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Biomedical subjects

I Bjarnason

Publications and source records attributed to I Bjarnason.

At least 109 records · Page 6Linked to original sources
PubMed1992

Glucose and citrate reduce the permeability changes caused by indomethacin in humans.

Nonsteroidal anti-inflammatory drug (NSAID)-induced increased intestinal permeability appears to be a prerequisite for NSAID enteropathy. It has been suggested that early metabolic events leading to the permeability changes may involve inhibition of glycolysis and the tricarboxylic acid cycle, in which case the coadministration of glucose and citrate (the substrates for these metabolic pathways) with indomethacin may afford some protection. The present study, using a combined intestinal absorption-permeability test including 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and [51Cr]ethylene-diaminetetraacetic acid (EDTA) as test probes and the differential urine excretion ratio of [51Cr]-EDTA/L-rhamnose, showed that indomethacin (50 + 75 mg) increased intestinal permeability. A formulation of indomethacin containing 15 mg glucose and 15 mg citrate to each milligram of indomethacin did not increase intestinal permeability significantly above baseline values. When given alone with indomethacin, neither glucose nor citrate (45 mg to each milligram of indomethacin) had any protective effects. Pharmokinetic studies showed that the effects of glucose and citrate cannot be explained on the basis of altered drug absorption. These results suggest a new approach to reducing the small intestinal side effects of NSAIDs.

Adult↗
PubMed1992

Intestinal permeability in patients with Crohn's disease and their first degree relatives.

It has been reported that intestinal permeability to polyethylene glycol 400 is increased in patients with Crohn's disease and their apparently unaffected first degree relatives. Because of the implications that these findings have for the aetiology of Crohn's disease these studies were repeated. Patients with Crohn's disease (n = 28) and 32 first degree relatives from 11 families underwent a polyethylene glycol 400 (PEG400) intestinal permeability test and a hyperosmotic (1500 mosmol/l) absorption/permeability test using 3-0-methyl-D-glucose, D-xylose, L-rhamnose, lactulose, and 51chromium labelled ethylenediamine-tetraacetate. The five hour urine excretion of polyethylene glycol 400 did not differ significantly between controls (n = 25) and first degree relatives, 25.5 (3.3)% v 24.6% (4)% (mean(SD)) p greater than 0.1, respectively. Patients with small bowel involvement excreted significantly less (p less than 0.01) polyethylene glycol 400 (16.3 (4.6)% than controls while those with Crohn's colitis did not (26.4 (3.9)% p greater than 0.1). The permeation of the monosaccharides in patients with Crohn's disease and their first degree relatives did not differ from normal subjects. The permeation of lactulose and 51chromium ethylenediaminetetraacetate was not significantly altered in first degree relatives but was significantly increased in the patients, as was the lactulose/L-rhamnose urine excretion ratio which is a specific measure of small intestinal permeability. These studies show normal absorption and permeability in first degree relatives of patients with Crohn's disease. A genetically determined abnormality of intestinal permeability is not likely to be an important aetiological factor in Crohn's disease.

Adolescent↗
PubMed1992

Increased expression of c-myc proto-oncogene in biopsies of ulcerative colitis and Crohn's colitis.

The steady state levels of c-myc mRNA have been measured in RNA samples extracted from colonoscopic biopsies of inflammatory bowel disease patients obtained at routine endoscopy sessions. Biopsies were immediately frozen in liquid nitrogen limiting the ischaemic time to less than 15 seconds, and can be stored for up to 96 hours before separation of RNA. Yields of RNA using biopsies were 0.137 (0.041)% wet wt (mean (SD), n = 68), these are significantly better than those obtained from surgical material (0.064 (0.063)% wet wt (mean (SD), n = 21) where the tissue ischaemic time was 45 minutes to one hour 40 minutes. Functional activity of RNA extracted was demonstrated by the ability to direct in vitro protein translation in the rabbit reticulocyte system. We have used this technique to show that there is an increased ratio of steady state c-myc proto-oncogene expression in inflamed tissue from 18 patients with left sided ulcerative colitis and five patients with segmental Crohn's colitis, compared with an uninvolved region of the colon in each case. No difference in c-myc expression was seen in biopsies at least 30 cm apart in 11 control patients with no macroscopic or histological abnormalities. Increased expression of c-myc in inflammatory bowel disease is consistent with the activation of this proto-oncogene during altered cell cycle control resulting from the inflammatory process.

