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Biomedical subjects

I Bjarnason

Publications and source records attributed to I Bjarnason.

At least 127 records · Page 7Linked to original sources
PubMed1990

Experimental evidence of the benefit of misoprostol beyond the stomach in humans.

Nonsteroidal antiinflammatory drugs (NSAID) cause inflammation of the small intestine in 60 to 70% of patients receiving these drugs for more than 6 months. The importance of the inflammation lies in the associated complications of blood and protein loss and in the occasional development of unique small intestinal strictures requiring surgery. The pathogenesis of the inflammation is unknown. However, increased intestinal mucosal permeability due to NSAID appears to be a prerequisite; increased permeability allows exposure of the mucosa to lumenal toxins, which results in neutrophil chemotaxis and, hence, inflammation. In a study assessing the possible protective effect of misoprostol on indomethacin-induced increased small intestinal permeability, 12 volunteers underwent combined absorption/permeability tests prior to and following administration of misoprostol and/or indomethacin. Indomethacin increased intestinal permeability significantly as assessed by 51Cr-EDTA/L-rhamnose urine excretion ratio, and concomitant administration of misoprostol produced a significant protective effect. These results conform to the suggestion that NSAID-induced changes in intestinal permeability may be due to an imbalance between mucosal prostaglandins and leukotrienes. Longterm studies of the coadministration of misoprostol with NSAID are indicated to assess whether this agent reduces the severity of NSAID enteropathy.

Alprostadil↗
PubMed1989

Misoprostol reduces indomethacin-induced changes in human small intestinal permeability.

This study examined whether indomethacin-induced increases in small intestinal permeability in man are prevented by concomitant administration of a prostaglandin analog (misoprostol). Twelve male volunteers were tested as baseline, following misoprostol alone (200 micrograms, at -16, -12, -8.5, -4, -1.5, and +4 hr); following indomethacin alone (75 mg, at -8; 50 mg, -1 hr); and following coadministration of misoprostol and indomethacin as specified above. A 100-ml test solution containing 3-O-methyl glucose (0.2 g), D-xylose (0.5 g), L-rhamnose (1.0 g), and [51Cr]EDTA (100 microCi) was ingested at 8 AM, and a 5-hr collection made for marker analysis to assess active and passive carrier-mediated transport and trans- and intercellular permeation, respectively. Indomethacin increased the permeation of [51Cr]EDTA selectively, and this increase was significantly reduced by the coadministration of misoprostol. These changes were mirrored by changes in [51Cr]EDTA-L-rhamnose urine excretion ratios, which indicates that paracellular permeability was specifically altered. This study supports the suggestion that NSAIDs alter intestinal permeability by a mechanism involving reduced prostaglandin synthesis and indicates that coadministration of misoprostol with NSAIDs may reduce the frequency and severity of NSAID-induced small intestinal inflammation.

3-O-Methylglucose↗
PubMed1989

Intestinal permeability to 51Cr-labelled ethylenediaminetetraacetate in food-intolerant subjects.

Intestinal permeation of 51Cr-labelled ethylenediaminetetraacetate (51Cr-EDTA) was normal in 8 food-intolerant patients. Following ingestion of the offending food stuff there was a significant (p less than 0.003) decrease in the permeation of 51Cr-EDTA but the same phenomenon was observed in control subjects (n = 5) following cereal. Eight patients were tested following ingestion of lentil puree and subsequently with lentil puree containing the food to which they were sensitive. In these patients there was a significant increase in the permeation of 51Cr-EDTA following the 2nd test (p less than 0.01), but this was of insufficient magnitude to be of diagnostic use. These results show that food intolerance does involve some, but not gross changes in intestinal permeability to 51Cr-EDTA.

Adult↗
PubMed1989

Small intestine permeability in schizophrenia.

Gastrointestinal permeability was assessed by means of absorption of 51Cr-labelled EDTA in 24 patients with schizophrenia (12 in relapse and 12 in remission). The results were compared with those for patients with coeliac disease and those for normal controls. Significant differences between the schizophrenic patients and the normal controls were not established. The results for the schizophrenic patients in remission were no different from those for the patients in relapse, and there was no evidence from the study of an effect on gastrointestinal permeability of either anticholinergic or antidepressant medication. It is concluded that schizophrenia is, at least in the majority of cases, unrelated to coeliac disease.

Adolescent↗
PubMed1989

The changing gastrointestinal side effect profile of non-steroidal anti-inflammatory drugs. A new approach for the prevention of a new problem.

The most serious side effects of non-steroidal anti-inflammatory drugs (NSAIDs) involve gastroduodenal perforations and massive haemorrhage. It is becoming increasingly clear, however, that it is the small intestine that bears the main brunt of NSAID-related gastrointestinal toxicity. Hence 70% of patients receiving NSAIDs in the long term have evidence of small-intestinal inflammation, and the same patients lose blood and protein as a consequence. Many patients have asymptomatic ileal dysfunction and occasionally may develop unique small-intestinal strictures necesitating surgery. The pathogenesis of the intestinal inflammation is beginning to emerge. There are data to support that an imbalance between prostaglandins and leukotrienes is important in disrupting small-intestinal integrity during drug absorption. Furthermore, a simple mixture of glucose and citrate with indomethacin appears to minimize the damage. Whether this overcomes a metabolic block caused by NSAIDs and replenishes ATP levels or acts by scavenging oxygen free radicals is unknown, but our further understanding of the mechanism may revolutionize our approach to prevention of the gastrointestinal toxicity of NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Effect of prostaglandin on indomethacin-induced increased intestinal permeability in man.

