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J Northover

Publications and source records attributed to J Northover.

At least 19 recordsLinked to original sources
PubMed2006

The effect of surgically induced ischaemia on gene expression in a colorectal cancer xenograft model.

Delays in tissue fixation following tumour vascular clamping and extirpation may adversely affect subsequent protein and mRNA analysis. This study investigated the effect of surgically induced ischaemia in a xenograft model of a colorectal cancer on the expression of a range of prognostic, predictive, and hypoxic markers, with a particular emphasis on thymidylate synthase. Vascular occlusion of human tumour xenografts by D-shaped metal clamps permitted defined periods of tumour ischaemia. Alterations in protein expression were measured by immunohistochemistry and spectral imaging, and changes in mRNA were measured by reverse transcriptase-polymerase chain reaction. Thymidylate synthase expression decreased following vascular occlusion, and this correlated with cyclin A expression. A similar reduction in dihydropyrimidine dehydrogenase was also seen. There were significant changes in the expression of several hypoxic markers, with carbonic anhydrase-9 showing the greatest response. Gene transcriptional levels were also noted to change following tumour clamping. In this xenograft model, surgically induced tumour ischaemia considerably altered the gene expression profiles of several prognostic and hypoxic markers, suggesting that the degree of tumour ischaemia should be minimised prior to tissue fixation.

Animals↗
PubMed2000

Predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial.

OBJECTIVE: To investigate predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial. DESIGN: Prospective design in which participants completed a postal questionnaire before being sent their invitation for screening. SETTING: Welwyn Garden City and Leicester, United Kingdom. PARTICIPANTS: A total of 2758 patients aged 55 to 64, registered with general practices in the two centres, who (a) expressed interest in having the screening test, (b) completed a postal questionnaire, and (c) were subsequently invited for screening. MAIN RESULTS: The attendance rate among questionnaire responders was 76.1%. Multiple logistic regression analysis yielded a final model that included nine independent predictors of attendance. Patients with the following characteristics were more likely to attend: men; home owners; non-smokers; those who had regular check ups at the dentist; those with better subjective health; those who minded less about having medical tests; those who said they would definitely rather than probably take up the offer of sigmoidoscopy screening; and those who perceived less barriers and more benefits to having the test. CONCLUSIONS: The findings are broadly consistent with previous studies of screening participation, although subjective health emerged as an important predictor in this study. There was no evidence for "reverse targeting": attenders were not at lower (or higher) risk for colorectal cancer compared with non-attenders. The findings relating to attitudes and beliefs could be used in efforts to improve attendance, for example by developing information leaflets that address barriers to screening. Other findings could be used to target interventions to subgroups that have relatively low rates of screening participation.

Age Factors↗
PubMed1999

Inherited susceptibility to colorectal adenomas and carcinomas: evidence for a new predisposition gene on 15q14-q22.

BACKGROUND & AIMS: The aim of this study was to evaluate the role of known colorectal adenoma and carcinoma susceptibility genes and to locate a novel susceptibility gene in an Ashkenazi family (SM1311) with dominantly inherited predisposition to colorectal adenomas and carcinomas. METHODS: Clinicopathologic and family history data were collected. Genetic linkage and mutational analyses were used to investigate the genetic basis of the family's disease. RESULTS: Affected members of SM1311 develop multiple tubular, villous, tubulovillous, and/or serrated colorectal adenomas throughout the large bowel, and some develop colon carcinoma. There are no extracolonic features clearly associated with disease in SM1311. We have shown that the family's phenotype does not result from APC mutations (including the I1307K variant) or from genetic changes in the other known genes that predispose to colon cancer. Using genetic linkage analysis, supplemented by allele loss in tumors, we have provided evidence for a new colorectal cancer susceptibility gene, CRAC1 (colorectal adenoma and carcinoma), mapping to chromosome 15q14-q22. CONCLUSIONS: We provide evidence for a novel colorectal adenoma and carcinoma susceptibility gene on chromosome 15q14-q22. Further studies are needed to confirm this localization and to evaluate the contribution of CRAC1 to this disease.