Adult↗
PubMed1992

Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy.

This study assessed the effect of metronidazole on the gastroduodenal mucosa, intestinal permeability, blood loss, and inflammation in patients on non-steroidal anti-inflammatory drugs (NSAIDs). Thirteen patients were studied before and after 2-12 weeks' treatment with metronidazole 800 mg/day, while maintaining an unchanged NSAID intake. Intestinal inflammation, as assessed by the faecal excretion of indium-111 labelled neutrophils, and blood loss, assessed with chromium-51 labelled red cells, were significantly reduced after treatment (mean (SD) 111In excretion 4.7 (4.7)% v 1.5 (1.3)% (N < 1.0%), p < 0.001, 51Cr red cells loss 2.6 (1.6) ml/day v 0.9 (0.5) ml/day (N < 1.0 ml/day), p < 0.01). Intestinal permeability assessed as the 5 hour urinary excretion ratio of 51CrEDTA/L-rhamnose did not change significantly (0.133 (0.046) v 0.154 (0.064), p > 0.1) and there were no significant changes in the endoscopic or microscopic appearances of the gastroduodenal mucosa. These results suggest that the neutrophil is the main damaging effector cell in NSAID induced enteropathy. The main neutrophil chemo-attractant in this enteropathy may be a metronidazole sensitive microbe.

Aged↗
PubMed1991

The effect of elemental diet on intestinal permeability and inflammation in Crohn's disease.

This study examines whether treatment of acute Crohn's disease with an elemental diet improves intestinal integrity and inflammation as assessed by a 51Cr-labeled ethylenediaminetetraacetatic acid (EDTA) permeability test and the fecal excretion of 111In-labeled autologous leukocytes, respectively. Thirty-four patients with active Crohn's disease completed a 4-week treatment course with an elemental diet. Active disease was characterized by increased intestinal permeability [24-hour urine excretion of orally administered 51Cr-EDTA, 6.4% +/- 0.6% (mean +/- SE); normal, less than 3.0%] and by high fecal excretion of 111In-labeled leukocytes (14.2% +/- 1.1%; normal, less than 1.0%). Twenty-seven (80%) went into clinical remission, usually within a week of starting treatment. After 4 weeks of treatment, there was a significant decrease in both the urine excretion of 51Cr-EDTA (to 3.4% +/- 0.5%; P less than 0.01) and the fecal excretion of 111In (to 5.7% +/- 1.0%; P less than 0.001), indicating that such treatment is not just symptomatic. A framework for the mechanism by which elemental diet works, centering around the importance of the integrity of the intestinal barrier function, is proposed, and also appears to provide a logical explanation for some relapses of the disease.

Acute Disease↗
PubMed1991

The relationship between nutritional status and serum soluble interleukin-2 receptor concentrations in patients with Crohn's disease treated with elemental diet.

Serum soluble interleukin-2 receptor concentrations (sIL-2R) were measured and correlated with indices of disease activity and nutrition in 13 patients with active Crohn's disease treated with an elemental diet. The initial serum sIL-2R concentrations were raised, 1121 +/- 181 U/ml (mean +/- SEM) compared to controls, 177 +/- 22.9 U/ml (n = 18) (p < 0.001). Four weeks' treatment resulted in significant improvement in disease activity (Harvey-Bradshaw index) and 4-day faecal (111)Indium-leucocyte excretion. Serum sIL-2R concentrations did not change significantly after treatment, 789 +/- 79.8 U/ml (p > 0.05). Serum sIL-2R concentrations were inversely correlated with albumin, pre-albumin, creatinine-height index and total body potassium. Only those patients with markedly elevated sIL-2R concentrations (>800 U/ml) and severe nutritional depletion prior to treatment, showed significant reductions in sIL-2R levels with elemental dietary treatment. These results demonstrate an association between nutritional impairment and immune activation in Crohn's disease.

Journal Article↗
PubMed1991

Importance of local versus systemic effects of non-steroidal anti-inflammatory drugs in increasing small intestinal permeability in man.

