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Biomedical subjects

B B Scott

Publications and source records attributed to B B Scott.

At least 19 recordsLinked to original sources

Randomised controlled trial of azathioprine withdrawal in ulcerative colitis.

OBJECTIVE: To determine whether azathioprine can prevent relapse in ulcerative colitis. DESIGN: One year placebo controlled double blind trial of withdrawal or continuation of azathioprine. SETTING: Outpatient clinics of five hospitals. SUBJECTS: 79 patients with ulcerative colitis who had been taking azathioprine for six months or more. Patients in full remission for two months or more (67), and patients with chronic low grade or corticosteroid dependent disease (12) were randomised separately. 33 patients in remission received azathioprine and 34 placebo; five patients with chronic stable disease received azathioprine and seven placebo. MAIN OUTCOME MEASURE: Rate of relapse. Relapse was defined as worsening of symptoms or sigmoidoscopic appearance. RESULTS: For the remission group the one year rate of relapse was 36% (12/33) for patients continuing azathioprine and 59% (20/34) for those taking placebo (hazard rate ratio 0.5, 95% confidence interval 0.25 to 1.0). For the subgroup of 54 patients in long term remission (greater than six months before entry to trial) benefit was still evident, with a 31% (8/26) rate of relapse with azathioprine and 61% (17/28) with placebo (p less than 0.01). For the small group of patients with chronic stable colitis (six were corticosteroid dependent and six had low grade symptoms) no benefit was found from continued azathioprine therapy. Adverse events were minimal. CONCLUSIONS: Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug. Demonstration of the relapse preventing properties of azathioprine has implications for a large number of patients with troublesome ulcerative colitis, who may benefit from treatment with azathioprine.

Azathioprine

Is persistent adenovirus 12 infection involved in coeliac disease? A search for viral DNA using the polymerase chain reaction.

It has been shown that partial amino acid sequence homology between alpha gliadin and an early region protein (E1B-58 kDa) of adenovirus 12 results in immunological cross reaction. This led to the proposal that prior infection by adenovirus 12 could be associated with the development of coeliac disease. To examine this hypothesis, evidence was sought of persistent adenovirus 12 infection in the small intestinal mucosa of patients with coeliac disease. DNA isolated from biopsy samples from 24 control and 18 coeliac disease patients was analysed by the polymerase chain reaction for adenovirus 12 DNA encoding the E1B-58 kDa protein. Four of 18 coeliac disease and two of 24 control patients were positive. There is thus a low prevalence of this infection on both groups of patients but certainly no significantly increased incidence in coeliac disease. These results suggest that persistent adenovirus 12 infection is not a major element in the pathogenesis of coeliac disease.

Adenoviridae

Ulcerative colitis: one disease or two? (Quantitative histological differences between distal and extensive disease).

Cell counts and measurements of mucosal architecture were made on rectal biopsies from nine patients with total colitis, eight with left sided colitis, 15 with distal colitis, and 11 with proctitis. The mean total lamina propria cell count in proctitis and distal colitis approached twice that of extensive left sided and total colitis (p less than 0.001) and in distal proctocolitis the cell numbers are further increased in the chronic over the acute phase. This difference was not explained by age, duration, activity, or treatment. The predominantly increased lymphoid and mononuclear cell infiltrate in distal proctocolitis indicates a different pattern of immune response, suggesting a separate process from extensive colitis or a more intense reaction resulting in localisation of disease.

Adolescent

Changes in anti-endotoxin-IgG antibody and endotoxaemia in three cases of gram-negative septic shock.

Circulating endotoxin levels and IgG antibodies to a range of Gram-negative bacterial lipopolysaccharides (LPS) (endotoxins) of different sizes and structures were measured daily in three cases of septic shock. There was an inverse relationship between endotoxin levels and cross-reactive antibodies to the core glycolipid (CGL) region of lipopolysaccharide. This suggests that antibody to LPS-CGL was initially consumed by a superabundance of endotoxin, and that a resurgence of intrinsic anti-LPS-CGL antibody levels may be associated with a reduction of circulating endotoxin. The implications of these findings for passive antibody therapy of septic shock are discussed.

