radiotherapy continues to enjoy a prominent role in the treatment of certain human tumors. Unfortunately, the undesired effect of radiation upon normal intestinal tissue often limits its therapeutic potential. While there is abundant information on the effects of radiation on the morphology of the intestine and on the proliferative process which occurs in the intestinal crypts, there is a paucity of information on the early and late effects of sublethal doses of radiation upon the absorptive functions of the intestine. The intestinal epithelium has a rapid turnover rate and is highly radiosensitive. Radiotherapy for malignant human neoplasms is a relatively safe and effective form of treatment, but it may become limited by its undesired side effects upon the gastrointestinal tract. A variety of clinical tests have been suggested as potential indicators of impending intestinal damage, but there is little information on the time course of radiation damage and the associated impairment of intestinal function. Such basic information is essential to assess early functional changes and to thereby allow for the development of suitable clinical tests to allow for the prediction of impending intestinal damage. Provision of this information to the radiotherapist would permit alterations to the timing or dose schedules of radiotherapy and would allow continued treatment, while avoiding or reducing unwanted side effects. In recent years, there has been extensive research on radiation injury to small intestine. This article will review some of the progress in this field, and will focus on potential future therapy to prevent or treat radiation damage to the intestine. These agents include WR-2721, enprostil, vasopressin, defined-formula diets and alterations in the ratio of dietary polyunsaturated-saturated fatty acids.

Alterations in transport function have been described 6 weeks after surgical resection of 50% of the distal small intestine. Previous studies demonstrated a modest increase in the jejunal uptake of medium chain length fatty acids following resection, while the uptake of many other lipids (cholesterol, bile acids, fatty alcohols, short and long chain length fatty acids) appears to be unaffected. Marked changes in the kinetic constants for the carrier-mediated uptake of four sugars and leucine were observed following resection, but the changes in transport were not associated with changes in the mucosal surface area. This study was undertaken to examine the possible adaptive mechanisms that occur with ileal resection in the rabbit. A 29% increase in the wet weight of jejunal mucosal scrapings and a 53% increase in jejunal brush border membrane (BBM) protein was observed following resection. The jejunal BBM sucrase (S) was unchanged following ileal resection, but alkaline phosphatase (AP) total activities were increased in the resected rabbits. This resulted in a 45% increase in the ratio of AP/S with resection. The lipid composition (total free fatty acids, total bile acids, total cholesterol, total phospholipids, individual phospholipids, and the ratio of total phospholipids/total cholesterol) of BBM was similar in control and resected rabbits. This suggests that quantitative rather than qualitative changes in the membrane composition may be responsible for the transport changes observed in resected animals.

With the exponential increase in research in the field of Helicobacter pylori a paradigm shift has occurred. It is now recognized that H pylori is a chronic infection of the stomach causing inflammation. Some patients remain asymptomatic, while others may develop dyspepsia, duodenal or gastric ulcer, gastric cancer or a mucosa-associated lymphoid tissue lymphoma. However, the role of H pylori in contributing to nonulcer dyspepsia or nonsteroidal anti-inflammatory drug gastropathy remains controversial. An effective vaccine against H pylori is years away. Major interest has focused on the questions "who should be investigated and therefore treated" and "what is the latest gold standard for eradication of H pylori "? In Europe, guidelines have been developed to help the practitioner answer these important questions. Canadian guidelines will soon be available. For persons with known peptic ulcer disease there should be unequivocal acceptance that the good clinical practice of eradicating H pylori will result in substantial savings in health care expenses. The original 'classical triple therapy' (bismuth, metronidazole and tetracycline [BMT]) has now been surpassed by the combination of a proton pump inhibitor (PPI) plus two antibiotics (metronidazole plus clarithromycin; amoxicillin plus clarithromycin; or amoxicillin plus metronidazole), each given twice a day for one week. In Canada, the regimen of omeprazole plus one antibiotic (amoxicillin or clarithromycin) was approved recently but gives an eradication rate that is lower than the current target of 90%. According to the European (Mäastricht) recommendations, if a single treatment attempt with PPI plus two antibiotics fails, PPI plus BMT is recommended.

Two cases of Crohn's disease in a husband and wife are described and compared with the seven previously reported cases of chronic idiopathic inflammatory bowel disease occurring in spouses.

The unstirred water layer (UWL) and the brush-border membrane represent the major barriers to intestinal absorption. Enhanced uptake of several nutrients has been described in diabetes mellitus, and this study was undertaken in the rat to define whether these absorptive changes are due to alterations in the characteristics of these barriers. Using in vitro techniques the effective resistance of UWL was measured with lauryl alcohol, the rate of uptake (Jd) of which is limited by diffusion across the UWL. At all rates of stirring of the bulk phase, the effective resistance of UWL was less in diabetic than control rats. The Jd of a homologous series of saturated fatty acids (4:0-18:0) and cholesterol was higher than disks of intestine of diabetic than control intestine; this enhanced uptake of lipid could not be demonstrated using intestinal biopsies. The change in incremental free energy of transfer of fatty acid uptake into disks was higher in diabetic than control animals after correction for UWL effects. After correction for UWL, the Michaelis constant for Jd of D-glucose was similar in diabetic and control jejunum, and the greater Jd of glucose in diabetics was due to a higher maximal transport rate (Jmd) and a higher passive permeability coefficient. It is concluded that the enhanced uptake of glucose, fatty acids, fatty alcohols, and cholesterol into diabetic intestine is due to a reduction in the effective resistance of the UWL, an increase in the passive permeability properties of the membrane, and a rise in the Jmd for D-glucose.

The baseline permeability of small bowel in 57 healthy volunteers was assessed by measuring the mannitol and chromium-EDTA recovery in a 5-hour urine collection after ingestion of a drink containing a mixture of 1 g of mannitol and 3.7 MBq of 51Cr-EDTA. Subjects were treated with medication for 1 week followed by permeability studies as described above. The regimens used were diclofenac sodium (Voltaren) 50 mg po tid (21 subjects), Voltaren SR 75 mg bid for 1 week (34 subjects), indomethacin 50 mg tid (10 subjects), and tenoxicam (Mobiflex) 20 mg daily (13 subjects). There was no significant difference between the mannitol recoveries at baseline or after any of the drugs. The permeability was clearly increased by indomethacin and by Voltaren SR. Conventional-release Voltaren increased permeability, but the results were not significantly above baseline. Mobiflex had no influence on the measured permeability. Our results suggest that the SR preparation of diclofenac has a more pronounced effect than regular diclofenac sodium; thus different NSAIDs and different preparations of the same NSAID may have different effects on small bowel permeability.

