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Biomedical subjects

J Meddings

Publications and source records attributed to J Meddings.

12 recordsLinked to original sources
PubMed2004

Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario.

BACKGROUND: Post-infectious irritable bowel syndrome is a common clinical phenomenon of uncertain aetiology. AIM: To test the association between intestinal permeability and irritable bowel syndrome symptoms 2 years after a large waterborne outbreak of bacterial gastroenteritis. METHODS: Consecutive adults with Rome I irritable bowel syndrome and controls without irritable bowel syndrome attending a community clinic were enrolled. Intestinal permeability was measured as the ratio of fractional urinary excretions of lactulose and mannitol, and compared among cases vs. controls and predictors of abnormal intestinal permeability were assessed. RESULTS: A total of 218 subjects (132 irritable bowel syndrome cases and 86 non-irritable bowel syndrome controls) completed the study protocol. About 27 (12%) had been diagnosed with the irritable bowel syndrome before the outbreak and 115 (53%) had been ill during the outbreak. Lactulose-mannitol ratios were increased among cases vs. controls (Mann-Whitney mean rank 118.8 vs. 95.3, P = 0.007), and cases were more likely to have a ratio >0.020 (P = 0.007). Among cases, those with increased intestinal permeability were more likely to report increased stool frequency. Both irritable bowel syndrome symptoms and male gender, but not diarrhoeal illness during the outbreak, were significant predictors of abnormal permeability. CONCLUSIONS: Irritable bowel syndrome symptoms are associated with a subtle increase in intestinal permeability irrespective of prior gastroenteritis. This may improve understanding of the aetiology of both sporadic and post-infectious irritable bowel syndrome.

Acute Disease↗
PubMed2004

Octreotide in intestinal lymphangiectasia: lack of a clinical response and failure to alter lymphatic function in a guinea pig model.

Intestinal lymphangiectasia, which can be classified as primary or secondary, is an unusual cause of protein-losing enteropathy. The main clinical features include edema, fat malabsorption, lymphopenia and hypoalbuminemia. Clinical management generally includes a low-fat diet and supplementation with medium chain triglycerides. A small number of recent reports advocate the use of octreotide in intestinal lymphangiectasia. It is unclear why octreotide was used in these studies; although octreotide can alter splanchnic blood flow and intestinal motility, its actions on lymphatic function has never been investigated. A case of a patient with intestinal lymphangiectasia who required a shunt procedure after failing medium chain triglycerides and octreotide therapy is presented. During the management of this case, all existing literature on intestinal lymphangiectasia and all the known actions of octreotide were reviewed. Because some of the case reports suggested that octreotide may improve the clinical course of intestinal lymphangiectasia by altering lymphatic function, a series of experiments were undertaken to assess this. In an established guinea pig model, the role of octreotide in lymphatic function was examined. In this model system, the mesenteric lymphatic vessels responded to 5-hydroxytryptamine with a decrease in constriction frequency, while histamine administration markedly increased lymphatic constriction frequency. Octreotide failed to produce any change in lymphatic function when a wide range of concentrations were applied to the mesenteric lymphatic vessel preparation. In conclusion, in this case, octreotide failed to induce a clinical response and laboratory studies showed that octreotide did not alter lymphatic function. Thus, the mechanisms by which octreotide induced clinical responses in the cases reported elsewhere in the literature remain unclear, but the present study suggests that it does not appear to act via increasing lymphatic pumping.

Adult↗
PubMed2001

Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage both in the upper and lower gastrointestinal tract. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Our objective was to compare the effect on gastrointestinal permeability of acute equieffective doses of four different NSAIDs; three were designed to reduce gastrointestinal mucosal injury. MATERIALS: Healthy volunteers underwent sugar tests in a randomised fashion, 15 days apart, at: (1) baseline; (2) after two days of 75 mg slow release (microspheres) indomethacin; (3) after two days of 7.5 mg oral meloxicam which preferentially inhibits cyclooxygenase 2; and (4) after two days of 750 mg naproxen. A subgroup of subjects was tested after two days of 200 mg celecoxib. In each test, subjects ingested a solution containing sucrose, lactulose, and mannitol and sucralose, to evaluate gastroduodenal, intestinal, and colonic permeability, respectively. RESULTS: Gastric permeability was significantly affected by naproxen (p<0.05) but not by slow release indomethacin, meloxicam, or celecoxib. Intestinal permeability was significantly increased by the first three NSAIDs (p<0.05) but not by celecoxib. Abnormal lactulose/mannitol ratios were observed in 42% of meloxicam treatments, in 62% during indomethacin, and in 75% of subjects treated with naproxen. Finally, colonic permeability, as measured by sucralose, was not significantly increased by any of the four drugs. CONCLUSION: Our study provides evidence that the newly developed NSAIDs reduce gastric mucosal permeability significantly. However, most produced significant alteration of small intestinal permeability. In contrast, our results suggest that celecoxib seems to exhibit the most desirable gastrointestinal side effect profile.

