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J D Hardcastle

Publications and source records attributed to J D Hardcastle.

At least 55 records · Page 3Linked to original sources
PubMed1995

Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5.

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.

3T3 Cells↗
PubMed1995

Faecal occult blood testing and colonoscopy in the surveillance of subjects at high risk of colorectal neoplasia.

Colonoscopy is the established method of surveillance of subjects at high risk of developing colorectal neoplasia but the procedure is expensive, time consuming and occasionally hazardous. Faecal occult blood tests can be prepared at home and are cheap, simple and safe. Hemeselect is an immunological faecal occult blood test that is more sensitive for colorectal cancer than Haemoccult. The aim of this study was to determine the sensitivity of the Hemeselect test for asymptomatic colorectal neoplasia in subjects at high risk of the disease who were undergoing colonoscopy, thus assessing its suitability as an alternative means of screening high-risk groups. A total of 919 asymptomatic subjects were asked to complete Hemeselect tests. These were completed satisfactorily by 808 individuals (compliance rate 88 per cent) and were positive in 164 patients (20 per cent). At colonoscopy 11 cancers were detected in ten patients (seven Hemeselect positive) and 36 (16 Hemeselect positive) had at least one adenoma 1 cm or more in diameter. The test sensitivites of Hemeselect for carcinoma and large (1 cm or more) adenomas were 70 and 44 per cent respectively. In a subset of 417 subjects who also completed Haemoccult tests, the sensitivities were 33 and 18 per cent. Hemeselect specificity is 88 per cent compared with 98 per cent for Haemoccult. While the sensitivity of Hemeselect is higher than that of Haemoccult, it is still insufficient to replace colonoscopy in high-risk groups.

Colonoscopy↗
PubMed1995

Fecal alpha 1-antitrypsin detection of colorectal neoplasia. An evaluation using HemoQuant.

Fecal alpha 1-antitrypsin measurement may be of value for the detection of colorectal neoplasia and is compared with the HemoQuant test in 119 subjects with either a screen-positive Hemoccult result (N = 78) or iron-deficiency anaemia (N = 41). Nineteen patients were found to have colorectal cancer, 35 had colorectal adenomatous polyps, 5 had inflammatory bowel disease, and 60 had no detected cause of occult blood loss. Of the cancer patients, 63% (12/19) were detected by fecal alpha 1-antitrypsin and 63% (12/19) by HemoQuant. Of the adenomas > 1 cm in diameter 33% (7/23) were detected by fecal alpha 1-antitrypsin and 26% (6/23) by HemoQuant. There was a poor correlation between fecal alpha 1-antitrypsin and HemoQuant results for colorectal cancers (r = 0.37, P > 0.05), and combining the tests, the sensitivity for colorectal cancer was increased to 84% (16/19). Fecal protein loss, as measured using alpha 1-antitrypsin, appears to involve largely different mechanisms from that of blood loss from colorectal cancers.

Adenomatous Polyps↗
PubMed1995

Is an immunological faecal occult blood test better than Haemoccult? A cost-benefit study.

Immunological faecal occult blood (FOB) tests have theoretical advantages over their guaiac counterparts in that they are specific for human haemoglobin. HemeSelect is a semi-quantitative immunological FOB text. Faecal material is eluted into test diluent and serial dilutions are performed. The manufacturers recommend that erythrocyte agglutination at 1:8 dilution is considered a positive reaction. However, further serial dilutions can be carried out and the highest dilution at which the test remains positive determined. At 1:8 dilution, the test has been shown to be more sensitive for symptomatic colorectal cancer than Haemoccult. The aim of this study is to compare the positive rates, neoplastic yield and costs of Haemoccult with HemeSelect at various dilutions in asymptomatic average risk subjects aged 50-74. 1489 subjects satisfactorily completed both tests, 145 (9.7%) returned positive Hemeselect tests (read at 1:8 dilution, 38 patients with neoplasms > or = 1 cm) and 17 positive Haemoccult tests (1.1%). All positive Hemeselect tests were further serially diluted. As the Hemeselect dilution increased to 1:16, 1:32, 1:64 and 1:128 so the positive rate and yields of neoplasms > or = 1 cm progressively fell to 6.8% & 35, 3.6% & 20, 2.7% & 18 and 1.5% & 12, compared with 1.1% and eight neoplasms > or = 1 cm for Haemoccult. In spite of the unit cost of the Hemeselect test being greater than Haemoccult, the cost per neoplasm > or = 1 cm was lower for Hemeselect at 1:8 and 1:16 dilutions than Haemoccult. However, for an equivalent neoplastic yield, Haemoccult was cheaper. Hemeselect is a versatile test whose positive rate can be tailored according to the risk of the group being screened.