Adult

What is colitis? Statistical approach to distinguishing clinically important inflammatory change in rectal biopsy specimens.

Measurements of mucosal dimension, architecture, and cell counts in both lamina propria and epithelium were made on rectal biopsy specimens from 20 patients with irritable bowel syndrome ("normal" controls); 54 patients with ulcerative colitis, Crohn's disease, and non-specific proctitis; eight patients with small bowel Crohn's disease; and 34 in whom the rectal biopsy specimen was not diagnostic. Discriminant analysis was applied to multiple variables based on the measurements, and three variables were identified as of high predictive value. The most powerful discriminant was increased lamina propria cellularity in all forms of chronic colitis. The ratios of surface length to mucosal length and of surface epithelial height to crypt epithelial height also emerged as discriminants. Chronic inflammatory bowel disease was distinguished from normal in 95% of cases with a definite pathological diagnosis, and 85% of borderline cases were correctly classified as either normal or inflammatory when judged by the final diagnosis after follow up. This study provides a basis for automated diagnosis of rectal biopsy specimens and provides objectively validated criteria which can also be applied in routine histological diagnosis.

Adult

Endotoxin-polymyxin complexes in an improved enzyme-linked immunosorbent assay for IgG antibodies in blood donor sera to gram-negative endotoxin core glycolipids.

Common or cross-reactive epitopes of Gram-negative endotoxins are found in the inner-core glycolipid region of the outer membrane lipopolysaccharides (LPS). Hydrophobic LPS from rough mutants of Gram-negative bacteria, lacking serotype polysaccharide O-antigen chains, did not bind satisfactorily to polystyrene microplates for ELISA detection of cross-reactive IgG anti-endotoxin antibodies. When these LPS molecules were reacted with the cationic polypeptide polymyxin B, complexes were formed which were stable when coated on microplates. LPS-polymyxin complexes allowed optimisation of conditions for an ELISA for IgG antibodies to the core glycolipid region of endotoxins which could be used for screening large numbers of blood donor sera.

Antibodies, Anti-Idiotypic

Serological relationships between Escherichia coli and Salmonella smooth- and rough-mutant lipopolysaccharides as revealed by enzyme-linked immunosorbent assay for human immunoglobulin G antiendotoxin antibodies.

Reactions of sera from healthy blood donors to smooth and rough mutant lipopolysaccharides (LPS) from Escherichia coli O111:B4 and Salmonella minnesota which had been complexed with polymyxin B were determined by enzyme-linked immunosorbent assay. Relative enzyme-linked immunosorbent assay reactivities were examined for prima facie evidence of cross-reactivity by analyses of correlation and relative scatter. Patterns of reactivity were interpreted in relation to published structures. Evidence was obtained for two dominant epitopes associated with the lipid A-2-keto-3-deoxyoctulosonic acid and heptose regions of the LPS core. Sera demonstrated apparent exclusive antibody homogeneity in that given sera showed only one of the two possible specificities, which occurred with equal frequency. Cross-reactivity was found in the lipid A-2-keto-3-deoxyoctulosonic acid region for all LPS. Cross-reactivity was found in the heptose region for larger rough mutant S. minnesota LPS and smooth S. minnesota LPS and for E. coli O111:B4 LPS but not for E. coli rough mutant J5 LPS, whose heptose region appears to be different from those of the other organisms.

Antibodies, Bacterial

T-lymphocyte populations in normal and coeliac small intestinal mucosa defined by monoclonal antibodies.

Counts of T-lymphocytes within surface and crypt epithelium and lamina propria of normal and coeliac small intestinal mucosa using an immunoperoxidase method are described and related statistically to changes in mucosal structure determined by quantitative histology. The use of multiple pan-T-lymphocyte and subset antibodies allowed comparison of marker patterns in normal and abnormal mucosa. Total numbers of surface epithelial T-lymphocytes and subtypes were not found to be increased in coeliac disease, but there was an increase in density per unit length of epithelium. Distinctive changes in expression of Leu 1, Leu 2, and Leu 5 by the surface epithelial T-lymphocytes suggest that, although their total numbers are not increased, these cells are not passively crowded but have an active role, possibly as committed cytotoxic lymphocytes. Natural killer cells do not appear to be a major population in normal or coeliac small intestinal mucosa.