In the past year, there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 1500 papers were assessed. Some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist. Relevant review articles have been highlighted, and important clinical learning points have been stressed. The topics are varied in scope and wherever possible show a logical progression from basic physiology to pathophysiology to clinical disorders and management.

This study was undertaken to determine the effect of chronic feeding of ethanol on the in vitro jejunal uptake of lipids and glucose. The first group of rabbits was fed ad libitum (CAL); the food intake of a second control group [weight control (WC)] was restricted to match their gain in body weight with that of a chronically ethanol-fed group (ETH); and the food intake of a third control group [food control (FC)] was restricted to match the food intake with that of ETH. There was a marked decline in cholesterol uptake in WC and FC compared with CAL, and cholesterol uptake in ETH was intermediate between the higher value in CAL and the lower value in WC and FC. The uptake of fatty acids 4:0-12:0 was similar in the CAL, FC, WC, and ETH groups, both when the bulk phase was stirred and unstirred; the uptake of fatty acids 16:0 and 18:0 was lower in WC and FC than in CAL; and the uptake of fatty acids 14:0, 16:0, and 18:0 was even lower in ETH. The uptake of a homologous series of fatty alcohols was greater in WC and ETH than in CAL at five different rates of stirring of the bulk phase. When the uptake of fatty acids 6:0-12:0 was corrected for unstirred layer resistance, a linear relation was noted between fatty acid chain length and the natural logarithm of rate of uptake/aqueous diffusion coefficient, and the steeper slope in WC and ETH than in CAL represented a higher incremental change in free energy. Glucose uptake was similar in CAL, WC, and FC but was greater in ETH from 5 to 40 mM glucose. These studies demonstrate that 1) weight restriction, food restriction, and chronic ethanol feeding are associated with a change in the effective resistance of the unstirred layer and in the passive permeability properties of the rabbit jejunum, and 2) ethanol has a differential effect on passive permeation of short-, medium-, and long-chain fatty acids and cholesterol.

As techniques for immune suppression improve, the clinical utility of small bowel transplantation will increase. Recent reports of long-term (over 1 year) survival with totally enteral nutrition following bowel transplantation have increased interest in this area and prompted the present review of the state of the art of small bowel transplantation. Background methodology is emphasized, in order to allow for more critical review of reported models, and to provide a framework for comparing results. The functional capacity of bowel following transplantation, and the effects of immune suppression on bowel function are reviewed in detail. Prospects for future direction in basic and clinical research are discussed.

The authors tested the hypothesis that the intestinal morphology and uptake of nutrients after resection of the distal half of the small intestine of rats responds to alterations in the dietary content of saturated (SFA) and polyunsaturated (PUFA) fatty acids. Adult female Sprague-Dawley rats were subjected to a sham operation or to the surgical resection of the distal half of the small intestine, leaving the ileocecal valve intact. The animals were fed chow for 3 weeks, then either chow or isocaloric semisynthetic SFA or PUFA diets for a further 2 weeks. Food consumption, weight gain and jejunal mucosal surface area were unchanged after ileal resection. A microdensitometric autoradiographic technique was used to examine the distribution of 3H-leucine and 3H-lysine along the villus: approximately 70% of uptake occurred in the upper 30% of the enterocytes of the villus in chow-fed rats, and this portion was unchanged by ileal resection. The jejunal uptake of 40 mM of glucose, observed in vitro, was twice as high in animals that had undergone resection and were fed SFA than in those fed PUFA. In summary, (1) there is a separation between the adaptation of intestinal transport function and dynamic/static morphology after ileal resection, and (2) glucose uptake after ileal resection is enhanced by SFA in the diet and is not explained by any changes in the animals' food intake, weight gain or intestinal morphology.

Enprostil®, a synthetic E2 prostaglandin, was administered in a dose of 5 μg/kg body weight by gastric tube to rats for 14 days following abdominal irradiation with a single dose of 600 cGy from a 137Cs source. Enprostil® prevented the body weight loss and the reduced food intake observed in irradiated animals given placebo, and also prevented the irradiation-associated decline in the mucosal weight and surface area of the ileum. Enprostil® given to nonirradiated animals reduced the maximal transport rate (Vmax) and the apparent Michaelis constant (Km*) for the ileal uptake of D-glucose, but did not prevent the irradiation-associated decline in the ileal uptake of glucose. Thus, there is a dissociation of the effects of Enprostil® on the morphological and the absorptive properties of the intestine. It is concluded that a 2-week course of a daily oral dose of E2 prostaglandin begun shortly after a single exposure to nonlethal abdominal irradiation prevents the radiation-associated reduction in the intestinal mucosal surface area and the animal’s body weight, but does not prevent the malabsorp-tion of glucose.

In-depth meetings of the XIth International Workshop on Gastroduodenal Pathology and Helicobacter pylori led to the presentation and discussion of extensive new data on H. pylori and its diseases. The mode of transmission of H. pylori remains unclear, and it remains unknown why only a small proportion of infected individuals develop duodenal or gastric ulcer disease and even fewer develop gastric cancer. The role of H. pylori eradication in persons with uninvestigated dyspepsia remains controversial. New clinical trials of H. pylori treatment show symptom relief and improvement in the quality of life of persons with functional dyspepsia, especially in those with ulcer-like or reflux-like dyspepsia. Clearly the move is toward symptom-based management of persons with dyspepsia, with fewer endoscopies being needed in the otherwise healthy young dyspeptic patients. It remains controversial whether eradicating H. pylori in duodenal ulcer or functional dyspepsia increases the risk of subsequent development of gastroesophageal reflux disease. The one-week proton pump inhibitor-based triple regimens remain the gold standard of H. pylori therapy, but some of the ranitidine bismuth citrate plus two antibiotic regimens also achieve an 80% H. pylori eradication rate on an intention-to-treat basis. While the urea breath test remains the noninvasive test of choice, interesting new data are available on the use of stool antigen testing to diagnose H. pylori infection. The number of H pylori-associated gastroduodenal diseases grows to include possible liver, vascular, immune and skin conditions.