Adenoma↗
PubMed1999

Colorectal cancer.

Explore the source record for details and available documents.

Colorectal Neoplasms↗
PubMed1999

[Value of human colonic cancer models by surgical cecal implantation in nude mice].

A better understanding of the nature and treatment of colon cancer, and of by metastatic dissemination should be achieved by the use and study of appropriate animal models. Such models can be created by grafting human cancer cells or tumour fragments orthotopically into the colon or caecum of nude mice. This review examines the rationale behind these models and the principal results of orthotopic transplantation. Despite the fact that they require surgical expertise and are time-consuming, they provide valuable information on the mechanism of metastasis and the efficacy of novel treatments.

Animals↗
PubMed1996

Vaginal endosonography to diagnose enterocoele.

Radiological diagnosis of enterocoele is possible using evacuation proctography, but the standard technique must be modified to reveal the small bowel. Since prolapsed bowel is interposed between the vagina and rectum, diagnosis may be possible using vaginal endosonography. We describe a simple ultrasound technique to diagnose enterocoele, which has been validated by comparison with proctography. 17 women were examined with vaginal endosonography, and a diagnosis of enterocoele made if bowel was visualized in the rectovaginal space when bearing down. The findings were compared with subsequent proctography. In eight cases (47%) bowel prolapsed into the rectogenital space during straining, obscuring the rectum, while this did not occur in the remaining nine subjects (53%). Proctography confirmed an enterocoele in six of the eight cases in whom it had been diagnosed on endosonography, and confirmed the absence of enterocoele in all of the nine cases negative on endosonography. These values gave vaginal endosonography a sensitivity of 100% and specificity of 82%, with a positive predictive value of 75%, and negative predictive value of 100% for a prevalence of abnormality of 0.35. Vaginal endosonography is a quick, easy and convenient alternative to evacuation proctography for the radiological diagnosis of enterocoele.

Adult↗
PubMed1995

Level of expression of E-cadherin mRNA in colorectal cancer correlates with clinical outcome.

A series of colorectal carcinomas (n = 49) resected from patients with known clinical outcomes were analysed for E-cadherin expression using in situ hybridisation to measure mRNA. Patients surviving 5 years or longer (n = 31) exhibited significantly higher levels of E-cadherin mRNA than those surviving less than 5 years (n = 18, P = 0.003). These preliminary results from this small sample suggest that E-cadherin expression may be a useful prognostic marker in colorectal cancer patients.

Cadherins↗
PubMed1994

A comparison between cytology and histology to detect anal intraepithelial neoplasia.

INTRODUCTION: Anal intraepithelial neoplasia (AIN), which may be a precursor of anal carcinoma, has been identified on histology following minor anal surgical procedures, in particular the removal of perianal condylomata, in increasing numbers of homosexual and bisexual men. Anal cytology has recently been proposed as a useful method of identifying AIN lesions. OBJECTIVE: To compare anal cytology with histology as a method of detecting AIN. METHODS: 215 homosexual and bisexual men attending a central London sexually transmitted diseases clinic had an anal cytological smear performed under standard conditions. The perianal area and anal canal were then examined using a colposcope, and areas macroscopically suggestive of intraepithelial neoplasia were biopsied. RESULTS: 176 of the 215 patients were biopsied of whom 76 had AIN on histology. 154 of the 215 patients had an adequate anal smear of whom 46 and 85 had cytological features of both HPV and AIN, or HPV alone respectively. Including features of HPV alone as an abnormal smear, anal cytology, when compared with anoscopy and histology as the gold standard for diagnosing AIN, resulted in a sensitivity of 87.5%, a specificity of 16.3%, a positive predictive value of 37.4% and a negative predictive value of 69.6%. Restricting abnormal smears to those with features of both HPV and AIN resulted in a sensitivity of 33.9%, a specificity of 72.5%, a positive predictive value of 41.3% and a negative predictive value of 65.7%. CONCLUSION: Anal cytology is a sensitive but nonspecific method of identifying patients with biopsy proven AIN if cytological features of HPV alone are included as abnormal smears. Specificity is improved by restricting abnormal smears to those with features of both HPV and AIN but this markedly lowers the sensitivity of the test. At present, anoscopy and histology are required in addition to anal cytology to differentiate between patients who simply have anal condylomata and those who also have AIN.

