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Biomedical subjects

N Scott

Publications and source records attributed to N Scott.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cyclooxygenase-2 expression in colorectal cancer liver metastases.

Cyclooxygenase-2 (COX-2) is up-regulated in 85-90% of primary human colorectal cancers and is a putative target for the chemopreventative activity of non-steroidal anti-inflammatory drugs. However, COX-2 expression by human colorectal cancer liver metastases has been poorly characterized. We studied a consecutive series of 38 patients who underwent liver resection for metastatic disease, for whom long-term (up to 57 months), prospective follow-up data were available. Semi-quantitative immunohistochemistry for COX-2 was performed on 54 metastases from 35 patients, for whom adequate histological material was available. Diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastases (COX-2 score 1, n = 25; score 2, n = 29). There was no relationship between metastasis size or differentiation grade and the level of COX-2 protein expression. There was no difference in colorectal cancer-free or overall survival between patients with high (score 2) and low (score 1) COX-2 scores (Kaplan-Meier survival analysis and log rank test, both P = 0.97). Multivariate Cox regression analysis identified age, incomplete resection and presence of extra-hepatic disease as independent predictors of disease-free and overall survival following surgery. COX-2 protein was also localized to a subset of stromal fibroblasts and mononuclear cells within metastases as well as hepatocytes from resection specimens. COX-2 protein was expressed by cancer cells in all human colorectal cancer liver metastases which were studied. Investigation of the effect of selective COX-2 inhibition on metastasis growth and metastasis cancer cell proliferation/apoptosis in vivo are warranted.

Colorectal Neoplasms↗
PubMed1999

Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of Min mice.

Expression of cyclooxygenase 2 (COX-2) is believed to play an important role in adenoma formation in murine polyposis models, and inhibition of COX-2 activity may, at least, partly explain the chemopreventative activity of non-steroidal anti-inflammatory drugs against colorectal cancer in humans. However, the mechanism by which COX-2 acts in intestinal tumorigenesis remains unresolved because of conflicting data on the cellular localization of COX-2 in intestinal mucosa. Using immunohistochemistry with specific COX-2 antiserum, we have shown that COX-2 protein is localized to interstitial cells at the base of and within adenomas of the small and large intestine of multiple intestinal neoplasia (Min) mice. No COX-2 staining was observed in dysplastic epithelial cells within adenomas or in histologically normal epithelium. Moreover, COX-2 staining was observed in lamina propria cells of histologically normal intestine of Min mice. No staining was demonstrated in wild-type littermates. The rat monoclonal antibody F4/80 was used to show that COX-2-positive cells represented a subset of the macrophage population present in the intestine of Min mice. Localization of COX-2 to macrophages implies a paracrine effect of COX-2 function on epithelial cells in adenomas and also on histologically normal epithelium. Up-regulation of COX-2 expression in lamina propria macrophages may precede loss of the second functional Apc allele in epithelial cells before adenoma formation in the Min mouse model of intestinal tumorigenesis.

Adenoma↗
PubMed1998

A histopathological assessment of the response of rectal adenocarcinoma to combination chemo-radiotherapy: relationship to apoptotic activity, p53 and bcl-2 expression.

AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.

Adenocarcinoma↗
PubMed1998

The release of free prostate specific antigen into the circulation during transurethral resection of the prostate: kinetics and interaction with serum protease inhibitors.

OBJECTIVE: To determine the nature and extent of the release of prostate specific antigen (PSA) and its interaction with its plasma protein-derived inhibitors after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Twenty-three consecutive patients undergoing routine TURP for benign prostatic hyperplasia had blood samples taken pre-operatively and then post-operatively at 8-hourly intervals for 24 h. Further samples were obtained at 48 and 72 h post-operatively. Serum free and total PSA were determined by immunofluorometric assay. The major plasma protein inhibitors for PSA were also determined by immunoassay. RESULTS: The mean free and total PSA fractions increased significantly post-operatively with levels greatest immediately after surgery. There was also a gradual increase in the complexed PSA fraction, reaching a peak at 48 h. The concentration of the major serum inhibitors of PSA (alpha-1-antichymotrypsin and alpha-2-macroglobulin) also declined immediately after surgery. CONCLUSION: Increases of serum total PSA in patients after TURP are caused by increases in the free PSA fraction. The exponential decline in free PSA concentrations is consistent with the complexing of PSA with its protease inhibitors present in the plasma. The formation of this complex suggests that the free PSA released into the circulation at the time of TURP is the enzymatically active form.

