A new technique for renal allograft biopsy.
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Biopsy, Needle↗
Biomedical subjects
G R Giles
Publications and source records attributed to G R Giles.
The relationship between plasma pharmacokinetics and tissue metabolites of 5-fluorouracil (5-FU) in patients with colorectal cancer.
To assess the relationship between the plasma pharmacokinetics of 5-Fluorouracil (5-FU) and the levels of intracellular 5-FU metabolites, we have studied eight patients presenting with primary carcinomas of the colon and rectum. Serum 5-FU levels and fluorinated metabolites within normal and malignant tissue were estimated using chromatographic methods. An analysis of the total fluorinated products against plasma halflife, plasma clearance and maximum plasma concentration failed to demonstrate any significant correlation. Furthermore the differing levels of 5-FU metabolites in normal and malignant tissue could not be correlated with the pharmacokinetic parameters studied. It is concluded that the cellular levels of active 5-FU metabolites reflect local cellular activity rather than the handling of the drug in vivo.
Aged↗
Monitoring of renal allografts by Doppler ultrasound.
Cyclosporin (CyA) associated renal dysfunction may be due to an arteriolopathy which reduces graft perfusion. We have prospectively monitored 27 renal allograft recipients, within 30 days of transplantation, by continuous wave Doppler ultrasound. Changes in the frequency shift waveform should indicate alterations in renal blood flow. Objective analysis was made in 112 waveforms by determining the ratio of the area under the frequency shift/time curve of the first half and the second half of the cardiac cycle (AUC 1/2 ratio). The AUC of the first half of the cycle indicates systolic blood flow plus the first part of diastolic flow, whereas the AUC of the second half indicates the remainder of diastolic flow. The AUC 1/2 ratio during ATN was not significantly different from that during stable renal function. However the ratio was significantly higher during acute rejection episodes and CyA nephrotoxicity. Although a statistical difference was demonstrated between acute rejection and CyA nephrotoxicity, the AUC 1/2 ratio alone does not differentiate these 2 conditions. These preliminary findings suggest CyA nephrotoxicity does reduce renal allograft blood flow and that this non-invasive technique may have a useful role to play in monitoring of patients immunosuppressed with CyA.
Cyclosporins↗
A comparison of methods of removing inhibitors to the chromogenic Limulus assay in normal and jaundiced blood.
A comparative study was performed of methods of removing inhibitors to the quantitative chromogenic method of Limulus assay for endotoxin in normal and jaundiced plasma. Chloroform treatment failed to remove inhibitors in normal and jaundiced plasma and did not prevent inhibition of colorimetry by bilirubin. Perchloracetic acid (PCA) treatment decolourised jaundiced samples but gave unreliable results due to poor pH control. Boiling and dilution gave reliable results in jaundiced and normal plasma without significant loss of sensitivity and is the method of choice.
Chloroform↗
Monoclonal immunoscintigraphy for the detection of primary colorectal cancers: a prospective study.
A prospective study to investigate the value of monoclonal antibody (McAb) immunoscintigraphy for the detection of primary tumours of the colon and rectum has been undertaken. Twelve patients received 1 mg 131I-labelled McAb YPC 2/12.1, an antibody raised to a human colonic carcinoma membrane preparation. Imaging of the blood pool was achieved using 99mTc-labelled red cells. After surgery specimens were scanned and samples of normal and malignant tissue excised to obtain antibody binding ratios. In only one patient was the primary tumour visualized pre-operatively. Images of the resected specimens revealed the primary tumour in ten cases but this appeared to be a function of increased blood pool within the tumour rather than specific antibody localization. The mean tumour/normal tissue count ratio was 1.27:1 (range 0.63:1-1.93:1). It is concluded that the McAb YPC 2/12.1 is unlikely to be of use clinically. Furthermore when selecting McAbs for the purposes of immunoscintigraphy the results of in vitro binding to malignant cell lines, immunohistological studies and xenograft experiments may be misleading and careful clinical evaluation is necessary.
Antibodies, Monoclonal↗
Distal splenorenal (Warren) shunt in the management of actively bleeding oesophageal varices.
Distal splenorenal shunts have been performed on 53 patients during or soon after variceal haemorrhage. In 38 patients active haemorrhage was occurring at the time of operation or was controlled by tamponade and 12 of these patients died. There was no mortality in the semi-elective group. A higher mortality was found in patients with poor liver reserve and in whom prolonged conservative management had been attempted. Rebleeding occurred in 20 per cent of patients in the early postoperative period and this was a significant factor in the death of three patients. Of 39 patients with longer term follow-up, 8 suffered minor encephalopathy. Subsequent mortality could be related to the progression of liver disease and was no worse than that seen in a population of cirrhotic patients.
Adolescent↗
Natural killer-cell activity, interferon-alpha 2 production, and interleukin-2 production in cyclosporine-treated and conventionally immunosuppressed human allograft recipients.