Adult↗
PubMed2000

Barrier dysfunction and Crohn's disease.

Crohn's disease is a debilitating illness of unknown etiology. A current hypothesis of disease pathogenesis suggests that this illness represents an abnormal immunological reaction to a luminal antigen. As part of this theory it is suggested that the luminal antigen is delivered to the mucosal immune system by a paracellular route. If this theory is correct several testable predictions can be made. In this manuscript these predictions are presented and the evidence to support or refute them is presented.

Crohn Disease↗
PubMed2000

Gastric cancer and other endoscopic diagnoses in patients with benign dyspepsia.

BACKGROUND: It has been suggested that endoscopy could be replaced with non-invasive assessment of helicobacter status in the initial work up of young dyspeptic patients without sinister symptoms. AIMS: To determine the incidence of gastro-oesophageal malignancy in young dyspeptic patients. METHODS: The Alberta Endoscopy Project captured clinical and demographic data on all endoscopies performed from April 1993 to February 1996 at four major adult hospitals in Alberta. The endoscopic and histological diagnosis in a subgroup of patients under 45 years of age without alarm symptoms that had undergone gastroscopy was reviewed. In addition, a random list of 200 patients was generated and their medical records reviewed in order to assess the proportion with symptoms suitable for a non-invasive management strategy. RESULTS: Gastroscopy was performed in 7004 patients under 45 years. In 3634 patients (56% female) alarm type symptoms were absent; 78.9% of patients had symptoms amenable to a non-invasive initial approach, giving a corrected sample size of 2867 patients (correction factor 0.789). Three gastric cancers, one case of moderate dysplasia, 10 biopsy proved cases of Barrett's oesophagus, and 19 oesophageal strictures/rings were detected within this sample. The corrected prevalence of gastric cancer in this select population was 1.05 per thousand patients. DISCUSSION: Endoscopy yielded three gastric cancers in this sample of under 45 year old dyspeptic patients without sinister symptoms. While initial non-invasive screening with one-week triple therapy for helicobacter positive individuals is unlikely to have a detrimental outcome the physician is advised to consider endoscopy in patients with persisting, recurrent, or sinister symptoms.

Adult↗
PubMed1999

Tumor necrosis factor inhibitor ameliorates murine intestinal graft-versus-host disease.

BACKGROUND & AIMS: Transfer of T helper cells from DBA/2 mice to irradiated allogeneic B6D2F1 mice leads to development of colonic graft-versus-host disease with pathological features of inflammatory bowel disease. To examine the role of tumor necrosis factor (TNF) in graft-versus-host disease enteropathy, an adenoviral vector encoding a TNF inhibitor protein was administered. METHODS: Irradiated B6D2F1 mice were infused with DBA/2 bone marrow and spleen cells. Mice then received either a control beta-galactosidase-encoding adenovirus or an adenovirus encoding a TNF inhibitor, composed of the extracellular domain of the human 55-kilodalton TNF receptor linked to the murine immunoglobulin G1 heavy chain. Mucosal permeability to sucralose and colonic histology were assessed 14 and 25 days after transplantation. RESULTS: Less diarrhea was observed in DBA/2 --> B6D2F1 mice expressing the TNF inhibitor, and colonic sections from these mice had significantly less inflammation and epithelial cell abnormalities. In TNF inhibitor recipients, mucosal permeability to sucralose was similar to that in nonirradiated control mice and significantly less than in recipients of the control adenovirus. CONCLUSIONS: TNF inhibition decreases the severity of enteropathy in the DBA/2 --> B6D2F1 murine model of colonic graft-versus-host disease.

Animals↗
PubMed1999

Sugar tests detect celiac disease among first-degree relatives.