The rate of uptake (Jd) of cholesterol into the intestine is influenced by the effective resistance of the unstirred water layer, the concentration of the probe molecule at the aqueous-membrane interface, and the passive permeability characteristics of the membrane. This study was undertaken to determine the influence of the bile acid micelle and the unstirred water layer on the Jd of cholesterol into rabbit jejunum, using everted sacs, full-thickness biopsies, and disks. When the bulk phase was stirred and the resistance of the unstirred layer was low, there was a linear relation between cholesterol concentration in the bulk phase and Jd when the concentration of taurodeoxycholic acid (TDC) was constant, but increasing TDC in the presence of a constant concentration of cholesterol was associated with a decline in Jd. When the concentration of both TDC and cholesterol was varied but the ratio of TDC to cholesterol was maintained constant, Jd increased slightly. The Jd of cholesterol was higher into sacs than into biopsies, which in turn was greater than into disks; Jd into disks was much lower when the resistance of the unstirred layer was high. These results suggest that 1) the bile acid micelle serves to provide a reservoir for partitioning of the cholesterol from the micelle into the aqueous phase from which the cholesterol is absorbed; 2) the Jd of cholesterol into disks of jejunum is influenced by the effective resistance of the unstirred water layer; and 3) although the quantity of cholesterol Jd varies markedly between sacs, biopsies, and disks, the qualitative aspects of the role of the bile acid micelle in cholesterol absorption were similar using the different in vitro techniques.

This study compared the 24 h intragastric pH profile and bioavailability at repeated dosing conditions of the omeprazole 20 mg enteric-coated tablet versus the 20 mg capsule. Forty duodenal ulcer patients in asymptomatic remission completed this randomized open two-way crossover study. Omeprazole 20 mg tablets or capsules were administered for seven days in each period. A 24 h pH recording was performed before the start of treatment and on day 7 of each treatment period. Plasma concentrations of omeprazole were determined 24 h after the dose. The treatment periods were separated by two to four weeks. The difference in percentage of time with pH of at least 3 was less than 16% in favour of the tablet (not significant). The estimated mean area under the plasma concentration-time curve as well as the maximum plasma concentration (Cmax) for omeprazole were 18% and 41% higher, respectively, for the tablet versus the capsule, with the latter percentage being statistically significant. The time to reach Cmax (tmax) with the tablet was, on average, about 0.5 h longer than to reach the tmax of the capsule. This study indicates that the enteric-coated tablet formulation of omeprazole is biodynamically equivalent to the capsule regarding their effects on intragastric pH during repeated dosing.

Na(+)-K(+)-adenosinetriphosphatase (ATPase) plays a key role in the absorption of electrolytes, water, and nutrients from the small intestine. The expression of Na(+)-K(+)-ATPase was examined in isolated enterocytes during the course of the ileal inflammatory response elicited by intraluminal administration of 2,4,6-trinitrobenzenesulfonic acid. The ileal inflammatory response was characterized by a marked cellular infiltrate, villous atrophy, and crypt hyperplasia along with fibrosis and smooth muscle hypertrophy. Peak levels of myeloperoxidase were observed at day 7, and ileal mucosal injury was paralleled by increases in ileal mucosal permeability. Ileal enterocytes were harvested from days 3 to 30 after the induction of ileitis. Decreases in Na(+)-K(+)-ATPase functional activity were observed from days 3 to 21 and were accompanied by corresponding decreases in Na(+)-K(+)-ATPase pump abundance, alpha 1- and beta 1-protein expression, and mRNA abundance, whereas Na(+)-K(+)-ATPase turnover, Michaelis-Menten constant values, and inhibition constant values for Na+ and ouabain, respectively, were unaltered. Alterations in transcriptional and posttranscriptional events may determine the changes in Na(+)-K(+)-ATPase activity in this particular model. Additionally observed increases in thymidine kinase and ornithine decarboxylase activities appear to signify alterations in the state of differentiation of the ileal epithelium and may determine the phenotypic expression of enterocyte transporters and permeability in the setting of inflammation.

Modern medical therapy is increasingly based on evidence. The evidence presented here is that budesonide (Entocort, Astra Pharma) 9 mg/day is superior to placebo and equivalent to systemically active glucocorticosteroids in achieving disease remission in patients with active Crohn's disease, and in prolonging the recurrence time of symptomatic disease. Budesonide causes less disturbance to adrenal function than prednisone or prednisolone and may cause fewer steroid-associated symptoms. Thus, budesonide is the safer, more effective steroid of choice to treat patients with Crohn's disease.

The efficacy of anatacid in the treatment of benign gastric ulcer is less well established than in the treatment of duodenal ulcer. The objective of this study was to monitor ulcer healing and symptom relief in 38 patients with gastric ulceration treated for 6 weeks with cimetidine (Tagamet®) 300 mg q.i.d. or an aluminum-magnesium containing antacid (Mylanta II®) 10 ml q.i.d. (acid neutralizing capacity 203.2 mEq/day). The study was single-blind; the study physicians and those providing endoscopic assessments were not aware of the patients' treatment. Entered into the study were 19 male and 19 female patients ranging in age from 17 to 70 years, with a mean age of 52 years. None of the patients had taken cimetidine in the previous month, and none abused alcohol or nonsteroidal anti-inflammatory agents, but two-thirds of the patients were smokers. Five patients in the antacid group withdrew for numerous reasons including continued pain, noncompliance, and side effects. All patients in the cimetidine group completed the study, and no side effects were noted. There was no difference between the antacid- and the cimetidine-treated patients in the relief of symptoms. There was a significant difference in the 6-week ulcer healing between the groups, with 14/9 (74%) healed in the cimetidine group compared with only 6/4 (43%) healed in the antacid group (p > 0.025). Thus, Mylanta II, 10 ml four times daily, is comparable to cimetidine 300 mg q.i.d. in the symptomatic relief of benign gastric ulceration, but ulcer healing was superior using cimetidine.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.

