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Biomedical subjects

I C Talbot

Publications and source records attributed to I C Talbot.

At least 163 records · Page 9Linked to original sources

Observer variation in the assessment of dysplasia in ulcerative colitis.

Six histopathologists allocated 100 sections from patients with long-standing ulcerative colitis into four diagnostic categories, regular hyperplasia, reactive atypia, low-grade and high-grade dysplasia. Their allocations were analysed using kappa statistics, including Fleiss's multiple kappa for groups of observers, and agreement on specific diagnoses was explored by constructing a conditional probability matrix. The nature of their disagreements was investigated using coefficients for systematic and haphazard errors. Over the four diagnostic categories there was a wide range of pairwise agreement from a low of 49% up to 72% and kappa values were only 'fair' or 'moderate'. As expected, agreement over the two categories 'dysplasia' vs 'no dysplasia' was better, ranging from 68% to 84%, and for 'atypia present' (reactive atypia, low- and high-grade dysplasia) vs "no atypia' two pairings achieved over 90% and 11 pairings over 80% agreement. In view of its clinical importance, conditional agreement on high-grade dysplasia, pairwise agreement on this diagnosis ranged from 100% down to as low as 33%. However, most of these disagreements fell into the low-grade dysplasia category so that closer follow-up and further biopsies would still have been indicated. It is a truism that the basis for safe management is careful co-operation between clinicians and pathologists who have all the relevant facts and who know and trust one another's judgement. Thus, several aspects of the ideal diagnostic process cannot be evaluated in inter-observer studies and the element of artificiality should be borne in mind when applying the findings to diagnostic practice. Nevertheless, the low level of agreement on the diagnosis of high-grade dysplasia achieved by certain pairings of specialist pathologists is a disturbing outcome of this study. Inaccuracies should be minimized by a concensus approach and we therefore recommend referral of putative cases of dysplasia to interested pathologists for further opinions. We would also advocate that pathologists faced with appearances which are indefinite between reactive atypia and dysplasia, would do better to describe them in terms of "atypia, significance uncertain', so that closer surveillance is undertaken, rather than force them into more precise diagnostic categories which may be incorrect.

Colitis, Ulcerative↗

DNA aneuploidy and cell proliferation in familial adenomatous polyposis.

Two hundred and thirteen samples from 20 patients with familial adenomatous polyposis (FAP) were investigated by flow cytometry and the results compared with 100 sporadic adenomas. Eleven of the 20 (55%) yielded one or more DNA aneuploid samples with an overall incidence within FAP adenomas of 12%. Despite a similar level of DNA aneuploidy in sporadic adenomas, it was commonly detected at a smaller polyp size. The degree of cell proliferation was found to be similar in the two groups (median %S+G2 15.8% v 16.4%) but larger FAP adenomas demonstrated a higher level of cell proliferation than smaller adenomas. DNA aneuploidy had no value as a predictor of a synchronous carcinoma and appeared to be an early change in the development of carcinoma in these patients.

Adenomatous Polyposis Coli↗

Invasive amoebiasis: an unusual presentation.

A 63 year old Asian woman who presented with three week's abdominal pain was found to have a hard right iliac fossa mass and rectal ulceration. Profuse rectal bleeding necessitated a laparotomy. An inflammatory paracaecal mass with fistulae involving appendix, small bowel, and bladder was excised with exteriorisation of the bowel ends. Microscopy showed invasive amoebae. Re-anastomosis was successfully done after treatment with metronidazole and diloxanide. There are no previous reports of a paracaecal amoeboma with fistulae to either the appendix, or urinary bladder.

Amebiasis↗

Treatment and outcome in 52 consecutive cases of ampullary carcinoma.

The results of treatment and outcome in 52 consecutive patients presenting to Leicester from 1972 to 1984 are presented. The number of patients diagnosed increased from two per year before the introduction of duodenoscopy to nearly five per year afterwards. Endoscopic drainage (ED) was attempted in 21 patients with a success rate of 81 per cent. In eight cases ED was used pre-operatively and in the remainder as definitive treatment. Twenty-four patients had a Whipple's resection (12.5 per cent mortality), four patients had a local resection (no deaths), ten patients had surgical bypass (60 per cent mortality) and thirteen patients had ED alone (23 per cent mortality). The major risk factor score was significantly greater in patients undergoing surgical bypass compared with Whipple's resection. Age and risk factor scores were significantly greater in patients who had ED drainage alone than in surgical patients. The 5 year survival rate for resection was 56 per cent versus 13 per cent for drainage procedures (P less than 0.001). Survival in resection cases was directly related to the degree of tumour differentiation and a new staging system. It is proposed that all patients with ampullary tumours should have endoscopic biopsy followed by ED; Whipple's resection remains the surgical treatment of choice.

Adenocarcinoma↗

Symptomatic submucosal lipoma of the large bowel.

Symptomatic large bowel lipomata may be of considerable size and usually present in middle age with symptoms of obstruction or bleeding. Although they are rare, their recognition is important so that patients may be spared unnecessary colonic resection for a presumptive malignant diagnosis. Colonoscopic removal may often be feasible. Six cases are reported together with a review of the literature emphasizing the characteristic features.

