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Biomedical subjects

N A Shepherd

Publications and source records attributed to N A Shepherd.

At least 19 recordsLinked to original sources
PubMed1992

Fat-wrapping in Crohn's disease: pathological basis and relevance to surgical practice.

The connective tissue changes that accompany intestinal Crohn's disease have received little attention from pathologists. This is particularly so with fat hypertrophy, and yet surgeons have long recognized the phenomenon of fat-wrapping in the intestines and used it to delineate the extent of active disease. A consecutive, unselected series of 27 intestinal resections performed on 25 patients for histologically confirmed Crohn's disease was studied to correlate fat-wrapping with other clinicopathological features. Fat-wrapping was identified in 12 of 16 ileal resections and in seven of 11 large bowel resections. It correlated closely with transmural inflammation and there was a relationship between fat-wrapping and other connective tissue changes including fibrosis, muscularization and stricture formation. Morphometry demonstrated that there was true hypertrophy and that fat-wrapping does not relate solely to bowel wall shrinkage. There was correlation with ulceration but in 11 cases macroscopic ulceration extended beyond the fat-wrapping and in six to surgical resection margins. The pathological features of 225 small intestinal resections were reviewed and fat-wrapping was seen only in Crohn's disease. Fat-wrapping correlates best with transmural inflammation and represents part of the connective tissue changes that accompany intestinal Crohn's disease. Findings also suggest that fat-wrapping alone should not be used as an accurate marker of disease extent at the time of surgery.

Adipose Tissue↗
PubMed1992

The role of pathology in pelvic ileal reservoir surgery.

The increasing use and success of pelvic ileal reservoir surgery places an ever more demanding role onto the surgical pathologist. Close surgical and pathological cooperation is critical for preoperative patient selection, for intraoperative diagnostic confirmation and for postoperative follow up. The long term consequences of pouch construction are, as yet, unknown, but there is much evidence to substantiate the need for life-long surveillance by clinical, endoscopic and pathological means to maximise the benefits of the pelvic ileal reservoir to the patient. This paper reviews the pathological input into these aspects of pelvic ileal reservoir surgery together with a critical appraisal of the likely long term consequences of pelvic ileal reservoir construction.

Adenomatous Polyposis Coli↗
PubMed1992

Endoscopic crescentic fold disease of the sigmoid colon: the clinical and histopathological spectrum of a distinctive endoscopic appearance.

In this paper we describe an endoscopic appearance of the sigmoid colon characterised by mucosal swelling, erythema and haemorrhage strictly localised to the crescentic mucosal folds. In a 5-year period these changes were seen in 34 (1.42%) of 2380 colonoscopies and fibreoptic sigmoidoscopies. The majority of patients were middle-aged or elderly. Diverticular disease was present in most (82%) but the abnormalities were confined to the crescentic mucosal folds with sparing of the diverticular orifices. The majority of patients presented with a history of bleeding per anum. Histologically there was a spectrum of changes varying from minor vascular congestion to florid active inflammatory disease with crypt architectural abnormalities mimicking ulcerative colitis, but rectal biopsies were invariably normal. Three patients later progressed to typical distal ulcerative colitis and two other patients presenting to us with endoscopic crescentic fold disease had a previous histologically documented history of distal ulcerative colitis. In three patients the histological features were of mucosal prolapse. About half the patients required some form of therapy to control their symptoms. Steroids and/or sulphasalazine were of value although two patients subsequently underwent sigmoid resection, one to control bleeding and the second for a diverticulosis-associated stricture. Whilst endoscopic crescentic fold disease represents a specific endoscopic appearance the clinical and histological features indicate a wide spectrum of disease.

Adult↗
PubMed1992

An Eudragit-coated prednisolone preparation for ulcerative colitis: pharmacokinetics and preliminary therapeutic use.

Prednisolone metasulphabenzoate, a steroid with poor colonic absorption, was coated with the pH-dependent acrylic resin Eudragit S, as a means of delivering an orally administered preparation to the proximal colon. The therapeutic potential of delivering this steroid with potentially less systemic side-effects to the proximal colon was assessed in extensive ulcerative colitis. Plasma and urine prednisolone profiles in 6 healthy volunteers confirmed minimal absorption from Eudragit S-coated prednisolone metasulphabenzoate compared to prednisolone acetate: peak plasma prednisolone concentrations 29 +/- 21 ng/ml vs. 570 +/- 185 ng/ml (P less than 0.01), area under curve measurements 204 +/- 214 vs. 2724 +/- 1236 ng.h/ml (P less than 0.01). Prednisolone metasulphabenzoate coated with Eudragit S (30-60 mg daily) was then administered for 12 weeks to 12 patients with colonoscopically proven extensive ulcerative colitis in relapse. Symptoms, sigmoidoscopic appearances and rectal histological abnormalities all improved during therapy. Complete clinical remission occurred in 7 patients, a partial response in 2 patients and no response in 3 patients. Cortisol responses to tetracosactrin demonstrated no significant adrenal suppression following treatment. Eudragit S-coated prednisolone metasulphabenzoate may be a useful treatment for extensive ulcerative colitis, without risk of systemic steroid side-effects.