Humans↗
PubMed1996

Genes mediating programmed cell death: an immunohistochemical study of bcl-2, c-myc and p53 expression in colorectal neoplasia.

Aims-To describe the expression of three genes involved in the regulation of cell proliferation and programmed cell death (apoptosis) in normal, dysplastic and malignant large bowel epithelium, and to relate any alterations to important biological and clinical variables.Methods-Immunohistochemistry was used to assess bcl-2, c-myc and p53 gene expression in 70 colorectal carcinomas, 36 adenomas and three samples of normal mucosa.Results-Bcl-2 and c-myc protein were detected in all samples of normal mucosa and most adenomas. P53 was never found in normal mucosa and was expressed in only 5% of adenomas. Sixty nine of 70 carcinomas expressed c-myc protein; p53 was found in 46% and bcl-2 was present in 35%. Bcl-2 expression correlated with a higher degree of tumour differentiation whereas the opposite was true for c-myc. Strong staining for c-myc protein predicted survival in univariate analysis. No correlation was found between p53 and bcl-2 expression.Conclusions-While c-myc and bcl-2 proteins are overexpressed at an early stage of the large bowel adenoma-carcinoma sequence, alterations to the p53 protein level only occur as a late event in large, highly dysplastic adenomas and carcinomas. Bcl-2 may therefore protect the growing adenoma against excessive programmed cell death and mutated p53 may play a similar role in carcinomas. In vitro there is a reciprocal relation between p53 and bcl-2 expression. This could not be confirmed in vivo. Similarly, there was no relation between bcl-2 and c-myc status, despite evidence that these proteins cooperate to cause neoplastic transformation. C-myc may be a prognostic indicator in large bowel cancer. There is no evidence in the present series that bcl-2 status will affect survival.

Journal Article↗
PubMed1995

Total mesorectal excision and local recurrence: a study of tumour spread in the mesorectum distal to rectal cancer.

Total mesorectal excision (TME) appears to be associated with a reduced local recurrence rate following surgery for rectal cancer. Of 20 patients with rectal cancer in whom TME was performed, adenocarcinoma was found in the distal mesorectum in four. Distal mesorectal spread often extended further than intramural spread. Patients with tumour in the distal mesorectum had a worse outcome at 4-year follow-up, a greater risk of local recurrence and an increased frequency of distant metastasis. Distal tumour spread is, therefore, a marker of poor prognosis in rectal cancer. This study provides further evidence that incomplete excision of the mesorectum contributes to local recurrence in a proportion of patients with rectal cancer, particularly in those with tumours in the middle and lower third of the rectum.

Adenocarcinoma↗
PubMed1995

Manometric asymmetry in the anal canal in controls and patients with fecal incontinence.

PURPOSE: This study was designed to ascertain the existence of manometric asymmetry in the anal canal in controls and in patients with fecal incontinence. METHODS: A computerized manometric technique with an eight-channel perfusion catheter was used. Coefficient of variation (CV, a mathematical expression of the degree or magnitude of deviation of a set of data points from the mean) was developed in this study as an index of anal canal manometric asymmetry. RESULTS: At 1 cm from the anal verge, mean CV was 9.3 and 8.7 percent in asymptomatic control males and females, respectively. During a maximum voluntary squeeze effort, mean CV in control males was 9.3 percent and was not significantly different (P = 0.28) from that in control females (7.8 percent). In 14 consecutive female patients with fecal incontinence, mean CV at rest (1 cm from the anal verge) was 21 percent and was significantly higher (P < 0.01) than in control females. Similarly, during a maximum voluntary squeeze effort, mean CV in patients with fecal incontinence was 20.5 percent and was significantly higher (P < 0.01) than in the female control group (7.8 percent). CONCLUSION: It is concluded that CV, a method of expressing anal sphincter manometric asymmetry, is a useful manometric parameter in the assessment of anorectal function.

Adult↗
PubMed1995

Psychometric profiling of the elderly using the Cambridge Cognitive Examination.