Adult↗

Increased neuropeptide Y-immunoreactive innervation of aganglionic bowel in Hirschsprung's disease.

The pathophysiology of Hirschsprung's disease has not been fully elucidated but is known to have a neurogenic basis. In recent years, new neural proteins and peptides have been discovered and our aim in this study was to use immunocytochemistry to investigate their involvement in the neuronal abnormalities associated with this condition. Large bowel samples from 9 children undergoing surgery for Hirschsprung's disease were compared with those taken from 8 children with other gastrointestinal diseases but no aganglionosis. Immunocytochemistry was carried out using antibodies to a wide range of neuron specific proteins and peptides. Examination of sections immunostained for the general neuronal markers, protein gene product 9.5, neuron specific enolase and neurofilament triplet proteins, allowed rapid identification of aganglionic segments. Nerves containing vasoactive intestinal polypeptide/peptide histidine methionine (VIP/PHM), galanin, substance P, somatostatin, met-enkephalin or calcitonin gene-related peptide (CGRP) showed a marked reduction in all layers of the aganglionic bowel. However, scattered VIP/PHM immunoreactive fibres were also found in the hypertrophied nerve bundles. In contrast with these reduced peptide-containing nerves, fibres displaying NPY immunoreactivity showed a marked increase in all aganglionic segments, particularly in the circular muscle where few are found normally. Our findings shed further light on the neurobiology of aganglionic bowel and suggest that immunostaining of neural proteins and the peptide NPY can aid rapid histopathological diagnosis of congenital aganglionosis.

Child, Preschool↗

Tumour basement membrane laminin in adenocarcinoma of rectum: an immunohistochemical study of biological and clinical significance.

Well-defined basement membrane laminin was seen in 98/158 (62%) rectal adenocarcinomas stained by an immunoperoxidase method. Only 27 (28%) patients with laminin-positive tumours developed distant metastases, compared with 39 (65%) patients with laminin-negative carcinomas. The corrected 5-year survival rates for patients with laminin-positive and laminin-negative tumours were 65% and 23%, respectively. Twenty-five out of 30 (83%) well-differentiated adenocarcinomas and only 3/15 (17%) poorly differentiated tumours contained basement membrane laminin, with moderately differentiated carcinomas showing intermediate laminin status (70/110, 64%, laminin positive). Forty-three of 60 (72%) of laminin-negative tumours had metastasized to regional lymph nodes. These data suggest that laminin may be a marker for differentiation. However, laminin status yields information about tumour behaviour which is not confined to stage and grade, and multivariate analysis shows that it is a better indicator of prognosis than tumour grade as assessed by conventional histology. Although laminin status alone is a less useful predictor of prognosis than Dukes' stage, a patient with a laminin-positive adenocarcinoma of rectum is 2.7 times as likely to survive 5 years than a patient with a laminin-negative tumour. Assessment of laminin status, together with Dukes' stage is, therefore, commended as a more precise and objective indicator of prognosis than histological degree of differentiation in colorectal carcinoma.

Adenocarcinoma↗

Cloning of mRNA sequences from the human colon: preliminary characterisation of defined mRNAs in normal and neoplastic tissues.

RNA has been extracted from the normal human colon, converted into cDNA and cloned in the bacterial plasmid pBR322. About 4,000 sequences from this library were screened with probes derived from normal mucosa, familial polyposis mucosa, colonic adenocarcinomas and the colon tumour cell line HT29. Some mucosal sequences showed greatly reduced levels of transcription in neoplastic conditions, while a few showed elevated transcription. These have been further characterised by Northern and RNA dot-blot analysis.

Base Sequence↗

Tumours and pseudotumours of the region of the ampulla of Vater: an endoscopic, clinical and pathological study.

From a large series of patients referred for endoscopic retrograde cholangiopancreatography to one endoscopist, 49 patients had the duodenoscopic appearance of a periampullary tumour. Thirty eight of these lesions were neoplastic, but the remaining 11 patients had inflammatory non-neoplastic lesions (pseudotumours). These could not be distinguished from the neoplasms on endoscopic appearances. The cholangiopancreatograms were similar except that the diameter of the pancreatic duct tended to be higher in the tumour group and gall stones were present significantly more often in the patients with pseudotumour. Endoscopic biopsy correctly diagnosed 28 of 34 ampullary carcinomas. Two of the 11 pseudotumour patients were subjected to surgical excision biopsy because of suspicious histological features of endoscopic biopsy. In the neoplastic group 19 patients underwent Whipple's procedure, seven surgical bypass, seven endoscopic sphincterotomy only and five died without successful biliary drainage. The overall one year survival was 44.7%. By contrast, the patients with pseudotumours were clinically well at a median follow up 24 months (range 12-41 months), after endoscopic sphincterotomy except for one 89 year old patient who died 22 months later from unrelated causes.