This study was done to determine whether sigmoidoscopy could theoretically constitute sufficient investigation for some patients with bright red rectal bleeding.One hundred and forty-three patients undergoing investigative colonoscopy for bright red rectal bleeding and whose source of bleeding was identified were studied. The investigation took place in a large urban hospital over an 11-month period. Data obtained included changes in stool pattern, characteristics of the bleeding, lesions identified, and the distance of the lesion from the anus.In patients younger than 55 yr, all serious lesions except for one malignancy in a patient with massive bleeding lay within 60 cm of the anus and theoretically within reach of the fiberoptic sigmoidoscope. The mixing of red blood with stool was commonly due to distal lesions, especially hemorrhoids.In young persons with bright red rectal bleeding, fiberoptic sigmoidoscopy may prove to constitute appropriate initial investigation.

Gastric and duodenal biopsies from 90 patients with various acid peptic disorders-reflux esophagitis (n = 24), gastric ulcer (n = 13), duodenal ulcer (n = 47) and nonulcer dyspepsia (n = 6)-were examined. Seven patients with minimal dyspeptic symptoms and an endoscopically and histologically normal stomach and duodenum served as controls. Immunoperoxidase staining for gastrin-producing G cells, somatostatin-producing D cells and serotonin-producing EC cells was carried out on fundic, antral and duodenal biopsies, and was quantified using a Zeiss MOP Videoplan using the peroxidase-antiperoxidase technique of Sternberger. In the gastric antrum, a G:D:EC cell ratio of approximately 1.6:1:1-was observed. In the duodenum the corresponding ratio was 1:1:2.4. No significant differences were observed within any of the major diagnostic categories. Patient age, sex, duration of symptoms, smoking habits, alcohol consumption and nonsteroidal anti-inflammatory drug use had no effect on endocrine cell densities. Reduced G cell density in the descending duodenum was observed in the presence of mild duodenitis in four patients. In four patients with evidence of antral intestinal metaplastic changes, a significant increase in duodenal G cell densities was found. These results suggest that a change in the number of G, D or EC cells does not play a primary role in the pathophysiology of acid peptic disorders in the majority of patients.

A 65-year-old man presented with massive lower gastrointestinal tract hemorrhage. Minimal changes were noted on sigmoidoscopy, no bleeding lesions were identified on arteriography or red blood cell scan, and barium enema examination demonstrated only diverticular disease and minimal cecal deformity, interpreted as secondary to a recent appendectomy. Colonoscopy demonstrated multiple deep cecal ulcers. These were presumed to be due to an infectious etiology, since the stools were culture-positive for Salmonella typhimurium. The hemorrhage stopped within 24 hours of treatment with Ampicillin, Flagyl, and Gentamicin. The patient has remained well over a 12-month follow-up period. Repeat colonoscopy demonstrated healing of the cecal ulcers and there was also clearing of the Salmonella from the stools. This case report serves to remind us of the different methods used to diagnose lower gastrointestinal tract hemorrhage, and the importance of considering infectious causes of colitis.

Six healthy volunteers and six patients with asymptomatic duodenal ulcer disease received placebo or 300 mg nizatidine once at night or twice daily (morning and evening) for a week in a random, cross‐over fashion. Steady‐state serum nizatidine concentrations and gastric pH were measured over a 24‐hour period. No significant differences in the pharmacokinetic indices were observed between the healthy volunteers and patients with duodenal ulcer disease. In patients with duodenal ulcers, significantly lower peak serum concentrations, longer half‐life (t 1/2 ) and larger volume of distribution (V d ) were observed after the night doses compared with the daytime doses. The diurnal variation in drug kinetics between the nighttime and daytime doses in the twice daily regimen may be caused by a slower absorption rate, paralleled with a higher extent of distribution. Despite lower serum nizatidine concentrations, gastric pH was higher in the evening than in the daytime; it is speculated that this was due to a time‐dependent enhanced distribution of the H 2 ‐receptor blocker into the site of action.

Gastroesophageal reflux disease (GERD) represents a spectra of symptoms and of reflux damage to the esophagus. This reflux damage is due to a prolonged acid exposure of the esophagus arising from an imbalance between protective motility factors and aggressive acid secretory factors. Initially, patients may be managed by modifying their food intake and by supportive anti-gravity measures. However, many individuals will require drug therapy. Symptomatic relief can be achieved with pro-kinetic agents, antacids, sucralfate suspension, H2-receptor antagonists and H(+)-K+ ATPase pump blockers. There are limitations in the study design of experiments which have compared one agent with another. Accepting these design limitations, it would appear that pump blockers lead to higher rates of endoscopic healing than the use of standard doses of H2-receptor antagonists. However, higher doses of H2-receptor antagonists will likely give higher rates of symptomatic relief and endoscopic healing of GERD. Recurrence of symptoms and esophagitis occur in a high proportion of patients with GERD, and some patients may need to be considered for maintenance therapy.

A discriminant function analysis was performed on several demographic, anthropometric, clinical, and laboratory data of 685 observations performed over 12 months on 137 patients with Crohn's disease. A Crohn's activity group scale (CAGS) was calculated. The CAGS has two advantages over the usual Crohn's disease activity index: it is objective, but more important is the fact that the values, when calculated longitudinally, have predictive value. Thus, calculation of CAGS is useful for counseling purposes and may also be useful in the design of future trials assessing therapy for Crohn's disease by allowing prerandomization stratification of patients with high or low probability of future recurrences of symptomatic disease activity.

Summary A number of bacterial, organoleptic and chemical evaluations were made on iced queen scallops in shell over 14 days total. The spoilage flora, qualitative and quantitative, is described. Organoleptic descriptions are given along with determinations of trimethylamine, total volatile bases, volatile reducing substances, glycogen, hypoxanthine, ribose fractions and optical density ratios at 248 nm before and after treatment with ion‐exchange resin. Hypoxanthine showed the most promise as a spoilage indicator while total volatile bases and optical density ratio showed some promise but to a lesser extent.