Adolescent

Duodenal bulb plasma cells in duodenitis and duodenal ulceration.

Using an immunoperoxidase technique IgA, IgM, IgE and IgG plasma cells were studied in endoscopic duodenal bulb biopsies taken from 14 controls, 25 patients with grade 1 duodenitis (Whitehead classification), 12 patients with grade 2 duodenitis and three with grade 3 duodenitis. The control counts were compared with those in the jejunum and rectum. In addition cell counts were compared in 16 pairs of patients, with and without duodenal ulcer, exactly matched for grade of duodenitis. The control counts were not significantly different from counts in jejunum or rectum except for IgG which were higher in the jejunum (p = 0.03). IgA plasma cell counts were significantly increased in both grade 1 and grade 2 duodenitis compared with controls (p less than 0.05 and p less than 0.01). There was no significant difference for the other plasma cells. All plasma cell counts were decreased in the small group of grade 3 duodenitis compared with the other groups. There was no significant difference between counts in duodenitis whether or not there was associated duodenal ulceration. The isolated IgA plasma cell response of the duodenal bulb mucosa in duodenitis is very different from that of the jejunal mucosa in coeliac disease, and the rectal mucosa in inflammatory bowel disease and bacterial colitis and probably represents the basic response to any mucosal damage.

Cell Count

Defining duodenitis: quantitative histological study of mucosal responses and their correlations.

Biopsies from 56 patients with endoscopically normal duodenal bulbs, duodenitis, or duodenal ulceration were studied for counts of plasma cells, polymorphs, and eosinophils and extent of gastric metaplasia, villous atrophy, and mucosal oedema. A correlation matrix showed that the counts of different types of plasma cells were closely correlated with each other and that there was also a close correlation between the presence of intraepithelial polymorphs, villous atrophy, and gastric metaplasia. Cluster and discriminant analysis indicated that the histological changes could be grouped by their statistical association into three simple categories: normal, which includes many cases incorrectly labelled in some classification systems as mild or chronic duodenitis; histologically defined mild duodenitis, characterised by an appreciable plasma cell response and oedema usually with intraepithelial polymorph infiltration and gastric metaplasia; and severe duodenitis, with an appreciable polymorph response and villous atrophy but decreased plasma cells. Decreased plasma cells may be an important indication of peptic ulceration.

Aged

The Cronkhite-Canada syndrome: an ultrastructural study of pathogenesis.

Electron microscopical and cytochemical studies of intestinal biopsies from a patient with typical features of the Cronkhite-Canada syndrome show that the primary process affects the crypts. This results in cystic dilatation associated with expansion and focal degeneration of the crypt compartment of the intestinal epithelium. The villous epithelium compartment is reduced but ultrastructurally normal. Inflammation and oedema of the lamina propria follows from leakage of mucin through breaks in the abnormal crypts.

Aged

Small intestinal plasma cells in coeliac disease.

Using a modified immunoperoxidase technique to achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue, IgA, IgM, IgE, and IgG plasma cells were studied in small bowel biopsies from 20 controls, 23 untreated coeliac patients, 19 treated coeliac patients, and seven patients with Crohn's disease not involving duodenum or jejunum. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 2.5:1:1:1 respectively. In patients with untreated coeliac disease, counts of all types of plasma cell were significantly increased approximately two-fold compared with controls although for IgG cells there was considerable overlap. The ratio of the mean plasma cell counts in the untreated coeliac patients was 3.5:1.5:2:1. Counts fell significantly after treatment with a gluten-free diet. There was no significant difference between counts in the controls and the Crohn's disease patients. The changes found in coeliac disease may simply be a non-specific response to mucosal damage. The increases in IgA and IgM plasma cells, however, suggest that the deposits of extracellular IgA and IgM observed in coeliac mucosa are locally produced, and the increase in IgE plasma cells raises the possibility that reaginic type hypersensitivity may be involved in coeliac disease.