Anal Canal↗
PubMed1993

The establishment of a polyposis register.

Guidelines are presented for the establishment of a regional or national register of patients with familial adenomatous polyposis. The detailed recommendations are based on the work in committees of the "Leeds Castle Polyposis Group" and the "EuroFAP". The aims of national and regional polyposis registers are discussed, and the stages of development of a register are reviewed: Ascertainment of probands, construction of pedigrees, identification of family members at risk, and screening of members at risk. The problem of data confidentiality is discussed.

Adenomatous Polyposis Coli↗
PubMed1993

Self-administered faecal occult blood tests do not increase compliance with screening for colorectal cancer: results of a randomized controlled trial.

In the UK, compliance with conventional faecal occult blood (FOB) tests such as Haemoccult is about 50% in the general population. It has been postulated that characteristics of the performance of conventional tests, in particular the need for dextrous gathering and manipulation of faeces, delay in receiving results, and the recommended dietary restrictions, may all diminish compliance. New FOB tests have been developed, popularly termed 'magic toilet paper' tests, which not only minimize faecal manipulation but are also self-reported. Compliance rates with two self-administered faecal occult blood tests (Early Detector and Coloscreen Self-Test) were compared with Haemoccult in a randomized trial involving 1,842 subjects aged 40-74 years. Use of self-administered FOB tests did not increase compliance significantly, with rates of 52.1% for Early Detector, 50.6% for Coloscreen and 49.1% for Haemoccult. Moreover, dietary restriction did not reduce compliance significantly (restricted 49.3%, unrestricted 51.8%). A wide variation (from 1.3% to 21.4%) in positivity rates was observed which was dependent on which of the three tests was used and whether dietary restrictions were applied. Since the physical aspects of test performance do not appear to determine an individual's decision to be screened, self-administered tests will not overcome the problem of poor compliance with FOB screening.

Adult↗
PubMed1992

Patient compliance with colorectal cancer screening in general practice.

A randomized controlled trial to test patient compliance with screening for colorectal cancer in association with general practice health checks was carried out in six practices (three urban and three rural). A total of 1588 patients aged 45-64 years were randomized to one of four intervention groups. In the first group patients were posted a Haemoccult test (Kline Beckman) kit. This group was not invited for a health check. In the second group patients were posted the Haemoccult test kit, together with an invitation to attend for a health check. In the third group patients were posted an invitation for a health check, which explained that the patient would be offered the Haemoccult test kit by the nurse at the health check. In the fourth group patients were just invited for a health check. It was found that combining faecal occult blood testing with the health check did not reduce attendance at the health check--43.5% of patients attended when the Haemoccult test kit was offered by the nurse at the health check, 43.6% attended when a test kit was included with the invitation to attend the health check and 42.9% attended when the health check invitation was posted on its own. Overall, compliance with Haemoccult testing was not significantly increased by associating it with a health check (26.2% versus 25.5%) but compliance was higher when the faecal occult blood testing kit was enclosed with the health check invitation than when it was offered at the health check (31.7% versus 20.6%, P less than 0.001). It is easier and cheaper to combine various screening procedures. Although the overall use of the Haemoccult test in the study population was low, there is no reason why the relatively higher compliance rate obtained on posting the test kit with a health check invitation cannot be achieved in previously unscreened populations with higher expected compliance rates. However, faecal occult blood screening for colorectal cancer should not be undertaken on a population basis until its effectiveness in reducing mortality has been proven by randomized trial.

Colonic Neoplasms↗