The defect in iron (Fe) absorption in X‐linked anaemia ( sla ) remains an enigma; absorption of a tracer dose of Fe is impaired in mice raised on an iron‐containing cube diet but not in those raised on an iron‐deficient diet. Because cobalt (Co) shares a similar intestinal transport pathway with Fe, a study was made of the effect of iron deficient diet on Co absorption. The duodenum of sla and genetically normal mice was perfused for 30 min with labelled solutions containing Co or Fe. Co uptake and transfer were similar in sla and normals fed cubes whereas Fe uptake and transfer were less in sla than in normals. The iron deficient diet caused an increase in the uptake and transfer of Co and Fe in sla and normals. When Co and Fe were perfused together in sla fed deficient diet, the uptake and transfer of each metal was less than when perfused alone. The distribution of Fe and Co in subcellular mucosal fractions was determined by a differential centrifugation technique. Deficient diet resulted in a directionally similar change in the subcellular dstribution of Co and Fe in sla and normals. The increase in Co as well as Fe absorption in the sla on an iron deficient diet to the same high level found in genetically normal animals, and the inhibitory effect of each metal on the absorption of the other suggests that the absorption defect in sla is unlikely to be due to a primary defect in the function of the transport carrier.

This study was undertaken to examine the effect of supplementing chow for 2 weeks with 2% cheno- (CDC) or ursodeoxycholic (UDC) acid or cholestyramine (CHOL) on the intestinal morphology and in vitro uptake of bile acids in adult rats. Food intake was higher in UDC and CHOL as compared with animals fed chow or CDC, or in animals pair-fed a chow-restricted diet (CRD). Body weight gain was lower in CDC and CRD but was unchanged by feeding UDC or CHOL. Jejunal mucosal surface area was similar in the five groups, although the ileal mucosal surface area was lower in UDC than in the other animals. Feeding UDC reduced the ileal uptake of cholic acid (C), taurocholic acid (TC), and glycocholic acid (GC). Feeding CDC had no effect on bile acid uptake except when compared with animals fed a chow-restricted diet. Feeding CHOL reduced the active ileal uptake of C, had no effect on the uptake of TC or GC or CDC, and was associated with increased uptake of stearic, linoleic, and linolenic acids. These effects were likely related to a direct effect of changes in the luminal bile acids rather than due to an indirect effect of the reduced food intake, since the ileal uptake of CDC and GC was greater in animals fed CDC than in those fed a chow-restricted diet with comparable weight gain. Thus, 2 weeks of feeding bile acids or bile acid binding agents may alter the form and function of the rat intestine, and as well may lead to changes in food intake and body weight gain.Key words: active transport, adaptation, bile acids.

Failure to account for the effect of the unstirred water layer and the contribution of passive permeation will lead to errors in the estimation of the kinetic constants of glucose uptake into the intestine. It is widely accepted that variations in the concentration of sodium in the bulk phase profoundly influence the rate of uptake of glucose in the intestine, but the kinetic basis for this effect remains in dispute. Accordingly, a previously validated in vitro technique was used to assess the effect of Na+ on the uptake of glucose into rabbit jejunum under conditions selected to reduce the unstirred layer resistance. Varying Na+ had no effect on the uptake of lauryl alcohol and therefore on unstirred layer resistance. The passive permeability coefficient for glucose uptake was estimated from the uptake of L-glucose, of D-glucose at 4 degrees C, or in the presence of 1 mM phlorizin or 40 mM galactose. The permeability for glucose increased as Na+ rose. The values of both the maximal transport rate and the Michaelis constant (Km) were influenced by Na+. A linear relationship was noted between Na+ and the maximal transport rate; the value of Km fell as Na+ was increased to 75 mequiv./L, but Km did not decline further with higher values of Na+. These results support the theoretical predictions of the presence of both an affinity and a velocity effect of the sodium gradient on the intestinal transport system for glucose.

The oral administration of pirenzepine (PRZ), an antimuscarinic agent, has a variable effect on gastric acid secretion in patients with duodenal ulcer, and it seems to potentiate cimetidine-induced inhibition of secretion. The possibility of a pharmacokinetic interaction between these drugs was examined in eight patients who received cimetidine and PRZ alone and in combination in a crossover fashion. Cimetidine, 600 mg b.i.d., PRZ, 50 mg b.i.d., or combination therapy were each given for 1 week before the study. Serum samples were serially drawn during each dosing interval for determination of cimetidine and PRZ concentrations by HPLC and RIA, respectively. Cimetidine given alone or with PRZ exhibited diurnal variation, as the peak serum concentration was lower after the nighttime dose than after the morning dose. PRZ showed intersubject variation. However, each drug failed to alter the pharmacokinetic indices of the other. The times to attain the peak serum concentration were not significantly different for cimetidine alone or with PRZ, arguing against an effect of PRZ on gastric motility in the doses we used. The greater and prolonged acid inhibition with the combination of cimetidine and PRZ, therefore, may stem from a synergistic action of both drugs on receptor sites on gastric parietal cells. Clinical Pharmacology and Therapeutics (1985) 38, 325–330; doi:10.1038/clpt.1985.180

Crohn's disease is known to produce malabsorption of calcium and vitamin D which affect the skeleton. A variety of techniques were used to assess the prevalence of mineral and bone abnormalities in 53 consecutive patients with Crohn's disease. Twenty healthy controls were compared with 28 men and 25 women with Crohn's disease. In males, the mean corrected serum calcium concentration was elevated, the mean winter plasma 25-hydroxyvitamin D was low, as was the bone volume on biopsy and the fractional absorption of {7Ca. In females, the corrected serum calcium was also higher than in controls, as was the serum alkaline phosphatase activity. The female patients had significant decreases in both summer and winter plasma vitamin D levels, metacarpal cortical thickness and fractional absorption of 47Ca. The disturbances in bone and mineral metabolism were generally mild and were not associated with use of glucocorticosteroids but were more severe in patients with a history of bowel resection. Thus, patients with Crohn's disease are at risk of developing metabolic bone disease and consideration should be given for an assessment of the skeleton in patients with Crohn's disease. especially in women and in patients with previous ilea! resection. A battery of tests may be needed to exclude the diagnosis of metabolic bone disease but a 25-hydroxyvitamin D assay and hand x·rays using industrial grade film are recommended as a valuable preliminary assessment.