Adolescent

Rectal mucosal plasma cells in inflammatory bowel disease.

To achieve optimum staining and reproducible counts of plasma cells in paraffin embedded tissue with the immunoperoxidase technique we have found it essential to obtain a plateau count by titration of antisera for each specimen. This modification was used to study IgA, IgM, IgE, and IgG plasma cells in rectal biopsies from 20 controls, 20 patients with ulcerative proctocolitis, 20 with Crohn's colitis, 20 with non-specific proctitis, 15 with bacterial colitis, and seven with Crohn's disease but no apparent large bowel involvement. Counts were correlated with the characteristic histological features of inflammatory bowel disease. In controls the ratio of the mean counts for IgA, IgM, IgE, and IgG plasma cells was 8:3:3:1. All types of plasma cells were very significantly increased in the patients with ulcerative proctocolitis, Crohn's colitis, and non-specific proctitis and counts correlated with the severity of inflammation. There was no significant difference between the counts in these three groups. All counts tended to be higher in bacterial colitis than in controls, the difference being significant for IgA and IgE. When matched for severity of inflammation there was no significant difference between the counts in bacterial colitis and inflammatory bowel disease. The counts in patients with Crohn's disease but no large bowel involvement were not significantly different from controls. These results suggest that changes in plasma cell counts in inflammatory bowel disease are a non-specific response to mucosal damage, possible by a luminal irritant, and do not differentiate the type of inflammatory bowel disease.

Adult

Small intestinal ulceration: diagnostic difficulties in relation to coeliac disease.

Seven cases of ulceration of the small intestine are described and the relationship to coeliac disease is discussed. Evidence for coeliac disease is found in all cases but is less strong in some than in others, and coeliac disease was proved in only two cases. The ulcers were examined histologically in each case and in three cases were associated with malignant histiocytosis but the others showed only non-specific chronic inflammation. This suggests a spectrum of disorders with an inconsistent relationship to gluten sensitivity and small intestinal lymphoma.

Adult

Gastro-oesophageal candidiasis.

A prospective search for gastro-oesophageal candidiasis was made by histological examination of all the biopsies taken from 465 patients endoscoped consecutively during a 12 month period. The criterion for diagnosis was the demonstration of infiltration of tissue or ulcer slough by yeasts and hyphae. Nineteen cases of candidiasis were found giving an overall incidence of 4%. There were 12 cases with oesophageal candidiasis, two with both oesophageal and gastric candidiasis, and five with gastric candidiasis. In none of the patients was candidiasis suspected before endoscopy. Symptoms referable to the candidiasis were uncommon and radiology was not helpful in diagnosis. There was associated local pathology (particularly peptic ulceration and carcinoma of the stomach or oesophagus) in all except two patients, which suggests that the candidiasis is usually secondary to mucosal damage. In the series, candidiasis was present in 27% of patients with oesophageal cancer, 20% of patients with gastric cancer, 16% of patients with benign gastric ulcers, and 15% of patients with oesophagitis.

Aged

Endoscopic small intestinal biopsy.

Ninety-three patients with suspected small bowel disease were investigated by duodenal forceps biopsy via a fiberoptic endoscope. Three biopsies were usually taken from the distal end of the second part of the duodenum, orientated on a square of plastic mesh, and examined by stereomicroscopy and histology. There were no failures or complications. Using strict criteria, sections from 56% of the 299 biopsies were satisfactory for histological interpretation (compared with 76% of 346 biopsies taken via a hydraulic multiple biopsy capsule from a separate group of patients). At least one biopsy was satisfactory from 87% of the patients. A previous study having shown that biopsies from this site are comparable to those from the conventional site at the duodenojejunal junction, it is concluded that endoscopic duodenal biopsy is a valid alternative to conventional suction biopsy and, moreover, has a number of advantages.

Adolescent