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Biomedical subjects

M D Hellier

Publications and source records attributed to M D Hellier.

At least 19 recordsLinked to original sources

Sulphasalazine treatment and the colorectal mucosa-associated flora in ulcerative colitis.

AIM: To study the influence of sulphasalazine treatment on the mucosa-associated bacterial flora of rectal biopsy tissue specimens in patients with ulcerative colitis. PATIENTS: Twenty-four patients had newly diagnosed active ulcerative colitis; 20 patients had acute relapse of ulcerative colitis (10 not taking maintenance sulphasalazine); (40 patients had quiescent ulcerative colitis; 21 not taking maintenance sulphasalazine). The influence of 3 weeks of sulphasalazine treatment on the mucosa-associated flora was studied in the patients presenting with active disease. RESULTS: Comparison of patients according to sulphasalazine usage revealed few differences in the mucosal flora. In patients with quiescent ulcerative colitis, Escherichia coli was found at lower counts in patients taking maintenance sulphasalazine; however, this effect was not evident in patients with active disease. Inconsistent changes in other facultatives were seen between the two active disease groups, particularly for a miscellaneous group of unidentified Gram-positive rods. Three patients, all receiving sulphasalazine, were colonized with Clostridium difficile, but this did not appear to influence their disease. CONCLUSION: Sulphasalazine treatment in ulcerative colitis causes only minor disturbance to the populations of bacteria colonizing the colorectal mucosa.

Adult

Inflammatory bowel disease and domestic hygiene in infancy.

To test the hypothesis that Crohn's disease is caused by delayed exposure to enteric infections, we did a case-control study. We compared 133 patients who have Crohn's disease and 231 with ulcerative colitis who have controls selected from the general population and matched for age and sex. Crohn's disease was more common in subjects whose first houses had a hot-water tap (odds ratio 5.0, 95% CI 1.4-17.3) and separate bathroom (3.3, 1.3-8.3). Ulcerative colitis showed no clear relation to household amenities in infancy. These findings may explain why the incidence of Crohn's disease has increased in developed countries over the past 50 years.

Adolescent

Adhesive and hydrophobic properties of Escherichia coli from the rectal mucosa of patients with ulcerative colitis.

The adherent properties and hydrophobicity of Escherichia coli isolates have been compared from the rectal mucosa of patients with active and inactive ulcerative colitis and from a control patient group. Patients with active colitis were colonised less frequently and with lower numbers of E coli than were control patients. Mannose resistant adhesion to HEp-2 cells was determined for 124 isolates of E coli and surface hydrophobicity was estimated by salt agglutination in 96 of these isolates. There was no significant difference in the distribution of adherent strains between the colitis patient groups or with disease activity. E coli from the control patients were marginally less adhesive than those from colitics. The hydrophobicity of isolates did not differ significantly between colitic and control groups nor were there significant differences correlated with disease activity. Furthermore, for these mucosal E coli isolates, hydrophobicity and mannose resistant adhesion were unrelated characteristics.

Agglutination Tests

The rectal mucosa-associated microflora in patients with ulcerative colitis.

The rectal mucosa-associated flora (MAF) of patients with ulcerative colitis has been studied in 25 patients with newly diagnosed disease, 20 with relapse of existing disease, and 44 who were in remission. Patients with active disease were re-examined twice during treatment. The MAF was simpler and less dense than the microflora of faeces. Obligate anaerobes usually predominated in the MAF although the ratio of obligate anaerobes to facultative species was lower than that found in faeces. Viable counts of the total flora and of its constituent genera varied considerably between patients. Counts of the total flora, of obligate anaerobes (including bifidobacteria, eubacteria and clostridia), and facultative organisms and micro-aerobes (enterobacteria and lactobacilli) were reduced in patients with active disease compared with those with inactive disease; corresponding carriage rates were also lower. Counts and carriage rates increased during treatment and approached those found in quiescent disease. The alterations in the MAF were especially marked in patients experiencing their first attack of ulcerative colitis. The relationship between these alterations and the aetiology and pathogenesis of this disease remains unclear.

Bacterial Infections

Search for enteric microbial pathogens in patients with ulcerative colitis.

Microbial pathogens were sought in faeces of patients with active ulcerative colitis and again after 3 months treatment. 64 patients were examined during their first episode of ulcerative colitis and 30 with relapse of chronic disease. At presentation, bacterial pathogens were not found; 1 patient had cryptosporidiosis. In 10 patients treatment appeared to result in some loss of colonisation resistance as evidenced by colonisation with beta-haemolytic streptococci, Staphylococcus aureus, candida and Clostridium difficile. Unidentified cytotoxic activity was present in the faeces of 4 patients at presentation and 2 patients during or after treatment. We conclude that enteric infection is an uncommon finding in patients with active ulcerative colitis.

Colitis, Ulcerative

Comparison of cimetidine and pirenzepine in the healing and maintenance of remission in duodenal ulcer.

The effect of cimetidine and pirenzepine on the maintenance of healing in duodenal ulceration has been compared in a multi-centre, controlled study. One hundred and sixty-six patients with endoscopically proven duodenal ulceration have been randomised to receive either cimetidine 200 mg t.i.d. and 400 mg nocte, or pirenzepine 50 mg b.i.d. for 6 weeks. Patients in each group were well matched for age, sex, weight and cigarette, alcohol and antacid consumption. After 6 weeks significantly more cimetidine-treated patients had healed ulcers: cimetidine showed 8 unhealed out of 79, and pirenzepine 19 out of 74 (p = 0.01). The follow-up phase lasted for 52 weeks or until patient withdrawal or ulcer relapse. During the follow-up phase 77.6% of cimetidine-treated and 68.8% of pirenzepine-treated patients relapsed. This difference in relapse rates is not statistically significant (p = 0.23).