OBJECTIVES: First-degree relatives of patients with celiac disease are at high risk for developing the disease themselves. Detection of serum antibodies and intestinal permeability tests have been useful to identify candidates for intestinal biopsies. Recently it was demonstrated that abnormal sucrose permeability is a very sensitive marker of active disease. Our objectives in this prospective study were (1) to assess the screening value of permeability tests, and (2) to compare the usefulness of these markers with that of the celiac disease-related serology in screening for celiac disease in a cohort of first-degree relatives of well-known patients. METHODS: We performed sugar tests in 66 first-degree relatives of probands. Subjects ingested 450 ml of a solution containing sucrose (100 g), lactulose (5 g), and mannitol (2 g). Subsequently, a complete overnight urine collection was obtained. Measurement of sugars was performed by high-performance liquid chromatography. All relatives were evaluated for antigliadin (type IgA and IgG) and endomysial antibodies and subjects positive for any test underwent intestinal biopsy. RESULTS: Twelve relatives were diagnosed as having small intestinal mucosal atrophy. Increased sucrose permeability was detected in 9 (75%) of these patients. Four false-positive determinations were found but all had gastric erosions, which is known to increase sucrose permeability independently of duodenal damage. Increased lactulose/mannitol ratios were observed in all new celiac patients. An additional nine relatives had positive results; however, four of them did not accept intestinal biopsy and the remaining five did not seem to have histological evidence of disease. Endomysial antibodies were detected in 11 of 12 patients and no false-positive cases were observed. Antigliadin antibodies were 75% sensitive and 88% specific. CONCLUSIONS: Our study demonstrated that screening using the endomysial antibody test is highly sensitive and specific for detecting celiac disease; however, almost 10% can be missed. The addition of lactulose/mannitol permeability testing to the screening protocol allowed us to detect all relatives who actually presented with evidence of gluten sensitivity. Sucrose permeability exhibited a lower sensitivity; however, it did detect other endoscopically visible lesions.

Adolescent↗
PubMed1996

Multiple sclerosis patients have peripheral blood CD45RO+ B cells and increased intestinal permeability.

Increased intestinal permeability and the CD45RO isoform expression of the leukocyte common antigen on peripheral blood CD20+ B cells are found in Crohn's disease. Others have observed that multiple sclerosis (MS) patients may have an increased risk of coacquisition of Crohn's disease. The aim of this study was to identify an association between these diseases using peripheral blood CD45 isoform expression and intestinal permeability in MS. Lactulose/mannitol permeability and peripheral blood CD20+ B cell CD45RO expression were defined in healthy controls, MS patients, and patients coincidentally affected by MS and Crohn's or MS and ulcerative colitis (UC). Five of 20 MS patients had increased intestinal permeability, a finding not previously reported. High levels of CD45RO were found on circulating CD20+ B cells from patients with MS. This has not been reported previously in MS and is found in very few other conditions. Eight patients with coincident MS and Crohn's disease or MS and UC were studied. Coincident MS and UC patients expressed CD45RO on CD20+ B cells, a finding not identified in UC patients alone. A subgroup of MS patients has increased intestinal permeability. These patients express CD45RO CD20+ B cells, also found in Crohn's disease.

Antigens, CD20↗
PubMed1992

Hemoprotein-dependent production of a neutrophil-activating factor from arachidonic acid.

Hemoproteins have been suggested to contribute to various forms of tissue injury by catalyzing the peroxidation of lipids. In this study, the ability of hemoglobin to catalyze the production of a neutrophil-activating factor from arachidonic acid was examined. Incubation of arachidonic acid, hydrogen peroxide, and hemoglobin at 37 degrees C for 30 min resulted in the production of a lipid-extractable substance that was chemotactic for neutrophils in vitro and could stimulate leukocyte adherence in vivo. These actions could be inhibited by two leukotriene B4 (LTB4) receptor antagonists. The peroxidation product cross-reacted significantly with an antibody directed against LTB4, but not with an antibody directed against LTC4. The production of this factor was hemoprotein dependent. Immunoreactive LTB4 and biological activity were produced only when hemoglobin, or another hemoprotein, cytochrome c, was present in the reaction mixture. The amount of the factor produced could be increased in a concentration-dependent manner by increasing the amounts of arachidonic acid or hydrogen peroxide in the reaction mixture. The production of this factor could be inhibited by 5-aminosalicylic acid, catalase, or deferoxamine. Separation of the lipid-extractable products of the peroxidation of arachidonic acid on high-performance liquid chromatography revealed that the immunoreactive (with anti-LTB4) and chemotactic substance had a retention time distinct from that of LTB4 and the hydroxyeicosatetraenoic acids. A lipid-extractable substance with significant cross-reactivity to anti-LTB4 could also be produced if plasma was substituted for arachidonic acid in the reaction mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1991

In vitro vascular responsiveness to norepinephrine in experimental portal hypertension.

It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease.

Animals↗