Acrylic Resins↗
PubMed1992

p53 expression is common in malignant mesothelioma.

The p53 tumour suppressor gene has been shown to be frequently mutated in a wide range of human neoplasms. This is accompanied by increased levels of p53 protein which become immunologically detectable in pathological material. We have investigated the possibility that the differential diagnosis between reactive and neoplastic mesothelium might be resolved using a polyclonal serum raised to human p53 protein, CM-1. None of 20 cases of reactive mesothelial proliferation showed p53 immunoreactivity while 70% (14 of 20) of cases of malignant mesothelioma showed p53 staining. We can thus infer that abnormalities of p53 appear to be a common event in malignant mesothelioma and that p53 immunostaining may be of value in the distinction of malignant mesothelioma from reactive hyperplasia.

Adult↗
PubMed1992

Changing pattern of gastric cancer in Oxfordshire.

This study compares the incidence rates of histologically confirmed gastric carcinoma in Oxfordshire in two five year periods (1960-64, 1984-88). Data were available for 215 patients in the first period, and 200 in the second. The overall incidence fell from 18/100,000 to 15/100,000 but when analysed for site, the incidence of antral tumours fell from 10 to 4.5/100,000. In contrast, there was an increase from 2.8 to 5.2/100,000 of tumours of the cardia. These changes were more pronounced in men. There was a marked association between smoking and tumours of the cardia (relative risk 4.5). Helicobacter pylori was associated with 37.5% of tumours in the 1960s series compared with 25% in the later series. The changing patterns of incidence of gastric carcinoma may, in part, be related to changes in smoking habits and perhaps a change in incidence of H pylori infection.

Age Factors↗
PubMed1991

14;18 translocation in primary intestinal lymphoma: detection by polymerase chain reaction in routinely processed tissue.

Chromosomal translocations involving the heavy chain immunoglobulin locus on chromosome 14 and a region on chromosome 18 encoding the bcl-2 gene [t(14;18)] are a characteristic and prevalent chromosomal abnormality in nodal malignant lymphoma, particularly follicular lymphoma. Using the polymerase chain reaction on routinely processed tissue, t(14;18) has been demonstrated in 22% of primary intestinal lymphomas, i.e. in two of nine cases of malignant lymphomatous polyposis, in four of 19 cases of polymorphic B-cell lymphoma and in one of four high-grade unclassified tumours. The findings in this study contradict those of other studies which have shown no such translocation in primary gastric and small intestinal lymphoma. The presence of t(14;18) indicates heterogeneity of molecular abnormalities within histopathologically homogeneous tumours and suggests that caution should be employed in using molecular cytogenetic data to support theories of tumour histogenesis. The low prevalence of this translocation in intestinal lymphoma makes the use of such a methodology as a primary diagnostic aid doubtful, although the technique may help to distinguish primary and secondary lymphoma and could also be used to demonstrate secondary spread.

Adult↗
PubMed1991

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S+G2+M phase fraction (flow cytometric analysis) and prognosis.

PCNA is a nuclear protein that is synthesized in late G1 and S phases of the cell cycle and is, therefore, correlated with the cell proliferative state. A new monoclonal antibody (PC10) to genetically engineered PCNA has been shown to label proliferating cells in formalin-fixed paraffin-embedded normal human tissues. Previous studies in lymphomas, using various markers of cell proliferation, have shown a strong correlation between indices of cell proliferation and histological grade. These studies have shown that within each histological subtype there is often a wide range of proliferative indices and that these may be of some prognostic significance. Thirty-one gastrointestinal lymphomas were studied. Our results show that there is a good correlation between PC10 index and histological grade of tumour (0.01 P greater than P greater than 0.001) and also a significant relationship between PC10 index and S+G2+M phase fraction as measured by flow cytometric analysis (r2 = 0.62; P less than 0.01). Twenty-three cases were available for survival analysis. In these cases a high PC10 score correlated with poor survival (P = 0.04). Based on this series, it appears that there is a significant relationship between PC10 index and histological grade, and between PC10 index and S+G2+M phase as measured by flow cytometric analysis. In addition, our results suggest that a high PC10 index is an adverse prognostic factor in primary gastrointestinal lymphoma.