Diabetes mellitus is known to be associated with enhanced intestinal absorption of lipids. A validated in vitro technique was used to examine the uptake of (3H) retinol (a lipid soluble vitamin) into the jejunum and ileum of streptozotocin (STZ)-induced diabetic rats. In addition, availability of vitamin A in the plasma and liver of diabetics which were pair-fed to non-diabetic control rats was investigated. The relationship between the duration of incubation and retinol uptake was curvilinear in both the jejunum and the ileum, but no difference in intestinal uptake was observed between the two groups of animals. A linear relationship was noted between the concentration of retinol and uptake into both the jejunum and ileum. There was no difference in the uptake of retinol between the diabetic and control animals. The hepatic concentration of vitamin A also remained unaffected by diabetes as indicated by similar values found between pair-fed diabetic and non-diabetic control rats. Unlike the liver, plasma retinol level was decreased in the diabetic animals; this effect does not appear to be caused by any change in the intestinal absorption of the vitamin.

The Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori was held in Lisbon, Portugal, from September 12 to 14, 1997. State-of-the-art reviews and research findings were presented to over 2000 participants. This review focuses on important new developments and serves as a rapid communication of clinically relevant material.

There is no information on the number of endoscopic procedures performed at major teaching hospitals across Canada. The directors of endoscopy units at eight teaching hospitals from Halifax to Vancouver volunteered demographic information on the unit at their location. There was a very wide range of endoscopic utilization, with approximately comparable rates of out-patient versus in-patient procedures and of gastroscopies versus colonoscopies, but there was no obvious linking of the ratios of in-patients:out-patients versus total number of designated gastrointestinal beds or total number of hospital beds. Thus, the appropriateness of endoscopic procedures needs to be based on standards of practice and accepted indications. The number of endoscopies performed per endoscopy unit support staff varied widely (from 323.7 to 1065.3 per year), and it would be interesting to learn whether this represents an opportunity for cost-saving in some units.

The absorption of lipids is generally accepted to be mediated by a process of passive diffusion, although some recent data have raised the possibility of a mediated component. Brush border membrane vesicles (BBMV) have been widely used to study nutrient transport, but have only recently been used to examine the uptake of lipids. Using a BBMV technique validated with studies of the uptake of D-glucose, we examined the uptake of linoleic acid into the jejunum of adult rabbits. The uptake of 100 microM linoleic acid was constant between 2 and 20 min, with no overshoot observed at earlier periods. Linoleic acid uptake was suppressed by 88% with 0.6 mM phloridzin and by 58% with 0.2 mM phloretin, but uptake of linoleic acid was unaffected by the absence of sodium, by the presence of a sodium gradient, or by varying the osmolarity of the buffer. Lysis of the BBMV incubated with linoleic acid by the addition of ice-cold deionized water did not alter the amount of linoleic acid associated with the BBMV. The linoleic acid concentration curve was linear up to 160 microM, when carried out under initial rate conditions and in the presence of 2 mM taurocholic acid. These results are compatible with the process of passive uptake of linoleic acid into BBMV of rabbit jejunum, but do not exclude the possible physiological importance of a membrane fatty acid binding protein.

SUMMARY Methods: This randomized, double‐blind, single‐centre, crossover study was designed to assess the effects of three regimens of ranitidine (150 mg b.d., 300 mg b.d. and 300 mg q.d.s.) and placebo on intra‐oesophageal and intragastric pH in subjects with gastro‐oesophageal reflux disease (GERD). Twenty‐six subjects were screened, and 9 were evaluable by the admission criteria. These 9 subjects received each of the regimens for 72 h, and a wash‐out period of at least 48 h followed each dosing period. Standard meals and beverages were provided. Results: With increasing doses of ranitidine, 24‐h intragastric mean H + and integrated H + fell, and the percentage of the time the pH was equal to or greater than 4 (% time pH ≥ 4) rose; the minimum effective dose for these effects was ranitidine 300 mg daily. With increasing doses of ranitidine there was also a progressive decline in mean 24‐h intra‐oesophageal H + and integrated H + , and increasing % time pH ≥ 4. The minimal effective dose was 300 mg daily for intra‐oesophageal mean H + and integrated H + , and 600 mg for % time pH ≥ 4. The minimal effective dose to decrease the number of reflex episodes was 1200 mg ranitidine. For the daytime upright position, a dose effect of increasing ranitidine was also seen, with minimal effective ranitidine doses of 300 mg for a decrease in mean H + , and 1200 mg for % time pH ≥ 4. Conclusion: If these higher doses of ranitidine are confirmed to be more effective than the standard 150 mg b.d. regimen for the treatment of patients with gastro‐oesophageal reflux disease, then the mechanism of this action probably relates to the lower exposure of the oesophageal mucosa to acid.

The aim was to determine whether the antiatherogenic effect of the calcium channel blocker isradipine on fatty streak formation was dependent upon a temporal relationship between cholesterol feeding and administration of the drug.The study was done in New Zealand White rabbits fed a diet supplemented with cholesterol (2.5% w/w) for three weeks. Such a regimen results in loss of endothelium dependent relaxation and accumulation of cholesterol in the aorta four weeks later. The calcium antagonist isradipine was given in a dose of 0.25 mg.kg-1.d-1 at specified periods during the study to seven subgroups of animals: (1) standard diet + 2.5% cholesterol for three weeks; (2) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks; (3) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks; (4) standard diet + 2.5% cholesterol+isradipine for three weeks followed by standard diet alone for four weeks; (5) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given throughout the seven weeks; (6) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given during the final four weeks only; (7) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks with isradipine given during the final eight weeks. Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine and the calcium ionophore A23187, and relaxant responses to sodium nitrite. Serum was collected for measurement of cholesterol and triglyceride concentration.When isradipine was given either during cholesterol feeding and continued for four weeks following it (subgroup 5) or during the four weeks following cholesterol feeding (subgroup 6), loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta was prevented. However, administration of isradipine during the period of cholesterol feeding alone (subgroup 4) was without effect. Also, administration of isradipine after lesions of fatty acid streak type were established appeared to have a favourable effect on removal of cholesterol from the aorta.Isradipine protects against the development of fatty streaks in rabbits fed a diet supplemented with 2.5% cholesterol. Administration of this drug after fatty streaks are formed also promotes their resolution.

host immune response, clinical epidemiology, as well as clearance and eradication of Hp.