This study examines whether NSAID induced disruption of small intestinal integrity is preventable by concomitant prostaglandin administration, and whether prostaglandins themselves interfere with intestinal permeability and absorption. Twelve subjects underwent testing following treatment as indicated: baseline, no treatment rioprostil, 300 micrograms, at -9 and -1 h indomethacin, 75 mg and 50 mg, at -9 and -1 h respectively rioprostil plus indomethacin, regimen as above. At 0800 h (0 h) subjects drink a solution containing 51CrEDTA 100 microCi, L-rhamnose 0.5 g, D-xylose 0.5 g and 3-O-methyl-glucose 0.2 g; this is followed by a 5-h urine collection. The amount of test substance in the urine reflects non-mediated intercellular and transcellular permeability, and passive and active carrier mediated transport systems, respectively. Permeation of L-rhamnose, D-xylose and 3-O-methyl-glucose is unaffected by rioprostil and/or indomethacin. Indomethacin significantly increases intestinal permeability to 51CrEDTA; coadministration of rioprostil, however, significantly decreases this detrimental effect of indomethacin. These findings suggest that prostaglandins are essential for maintaining small intestinal integrity in man and lend further support to the suggestion that NSAIDs damage the small intestine by reducing mucosal prostaglandin synthesis.

3-O-Methylglucose↗
PubMed1988

Clinicopathological features of nonsteroidal antiinflammatory drug-induced small intestinal strictures.

The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two patients had rheumatoid arthritis and 2 patients had osteoarthritis; all had received nonsteroidal antiinflammatory drugs for 1.5-30 yr. Three patients had an initial illness characterized by diarrhea, profound weight loss, and hypoalbuminemia. Intestinal radiology at this stage ranged from subtle changes to those of Crohn's disease. Three patients underwent surgery. At operation the bland external appearance contrasted with the striking mucosal appearances of multiple concentric, circumferential, diaphragmatic strictures that caused luminal stenosis to a pinhole. These septa were due to submucosal fibrosis and the histopathological picture appears to represent a new nosological entity.

Adult↗
PubMed1988

Diaphragm disease: pathology of disease of the small intestine induced by non-steroidal anti-inflammatory drugs.

Operative small bowel resection specimens received over a period of 16 years were reviewed to assess whether any intestinal disease could be directly attributed to the use of non-steroidal anti-inflammatory drugs (NSAID). Seven cases of intestinal disease associated with the use of NSAID were identified, all of which occurred in the final six years of the survey, which may reflect the increasing use of these compounds. A spectrum of patterns was found from multiple pathognomonic ileal mucosal diaphragms to broad strictures similar to those seen as a complication of enteric potassium. It seems likely that the formation of diaphragm lesions requires an additional factor, but what is not known as yet is whether the effects of NSAID are local or systemic.

Adult↗
PubMed1988

Malignant pancreatic somatostatinoma in a patient with dermatitis herpetiformis and coeliac disease.

A case of malignant somatostatinoma is reported in a patient with long-standing dermatitis herpetiformis and coeliac disease. The patient had non-specific abdominal pain of several years duration and came to attention because of weight loss despite strict adherence to a gluten-free diet. Plasma somatostatin levels were raised, and laparotomy showed a pancreatic tumour with metastases, which on histology, electron microscopy and immunohistochemistry proved to be a somatostatinoma. After a promising initial response to streptozotocin, she died 30 months later. This is the first reported occurrence of a somatostatinoma in a patient with coeliac disease, adding to the growing list of neoplastic complications in this condition.

Adenoma, Islet Cell↗
PubMed1987

Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs.

Nearly three-quarters of patients on long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) have small-intestinal inflammation, the consequences of which are largely unknown. Two potentially important complications, blood and protein loss from the small intestine, have been studied. 49 patients on NSAIDs underwent study with an indium-111 labelled leucocyte technique which localises and measures intestinal inflammation. 32 patients underwent simultaneous study with technetium-99m labelled red blood cells (RBC), which showed identical sites of localisation to 111In-leucocytes in 19. Intestinal blood loss was measured in 8 patients by use of chromium-51 labelled RBC, and a significant correlation between blood loss and intestinal inflammation was found. Intestinal protein loss was assessed in 9 patients with 51Cr-labelled proteins; patients with NSAID-induced small-intestinal inflammation were found to have a protein-losing enteropathy. These studies show that small intestinal inflammation caused by NSAIDs is associated with blood and protein loss, both of which may contribute to the general ill-health of rheumatic patients.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

In vitro measurement and adaptive response of Fe3+ uptake by mouse intestine.