Cell Cycle↗
PubMed1991

Human papillomavirus type 16 DNA in anal cancers from six different countries.

An association between anal squamous cell carcinoma and human papillomavirus (HPV) type 16 DNA has been documented in the UK. If HPV type 16 is an important aetiological factor in the development of this tumour it would be expected to occur in anal cancer tissues from other parts of the world. In this study a series of 173 anal squamous cell carcinoma tissue samples from five centres around the world have been examined by DNA hybridisation for HPV type 16 DNA sequences. HPV type 16 DNA was found in 50 of 173 (29%) of these. The prevalence of HPV associated anal squamous cell carcinoma was significantly lower in tissue from India and South Africa than in the Swiss, Polish, or Brazilian samples. HPV associated anal squamous cell carcinoma does occur in other countries and further investigations of the prevalence of these tumours in association with other HPV types are required.

Anus Neoplasms↗
PubMed1991

Pathological mimics of chronic inflammatory bowel disease.

When all of the macroscopic and microscopic features of Crohn's disease and ulcerative colitis are present, the correct diagnosis is usually made without difficulty. When some of the changes are absent, the accuracy of diagnosis is reduced. This review has outlined those diseases which feature some of these pathological changes and may masquerade as idiopathic chronic inflammatory bowel disease. Some of the pathological mimics are iatrogenic while other common diseases, such as bacterial infection, ischaemia, and diverticulosis may produce confusing histological appearances. The picture is complicated by the fact that many of these pathological imitators may themselves cause or predispose to chronic inflammatory bowel disease, or may complicate chronic inflammatory bowel disease. For example, drugs and infectious agents are recognisable causes of relapse in ulcerative colitis; Crohn's disease may cause diverticulitis in patients with diverticulosis; and lymphoma may complicate ulcerative colitis. It behooves all practising histopathologists to recognise these mimics of ulcerative colitis and Crohn's disease to ensure appropriate management for patients with inflammatory pathology of the intestines.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Epithelial-mesenchymal interactions can influence the phenotype of carcinoma metastases in the mucosa of the intestine.

In this paper we report two cases in which morphological differentiation of gastric adenocarcinoma has occurred when metastatic tumour was present within the lamina propria of the intestinal mucosa. In one case, there were metastases in the small intestinal mucosa and in the second case, in the mucosa of the appendix. The morphology of the intramucosal tumour simulated that of an adenomatous neoplasm. The recognition of this occurrence may be important in the differential diagnosis of primary and secondary adenocarcinomas of the gastrointestinal tract. The phenomenon is not only of diagnostic interest: the data presented here provide in vivo evidence that gastrointestinal carcinomas may differentiate in response to epithelial-mesenchymal interactions in a similar way to that seen in experimental models.

Adenocarcinoma↗
PubMed1990

Ki-ras oncogene mutations in non-HPV-associated anal carcinoma.

Human papillomavirus 16 (HPV 16) DNA is found in a high proportion of anal squamous cell carcinomas in whose genesis it is thought to play an important role. In addition, it can be shown to cooperate in vitro with activated ras oncogenes in cellular transformation. We have therefore screened a series of such tumours for activating mutations of the ras oncogene family using DNA amplified in vitro by the polymerase chain reaction (PCR) and a series of synthetic oligonucleotide probes. Mutations were seen in only two cases (both Ki-ras codon 12), neither of which was HPV-associated. Our results suggest that ras activation is not a common event in the genesis of these tumours and, when it does occur, it does not appear to cooperate with HPV.

Anus Neoplasms↗
PubMed1990

Clinical and pathological correlates of HPV type 16 DNA in anal cancer.

The aetiology of anal squamous cell carcinoma (SCC) has recently been associated with a sexually transmissible agent--human papillomavirus (HPV) type 16. In this study clinical and pathological data from a prospective series of 67 anal SCC collected over a three year period were compared with the HPV type 16 DNA content of these tumours to determine whether any of the clinical or histological parameters might predict HPV DNA content in a tumour specimen. Of twelve clinicopathological variables examined none was significantly correlated with HPV DNA content at the p = 0.01 level.

Adult↗