Natural killer (NK) activity, interferon (IFN)-alpha production, and interleukin-2 (IL-2) production were measured in renal transplant recipients undergoing immunosuppression with either azathioprine and steroids (Az + P) or cyclosporine (CyA). Overall, both IFN-alpha production and IL-2 production were impaired in these two groups compared with identical studies in healthy individuals. However, on the basis of control data these two patient groups were divided into those with "normal" NK activity and those with "low" NK activity. In the CyA group those with a low NK reaction produced less IL-2 and IFN-alpha than those with normal NK activity. No such relationship between cytokine production and NK activity was discerned in the Az + P group. These data conflict with in vitro studies, which have failed to demonstrate any effect of CyA on IFN-alpha production. In addition, they suggest that whereas cyclosporine influences NK activity in vivo by inhibiting cytokine production, other factors may play a role in impairing NK activity in conventionally immunosuppressed patients.
Adolescent↗
Is DNA aneuploidy a good prognostic indicator in patients with advanced colorectal cancer?
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Aneuploidy↗
DNA aneuploidy in colorectal adenomas.
The frequency of DNA aneuploidy was investigated by flow cytometry in 156 colorectal adenomas including 56 associated with 36 synchronous adenocarcinomas. Nine of 156 adenomas (6%) were DNA aneuploid. DNA aneuploidy correlated with increasing size (P less than 0.005) and histopathological type P less than 0.05) but not with dysplasia. Adenomas in associated with a synchronous adenocarcinoma did not have an increased incidence of DNA aneuploidy. Adenocarcinomas found in association with adenomas tend to have a lower incidence of DNA aneuploidy then the generality of colorectal cancers.
Adenocarcinoma↗
The role of a questionnaire and four biochemical markers to detect cancer risk in a symptomatic population.
The roles of a self-completed symptom questionnaire and four biochemical markers of disease were assessed to determine risk for gastric and colorectal cancer from within a hospital population and a random population. Eight-six patients with cancer, 168 subjects with benign conditions of the stomach and large bowel and 720 individuals from the community at large were investigated. Multivariate analyses of the questionnaire and biochemical data were performed individually and in combination using a data set comprising 54 cancer subjects, 80 patients with benign disease and 200 random individuals. The most favourable predictive equation derived was then applied to the remaining data set to determine its efficacy. In the primary analyses the questionnaire data identified 32 (60%) cancers successfully and using the biochemical markers alone 36 (67%) patients were also correctly classified as cancer bearing. However, the combination of the questionnaire and marker data improved the sensitivity for cancer to 50 cancers detected (92%) (P less than 0.02). Using the predictive equation from this combination of data to identify risk in the second data set 28/32 (88%) cancers were correctly identified with only an 11% false positive rate. An 18 month follow-up for the non-cancer group has to date revealed only one cancer (ca. pancreas). In this limited study, multivariate analysis of questionnaire and biochemical marker data does successfully identify individuals at "high risk' of harbouring gastric or colorectal cancer within a symptomatic population and may have a role in determining priority for investigation for a symptomatic individual.
Aged↗
DNA aneuploidy in ulcerative colitis.
The prevalence of deoxyribonucleic acid (DNA) aneuploidy in 297 samples from 38 patients with ulcerative colitis of varying duration was investigated by flow cytometry. In 12 patients colitis was complicated by the development of colorectal carcinoma: one had three synchronous carcinomas. Only four of 14 carcinomas were DNA aneuploid. Deoxyribonucleic acid aneuploidy occurred focally in the colorectal mucosa in the presence and absence of carcinoma: rates of aneuploidy (67% in cancer patients and 42% in non-cancer patients), were not significantly different (chi 2 = 1.0962, p = 0.295). A higher rate of DNA aneuploidy was found in dysplastic tissues (21%) compared with non-dysplastic tissues (15%), but again these differences did not reach statistical significance (chi 2 = 1.0747, p = 0.299). Deoxyribonucleic acid aneuploidy and dysplastic change occurred more often with increasing duration of ulcerative colitis (p less than 0.001, p less than 0.005 respectively). We conclude that flow cytometric analysis of cellular DNA content should not replace present morphological methods of assessment of premalignancy in ulcerative colitis, but may be a useful adjunct in the identification of abnormal mucosa.
Adult↗
Incorporation of intermediary products of 5-FU anabolism into colorectal cancer.
In 18 patients intermediary anabolic metabolites of 5-FU were measured in normal colonic mucosa and colorectal cancer tissue of intravenous bolus injection or continuous infusion. Higher total concentrations of 5-FU products were found in the cancers when compared with normal colonic tissue. There appeared to be no evidence, however, that some patients had a selectively increased ability to incorporate 5-FU into their tumours. Overall higher concentrations of tumour incorporation of 5-FU were found after bolus injection rather than the infusion method, although this difference is statistically not significant.