In order to define the importance of the mucosal uptake step in the intestinal regulation of iron absorption, unidirectional uptake rates of Fe3+ from a nitrilotriacetic acid chelate were measured in duodenal fragments from mice using an in vitro technique. [57Co]-Cyanocobalamin was used as a marker of adherent incubation medium. Uptake showed saturation kinetics over the concentration range 18-450 microM. Uptake was increased in fragments from hypoxic, dietary iron-deficient and pregnant mice. The enhanced uptake was due to an increase in Vmaxapp. However, the modest increase in uptake rates in pregnancy and the gross changes observed in iron-deficiency make the hypoxic model the most convenient. The increase in uptake in hypoxic animals was located to the duodenal region and was not associated with changes in either total mucosal iron content or epithelial cell turnover. The rate of uptake of iron via the serosa did not change with hypoxia. This study implies that flux of Fe3+ across the brush border is subject to adaptive regulation. The hypoxic model is suitable for investigation into the regulation of iron homeostasis.

Adaptation, Physiological↗
PubMed1987

Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans.

This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an 111In-leukocyte technique in patients with rheumatoid arthritis (n = 90) and osteoarthritis (n = 7), it appears that nonsteroidal antiinflammatory drugs cause small intestinal inflammation in two-thirds of patients on long-term treatment and on discontinuation, the inflammation may persist for up to 16 mo. The prevalence and magnitude of the intestinal inflammation was unrelated to the type and dose of nonsteroidal drugs and previous or concomitant second-line drug treatment. There was a significant inverse correlation (r = -0.29, p less than 0.05) between fecal 111In excretion and hemoglobin levels in patients treated with nonsteroidal antiinflammatory drugs. The kinetics of fecal indium 111 excretion in patients treated with nonsteroidal antiinflammatory drugs was almost identical to that of patients with small bowel Crohn's disease. Eighteen patients on nonsteroidal antiinflammatory drugs underwent a radiologic examination of the small bowel and 3 were found to have asymptomatic ileal disease with ulceration and strictures. Nineteen patients on nonsteroidal antiinflammatory drugs, 20 healthy controls, and 13 patients with Crohn's ileitis underwent a dual radioisotopic ileal function test with tauro 23 (75Se) selena-25-homocholic acid and cobalt 58-labeled cyanocobalamine. On day 4, more than half of the patients with rheumatoid arthritis had evidence of bile acid malabsorption, but the ileal dysfunction was much milder than seen in patients with Crohn's ileitis.

Adolescent↗
PubMed1987

Critical analysis of the accuracy of a combined test (75Se-HCAT and 58Co-B12) of ileal function using a whole-body counter.

The accuracy of a combined test (75Se-HCAT + 58Co-B12) of ileal function by whole-body counting has been assessed with particular attention being paid to the reliability of the 100% retention measurements, the accuracy of the crossover of 58Co into the 75Se channel and the effects of variable counting geometry. A linear relationship between 58Co crossover and body weight improved the accuracy of determining the crossover value for individual patients. Non-geometrical errors such as those associated with counting statistics and crossover were found to be small, with a coefficient of variation usually less than +/- 2% except in cases of very low 75Se-HCAT retention in the presence of substantial amounts of 58Co. The main sources of error were due to problems of variable counting geometry but there was very good agreement between 75Se and 58Co retentions measured by whole body counting and by excreta analysis which suggested that the overall error of the test was unlikely to exceed +/- 10%. A protocol is presented for use of the combined test on an outpatient basis and includes retention measurements at 4, 7, and 10 d post administration.

Cobalt Radioisotopes↗
PubMed1987

The gut and RA.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

The pathogenesis and consequence of non steroidal anti-inflammatory drug induced small intestinal inflammation in man.

Non steroidal anti-inflammatory drugs (NSAID's) have recently been shown to cause small intestinal inflammation in the majority of patients receiving these on a regular basis for more than one year. The development of inflammation is preceded by an NSAID effect to increase small intestinal permeability. Increased intestinal permeability is shown to be related to drug potency to inhibit cyclooxygenase and the effect is systemically mediated rather than a local irritant one. More recently, increased intestinal permeability due to NSAID's has been reduced by concomitant prostaglandin administration, showing that prostaglandins are essential for maintaining intestinal integrity in man. It is proposed that altered intestinal permeability allows the mucosa to be exposed to bacterial degradation products or other toxins and together with reduced chemotaxic response and altered neutrophil function due to NSAID's, this series of events leads to bacterial invasion of the mucosa which is evident by the techniques of 111Indium leucocyte scans and faecal collections. The consequence of such inflammation is that it may explain intestinal perforations and strictures which are occasionally seen in subjects on NSAID's. Most patients with NSAID-induced small intestinal inflammation may be bleeding from the intestine, loosing protein and some have ileal dysfunction. The small intestine may be a greater source of morbidity than the stomach, in patients receiving NSAID's.

Anti-Inflammatory Agents, Non-Steroidal↗