Alteration in dietary fatty acid composition produces changes in brush border membrane (BBM) fatty acid composition and changes in nutrient transport. Feeding a highly polyunsaturated fatty acid diet (P) reduces glucose uptake in diabetic rats to near control levels, whereas feeding a highly saturated fatty acid diet (S) enhances glucose uptake. Female Wistar rats were placed onto either a P or S diet for 5 weeks, injected with streptozotocin and continued on their respective diets for an additional 3 weeks. BBM were isolated, purified and extracted for analysis of fatty acyl constituents of phosphatidylcholine (PC) and phosphatidylethanolamine (PE). In jejunal and ileal BBM PC and PE, feeding S was associated with a decrease in total omega 6 fatty acids (18:2 omega 6), and an increase in the ratio of monounsaturated/saturated fatty acids as compared with animals fed P. In jejunal BBM PC and PE, the ratio of 18:2 omega 6/20:4 omega 6 was reduced in animals fed S as compared with those fed P. Diabetes was associated with fewer changes in BBM fatty acid composition in animals fed P as compared with those fed S. Feeding P to diabetic animals prevents the changes in BBM fatty acid composition observed when animals are fed S. Alterations in BBM lipid composition may be related to the enhanced permeability to glucose in animals fed S, while the similarity of BBM fatty acid composition in diabetic and control animals fed P may be related to the similar glucose uptake. The mechanisms controlling BBM lipid composition require further investigation, and may be important for the development of nutritional strategies for the control of diabetes.

This article has no abstract.

Dietary fat composition can influence membrane composition in a variety of cell types. Changes in dietary fat can alter the structure and function of lymphocyte membranes, liver plasma membranes, brain synaptosomes and cardiac mitochondria. In diabetics, uptake of glucose is enhanced due to a greater passive permeability of the intestine to glucose. This enhanced absorption from the intestine can be partially corrected by insulin administration and islet cell transplantation. In clinical practice, however, a more commonly used therapeutic modality for diabetics is diet modification. In this study, when diabetic rats were fed a high fat diet, high or low saturated to polyunsaturated fatty acid, there was an improvement in the plasma and urine glucose. This improved clinical response was also observed in the glycosylated hemoglobin response in the animals fed the high polyunsaturated to saturated fatty acid diet. The clinical improvement observed after feeding with these diets, however, was not seen during the oral and intravenous glucose tolerance tests. This study shows that dietary alteration can improve the clinical response in diabetic animals.

Intestinal active transport processes have been shown to be sodium dependent, but the effect of varying the concentration of sodium in the luminal bulk phase on the passive uptake of lipids has not been established. An in vitro technique was used to measure the uptake of fatty acids and alcohols into the rabbit jejunum under conditions of stirring of the bulk phase selected to reduce the effective resistance of the unstirred water layer (UWL). Sodium withdrawal had no effect on the uptake of a homologous series of fatty alcohols, and thus the UWL was not influenced by varying bulk-phase sodium; in contrast, the uptake of a homologous series of short-, medium, and long-chain-length saturated fatty acids (FA) was progressively inhibited by reducing bulk-phase sodium from 145 to 0 meq/l. There was no difference in FA uptake between the use of magnesium chloride and mannitol for maintenance of isotonicity with sodium withdrawal. At each sodium concentration, the uptake of FA rose with increasing FA chain length. The relation between sodium concentration and incremental change in free energy (delta delta Fw leads to 1) was described by a sigmoid-shaped curve. The uptake of cholesterol was also inhibited by reducing sodium in the bulk phase. In summary, varying bulk-phase sodium has no effect on UWL, and the influence of sodium on the uptake of FA is mediated by altering delta delta Fw leads to 1 and therefore the physicochemical properties of the brush-border membrane.

SUMMARY Six asymptomatic, non‐smoking men with endoscopically proven duodenal ulcer disease received single nocturnal doses of placebo, 40 mg famotidine and 300 mg ranitidine each for 1 week prior to serial measurement of pH, peptic activity and serum gastrin concentrations over 24 h and of acid output. The intragastric pH fluctuated between 1.53 and 5.07 when subjects were given placebo but within 2 h of taking famotidine or ranitidine it rose to 5.57 or higher; the effect lasted for 12 h from midnight. Peptic activity fell during famotidine and ranitidine treatment and the decline was somewhat greater 8–15 h after using famotidine. Serum gastrin levels did not change materially with any treatment. The study shows the equivalent effect of standard bed‐time doses of famotidine and ranitidine on intragastric pH, acid output and serum gastrin concentrations in asymptomatic men with duodenal ulcer disease.

The small bowel has undergone intense study. Part II of this review of the small bowel summarizes the current knowledge about the permeability of the gastrointestinal epithelium; the brush border membrane; motility; carbohydrates; diabetes; ethanol; diet; and diagnostic procedures.

Significant advances have been made in the study of the small bowel. Part II of this two-part review of the small bowel examines the early development and later ageing of the small bowel; the effect of diabetes, alcohol, radiation and HIV on the small bowel; enteral and parenteral nutrition; the brush border membrane and enterocyte proliferation; and peptide hormones (including transforming growth factors, motilin, peptide YY and cholecystokinin).

In the past year, there have been many advances in the area of small bowel physiology and pathology. More than 1500 papers were assessed in preparation for this review. Some were selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist. Relevant review articles have been highlighted, and important clinical learning points have been stressed. The topics are varied in scope, and wherever possible show a logical progression from basic physiology to pathophysiology to clinical disorders and management.

