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J D Hardcastle

Publications and source records attributed to J D Hardcastle.

At least 73 records · Page 4Linked to original sources
PubMed1994

Congenital hypertrophy of the retinal pigment epithelium and mandibular osteomata as markers in familial colorectal cancer.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) and multiple mandibular osteomata are markers of familial adenomatous polyposis (FAP). We have assessed their prevalence in non-polyposis familial colorectal neoplasia. Multiple mandibular osteomata were present in 1/29 (3%) patients with familial colorectal neoplasia. CHRPE was present in 11/33 (33%) patients with familial colorectal neoplasia compared with 3/36 (8%) with sporadic disease (P = 0.01) and 4/32 (12.5%) control subjects (P = 0.04). Seven patients with familial colorectal neoplasia had multiple areas of CHRPE compared with one with sporadic disease (P = 0.02) and one control subject (P = 0.02). There was no obvious correlation between calculated familial colorectal cancer risk and the presence of multiple areas of CHRPE. A proportion of patients with familial colorectal cancer have a marker found in FAP and may therefore have a constitutional genetic defect, at least in part responsible for their cancer, making them an interesting group for genetic study. Ophthalmoscopy may contribute to risk assessment in familial colorectal cancer.

Adult↗
PubMed1994

Planar, SPET and three-dimensional immunoscintigraphy of suspected recurrent colorectal cancer using 111In-B72.3 (Oncoscint CR-OV): effect of administered activity.

The monoclonal antibody conjugate 111In-B72.3 was the first such antibody-based radiopharmaceutical for tumour detection to be granted a propriety product licence in Europe. However, the optimum activity of 111In for planar and SPET imaging is yet to be established. A baseline study of 20 patients with suspected recurrent colorectal cancer has been carried out to assess any effect of administered activity of radionuclide on image quality and tumour detection. Ten patients were administered 80 MBq 111In-Oncoscint and 10 patients a larger amount of activity, 150 MBq (resulting in effective dose equivalents of 25 and 47 mSv, respectively). Planar, orthogonal SPET and 3D volume-rendered SPET images were obtained and the image quality was assessed. The clinical results were compared with computed tomography (CT) and in selected patients magnetic resonance imaging (MRI). No difference in the overall tumour detection was apparent between the two groups and the use of 150 MBq 111In for planar imaging alone cannot be justified. Orthogonal and 3D SPET imaging was helpful in confirming sites of uptake and may justify the use of the higher administered amount of activity; however, false-positive results raise the need for caution in the interpretation of these images. Volume-rendered 3D images offer an attractive method of displaying antibody data and require further evaluation.

Aged↗
PubMed1994

DNA content of rectal mucosa and rectal mucosal proliferation in individuals at high risk of colorectal cancer.

Genetic changes are important in the development of colorectal cancer. Ploidy and rectal mucosal proliferation were measured in histologically normal rectal mucosa of 85 individuals (mean age 59 years, range 29-74) who had a total colonoscopy. Fifty-one subjects had an adenoma or were undergoing adenoma surveillance. Twenty-two subjects had a strong family history of colorectal cancer and 12 individuals comprised a control group who had a normal colonoscopy without a family history of colorectal cancer. An abnormal DNA content (aneuploidy) was found in the normal mucosa of nine (10.6%) individuals. There was no significant difference in rectal mucosal proliferation with those who had aneuploidy and those who had diploidy. There was a trend towards increased proliferation in those with aneuploidy and adenomas, compared with controls. Of the 35 individuals undergoing adenoma surveillance, eight had recurrent adenomas, and three of these expressed aneuploidy. In the other 27, in whom no adenomas were found, no individual expressed aneuploidy (P = 0.01, Fisher's exact test). Aneuploidy within histologically normal mucosa is an unusual feature, which requires further investigation, particularly in patients developing adenomas.

Adenoma↗
PubMed1994

The management of acute sigmoid volvulus in Nottingham.

Forty previously undiagnosed cases of acute sigmoid volvulus presenting over five years in Nottingham are retrospectively reviewed. The average age was 71.6 years with an even sex ratio. Fifteen (38%) patients lived in nursing homes or institutions. At presentation, all had clinical features of large bowel obstruction, confirmed on plain abdominal X-ray. Sigmoidoscopy and rectal tube decompression was successful in 23 cases. The remaining 17 patients were treated surgically, within 24 hours, at which time the sigmoid was sutured to the abdominal wall (2 cases), resected and brought out as a colostomy (10 cases) or resected and primarily anastomosed (5 cases). Whilst in hospital, of those treated conservatively five died, and three from those treated surgically, four from those in which a colostomy was formed died and three from those in which a primary anastomosis was fashioned died. Of those that survived 11 from the conservative group had at least one recurrence, but none recurred following surgery. In conclusion, acute sigmoid volvulus affects an old and infirm population and carries a poor prognosis. Conservative management is initially preferable, but if emergency surgery is necessary a colostomy rather than primary anastomosis is indicated.