Increased small intestinal permeability caused by non-steroidal anti-inflammatory drugs (NSAIDs) is probably a prerequisite for NSAID enteropathy, a source of morbidity in patients with rheumatoid arthritis. This increased small intestinal permeability may be a summation of a local effect during drug absorption, a systemic effect after absorption, and a local effect of the drug excreted in bile, but the relative contribution made by these factors is unknown. We assessed the effect of indomethacin and nabumetone on intestinal permeability. The principal active metabolite of nabumetone, 6-methoxy-2-naphthylacetic acid, is not subject to appreciable enterohepatic recirculation. Twelve volunteers were studied before and after one week's ingestion of indomethacin (150 mg/day) and nabumetone (1 g/day) with a combined absorption/permeability test. Neither drug had a significant effect on the permeation of 3-0-methyl-D-glucose, D-xylose, and L-rhamnose. Indomethacin increased the permeation of radioactive 51chromium ethylenediaminetetra-acetic acid (51Cr EDTA) significantly from baseline (mean (SEM) 0.63 (0.09)% v 1.20 (0.14)%, p less than 0.01) but nabumetone did not (0.70 (0.10)% p greater than 0.1). These results were supported by the 51Cr EDTA/L-rhamnose urine excretion ratios, which reflect changes in intestinal permeability. They suggest that NSAIDs increase intestinal permeability during absorption or after biliary excretion and that the systemic effect is of minor importance.

Adult↗
PubMed1991

Elemental diet in the management of Crohn's disease during pregnancy.

Four patients with Crohn's disease were treated with an elemental diet during pregnancy. Two had active disease and two also had symptoms of small intestinal obstruction. All went into a clinical remission within a few days of starting treatment. Treatment periods varied from two to four weeks, and were followed by elemental diet as a supplement to normal food in two patients. At term, all delivered a healthy infant. These patients indicate that elemental diet is a safe form of treatment for Crohn's disease during pregnancy and may be considered as an alternative to conventional drug treatments which carry a theoretical risk of teratogenesis.

Adult↗
PubMed1991

The effect of polyacrylic acid polymers on small-intestinal function and permeability changes caused by indomethacin.

Non-steroidal anti-inflammatory drug (NSAID)-induced increased small-intestinal permeability appears to be a prerequisite for the development of NSAID enteropathy, which is a cause of much morbidity in patients with rheumatoid arthritis. We assessed, with a combined absorption-permeability test, the effects of Carbopol (a polyacrylic acid polymer capable of increasing mucus strength and viscosity) on intestinal function and whether it protected against indomethacin-induced increased intestinal permeability. Using a test solution of 3-0-methyl-D-glucose, D-xylose, L-rhamnose, and 51Cr-labelled ethylenediaminetetraacetic acid with 5-h urine collections for marker analyses, we tested 16 subjects, as base line, after 20 ml Carbopol 4 times daily for 4 days, after indomethacin alone (75 + 75 mg), and after coadministration of Carbopol and indomethacin. Carbopol had no significant effect on the permeation or absorption of the test substances. Indomethacin increased intestinal permeability significantly, and this was unaffected when Carbopol was coadministered with indomethacin, showing that Carbopol does not limit the immediate damage of NSAIDs on the small intestine.

Acrylic Resins↗
PubMed1990

Studies of intestinal lymphoid tissue. XIV--HLA status, mucosal morphology, permeability and epithelial lymphocyte populations in first degree relatives of patients with coeliac disease.

Fifty two first degree relatives of patients with coeliac disease were investigated for HLA status, small intestinal permeability, and mucosal morphology together with the size of the intraepithelial lymphocyte pool and indices of lymphocyte activation, in an attempt to identify genetically determined markers of the disease. Thirty eight per cent of these subjects had increased intraepithelial lymphocyte populations and a highly significant association with HLA-DR3 compared with controls. Their intestinal permeability to 51chromium-labelled ethylenediamine tetraacetate was invariably normal and there was no evidence of abnormal mucosal architecture, increased crypt cell mitotic activity or lymphocyte 'activation'. Although increased intraepithelial lymphocyte counts clearly do not cause alterations in intestinal structure or function, it is likely that this parameter together with the HLA-DR3 status identifies a genetically determined predisposition to the disease which may only become clinically evident with larger doses of ingested gluten.