Aged↗
PubMed1995

Serum thymidine kinase in colorectal neoplasia.

Thymidine kinase (TK), an enzyme known to be associated with DNA synthesis, has been measured in the serum of patients with asymptomatic colorectal adenomas (n = 40), asymptomatic colorectal carcinoma (n = 21) and patients known to have hepatic metastases form colorectal tumours (n = 33); enzyme levels have been compared with an age-matched group of asymptomatic people with no evidence of colorectal neoplasia at screening colonoscopy (n = 26). TK activity in patients with metastatic disease (median 4.23; range 2.03-14.12 pmol/ml/h) and in patients with adenomas (median 2.33; range 1.59-8.73 pmol/ml/h) was significantly higher than in the normal controls (median 2.04; range 1.29-5.40 pmol/ml/h). However TK activity in patients with asymptomatic cancer (median 1.85; range 1.00-4.50 pmol/ml/h) was not significantly different from the control group.

Adenoma↗
PubMed1995

The effect of calcium supplements on rectal mucosal proliferation.

Seventy-nine patients with colorectal adenomata were randomised to receive calcium carbonate (3,000 mg) or placebo in a double-blind randomised trial to assess the short- and long-term effects on rectal mucosal proliferation measured by the in vitro metaphase arrest technique crypt cell production rate (CCPR). There was no significant difference in mean CCPR between the groups before treatment or after 3 or 12 months. In those patients randomised to calcium, CCPR fell at both 3 months [9.0 (2.8) cc c-1 h-1, t = 3.15, d.f = 76, P = 0.002] and 12 months [9.2 (3.3) cc c-1 h-1 t = 2.7, d.f. = 74, P = 0.009] compared with pretreatment CCPR [12.2 (5.5) cc c-1 h-1]. We have demonstrated that calcium had no effect on mucosal proliferation compared with placebo. The results on adenoma formation are awaited.

Adenoma↗
PubMed1995

Alkaline gastro-oesophageal reflux: dual probe pH monitoring.

Although the aetiology of Barrett's oesophagus or columnar line oesophagus (CLO), remains unknown, bile reflux has been implicated as a factor in its pathogenesis. This study aimed to detect alkaline reflux in gastro-oesophageal reflux patients using dual probe pH monitoring. Thirty patients with histologically diagnosed CLO, 15 age and sex matched patients with oesophagitis (grade 1-3), and 15 healthy volunteers were studied by dual probe, 18 hour pH monitoring and analysis of the bile acid content of oesophageal refluxate. Total acid exposure and acid exposure in the upright and supine postures were greater in CLO subjects than in oesophagitis patients and controls. Furthermore, the number of reflux episodes lasting more than five minutes and the duration of the longest reflux episode were significantly greater in the CLO subjects than the oesophagitis and control subjects. Nine subjects with CLO and oesophagitis, however, were not identified as refluxers, although six had a bile acid concentration in their oesophageal aspirate higher than the 95th centile value of the controls. There was no correlation between the oesophageal pH and the bile acid contents of refluxate. It is concluded that dual probe pH monitoring is not useful in detecting alkaline refluxers. pH monitoring, although the only subjective test available to identify acid refluxers, is not a sufficiently sensitive test with which to define alkaline reflux.

Barrett Esophagus↗
PubMed1995

Effect of retesting with dietary restriction in Haemoccult screening for colorectal cancer.