OBJECTIVES: To (1) build a psychometric profile of elderly subjects attending specialists day care centers and residential homes using the Cambridge Cognitive Examination (CAMCOG); (2) identify factors that are predictive of the score obtained; and (3) determine whether scores from CAMCOG and the less time-consuming Mini-Mental State Examination (MMSE) were correlated sufficiently for the latter to replace the former for general cognitive screening. DESIGN: Nonrandom convenience sampling of elderly subjects attending specialist day care centers, residential homes, and units for the elderly mentally ill. SETTING: Belfast, Northern Ireland. MAIN OUTCOME: CAMCOG and MMSE scores with age, sex, educational level, marital status, visual and hearing ability, various central nervous system diseases, and handedness as independent variables. RESULTS: Age, sex, the wearing of glasses, Parkinson's disease, stroke, and epilepsy were found to be significant predictors of the CAMCOG score. This pattern held true for the MMSE score, except for stroke. CAMCOG and MMSE scores were correlated closely, even after deletion of overlapping scores. However, the CAMCOG score showed an increasing bias when the mean score increased. The cognitive function of the subjects attending the 3 types of establishment differed significantly, with those in the residential homes being the most heterogenous. CONCLUSIONS: The subjects profiled showed significant cognitive impairment. The MMSE score appears to give much the same information as the CAMCOG score in this general screening of our patient group. The population considered is probably representative of subjects attending similar units in the United Kingdom.

Aged↗
PubMed1995

Enhanced preservation of the auditory nerve following cochlear perfusion with nerve growth factors.

Survival of auditory neurons in the cochlea is thought to be an important factor in the success of cochlear implantations. Damage to the cochlear end-organ often produces loss of dendrites in the osseous spiral lamina. The authors have established a method that delivers water soluble pharmacologic agents to the cochlea using a mini osmotic pump with a polyethylene cannula that is inserted into the scala tympani via cochleostomy. The cannula is filled with an ototoxic agent, neomycin, that destroys the end-organ over the first 24 hours after insertion. Nerve growth factor (NGF), or a control substance, is placed in the pump reservoir and is pumped into the cochlea over a 2-week period. In this study, auditory nerve fibers in the osseous spiral lamina were counted in the apical, middle, and basal turns of the cochlea in 16 guinea pigs. At each location, fiber counts were significantly higher when neomycin was followed by perfusion with NGF, than when it was followed by infusion with control substances. The study demonstrates that NGF confers some protection against ototoxic induced degeneration of the auditory nerve in vivo.

Animals↗
PubMed1994

Role of circumferential margin involvement in the local recurrence of rectal cancer.

Local recurrence after resection for rectal cancer remains common despite growing acceptance that inadequate local excision may be implicated. In a prospective study of 190 patients with rectal cancer, we examined the circumferential margin of excision of resected specimens for tumour presence, to examine its frequency and its relation to subsequent local recurrence. Tumour involvement of the circumferential margin was seen in 25% (35/141) of specimens for which the surgeon thought the resection was potentially curative, and in 36% (69/190) of all cases. After a median 5 years' follow-up (range 3.0-7.7 years), the frequency of local recurrence after potentially curative resection was 25% (95% CI 18-33%). The frequency of local recurrence was significantly higher for patients who had had tumour involvement of the circumferential margin than for those without such involvement (78 [95% CI 62-94] vs 10 [4-16]%). By Cox's regression analysis tumour involvement of the circumferential margin independently influenced both local recurrence (hazard ratio = 12.2 [4.4-34.6]) and survival (3.2 [1.6-6.53]). These results show the importance of wide local excision during resection for rectal cancer, and the need for routine assessment of the circumferential margin to assess prognosis.

Adult↗
PubMed1993

Prognostic value of p53 overexpression and c-Ki-ras gene mutations in colorectal cancer.

BACKGROUND: Mutations in Ki-ras codon 12 and the p53 gene are common abnormalities in colorectal cancer. The occurrence of p53 overexpression and/or Ki-ras codon 12 mutations were analyzed in 100 colorectal adenomas to determine if they were related to patient survival. METHODS: p53 overexpression was identified by immunohistochemistry, and Ki-ras codon 12 mutations were detected using the polymerase chain reaction and a restriction enzyme digestion method. RESULTS: p53 overexpression was identified in 45% of tumors, with a higher frequency identified in DNA aneuploid and left-sided tumors than in DNA diploid and right-sided tumors. Mutations in Ki-ras codon 12 were identified in 24% of carcinomas. Individually, mutations in Ki-ras codon 12 or p53 overexpression were not prognostic indicators of survival. However, a statistically significant difference in survival was identified when these two oncogenic abnormalities were analyzed together. The median survival of patients whose tumors contained both oncogenic abnormalities was less than half of that of patients with either alteration alone or without either abnormality. CONCLUSIONS: Screening for multiple genetic abnormalities in colorectal cancers excised at surgery may prove to be a useful tool in determining prognosis.