Acute Disease↗
PubMed1994

Haemoccult screening for colorectal cancer: the effect of dietary restriction on compliance.

The aim of this study was to examine the effect of dietary restrictions on compliance with Haemoccult screening for colorectal carcinoma. One-hundred-and-fifty-three individuals were randomly allocated to perform Haemoccult tests with or without dietary restrictions, over 3 or 6 days. Those who failed to return completed tests within 6 weeks were sent a reminder letter. A small but significant improvement in compliance when testing over a 3-day period has been previously demonstrated but this difference was not seen in this study because of the small sample size. Overall, 72.8% compliance was achieved in those who were not asked to exclude certain foods during the test period compared with 51.8% in those in whom dietary restriction was requested (chi 2 = 7.45, P < 0.01). In a British population compliance with Haemoccult screening is adversely affected by the imposition of dietary restrictions.

Aged↗
PubMed1993

Effect of aspirin and non-steroidal anti-inflammatory drugs on colorectal adenomas: case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

OBJECTIVE: To examine the relation between the use of aspirin and non-steroidal anti-inflammatory drugs and the presence of asymptomatic colorectal adenomas. DESIGN: Case-control study of subjects participating in a randomised controlled trial of faecal occult blood screening for colorectal cancer. Data on analgesics and other drugs were obtained from a questionnaire which was mainly concerned with diet and was administered by an interviewer. SETTING: Nottingham. SUBJECTS: 147 patients with positive results in faecal occult blood tests who were found to have colorectal adenomas (cases), 153 age and sex matched control subjects with negative results in such tests (negative controls), and 176 control subjects with positive results in the tests who were found not to have colorectal adenomas (positive controls). MAIN OUTCOME MEASURES: Relative risk of developing colorectal adenomas according to frequency and duration of use of analgesics. RESULTS: Cases reported taking less aspirin and non-steroidal anti-inflammatory drugs than the negative controls, with the estimated relative risk for any use being 0.49 (95% confidence interval 0.3 to 0.8). The inverse association was less strong when cases were compared with the positive controls (0.66 (0.4 to 1.1)). The association was specific for aspirin and non-steroidal anti-inflammatory drugs there being no association with paracetamol or other drugs. Prescribed use of non-steroidal anti-inflammatory drugs for longer than five years was associated with the lowest risk (0.21 (0.1 to 0.8)), although the numbers reporting prolonged prescribed use were small. CONCLUSIONS: These findings support the hypothesis that aspirin and non-steroidal anti-inflammatory drug use protects against the development of colorectal neoplasia.

Acetaminophen↗
PubMed1993

Individuals with a strong family history of colorectal cancer demonstrate abnormal rectal mucosal proliferation.

Thirty-seven individuals with an increased lifetime risk of colorectal cancer because of family history and a control group (n = 21) with no such family history underwent colonoscopy. No neoplastic lesion was found in any individual. Rectal biopsies of macroscopically normal mucosa were taken 8 cm from the anal margin and mucosal proliferation assessed by the crypt cell production rate (CCPR). There was no difference in CCPR between the control group (median 10 (95 per cent confidence interval 7-11) cells per crypt per h) and those at intermediate risk (lifetime risk between 1:17 and 1:10, n = 14). However, there was a significant difference in CCPR between the control group and those at higher risk (lifetime risk > 1:10, n = 23) (median CCPR 13 (95 per cent confidence interval 10-17) cells per crypt per h, P = 0.004). A high risk of colorectal cancer derived from family history correlates with an increased colorectal mucosal proliferation rate.

Adult↗
PubMed1993

Change towards earlier stage at presentation of colorectal cancer.

A study was carried out to investigate the change in stage at presentation of patients with colorectal cancer over 10 years. Cases were identified from the control group of subjects enrolled into a randomized controlled study based on Haemoccult screening for colorectal neoplasia. Of 405 subjects in the control group (presenting with symptomatic colorectal cancer, 206 presented before 1989 and 199 since then. The number of patients with Dukes' stage A carcinoma diagnosed since 1989 rose from 21 (10.4 per cent) to 35 (18.1 per cent); this change occurred for rectosigmoid tumours (9.9 per cent before 1989, 28 per cent after 1989) but not for colonic cancer (10.9 per cent before 1989, 11.5 per cent thereafter). An increase in the proportion of patients with symptomatic early-stage rectosigmoid cancer has been observed in the past 10 years. No such change occurred in those with colonic cancer. This may reflect a change in awareness of te disease and its symptoms by patients and general practitioners.

Adult↗
PubMed1993

A hepatic invasive human colorectal xenograft model.

A hepatic invasive human colorectal xenograft model was derived in nude mice by selection through the liver of the parental cell line, C170. Following intraperitoneal injection, tumours selectively grew on the liver in > 80% of the animals within 15-20 days. The liver-invading xenograft line, renamed C170HM2, had a significantly greater expression of the Lewisx antigen compared to C170 (mean linear fluorescence per cell > 1000 compared with 500 for C170, P < 0.02). C170HM2 had significantly elevated proliferation (when compared with C170) in the presence of epidermal (P < 0.001) and basic fibroblast growth factor (P < 0.001). C170HM2 also mitogenically responded to type I collagen (derived from rat tails), unlike C170. C170HM2 tumours when invading the liver expressed both interstitial collagenase and gelatinase activity at the invading edge.

Animals↗
PubMed1993

Colorectal adenomas and energy intake, body size and physical activity: a case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

Most case-control studies of colorectal cancer have shown a positive association with energy intake. In contrast studies which have considered physical activity have found the most active to have a lower risk of colonic cancer and obesity appears to be no more than weakly related to colorectal cancer. We therefore compared energy intake determined by a diet history interview, self-reported height and weight, together with measures of lifetime job activity levels and leisure activity in the year prior to interview in 147 cases with colorectal adenomas and two control groups (a) 153 age-sex matched FOB-negative subjects (b) 176 FOB-positive subjects in whom no adenoma or carcinoma was found. Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals () adjusted for age, sex and social class. No association with weight or body mass index was found. The only association with physical activity found with both control groups was an inverse association with running or cycling for half an hour continuously at least once a week RR 0.46 (0.2-1.3) compared with control group (a), and RR = 0.32 (0.1-0.8) compared with (b), but few subjects engaged in such activity. There was an inverse association with energy intake (trend chi 2 = 5.3, P < 0.025) in the comparison with control group (a) only, a finding which is consistent with those of two previous studies of asymptomatic adenoma.

Adenoma↗
PubMed1993

The identification of high and low risk groups for colorectal cancer using rectal mucosal crypt cell production rate (CCPR).

Rectal mucosal proliferation was measured in 116 individuals using the metaphase arrest technique crypt cell production rate (CCPR). CCPR was found to be significantly elevated in individuals with adenomas (n = 42, CCPR = 13 cc c-1h-1, range 7-25 Cl 10-15) compared with normals (n = 21, CCPR = 10 cc c-1h-1 range 5-24 Cl 7-11, Mann-Whitney P = 0.001 z = 3.2). Mucosal proliferation was increased among individuals who were undergoing adenoma follow up but in whom no further adenomas were found (n = 37 CCPR = 12 range 5-26 cc c-1h-1 Cl 10-14) compared to controls (Mann-Whitney P = 0.01 z = 2.4) Proliferation in vegetarians i.e. low risk (n = 16) was similar to controls. Measurement of proliferative indices in rectal mucosa by the stathmokinetic technique CCPR can discriminate between high and low risk groups for colorectal cancer.

Adenoma↗
PubMed1993

Colorectal adenomas and diet: a case-control study of subjects participating in the Nottingham faecal occult blood screening programme.

Diets high in animal fat and protein and low in fibre and calcium are thought to be factors in the etiology of colorectal cancer. Intakes of these nutrients were determined in three groups participating in a randomised trial of faecal occult blood (FOB) screening. A diet history was obtained by interview from 147 patients with colorectal adenomas, 153 age and sex matched FOB-negative controls (a) and 176 FOB-positive controls without colorectal neoplasia (b). Unconditional logistic regression was used to estimate relative risks (RR) and 95% confidence limits (increases) adjusted for age, sex and social class. After adjustment for total energy intake, no associations were found with total, saturated or mono-unsaturated fat, or calcium intake. For total fibre intake there were non-linear relationships with both control groups with the crude RR for highest quintiles of total fibre intake compared to the lowest being 0.6, although this pattern was no longer apparent after adjustment for energy intake with group (a). In comparison with group (b) cereal fibre intake showed a more consistent inverse relationship with adenoma prevalence with the RR for ascending quintiles of intake being 1.0, 0.7 (0.3-1.6), 0.5 (0.3-1.1), 0.7 (0.4-1.4) and 0.3 (0.1-0.6) (trend chi 2 = 8.80, p = 0.003). In comparison with group (a), the adjusted RR for the highest quintile of cereal fibre intake compared with the lowest was 0.6, but no clear trend was apparent. There was an unexpected positive relationship between adenomas and polyunsaturated fat intake with the RR for having an adenoma being 1.0, 2.8 (1.3-6.1), 1.6 (0.7-3.4), 3.5 (1.6-7.5) and 2.3 (1.1-5.0) for ascending quintiles of polyunsaturated fat intakes (trend chi 2 = 4.8, P = 0.03) in comparison with group (a) only. Our data, while providing no support for the role of dietary animal fat or protein, do support the protective role of dietary cereal fibre in the etiology of colorectal adenomas.

Aged↗
PubMed1993

Screening and the costs of treating colorectal cancer.

The objective of this paper is to compare the hospital costs of treating patients with colorectal cancers detected as a result of a faecal occult blood screening programme with those of patients whose cancers present symptomatically (control group). Patient-specific cost estimates are made, using case records and hospital accounts, for 360 patients over 3 years. Mean treatment costs for the group offered screening and for the control group are calculated to be 3,179 pounds and 2,966 pounds respectively, although the difference between these means is insignificant. Low treatment costs in the case of screen-detected cancers are largely accounted for by polypectomy with no subsequent readmission; in the control group case, they tend to be accounted for by early patient death. For the sample as a whole, the costs of treating very early-, and very late-, stage cancer are significantly lower than those of treating cancers in the intermediate stages. On the basis of trial evidence, the introduction of mass screening for colorectal cancer is unlikely to give rise to substantial economies in the costs of treatment.

Colorectal Neoplasms↗
PubMed1993

Cell kinetics of the in vitro metaphase arrest technique and the clinical applications.

The in vitro metaphase arrest technique (crypt cell production rate-CPPR) has been used to measure human rectal mucosal proliferation. Study of preincubation times, dose response curves and lag phases suggest that a concentration of vincristine of 5 micrograms/ml and 16 hour preincubation with time point increments between 25 and 125 minutes give optimal conditions for measuring rectal mucosal proliferation. Twenty individuals had rectal CCPR repeated without intervention of any kind. Close correlation was found between the two values (r = 0.89 and P = 0.0001). The effect of polyethylene glycol bowel preparation was also studied in 35 subjects. There was good correlation (r = 0.66, P = 0.007). There was close correlation between rectal and caecal CCPR as measured in 20 patients who had colonoscopy (r = 0.72, P = 0.0003). The in vitro metaphase arrest technique is a useful parameter of rectal mucosal proliferation and may be used with confidence in a number of different clinical situations.

Biopsy↗
PubMed1993

Screening for gastric carcinoma in coal miners.

This study aimed to determine the prevalence of dyspeptic symptoms and premalignant gastric lesions in coal miners and sex matched population control subjects. Retired coal miners and men from the general population in north Nottinghamshire were sent a dyspepsia questionnaire to fill in, and those with upper gastrointestinal symptoms were invited for gastroscopy and biopsy. A total of 1272 men from the general population and 2099 retired coal miners aged 50-75 years took part in the study. Some 977 of 1272 (76.8%) control subjects and 1715 of 2099 (81.7%) miners replied to the questionnaire. A total of 308 of 977 (31.5%) controls and 620 of 1715 (36.2%) miners were positive for at least one symptom. There was a highly significant difference between the numbers of surface mine and underground workers who reported dyspeptic symptoms (66 of 300 (22%) v 425 of 1083 (32.2%) of p < 0.0001). Histology showed that significantly more miners than controls had acute on chronic gastritis (22 v 11%; p = 0.01) and intestinal metaplasia (23 v 8%; p = < 0.0001). Coal miners may be a suitable group for gastric premalignancy screening using an upper gastrointestinal symptom questionnaire and upper gastrointestinal endoscopy.

Age Factors↗
PubMed1993

Prolonged monitoring of the upper gastrointestinal tract using echo planar magnetic resonance imaging.

Upper gastrointestinal motility and transit has been studied in five human volunteers with the ultra high speed, magnetic resonance imaging (MRI) technique MBEST (Modulus Blipped Echo-planar Single pulse Technique), a variant of echo planar imaging. Snapshot images requiring a data acquisition time of only 64-128 msec allowed visualisation of peristalsis in the antrum and duodenum in real time, without motional image degradation, as would normally be seen using conventional MRI. Gastroduodenal flow of the luminal contents was visualised using water as a contrast medium, with appropriate adjustment of the time constant (T2) weighting of the system. Rapid (0.3 Hz) imaging of gastroduodenal motility in both transverse and coronal planes was achieved by respiratory gating to the imaging frequency, allowing repetition rates of up to 20 frames per minute for 2-3 hours. Fast replay of stored images, to produce a 'movie loop', allowed identification of fasting motility patterns of the gastric antrum and proximal small intestine, with depiction of the phases of the migrating motor complex. Images of the fed patterns after the ingestion of a test meal showed good separation of solid and liquid particulate matter and mixing waves in the gastric body. The potential for quantitative measurements with this new imaging modality of the gastrointestinal tract is under development, which will allow us to measure transit and correlate this with motility data.

Adult↗