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Biomedical subjects

J D Sanderson

Publications and source records attributed to J D Sanderson.

At least 19 recordsLinked to original sources
PubMed2004

Small-bowel barium follow-through is rarely required in patients with a normal ileoscopy and terminal ileal biopsy and a normal or unremarkable colonoscopy.

BACKGROUND: There is an increase of reliance on ileoscopy in preference to small-bowel barium follow-through in the diagnosis of terminal ileal Crohn disease. In this study the role of small-bowel barium follow-through after a normal or unremarkable ileocolonoscopy was investigated. METHODS: A retrospective analysis of all patients who had a colonoscopy followed by a small-bowel barium follow-through over a 7-year period was performed. Patients with a previously established diagnosis of inflammatory bowel disease and those who had colonoscopic evidence of inflammatory bowel disease were excluded. RESULTS: Of the 96 patients who had a normal ileoscopy and normal or unremarkable colonoscopy, 3 had abnormalities detected at small-bowel barium follow-through. Two patients had abnormal terminal ileal biopsies, although the terminal ileum appeared macroscopically normal. The small-bowel barium follow-through helped to establish the diagnosis of Crohn disease. The other patient presented changes consistent with a previously established diagnosis. Of the 47 patients who had a normal or unremarkable total colonoscopy without ileoscopy, I had abnormalities detected at small-bowel barium follow-through consistent with a previously established diagnosis. CONCLUSIONS: Small-bowel barium follow-through is rarely required in patients who have had a normal ileoscopy and terminal ileum biopsy and a normal or unremarkable colonoscopy. It should only be performed if there is a very high index of suspicion of small-bowel pathology. In patients with suspected Crohn disease, it is important to take terminal ileum biopsies even if the ileum appears macroscopically normal at ileoscopy.

Adolescent↗
PubMed2004

Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease.

Orofacial granulomatosis (OFG) is a condition of unknown aetiology with histological and, in some cases, clinical association with Crohn's disease (CD). However, the exact relationship between OFG and CD remains uncertain. The aim of this study was to determine whether OFG could be distinguished immunologically from CD by comparing non-specific and specific aspects of humoral immunity in serum, whole saliva and parotid saliva in three groups of patients: (a) OFG only (n = 14), (b) those with both oral and gut CD (OFG + CD) (n = 12) and (c) CD without oral involvement (n = 22) and in healthy controls (n = 29). Non-specific immunoglobulin (IgA, SigA, IgA subclasses and IgG) levels and antibodies to whole cells of Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans were assayed by enzyme-linked immunosorbent assay (ELISA) in serum, whole saliva and parotid saliva. Serum IgA and IgA1 and IgA2 subclasses were raised in all patient groups (P < 0.01). Salivary IgA (and IgG) levels were raised in OFG and OFG + CD (P < 0.01) but not in the CD group. Parotid IgA was also raised in OFG and OFG + CD but not in CD. The findings suggest that serum IgA changes reflect mucosal inflammation anywhere in the GI tract but that salivary IgA changes reflect involvement of the oral cavity. Furthermore, the elevated levels of IgA in parotid saliva suggest involvement of the salivary glands in OFG. Serum IgA antibodies to S. cerevisiae were raised markedly in the two groups with gut disease while serum IgA (or IgG) antibodies to C. albicans were elevated significantly in all three patient groups (P < 0.02). No differences were found with antibodies to S. mutans. Whole saliva IgA antibodies to S. cerevisiae (and C. albicans) were raised in the groups with oral involvement. These findings suggest that raised serum IgA antibodies to S. cerevisiae may reflect gut inflammation while raised SIgA antibodies to S. cerevisiae or raised IgA or IgA2 levels in saliva reflect oral but not gut disease. Analysis of salivary IgA and IgA antibodies to S. cerevisiae as well as serum antibodies in patients presenting with OFG may allow prediction of gut involvement.

Adolescent↗
PubMed2003

A prospective study of the technical feasibility of ileoscopy at colonoscopy.

BACKGROUND: Despite a well-documented diagnostic yield, ileoscopy at colonoscopy is not performed routinely. This is due to the perceived difficulty in intubating the ileocaecal valve, added procedure time and a lack of acceptance regarding diagnostic yield. Therefore, we conducted a study to investigate the technical feasibility of ileoscopy at colonoscopy. METHODS: Ileoscopy was studied prospectively in 120 patients undergoing diagnostic colonoscopy. After identification of the caecum, ileoscopy was attempted by one of four techniques. The time taken to pass from caecum to terminal ileum, the patient position, use of Hyoscine-n-butyl bromide and any ileal abnormalities were recorded in each case. RESULTS: Ileoscopy was successful in 117/120 (97%) cases with a median time of 55 s taken to intubate the ileo-caecal valve. A 'down and left' technique was used in most cases (74.4%). Switching the patient to supine aided ileoscopy in 24 cases (20.4%) and Hyoscine-n-butyl bromide was considered helpful in 25 (21.4%). Overall, the terminal ileum was abnormal in 24 of 117 (20.5%) patients. CONCLUSIONS: Ileoscopy can be achieved in nearly all patients undergoing diagnostic colonoscopy and the added procedure time is short. Added time, technical difficulty and limited yield are not valid reasons for choosing not to perform ileoscopy.

Abdominal Pain↗
PubMed2002

Related IgA1 and IgG producing cells in blood and diseased mucosa in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease in which the colonic mucosa is infiltrated with plasma cells producing IgG autoantibodies. It is not known whether this represents a local mucosal response which has switched to IgG or a peripheral response which may have been initiated by peripheral antigen which homed to the colonic mucosa. The clonal distribution of IgG secreting cells and isotype switched variants in UC is not known. AIMS: To investigate the clonal distribution of mucosal IgG in UC and to search for related IgG and IgA secreting cells in normal and diseased mucosa and blood in UC. To investigate characteristics which may discriminate between the mucosal and peripheral repertoire in the normal mucosa and in UC. PATIENTS: Blood and normal and diseased mucosa from two patients with UC were studied. METHODS: Immunoglobulin gene analysis and clone specific polymerase chain reaction were used to study the clonal distribution and characteristics of IgG and related IgA in the mucosa and blood of patients with UC. RESULTS: The IgG response in the mucosa of UC patients included widespread clones of cells that were present in both the diseased mucosa and blood but that were scarce in normal mucosa. Clonally related IgA class switch variants, all IgA1, were detected but also only in the diseased mucosa and blood. This suggests that these clones home preferentially to the diseased mucosa. We showed that J(H)1 usage was characteristic of the peripheral repertoire, and that examples of J(H)1 usage were observed in mucosal IgG in UC. CONCLUSIONS: Overall, these data are consistent with a model of UC in which a peripheral response is expressed and expanded in the colonic mucosa.

Antibody-Producing Cells↗
PubMed2001

Gastro-oesophageal reflux and duodenogastric reflux before and after eradication in Helicobacter pylori gastritis.

OBJECTIVE: Helicobacter pylori and duodenogastric reflux (DGR) are both associated with chronic gastritis, peptic ulcer and gastric cancer. The nature of their interrelationship remains unclear. H. pylori eradication has also been reported to result in new or worsening acid gastro-oesophageal reflux (GOR). The aim of this study was to investigate the relationship between GOR, DGR and H. pylori infection. METHOD: 25 patients with H. pylori gastritis underwent ambulatory 24-hour oesophageal and gastric pHmetry and gastric bilirubin monitoring before and 12 weeks after H. pylori eradication, confirmed by 14C urea breath testing (UBT). Ten healthy subjects served as a control group. RESULTS: There were no differences between patient and control groups for gastric alkaline exposure or gastric bilirubin exposure (P> 0.25 in all categories). Oesophageal acid reflux was higher in the study group (P< 0.02). No differences were detected in oesophageal acid reflux, gastric alkaline exposure, or gastric bilirubin exposure (P = 0.35, 0.18 and 0.11, respectively) before and after eradication. CONCLUSIONS: Acid GOR is not increased by H. pylori eradication. DGR in patients with H. pylori gastritis is similar to that in healthy, non-infected subjects. H. pylori eradication produces no change in GOR or DGR. In patients with chronic gastritis, H. pylori infection and DGR appear to be independent of each other.