Variations in the dietary fatty acid composition and cholesterol content are associated with alterations in the intestinal uptake of hexoses and lipids in control and diabetic rats. Changes in the composition of the brush membrane (BBM) lipids may provide a possible mechanism for the observed alterations in transport properties. Accordingly, control and streptozotocin diabetic animals were fed one of four isocaloric semisynthetic diets for two weeks: beef tallow with low cholesterol, beef tallow with high cholesterol, fish oil with low cholesterol or fish oil with high cholesterol. BBM were prepared and assessed for marker enzyme activity and lipid composition. Fish oil feeding was associated with a reduction in total phospholipid content in control and diabetic jejunal and ileal BBM; this fall in total phospholipids was due to a reduction in BBM sphingomyelin. Cholesterol supplementation increased control jejunal BBM sucrase activity in animals fed beef tallow but reduced sucrase activity in animals fed fish oil. In fish oil fed diabetic animals, jejunal and ileal BBM alkaline phosphatase activity was increased with cholesterol supplementation. The elevation in BBM total phospholipids (phosphatidylethanolamine) associated with diabetes in beef tallow fed animals was not observed in the jejunal BBM of animals fed fish oil or in the ileal BBM of animals fed fish oil with high cholesterol. Thus, (a) feeding an omega-3 polyunsaturated fatty acid diet (fish oil) reduced total phospholipid content in BBM of control and diabetic animals, primarily due to a reduction in sphingomyelin; and (b) feeding an omega-3 polyunsaturated fatty acid diet or dietary cholesterol supplementation alter the activity of BBM enzymes. These results suggest that variations in dietary fat composition and the associated changes in BBM composition and enzyme activity contribute to altered intestinal function in diabetes.

Seven of nine patients with ulcers recurring after a variety of gastric operations enjoyed loss of dyspeptic symptoms within 2 days of taking cimetidine, 1,200 mg/day for 6 weeks, and endoscopic confirmation of healing of the recurrent ulcer was established within 6 weeks of therapy. Once ulcer healing had been achieved in these seven patients, symptomatic remission persisted for over 19 months without maintenance therapy with cimetidine, and no complications suggestive of recurrent ulcerations occurred during this period in these seven patients. The eighth patient with a recurrent ulcer after vagotomy and pyloroplasty had symptoms suggestive of a gastric outlet obstruction in association with a bezoar and an elevated fasting serum gastrin concentration; cimetidine failed to heal the ulcer and a partial gastrectomy with Bill-roth I anastomosis was undertaken. The ninth patient lost his dyspeptic symptoms while on cimetidine, but 1 month after stopping therapy he succumbed to a massive hemorrhage; autopsy revealed a large pyloric channel ulcer. We suggest that cimetidine is helpful for the control of symptoms and the healing of recurrent ulcers after gastric surgery, but that endoscopy be repeated after an appropriate interval while such patients remain on cimetidine to assure that the disappearance of symptoms is truly associated with a lack of peptic ulceration. If the ulceration persists, we believe that cimetidine should be continued for a longer period.

Galectin-3 is an endogenous 13-galactoside binding protein whose expression has been correlated with tumor progression in the colon (Cancer 1995; 75: 2818-26) and other organs, but direct evidence for a role in tumor cell metastasis is lacking.Aim: The current study was designed to more directly assess the role of galectin-3 in colon cancer metastasis.Methods: Human colon cancer ceils with high metastatic potential (Lim6, HM7) in animal models of colon cancer metastasis and high native galectin-3 levels were stably transfected with a plasmid designed to express antisense galectin-3.Conversely, colon cancer ceils of low metastatic potential and low native galectin-3 (LS 174T) were transfected with a plasmid containing the complete 881 bp coding sequence of galectin-3 designed to confer expression of galectin-3 mRNA (sense).Stable transfection was confirmed by Southern analysis and by persistence of neomycin resistance.Liver colonization was assessed 4 weeks after splenic-portal inoculation or 6 weeks after cecal injection.Galectin-3 in the serum of colon cancer patients was measured by sandwich ELISA using monoclonal antibody TIB166 for capture and biotinylated affinity-purified polyclonal anti-galectin-3 for detection (detection level 2 ng/ml).Results: Introduction of galectin-3 antisense into Lim6 resulted in a 80% reduction in galectin-3 specific mRNA by quantitative dot blot analysis (normalized to actin).Northern analysis confirmed a decrease in the 1 kb product in these ceils.There was a 13-fold reduction in galectin-3 protein by Western analysis compared to parental cell line or vector-transfected controls.Similar results were obtained for HM7.Both total cellular and cell surface (FACS analysis) galectin-3 were reduced.Transfection of galectin-3 (sense) into LS 174% resulted in a 4.5-fold increase in mRNA and a 10-fold increase in galectin-3 protein.Down-regulation of galectin-3 by antisense transformation resulted in a significant (p<0.001)decrease in liver colonization (liver weight, number of tumor nodules and % parenchyma replaced by tumor) by Lim6 and HM7, while introduction of galectin-3 (sense) into LS174T resulted in a significant increase in liver colonization after both splenic-portal and cecal injection.Tumor tissue levels of galectin-3 in metastatic foci correlated with levels in injected cells.Manipulation of galectin-3 in these cell lines resulted in coordinately decreased (or increased) levels of MUC2 mucin, a major ligand for this lectin.Galectin-3 was also detected in the serum of 11/13 patients with colonic adenocarcinoma, with highest levels in those with distant metastatic disease. Conclusion:This study provides direct evidence that galectin-3 plays an important role in colon cancer metastasis.

A comprehensive review of dyspepsia is presented. Topics include causes of dyspepsia, prevalence, causes of symptoms (motility abnormalities, visceral hypersensitivity, psychosocial aspects, role of Helicobacter pylori), investigations of patients with dyspepsia and, finally, whether there is effective treatment.

The small bowel has undergone intense study. Part I of this two-part review of the small bowel focuses on gastrointestinal peptides; intestinal infections and human immunodeficiency virus; drugs; intestinal growth - mucosal proliferation and differentiation; nucleic acids, nucleotides and nucleosides; vitamins and minerals; Whipple's disease; radiation; and early development.

In the past year there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 500 papers were assessed, and some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist.