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Biomedical subjects

I C Talbot

Publications and source records attributed to I C Talbot.

At least 73 records · Page 4Linked to original sources
PubMed1996

Properties of HPV-positive and HPV-negative anal carcinomas.

Evidence of human papillomavirus (HPV) can be found in up to 85 per cent of anal carcinomas. In the vulva, a discrete subset of HPV-positive carcinomas which show koilocytic morphology and distinct clinical features has recently been identified (warty carcinoma). The morphological and prognostic features of HPV-positive and HPV-negative anal carcinomas were compared in this study of the tumour distribution of HPV DNA. Vulval and anal neoplasia are similar in many ways and we have also looked to see if their similarity extends to 'warty' morphology in relation to HPV status. Thirty-five resection specimens of anal carcinoma were examined with biotin-labelled probes for HPV 6, 11, 16, and 18 DNA, using a non-isotopic in situ hybridization (ISH) technique. No tumour was found to contain HPV 6, 11, or 18. Twenty-four (72 per cent) showed positivity for HPV 16 DNA. Staining was homogeneous and independent of local squamous, basaloid, or ductal differentiation. The majority of tumours showed staining suggestive of episomal, non-productive HPV infection. HPV-positive tumours were more likely to occur in the anal canal than perianally and to show a mixed squamous and basaloid appearance. No difference between the two groups was found in patient age, presence of adjacent dysplasia, ductal differentiation, or prognosis. There was no correlation between condylomatous tumour morphology and HPV 16 DNA positivity; thus, a subset equivalent to vulval warty carcinoma could not be identified.

Anus Neoplasms↗
PubMed1996

Pneumatosis coli: a proposed pathogenesis based on study of 25 cases and review of the literature.

Pneumatosis coli is a rare condition characterised by multiple gas-filled cysts within the bowel wall. We present 25 cases treated over the past 30 years. The patients' mean age was 59 years: 15 were female. Presenting symptoms included diarrhoea (n = 17), mucus discharge (n = 17), rectal bleeding (n = 15) and constipation (n = 12). Pneumatosis usually affected the left colon (96%), and diagnosis was by sigmoidoscopy and biopsy in 18 cases (72%). Pneumatosis coli was associated with psychiatric disorders (36%), chronic lung disease (20%) and colitis (12%). A redundant sigmoid colon was observed in 80% of cases on contrast radiology. Five patients had mucosal pseudolipomatosis on histological examination. Histological and immunohistochemical review indicated that the cysts were lined by cells of macrophage/monocyte phenotype and that many similar mononuclear cells were present in the adjacent submucosa and overlying mucosa. Treatment with antidiarrhoeals and anti-inflammatory drugs in 14 patients resulted in improvement in 9 cases (64%). Oxygen therapy (n = 9) always alleviated symptoms. There was a high recurrence rate (50-78%), but with further courses of therapy lasting remission was achieved in five patients. Two patients underwent colectomy. The associations of pneumatosis coli with psychiatric disorders and mucosal pseudolipomatosis are new and of possible pathogenetic significance. A novel pathogenetic mechanism is suggested to explain the association of pneumatosis coli and chronic respiratory disorders. A model of pneumatosis coli linking some of the apparently disparate pathogenetic theories is proposed.

Anxiety↗
PubMed1996

Infrequent alterations of the APC and MCC genes in gastric cancers from British patients.

We examined 26 gastric carcinomas from British patients for mutations of the APC gene using a single-strand conformation polymorphism (SSCP) and heteroduplex assay in conjunction with the protein truncation test (PTT). In addition, we performed loss of heterozygosity (LOH) analysis of the APC and MCC genes. We detected an inactivating somatic mutation in one gastric tumour. LOH of APC was observed in one of 12 informative cases (8%) and of MCC in two of 20 cases (10%). We thus find that alteration of the APC and MCC genes are infrequent in gastric cancers from the British population. Tumour-suppressor genes on other chromosomes must play a more significant role in the development of these tumours.

Adenomatous Polyposis Coli Protein↗
PubMed1996

The demonstration of pericryptal fibroblasts in background mucosa and dysplasia complicating ulcerative colitis.

The demonstration of pericryptal fibroblasts in background mucosa and dysplasia in ulcerative colitis was investigated by immunohistochemistry using monoclonal antibody for alpha-smooth muscle actin. Pericryptal fibroblasts were reduced in 18 (26%) of the 68 sections of non-dysplastic mucosa. The reduction was significantly correlated with goblet cell depletion and villous change. Pericryptal fibroblasts were more frequently reduced (50%) in dysplastic mucosa, the reduction being greater in villous than in non-villous dysplasia. Pericryptal fibroblast development was not related to grade of dysplasia (low or high-grade), distance from carcinoma (adjacent to or distant from carcinoma) or growth pattern (polypoid or non-polypoid). These findings suggest that: 1 reduction of pericryptal fibroblasts in background mucosa may relate to the development of dysplasia in ulcerative colitis, 2 reduction of pericryptal fibroblasts in villous regeneration, analogous to that in dysplasia, reinforces the hypothesis that villous change may be a marker for risk of development of carcinoma in ulcerative colitis.

Colitis, Ulcerative↗
PubMed1996

Leucocyte typing, cytokine expression, and epithelial turnover in the ileal pouch in patients with ulcerative colitis and familial adenomatous polyposis.

BACKGROUND/AIMS: Conventional histopathology, leucocyte typing, cytokine mRNA expression, and crypt cell turnover were compared in ileal pouch biopsy specimens from patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). METHODS: Biopsy specimens were taken from 17 patients with UC and seven with FAP at a median interval of 19 months (range 2-120) after ileostomy closure. All contained both epithelium and lamina propria. Cryostat sections were stained for lymphocyte subtypes (CD3, CD4, CD8), macrophages (CD68), common leucocyte antigen (CD45), and Ki-67, using a three stage immunoperoxidase reaction. Cytokine mRNA expression for interleukins 2 and 6, tumour necrosis factor alpha, and interferon gamma was studied using an in situ hybridisation technique. RESULTS: Lymphocyte subtype and macrophage populations in epithelium and lamina propria were similar in UC and FAP. The labelling index (Ki-67) was significantly increased in biopsy specimens from patients with UC (UC median = 43.3 (interquartile range (IQR) 38.9-48.2) v FAP 34.9 (29.9-35.2), p < 0.05). There was little or no epithelial mRNA expression for any cytokine in any of the specimens. Lamina propria mRNA expression for interleukin 2 was significantly increased in UC (UC median (IQR) 10.7 (5.4-14.2) cells per unit area v FAP 2.8 (1.5-6.6) p < 0.05) but not for tumour necrosis factor alpha, interleukin 6, and interferon gamma. CONCLUSIONS: While static morphological assessment (leucocyte type, conventional histopathological examination) was similar, tests of cell function (mRNA expression and labelling index) were different in ileal pouches in patients with UC compared with FAP. The study also showed that mRNA expression occurred almost entirely in the lamina propria.

Adenomatous Polyposis Coli↗
PubMed1996

Pathology of the rectal wall in solitary rectal ulcer syndrome and complete rectal prolapse.

BACKGROUND: The aetiology and pathology of rectal prolapse and solitary rectal ulcer are poorly understood. AIMS: To examine the full thickness rectal wall in these two conditions. METHODS: The pathological abnormalities in the surgically resected rectal wall were studied from nine patients with solitary rectal ulcer syndrome, 11 complete rectal prolapse, and nine cancer controls. Routine haematoxylin and eosin and Van Gieson staining for collagen were performed. RESULTS: The rectal wall from solitary rectal ulcer syndrome specimens was thickened compared with complete rectal prolapse and controls. The major difference was in the muscularis propria (2.2 v 1.1 v 1.2 mm, medians, p < 0.005) and particularly the inner circular muscular layer, and to a lesser extent the submucosal and outer longitudinal muscular layers. Some solitary rectal ulcer syndrome specimens showed unique features such as decussation of the two muscular layers (four of nine), nodular induration of inner circular layer (four of nine) and grouping of outer longitudinal layer into bundles (three of nine); these were not seen in complete rectal prolapse or control specimens. CONCLUSIONS: These features, which resemble the features of high pressure sphincter tissue, may be of aetiological importance, and suggest a different pathogenesis for these two disorders. Excess collagen was seen in both disorders, was more severe in solitary rectal ulcer syndrome specimens, and probably reflects a response to repeated trauma.

Adult↗
PubMed1996

A modifying locus for familial adenomatous polyposis may be present on chromosome 1p35-p36.

Mutations of the APC gene cause familial adenomatous polyposis (FAP) in humans and multiple intestinal neoplasia (Min) in laboratory mouse strains. A dominant modifying gene (Mom1), which partially suppresses the min phenotype, has been mapped to mouse chromosome 4. This region is syntenic with human chromosome 1p35-p36. The phospholipase A2 (Pla2s) locus is an excellent candidate for Mom1 and the equivalent human locus PLA2G2A is found on chromosome 1p35. It does not necessarily follow, however, than any modifier of mouse polyposis also influences human disease. In order to test whether a locus on 1p modifies FAP, subjects from 28 FAP families have been typed at microsatellite loci on this chromosome arm. The severity of their duodenal polyposis has also been assessed by endoscopy. Pedigree (lod score) linkage analysis found no evidence of a simple, dominant modifying gene, comparable with the action of Mom1 in inbred mouse strains. Given the more complex genetic and environmental interactions likely to exist in outbred human populations, it is probably more appropriate to use tests which do not specify a mode of inheritance. Using these methods of analysis, the data suggest that a locus on chromosome 1p35-p36 may influence the severity of duodenal FAP.

Adenomatous Polyposis Coli↗
PubMed1996

Genetic mapping of hereditary mixed polyposis syndrome to chromosome 6q.

Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas. HMPS appears to be inherited in an autosomal dominant manner. Genetic linkage analysis has been performed on a large family with HMPS. Data did not support linkage to the APC locus or to any of the loci for hereditary nonpolyposis colorectal cancer. Evidence that the HMPS locus lies on chromosome 6q was, however, provided by significant two-point LOD scores for linkage between HMPS and the D6S283 locus. Analysis of recombinants and multipoint linkage analysis suggested that the HMPS locus lies in a 4-cM interval containing the D6S283 locus and flanked by markers D6S468 and D6S301.

Adenoma↗
PubMed1996

Overexpression of p53 in duodenal tumours in patients with familial adenomatous polyposis.

Duodenal polyps and tumours of different histology from patients with familial adenomatous polyposis (FAP) were examined for p53 overexpression to determine the genetic events in duodenal tumorigenesis. Samples from endoscopic biopsy specimens of 152 duodenal adenomatous polyps (taken from 79 patients) and from 13 surgically resected adenomatous polyps or cancers (taken from nine patients) were studied by routine histological examination and immunohistochemistry. p53 was overexpressed in: 0 per cent of normal mucosa samples (none of 29), 25 per cent of tubular adenomas (28 of 111), 72 per cent of tubulovillous and villous adenomas (13 of 18) and 100 per cent of duodenal cancers (seven of seven); and in 28 per cent of mildly dysplastic polyps (32 of 113), 56 per cent of moderately or severely dysplastic polyps (nine of 16) and 100 per cent of cancers (seven of seven). Overexpression of p53 increased with passage down the adenoma-carcinoma pathway and might therefore be a valuable additional marker of risk for duodenal malignancy in patients with FAP.

Adenomatous Polyposis Coli↗
PubMed1996

Bcl-2 expression in colorectal tumors: evidence of different pathways in sporadic and ulcerative-colitis-associated carcinomas.

Colorectal cancers (CRCs) differ in their age at presentation, distribution, histological features, and prognosis. If tumor biology reflects genetic events, these tumors might be expected to show differences in their genetic pathways. In this study, we investigated the role of Bcl-2 in the development of three different tumor groups. Using markers at eight different microsatellite locl, we characterized one group of 34 left-sided sporadic CRCs as replication error negative (RER-) and another group of 18 left-sided sporadic CRCs as replication error positive (RER+). These tumors, together with a third group of 22 left-sided ulcerative-colitis-associated CRCs (UCACRCs), were then examined by immunohistochemistry for Bcl-2 overexpression. Of 34 of the RER- tumors, 21 (62%) and 10 of 18 (56%) of the RER+ tumors were positive for Bcl-2 overexpression. In contrast, only 5 of 22 (23%) of the UCACRCs showed similar overexpression. Our results show a significantly lower frequency of Bcl-2 overexpression in UCACRCs as compared with sporadic CRCs (P < 0.005) but no difference between sporadic left-sided RER+ and RER- CRCs. These data provide additional evidence that UCACRCs may develop along a pathway that is different from that of sporadic CRCs.

Carcinoma↗
PubMed1996

Colorectal cancer in idiopathic inflammatory bowel disease.

The development of colorectal cancer is the most serious long-term problem faced by patients with extensive ulcerative colitis and Crohn's colitis, with an incidence 20-fold higher and an average age of onset 20 years younger than colorectal cancer in the general population. This report summarizes the epidemiology, pathology, and recent advances in the molecular pathogenesis of colorectal cancer in inflammatory bowel disease and of its acknowledged precursor, mucosal dysplasia. It also reviews the rationale behind the use of endoscopic surveillance for dysplasia as a means of reducing cancer mortality, as well as some of the issues involved in its effective implementation.

Adenocarcinoma↗
PubMed1995

Juvenile polyposis.

Juvenile polyposis is an uncommon condition characterized by the development of multiple juvenile polyps, predominantly in the colon but also in the rest of the gastrointestinal tract. The condition usually presents in childhood; only 15 per cent of patients present as adults. The rarer and often fatal form, namely, juvenile polyposis of infancy, is typified by diarrhoea, protein-losing enteropathy, bleeding and rectal prolapse. The more common form of juvenile polyposis (affecting the colon, stomach and small bowel) occurs in the first or second decade with rectal bleeding and anaemia. A family history of the condition is found in 20-50 per cent of patients with apparently an autosomal dominant trait. The gene for juvenile polyposis has not yet been identified. Epithelial dysplasia is common and the cumulative risk of colorectal cancer is > 50 per cent. Various extracolonic abnormalities may also occur. Most patients are treated surgically for colonic polyps, although endoscopic polypectomy is also an option. The rest of the gastrointestinal tract should be screened as should asymptomatic first-degree relatives.

Adenomatous Polyposis Coli↗
PubMed1995

Persistence of idiopathic anal fistula may be related to epithelialization.

Anal fistulas may fail to heal because of continuing disease within the intersphincteric anal glands. Histological studies of the intersphincteric component of 18 consecutive idiopathic anal fistulas show that fistula persistence may be caused by epithelialization of the fistula track from internal or external openings. Some fistulas are lined by epithelium similar to that of anal gland ducts, but this may also represent epithelium derived from the transitional zone of the anal canal. Persistence may be related more to non-specific epithelialization of the track than to a chronically infected anal gland.

Anal Canal↗
PubMed1995

New grade-related prognostic variable for rectal cancer.

The effect of microacinar growth patterns on survival after radical surgery for rectal cancer was assessed in 138 consecutive patients. All had Dukes and Jass staging and a median follow-up of 95 (range 11-180) months. Tumour acini were classified according to size (microacinar, 28; macroacinar, 110). Patients with microacinar tumours had a significantly reduced 5-year survival rate compared with those with macroacinar lesions (43 and 68 per cent respectively, P = 0.004). When examined in the presence of other histological factors, acinar size had independent prognostic value (relative risk 2.37, P = 0.006). This was true even when the Dukes and Jass classifications were included in the model (relative risk 2.08, P = 0.02 and 1.95, P = 0.03 respectively). Histological classification of rectal tumours into microacinar and macroacinar types adds prognostic value to the Dukes and Jass classifications and may be a more objective criterion than conventional histological grading.

Follow-Up Studies↗