Aged↗
Lithium fluxes across the gastric mucosa after truncal vagotomy and drainage--an objective assessment of mucosal injury.
Gastric mucosal permeability to lithium has been measured in 20 patients with an untreated duodenal ulcer, eight patients who were asymptomatic for more than one year after truncal vagotomy and drainage, 14 patients with an endoscopically proven recurrent ulcer, and 21 patients with an unsatisfactory result from truncal vagotomy and drainage for other reasons. Lithium fluxes were lowest in the asymptomatic postoperative patients (0.149 +/- 0.028 mmol Li+/15 min), but were not significantly different to the measured fluxes in patients with a duodenal ulcer before treatment (0.160 +/- 0.020 mmol Li+/15 min) or a recurrent ulcer after truncal vagotomy and drainage (0.169 +/- 0.022 mmol Li+/15 min) (SEM). By comparison the mean lithium flux in patients who were dissatisfied with the results of their previous surgery for reasons other than a recurrent ulcer (0.234 +/- 0.019 mmol Li+/15 min) was significantly higher than that observed in patients with a duodenal ulcer (p less than 0.05), patients with a recurrent ulcer (p less than 0.05) or patients who were asymptomatic after definitive ulcer surgery (p less than 0.02). Furthermore, when the lithium fluxes observed in 11 patients whose major postoperative complaint was bile vomiting (0.243 +/- 0.027 mmol Li+/15 min) were compared with results from the remaining 52 patients included in the study (0.173 +/- 0.012 mmol Li+/15 min) fluxes were significantly higher in the 'bile vomiters' (p less than 0.05).
Adult↗
Validation of a self administered questionnaire to elicit gastrointestinal symptoms.
Self administered questionnaires are becoming popular investigative tools in medical research, yet few reports state the extent of methods used to validate these questionnaires before their general use. A pilot study was therefore carried out to validate a 41 item questionnaire for use in a population screening study for gastrointestinal disease. Participants in the study comprised 69 population controls, 40 patients with benign disease, and 35 patients with gastrointestinal cancer. Acceptability, ease of completion, reliability, and reproducibility of the questionnaire were all assessed. Only one subject refused to complete the questionnaire. Ninety six per cent of the questions were completed by each subject and only one response in 1440 was altered in the reproducibility study. The questionnaire disclosed symptoms similar to those elicited by a clinician and highlighted unreported gastrointestinal symptoms in the control group. Three questions were found to be unreliable and were altered before the questionnaire was put into general use. It is concluded that a pilot study to validate a new questionnaire is simple to perform and necessary to identify unreliable questions.
Gastrointestinal Neoplasms↗
Deranged liver blood flow patterns in the detection of liver metastases.
Hepatic flow scintigraphy has been used to evaluate 150 patients with gastrointestinal carcinoma. A normal range has been obtained on a group of 23 healthy volunteers. The flow scintigraphic findings have been correlated with the presence of metastases at the time of primary surgical therapy. The group of patients with livers ostensibly clear of metastases have been followed up over a one-year period. At one year the specificity of the investigation is 72 per cent with a sensitivity of 96 per cent. We conclude that flow scintigraphy is capable of not only detecting established hepatic metastases, but will also identify patients harbouring occult metastatic disease.
Gastrointestinal Neoplasms↗
Factors affecting survival in patients presenting with synchronous hepatic metastases from colorectal cancer: a clinical and computer analysis.
A review of 90 patients presenting in Leeds over the period 1976-80 with synchronous hepatic metastases from colorectal cancer has been undertaken. The median survival for the group was 10.3 months (range 1-48 months). A multivariate analysis identified factors in the history and examination of the patient, results of biochemical and haematological investigations and characteristics of both the primary and secondary tumour, which influenced survival. Recognition of these factors allowed both a clinical scoring index and computer survival model to be constructed. When applied to the group as a whole both were reasonably accurate at predicting survival (62 per cent for the survival model and 66 per cent for the scoring index). However, the computer model correctly identified 80 per cent of the 'long-term' survivors (greater than 12 months from the time of diagnosis). It is concluded that many trials of therapy for hepatic metastases from colorectal cancer have failed to consider the natural history of the disease and the identification of prognostic indices should allow for adequate stratification within the treatment arms of any future study.
Adult↗
Free radical detoxifying systems in human colorectal cancer.
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Adenocarcinoma↗
Phase II trial of epirubicin in gastric cancer.
Patients with advanced inoperable or recurrent adenocarcinoma of the stomach received an iv bolus of epirubicin (75 mg/m2) every 3 weeks. Partial responses were observed in four of 24 evaluable patients (17%). Treatment was generally well tolerated; a drop in left ventricular ejection fraction was observed in one patient who had received 450 mg/m2 of epirubicin.
Adenocarcinoma↗