Adult

Comparative trial of sodium cromoglycate enemas with prednisolone enemas in the treatment of ulcerative colitis.

A double blind multicentre study comparing sodium cromoglycate (600 mg/100 ml) by enema with prednisolone (20 mg/100 ml) by enema is reported. The study was conducted over a nine week period in the treatment of 70 patients with ulcerative colitis. Analysis of symptoms showed significant decreases in scores for patients in both groups, both at four and eight weeks; the only difference between the two groups was a significantly greater improvement in the reduction of rectal bleeding after four weeks in the prednisolone group. On sigmoidoscopy, both treatment groups showed a highly significant improvement after four and eight weeks with no significant differences being seen between the groups. Histology of the rectal biopsies showed a significant improvement in the inflammation of the mucosa for both treatment groups after four and eight weeks with no differences being observed between the groups. There were no significant changes in eosinophils from baseline and no difference between the groups at four and eight weeks.

Adolescent

Time relationships between cessation of smoking and onset of ulcerative colitis.

From 5 centres 154 patients with ulcerative colitis and a history of smoking completed a questionnaire about the temporal relationship between diagnosis of colitis and cessation of smoking. One hundred and thirty-eight of these were ex-smokers and 107 (69.5%) had stopped smoking before the diagnosis of colitis was made. Fifty-six patients (52%) developed colitis within 3 years of stopping smoking. The findings suggest that smoking exerts protective effect against the development of ulcerative colitis.

Adolescent

A double-blind controlled trial of the effect of sodium cromoglycate in preventing relapse in ulcerative colitis.

A double-blind controlled trial of the effect of sodium cromoglycate (SCG) in preventing relapse in ulcerative colitis has been completed in 100 subjects. In patients already taking sulphasalazine, SCG did not prove to be of any additional benefit. However, in patients not on any other maintenance therapy, the relapse rate was 40% for SCG as compared with 75% for placebo. A large study of the effect of SCG in patients intolerant of sulphasalazine is indicated.

Adult

Intestinal perfusion studies in tropical sprue. 2. Movement of water and electrolytes.

Jejunal absorption of sodium and water has been investigated in 10 normal Indians and 11 patients with chronic tropical sprue. Normal saline and solutions containing amino acids and dipeptides were studied. In both groups little absorption of sodium and water from normal saline was seen. Mean water and sodium absorption from the free amino acid or dipeptide solutions showed no significant difference between the groups and was similar to absorption from normal saline. These results differ from data obtained in normal English subjects where at these concentrations significant stimulation of sodium and water absorption was seen. In a proportion of subjects in both groups net secretion was observed. However, no correlation was seen between mucosal histology or luminal bacteriology and sodium or water movement. These findings in patients with chronic tropical sprue are similar to findings in normal Indians and suggest that jejunal handling of sodium and water is abnormal when compared with normal English subjects, but that the mucosa is not in a secretory phase as seen in certain other diarrhoeal states or in the acute early phase of sprue.

Amino Acids

Intestinal absorption in normal Indian and English people.

The absorption of glycine, glycylglycine, water, and electrolytes was studied by intestinal perfusion in normal Indian and English people. Compared with the English people the Indians showed impaired absorption of all four substances. In the Indians the absorption of glycine and glycylglycine was impaired to the same extent, so that the kinetic advantage of glycylglycine as compared with glycine was preserved. The reduced absorption in the Indians may be the functional counterpart of the minor morphological changes seen in the jejunal mucosa of people living in southern India.

England

Intestinal perfusion studies in tropical sprue. 1. Amino acid and dipeptide absorption.

Intestinal absorption of glycine 20 mmol/1, glycyl-glycine 10 mmol/1 plus L-leucine 10 mmol/1, and glycyl-L-leucine 10 mmol/1 has been studied by intestinal perfusion in 11 patients with tropical sprue and 10 control subjects. The patients with sprue had a significant reduction in the rate of absorption of glycine from a 20 mmol/1 solution, but there were no significant differences in the absorption of the other substances. The failure to demonstrate any difference in the absorption of these substances is probably related to their low concentration relative to the maximum absorptive capacity of the intestine. In both groups of subjects the kinetic advantage of glycyl-glycine absorption as compared with glycine absorption was maintained. When the dipeptides were perfused, free amino acids appeared in the perfusate presumably by "back diffusion" from the mucosal cells. In the case of glycyl-L-leucine considerably more glycine and leucine were found in the perfusate in patients with sprue than in the control subjects. There was no correlation between peptide absorption and the concentration of total glycly-glycine hydrolase and glycyl-L-leucine hydrolase, measured as combined brush border and cytosol enzymes. The concentrations of these enzymes were similar in both groups of subjects.

Amino Acids

The effect of amino acids and dipeptides on sodium and water absorption in man.

A perfusion technique has been used to quantitate the effect of the amino acids glycine and alanine and the dipeptides glycyl-glycine and glycyl-L-alanine on sodium and water absorption from the human jejunum. Although no net absorption of sodium and water was seen in the absence of non-electrolytes, a significant stimulation occurred in the presence of both free amino acids and dipeptides. In the case of glycine and alanine, sodium and water absorption increased linearly with increasing concentration of the amino acid and saturation was not demonstrated over the range of concentrations studied. Molar ratios for net absorption of free amino acid and sodium were approximately 1:1 for all but the highest concentration of alanine. In contrast, the corresponding molar ratios for the two dipeptide solutions and sodium were approximately 1:2. Possible explanations for these observations are discussed.

Adult