Adolescent↗
PubMed1990

Experience with a gastrointestinal marker (51CrCl3) in a combined study of ileal function using 75SeHCAT and 58CoB12 measured by whole body counting.

Introduction of a radioactive gastrointestinal marker (51CrCl3) into a combined study (75SeHCAT + 58CoB12) of ileal function by whole body counting has been undertaken. The technique was assessed in 23 subjects (15 patients with inflammatory bowel disease, six on non-steroidal anti-inflammatory drugs for rheumatoid arthritis, and two normal subjects). Mean (SD) 51CrCl3 retention was only 4.1 (6.0)% on day 4, and was similar on day 7 in subjects given a second dose of 51CrCl3 on day 4. Only one subject had more than 20% of 51CrCl3 retention after four days. A 51CrCl3 correction method adequately corrected for colonic hold up of 58CoB12, when compared with final equilibrium values of 58CoB12 retention. Use of the non-absorbed 58CoB12 fraction as a gastrointestinal marker gave good agreement with the 51CrCl3 method in correcting 75SeHCAT values. In all subjects studied, corrections for colonic retention of 75SeHCAT on day 4, were small (less than 7% of dose) and did not affect the assessment of any subject. In conclusion, an additional gastrointestinal marker such as 51CrCl3 is unnecessary in our combined study since that role can be effected, when indicated by the non-absorbed 58CoB12 fraction.

Adolescent↗
PubMed1990

Ten years' experience with an elemental diet in the management of Crohn's disease.

The immediate and longterm outcome of treating patients with acute Crohn's disease with an elemental diet was studied retrospectively. Successful diet induced remission was achieved in 96 of 113 patients (85%) regardless of age, sex, site or severity of disease, or associated complications of strictures, fistula, or perianal disease. Treatment was unsuccessful in 17 patients (15%), but there were no features at the outset of treatment that distinguished these patients from those who had successful remission. The longterm outcome of treatment was assessed over a five year period by analysis of life tables and survival curves. Twenty two per cent of the patients relapsed within six months of treatment and thereafter the annual relapse rate was 8-10%. Patients with disease complicated by fistula or perianal involvement had early relapse, approaching 100% for the latter. A further retrospective comparison of longterm outcome of diet v steroid induced remissions showed no significant difference in the relapse rates between the two groups at one, three, and five years.

Adolescent↗
PubMed1990

Treatment of non-steroidal anti-inflammatory drug induced enteropathy.

Non-steroidal anti-inflammatory drug induced small intestinal inflammation may have an adverse effect on the joints of patients with rheumatoid arthritis. We therefore assessed small intestinal and joint inflammation in patients with rheumatoid arthritis before and after three to nine months' treatment with sulphasalazine (n = 40) and other second line drugs (n = 20), while keeping the dosage of non-steroidal anti-inflammatory drug at the same level. Sulphasalazine significantly decreased the mean (SD) faecal excretion of 111indium labelled leucocytes from 2.39 (2.22)% to 1.33 (1.13)% (normal less than 1%, p less than 0.01) and improved the joint inflammation as assessed by a variety of parameters. There was no significant correlation between the effects of sulphasalazine treatment on the intestine and the joints. Treatment with other second line drugs had no significant effect on the faecal excretion of 111indium (1.58 (1.04)% and 1.86 (1.51)%, respectively) but improved joint inflammation significantly. The lack of correlation between the intestinal and joint inflammation and their response to treatment suggests that the two are not causally related.

Adult↗
PubMed1990

"Diaphragm-like" strictures of the small bowel in patients treated with non-steroidal anti-inflammatory drugs.

The radiological findings are described in four patients who developed strictures of the small bowel, and who had received non-steroidal, anti-inflammatory drugs (NSAIDs) for 1.5-15 years. Clinical presentation was that of subacute small bowel obstruction. Small bowel barium studies showed multiple discrete strictures. Some strictures were indistinguishable from those of regional enteritis. Others however were narrow "diaphragm-like" septae encroaching on and markedly narrowing the ileal lumen, and shown histologically to be due to submucosal fibrosis. It is suggested that these strictures are likely to be consequent on NSAIDs administration and that radiologists and surgeons need to be aware of these "diaphragms" which can be very difficult to detect on barium examination, either small bowel follow-through or enteroclysis, and at laparotomy.

Adult↗