Adult↗
PubMed2000

Immunohistochemical analysis of ageing human B and T cell populations reveals an age-related decline of CD8 T cells in spleen but not gut-associated lymphoid tissue (GALT).

It is thought that senescence of the immune system is responsible, at least in part, for many health problems associated with ageing. Previous studies on changes in lymphocyte composition have used flow cytometry to study peripheral blood lymphocytes (PBL's), or cells isolated from rodent tissue, and have yielded conflicting results. We have used immunohistochemistry to determine whether the B and T cells in human tissue from spleen and gut are affected by age. Areas of germinal centre, mantle zone and marginal zone of B cell follicles were measured. In addition, CD4 and CD8 T cells in T cell areas and in B cell follicles were counted. We observed a striking age-related decrease in the proportion of CD8+ T cells in the T cell zones of the spleen. This decrease was not apparent in the T cell population that occupies splenic B cell areas, or in GALT. Further differences, in CD4+ cells, were seen between T cell populations in the T cell zones and those in B cell areas. These findings highlight differences between lymphocyte populations in different lymphoid tissues, and different compartments within each tissue, which may be of importance in future studies of the ageing immune system.

Adolescent↗
PubMed1999

Expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma: an immunopathological study with clinical correlation.

AIMS: Changes in the histochemical characteristics of the surface epithelial mucins is the hallmark of Barrett's metaplasia. The study investigated the pattern of expression of MUC1 and MUC2 mucin gene products in Barrett's metaplasia, dysplasia and adenocarcinoma as possible indicators of increased malignant potential. METHODS AND RESULTS: Tissue sections from 51 patients with Barrett's intestinal metaplasia, nine with dysplasia (three indefinite) and 28 resected adenocarcinomas were stained with monoclonal antibodies to MUC1 and MUC2. The majority of the patients were men (70/88, 80%) who were treated over a period of 3 years. None of the patients with dysplasia or carcinoma were under surveillance at the time of presentation. All 51 biopsies with Barrett's metaplasia expressed MUC2 and MUC1 was consistently absent. Neither MUC1 or MUC2 were expressed in the dysplastic epithelium whether in its pure form (6/6) or when associated with carcinoma (26/28) (P < 0.005). Three biopsies which were initially classified as high-grade dysplasia expressed MUC1 and these turned out to be carcinomas on further investigations. MUC1 was also expressed in 12/28 (43%) of the adenocarcinomas and majority of these were poorly differentiated stage 3 tumours (P < 0.05). MUC2 was only positive in mucin-secreting carcinomas (4/28; 14%) irrespective of the tumour stage. CONCLUSION: Despite the large number of patients with Barrett's metaplasia and carcinoma, very few patients presented with dysplasia, implying that Barrett's oesophagus is a silent disease in the community presenting late as carcinoma. The study has demonstrated aberrant expression of MUC2 (an intestinal mucin) in Barrett's metaplasia and this expression is lost when the cells become dysplastic. The lack of MUC1 in dysplastic epithelium and its expression in carcinoma could be utilized as a marker which could differentiate dysplasia from carcinoma in mucosal biopsies. Furthermore, expression of MUC1 in advanced stage oesophageal cancers (as in breast cancer) suggests an unfavourable prognosis.

Adenocarcinoma↗
PubMed1997

Two-year-outcomes analysis of Crohn's disease treated with rifabutin and macrolide antibiotics.