Adult↗

Pulmonary megakaryocytes: "missing link" between cardiovascular and respiratory disease?

Pulmonary megakaryocytes were quantitated in a series of 30 consecutive hospital necropsies using a two stage immunoperoxidase stain for factor VIII related antigen. In all 30 cases they were found with a mean density of 14.65 megakaryocytes/cm2 in lung sections of 5 micron in thickness. The maximum concentration of intrapulmonary megakaryocytes was consistently found to be in the central zone of the right upper lobe. Less than 22% of the observed cells possessed abundant cytoplasm, the rest appearing as effete, naked, and seminaked nuclei. The mean megakaryocyte count was found to be increased in association with both respiratory pathology (positive smoking history and impaired lung function) and cardiovascular disease states--shock; thromboembolism; myocardial infarction; and severe atheroma in the abdominal aorta, the coronary circulation, and the circle of Willis. Pulmonary megakaryocytes probably embolise from bone marrow. This may reflect stimulated thrombopoiesis, caused by increased platelet consumption in association with atherosclerotic disease, but it cannot be taken to confirm that the lung is the principal site of platelet production.

Cardiovascular Diseases↗

Follicular thyroid tumours: a study of laminin and type IV collagen in basement membrane and endothelium.

Immunocytochemical stains for laminin and type IV collagen can be used as markers for basement membrane and vascular endothelium. Thirty four follicular thyroid lesions were examined using these techniques to investigate two aspects: firstly, the relation between the extent of invasion and the integrity of basement membrane; secondly, whether the techniques could enhance the detection of tumour vascular invasion. The results showed that although basement membrane was lost in widely invasive tumours, preservation was seen in most but not all encapsulated tumours. The potential for improved recognition of vascular invasion was also found.

Basement Membrane↗

Clinical diagnosis: a post-mortem assessment of accuracy in the 1980s.

The clinical diagnoses of a series of 400 patients dying in hospital were compared with the pathological findings at autopsy. The clinical diagnoses were precisely confirmed in only 46.75% of cases (average age 65.3 y). Potentially treatable disease was missed in 13% of patients (average age 72.7 y). The most frequent errors, both of under-diagnosis and over-diagnosis, were for pulmonary embolus, pneumonia and myocardial infarction. Over-diagnosis increased with length of hospital stay. Peritonitis and other deep-seated sepsis were surprisingly frequently missed in life. The findings closely parallel those from other units both in Britain and overseas, and suggest that there is currently a high diagnostic error rate, which varies remarkably little from one institution to another.

Adolescent↗

Ischaemic proctitis and adventitial fibromuscular dysplasia of the superior rectal artery.

A case of ischaemic proctitis apparently caused by adventitial fibromuscular dysplasia of the superior rectal artery is reported and the results of a survey of 50 superior rectal and marginal arteries from post mortem and surgical cases are described. Abnormal musculature was demonstrated in varying degree in the adventitia of 28 of 50 asymptomatic patients. Our findings indicate that a spectrum of this vascular abnormality exists in the elderly which is rarely severe enough to contribute to symptomatic large bowel ischaemia.

Adolescent↗

Laminin and fibronectin in rectal adenocarcinoma: relationship to tumour grade, stage and metastasis.

Using an immunoperoxidase procedure, we have examined the distribution of laminin and fibronectin in normal human large intestinal mucosa and in 50 cases of rectal adenocarcinoma for which extensive clinical follow up was available. In normal tissue, laminin staining was largely restricted to basement membranes, including that underlying the epithelial cells, whereas fibronectin was found in both basement membranes and surrounding connective tissue. In rectal carcinomas, basement membrane-like staining for laminin associated with tumour cells was found in only 27 out of the 50 cases studied. Statistical analysis showed that the presence of laminin-containing basement membranes was correlated with low histological grade (well-differentiated tumours), but not with stage (progression through the bowel wall and the development of lymph node metastases) and, in a highly significant way, with a reduced incidence of distant metastases and increased patient survival. Although fibronectin was found in tumour cell basement membranes where these were present, it was also found in the stroma of all 50 tumours. There was no apparent correlation between the presence of stromal fibronectin and grade, stage or development of metastases. Finally, attention is drawn to some of the technical difficulties in detecting basement membrane antigens in formalin-fixed tissue, the material most frequently available for retrospective study.

Adenocarcinoma↗

Total parenteral nutrition in infancy: effect on the liver and suggested pathogenesis.

Biochemical, histological, and electron-microscopic investigation of seven preterm infants who became jaundiced after prolonged total parenteral nutrition showed conjugated hyperbilirubinaemia apparently due to cholestasis without significant primary liver cell injury. In the absence of evidence indicating a direct toxic effect on the liver of this form of nutrition the necropsy findings in one child and analogy with the effects of total parenteral nutrition in animals suggest that the cholestasis is the result of suppression of trophic and/or secretion-stimulating hormone(s) normally produced by the gut, due to absent enteral nutrition. Biochemical and electron-microscopic findings suggest that liver cell damage occurs after resumption of enteral nutrition.

Humans↗