OBJECTIVES: To determine the detection rate, false positive and false negative rates associated with a policy of retesting with dietary restriction after an initial positive Haemoccult screening test for colorectal cancer, in order to compare the cost effectiveness of such a policy with the alternative, in which all subjects with a positive test would proceed directly to diagnostic colonoscopy. METHODS: Over four years in a large randomised control trial in Nottingham 35,260 subjects had a mean of 1.5 screening rounds each at two-yearly intervals, and were followed up for a minimum of 27 months. During this period subjects with positive screening tests were asked to repeat the test with dietary restrictions. Estimates of costs of the initial screening and of diagnostic colonoscopy were used to estimate the cost for each cancer detected by the different policies. RESULTS: 1209 subjects had a positive initial screening test and 1033 (85.4%) completed the retests. Four hundred and ninety nine subjects were investigated and 89 cancers detected. In the 710 subjects with negative retests six interval cancers were diagnosed in the two years after screening. If these had been detected by screening under a policy of immediate colonoscopy, test sensitivity would have been improved from 53.6% to 57.2% (P = 0.02), but the cost for each cancer detected would have increased from pound 773 to pound 1509. CONCLUSION: Retesting with dietary restrictions reduces costs and maximises the benefit of limited colonoscopy resources, but results in a small but significant reduction in test sensitivity compared with a policy for immediate colonoscopy.

Colonoscopy↗
PubMed1994

Enhanced cell-mediated tumor killing in patients immunized with human monoclonal antiidiotypic antibody 105AD7.

A human antiidiotypic monoclonal antibody (105AD7) has been shown to induce antitumor cellular responses in animals and appears to prolong survival in patients with metastatic colorectal cancer without associated toxicity. Proliferative leukocyte responses to the targeted tumor antigen gp72 were observed in these patients and plasma interleukin 2 levels were increased following immunization. Autologous tumor tissue was not available in these patients, so antitumor cytotoxicity could not be measured. This issue has now been addressed in an adjuvant clinical study in primary rectal cancer patients. Six patients with rectal cancer were immunized preoperatively with 105AD7. Peripheral blood lymphocytes taken prior to immunization were tested against tumor cells extracted from biopsies also obtained prior to immunization or from natural killer (NK)-sensitive target cells. Cryopreserved lymphocytes taken before and after tumor immunization, fresh peripheral blood lymphocytes taken immediately prior to surgery, and lymphocytes from tumor-draining lymph nodes were tested against autologous cells from the resected specimen or NK-sensitive target cells. Significant killing of autologous tumor cells, which was not due to NK activity, was seen with cryopreserved lymphocytes or lymph node cells of three patients at 1-2 weeks postimmunization with 105AD7 but not on pretreatment biopsies. Enhanced NK activity was seen 2-3 weeks postimmunization in 3 of 6 patients. These results indicate that 105AD7 human monoclonal antibody immunization enhances cytotoxicity in rectal cancer patients by specific and nonspecific effector mechanisms.

Aged↗
PubMed1994

Clinical outcome of colorectal cancer patients treated with human monoclonal anti-idiotypic antibody.

A human monoclonal anti-idiotypic antibody (105AD7) has been developed which mimics a colorectal-tumour-associated antigen and induces cellular anti-colorectal tumour immune responses in animals. Thirteen patients with advanced colorectal cancer were immunized with 105AD7 and their survival was compared with that of a contemporary group of unimmunized patients with similar disease status. No toxicity related to anti-idiotype immunization was seen. Cellular responses to anti-idiotypic immunization were indicated by lymphocyte proliferation to gp72-positive tumour cells, and production of interleukin-2; anti-tumour antibodies were not detected. Median survival following diagnosis of advanced disease of immunized patients was 12 months, compared with 4 months in unimmunized patients. The improved survival of immunized patients in this study without associated toxicity suggests that 105AD7 immunization may have considerable potential for immunotherapy of colorectal cancer.

Aged↗
PubMed1994

Population screening for colorectal cancer: comparison between guaiac and immunological faecal occult blood tests.

There is concern about the low sensitivity of the guaiac-based Haemoccult test in mass population faecal occult blood (FOB) screening for the early detection of colorectal carcinoma. Hemeselect, an immunological FOB test, has been shown to be more sensitive for symptomatic colorectal cancer and may prove to be a more reliable screening method. In Brighton and Guildford, 4018 asymptomatic subjects aged 50-75 years were offered screening with Haemoccult and Hemeselect. A total of 1489 (37.7 per cent) completed both tests, of which 17 (1.1 per cent) were positive for Haemoccult and 145 (9.7 per cent) positive for Hemeselect (a total of 148 subjects had positive tests). Seven subjects (4.7 per cent) refused to be investigated. Colonic investigation in the remainder revealed nine cancers and 49 patients with 67 adenomas (32 tumours 1 cm or more in size). All cancers (Dukes A, six; B, one; C, two) were detected by Hemeselect (positive predictive value 6.2 per cent) but only one patient was Haemoccult positive (positive predictive value 5.9 per cent). Hemeselect detected 65 adenomas (31 of 1 cm or more) in 48 patients (positive predictive value 33.1 per cent) compared with 11 adenomas (seven of 1 cm or more) in eight patients who were positive for Haemoccult (positive predictive value 47.1 per cent). The test specificity for neoplasia was respectively 94.9 and 99.6 per cent. The Hemeselect positive rate is high but its substantial positive predictive value for cancer warrants continuing evaluation.

Aged↗
PubMed1994

Taurolidine peritoneal lavage as prophylaxis against infection after elective colorectal surgery.

A total of 300 patients undergoing elective colorectal surgery over a 3-year period were randomly assigned to receive intraoperative peritoneal lavage with either taurolidine or saline. Culture swabs were taken from the region of surgery before and after lavage and the development of postoperative infection monitored. Of the positive culture swabs before lavage, a significantly higher proportion were negative after lavage with taurolidine than after that with saline. However, there was no difference in the incidence of postoperative infection between groups, suggesting that taurolidine intraoperative peritoneal lavage confers no clinical benefit over that with saline.

Anti-Infective Agents, Local↗
PubMed1994

Wheat fibre, lactulose and rectal mucosal proliferation in individuals with a family history of colorectal cancer.

In a single-blind study 38 individuals at increased risk of developing colorectal cancer because of a family history of the disease were randomized to take 10.5 g wheat fibre (Trifyba) or 60 ml lactulose daily for 12 weeks. Rectal biopsies were taken before and after treatment and rectal mucosal proliferation was measured by the crypt cell production rate (CCPR). The mean(s.d.) CCPR was significantly lower in those taking wheat fibre after 12 weeks (7.2(3.4) crypt cells per crypt per h) compared both with values obtained before treatment with wheat fibre (10.2(5.1) crypt cells per crypt per h; P = 0.02) and after treatment with lactulose (9.4(3.8) crypt cells per crypt per h; P = 0.05). Proliferation in the lactulose group was not significantly different at 12 weeks compared with the value obtained before treatment. This study confirms an antiproliferative effect of wheat fibre in a group of high-risk individuals.

Adult↗
PubMed1994

Colorectal cancer screening and quality of life.

To evaluate the quality of life of patients following surgery for colorectal cancer, and to compare the quality of life between patients whose cancer was detected as a result of faecal occult blood screening with that of patients whose cancer presented symptomatically, an analysis was conducted within the context of the randomized controlled trial of colorectal cancer screening, University Hospital, Nottingham, UK. A total of 418 survivors of the trial's test and control groups and 33 randomly selected cancer patients completed quality of life questionnaires (Nottingham Health Profile and Health Measurement Questionnaire). The mode of entry to diagnosis and treatment (screening vs. non-screening) appeared to exert no major impact on post-intervention quality of life. The stage of cancer progression was not closely related to outcome life quality. A quality of life coefficient for surviving patients based on the Rosser classification was estimated to lie within the range 0.948-0.981. This figure accords well with the estimates of other studies of interventions in populations of similar age. Overall, there are no grounds for believing that faecal occult blood screening for colorectal cancer per se significantly influences patients' post-intervention quality of life.

Aged↗
PubMed1994

Blood transfusion and survival in colorectal cancer.

PURPOSE: This study examined the effect of blood transfusion on the prognosis of patients undergoing surgery for colorectal cancer. METHODS: Potentially curative resections for colorectal cancer were performed in 266 patients who were followed prospectively, with a minimum follow-up of 41 months. They were divided into transfused (n = 121) and nontransfused (n = 145) groups according to their perioperative blood transfusion requirements. RESULTS: There were significantly more rectal tumors (chi 2 = 9.5, df = 1, P = 0.002) and fixed tumors (chi 2 = 4.5, df = 1, P = 0.03) in the transfused group. There was no statistically significant difference between the two groups with regard to recurrence-free survival (chi 2 = 1.1, df = 1, P = 0.3) and overall survival (chi 2 = 2.8, df = 1, P = 0.09). CONCLUSION: In this study we have found no statistically significant effect of perioperative blood transfusion on the prognosis of colorectal cancer patients.

Adult↗