Fifty-two patients with severe Crohn's disease were enrolled in this study. Six (11.5%) were intolerant of the medication and had to be excluded. The remaining 46 patients were treated with rifabutin in combination with a macrolide antibiotic (clarithromycin or azithromycin). Patients were treated for a mean of 18.7 (range 6-35) months and followed up for 25.1 (range 7-41) months. Of the 19 patients who were steroid dependent at the start of this study, only two continued to require steroids when treatment was established. A reduction in the Harvey-Bradshaw Crohn's disease activity index occurred after 6 months' treatment (P = 0.004, paired Wilcoxon test) and was maintained at 24 months (P < 0.001). An improvement in inflammatory parameters was observed as measured by a reduction in erythrocyte sedimentation rate (P = 0.009) and C-reactive protein (P = 0.03) at 18 months compared with pretreatment levels, and an increase in serum albumin at 12 months (P = 0.04). When subsets of the study population were analysed, patients with pan-intestinal disease achieved better remission at 2 years than did those with less extensive involvement (P = 0.04, Mann-Whitney U-test). No difference in treatment response by age, disease duration, the presence of granulomas on histology, or the occurrence of drug-induced side-effects, was observed. These data suggest that treatment with rifabutin and clarithromycin or azithromycin may result in a substantial clinical improvement in Crohn's disease and justify the conduct of a randomized controlled trial.

Adolescent↗
PubMed1996

A case of Churg-Strauss syndrome: tissue diagnosis established by sigmoidoscopic rectal biopsy.

A case is presented of Churg-Strauss syndrome in a young man in whom the definitive diagnostic procedure was a full thickness sigmoidoscopic rectal biopsy, with submucosal sampling. Gastrointestinal changes in Churg-Strauss syndrome, a rare systemic illness characterised by asthma, blood and tissue eosinophilia, vasculitis, and granulomatous inflammation are common but poorly reported. The endoscopic and histopathological features of a case are described and emphasise the potential value of a limited sigmoidoscopy in establishing the diagnosis, when lower gastrointestinal symptoms are present.

Adult↗
PubMed1992

Vagally mediated feeding responses to phloridzin infusion in the rabbit.

Rabbits were infused with the plant glycoside, phloridzin, which blocks absorption of glucose across a number of bodily tissues. Feeding was dramatically increased in the first 0.5 h following phloridzin infusion into either the duodenum or the hepatic-portal vein of intact rabbits. Food intake covaried inversely with glycemic levels after phloridzin infusion into the hepatic-portal vein, but rabbits did not show a systematic relationship between blood glucose levels and food intake following duodenal infusion of phloridzin. When administered into the general circulation via the jugular vein, phloridzin did not elicit feeding. Finally, vagotomized rabbits did not show the hyperphagic response to phloridzin that was observed in intact rabbits. It was concluded that the feeding response to phloridzin is vagally mediated and appears to be induced by glucose transport inhibition at some peripheral site.

Animals↗
PubMed1992

IS902, an insertion element of the chronic-enteritis-causing Mycobacterium avium subsp. silvaticum.

An insertion sequence element of Mycobacterium avium subsp. silvaticum was isolated and its complete nucleotide sequence determined. IS902 is 1470 bp in size and is repeated 10-12 times per genome. An open reading frame of 1200 bp was identified, encoding a protein product of Mr 43932. This protein is highly similar to the predicted proteins of IS900 of Mycobacterium paratuberculosis, IS116 of Streptomyces clavuligerus and IS110 of Streptomyces coelicolor. IS902 lacks terminal inverted repeats and flanking direct repeats but displays insertion site specificity.

Amino Acid Sequence↗
PubMed1992

p43, the protein product of the atypical insertion sequence IS900, is expressed in Mycobacterium paratuberculosis.

The novel mycobacterial insertion sequence IS900 was analysed by coupled transcription-translation, of both strands independently, in a cell-free E. coli extract using an exogenous promoter. This revealed only one protein product, p43, as predicted from the nucleotide sequence. The protein was readily translated in recombinant E. coli, using the tac promoter, though it did not appear as a major product by SDS-PAGE analysis. A synthetic peptide was used to generate and affinity-purify a specific anti-p43 antibody, which clearly identified the protein in recombinant E. coli. p43 was relatively stable in exponential phase and stationery phase bacteria, though a 28 kDa processed form was seen to accumulate over a period of hours. Both forms appeared in the soluble fraction of the bacterial lysate. The anti-p43 antibody also identified p43, as a 28 kDa processed product, in Western blots of protein extracts from Mycobacterium paratuberculosis, indicating a level of expression which would be unusually high for a classical transposase. These data have important implications for the relationship between IS900 and its host.

Amino Acid Sequence↗