Adenocarcinoma↗
PubMed1993

High gastric juice ascorbic acid concentrations in members of a gastric cancer family.

Gastric juice ascorbic acid, total vitamin C, nitrite and N-nitroso-compound concentrations were determined in fasting gastric juice from four second generation members of a gastric cancer family, all of whom had Helicobacter pylori-associated chronic gastritis and intestinal metaplasia. Juice pH, nitrite and N-nitroso-compound concentrations were low. Juice ascorbate levels were comparable to those found in subjects with normal histology. The findings are contrary to our previous experience with juice ascorbate in H. pylori gastritis.

Adult↗
PubMed1993

Oxygen free radicals and platelet and granulocyte aggregability in renal transplant patients.

Oxygen free radical reaction products (plasma malondialdehyde), the free radical scavengers plasma thiol and red cell superoxide dismutase (SOD), and whole blood platelet and granulocyte aggregation were measured in 23 renal transplant patients and 23 age-matched controls. Malondialdehyde-like material (MDA) was significantly increased in transplant patients compared with controls (transplants MDA [median, range], 7.7 [5.3-11.5] nmol/ml; controls MDA, 6.3 [5.4-8.7] nmol/ml; P < 0.001). The patients also had increased red cell superoxide dismutase (transplants SOD, 128.1 [89.4-93.8] U/0.5 ml red cells; controls SOD, 95.9 [62.0-132.6] U/0.5 ml red cells; P < 0.001) and reduced plasma thiol (transplants thiol, 428 [266-496] mumol/L; controls thiol, 445 [358-501] mumol/L; P < 0.05). These factors were not influenced by immunosuppressive therapy, duration of transplantation, or creatinine concentration. Transplant patients had significantly higher levels of collagen-induced and spontaneous whole blood platelet aggregation compared with controls (collagen: transplants, 72 [4-93%]; controls 43 [6-94]%; P < 0.001; spontaneous: transplants 46 [11-93]%; controls 37 [10-75]%; P < 0.05). Spontaneous platelet aggregation, however, was significantly correlated with creatinine concentration (r = 0.525, P < 0.02, Spearman's correlation), and was raised only in those patients with a degree of renal impairment. Granulocyte aggregation was increased in patients receiving cyclosporine (CsA [n = 15], 57 [36-66]%; no cyclosporine [n = 8], 45 [37-62]%; controls [n = 23]; 39 [31-61]%; P = 0.004). Renal transplant patients are subject to oxidative cell damage, and may be at increased risk of vascular thrombosis. Possible contributory factors include an immunological reaction to the graft and/or the effects of immunosuppressive therapy.

Adolescent↗
PubMed1993

Preliminary evaluation of a Low-Cost VideoConferencing (LCVC) system for remote cognitive testing of adult psychiatric patients.

Mini-Mental State Examination scores were compared in an adult psychiatric population when the test was performed face to face and over a Low-Cost VideoConferencing System (LCVC). The minor changes to the instrument that are required to make it compatible with the LCVC are described. The high correlations achieved between the test scores in the two conditions suggests that this cognitive screening test may be reliably performed in this group of patients over the LCVC.

Adult↗
PubMed1993

p53 expression and K-ras mutation in colorectal adenomas.

The frequency of p53 overexpression and K-ras codon 12 mutation was investigated in a series of colorectal adenomas. p53 was detected by immunohistochemistry in only 5% of tumours, whereas K-ras mutation was found in eight of 30 adenomas examined. In vitro, mutant p53 and ras genes cooperate to transform primary rat cells into a tumourigenic cell line. The presence of both p53 overexpression and K-ras mutation in a benign tubulovillous polyp in the present series suggests that in vivo this combination of events is insufficient to cause malignant transformation of a large bowel adenoma.

Adenoma↗