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Biomedical subjects

G R Giles

Publications and source records attributed to G R Giles.

At least 73 records · Page 4Linked to original sources

CAPD--a risk factor in renal transplantation?

Theoretical considerations suggest that patients undergoing continuous ambulatory peritoneal dialysis (CAPD) may fare less well after renal transplantation than their haemodialysed (HD) counterparts. Review of 121 consecutive cadaveric renal allografts performed in this centre indicate this to be the case with graft survival rates at 1 year of 63.5 per cent in the HD group compared with 35.5 per cent in the CAPD-treated patients. This difference appeared to be independent of the duration of dialysis and, although a significant blood transfusion effect was seen in the HD group, no such trend was evident in the CAPD group. Studies of T cell subsets (using monoclonal antibodies) in the two groups suggests that, in part at least, the differences in graft survival rates may be attributable to the maintenance or restoration of immunological integrity in the CAPD group.

Adult↗

Evaluation of an enzyme-linked immunosorbent Raji cell assay (ELISA) in the investigation of gastrointestinal cancer.

The levels of circulating immune complexes (CICs) have been estimated in a group of patients with colorectal cancer and gastric cancer, in addition to which a normal range has been established in a group of patients with benign gastrointestinal disease. A newly developed enzyme-linked immunosorbent Raji cell assay has been used in this study. Overall only 30% of patients with gastrointestinal cancer showed elevation of CIC levels outside the normal range. Elevated levels correlated with tumour differentiation bud did not correlate with site of disease or with the presence of metastases. In an attempt to define the specificity of CIC estimation, soluble tumour extract was added to sera from tumour-bearing patients. Specific IC elevations were produced by addition of allogeneic tumour extract of colon cancer in patients with colorectal cancer; this phenomenon was not seen when the same extract was added to the sera of patients with gastric cancer.

Antigen-Antibody Complex↗

The response to interferon of NK and K cells from conventionally immunosuppressed and cyclosporine-treated renal allograft recipients.

Interferon is a potent stimulator of natural killer (NK) and killer (K) cell activity in human beings, both these cytotoxic functions representing host defense mechanisms against viral infections and lymphoid malignancy. Both NK and K cell functions are markedly impaired in conventionally immunosuppressed allograft recipients but coincubation of lymphocytes from these patients with purified human lymphoblastoid interferon considerably augments both these activities. Cyclosporine immunosuppression causes only a moderate, but significant, impairment of NK activity--but K cell activity appears to be normal. Again IFN increases NK activity of the lymphocytes of these patients but produces a fall or only moderate increases in K cell activity. We conclude that these data support the functional distinction between NK and K cells and suggest that immunosuppressive agents act at the pre-NK/K cell stage of maturation, though possibly via different mechanisms.

Adolescent↗

Multivariate analyses as aids to diagnosis and assessment of prognosis in gastrointestinal cancer.

The role of carcinoembryonic antigen (CEA), gamma glutamyl transpeptidase (gamma GT), phosphohexose isomerase (PHI), pseudouridine (psi) and acute phase reactant proteins (C-reactive protein (CRP) alpha 1-antichymotrypsin (ACT) and alpha 1-acid glycoprotein (AGP] in assessing the prognosis of gastrointestinal neoplasms and the discriminant function in distinguishing benign from malignant diseases of the GI tract was examined. In stomach cancer pre-operative levels of CRP can help in the identification of the patients with a resectable tumour; the pre-operative biochemical measurements do not give any further information on prognosis once stage and site are taken into account. In colorectal cancer pre-operative ACT levels give additional prognostic information once the clinical factors, Dukes stage, sex and age have been accounted for; PHI levels are on the border line of significance. A discriminant function has been devised using sex, CEA, psi, gamma GT, ACT and PHI that can identify 89% of Dukes "D" patients prior to surgery with a misclassification of 7% of other cases of colorectal cancer. A discriminant function using all the biochemical variates separated the cancer from non-cancer patients. The false positive rate for cancer was 16% and a false negative rate of 19%, when the cut-off level was set at 0.7.

Adult↗

Vitamin A and its transport proteins in patients with chronic renal failure receiving maintenance haemodialysis and after renal transplantation.

Serum vitamin A, retinol binding protein, prealbumin and transferrin have been studied in chronic renal failure patients receiving maintenance haemodialysis and after renal transplantation. Vitamin A and retinol binding protein were uniformly raised in haemodialysis patients and this was unrelated to the period on dialysis. There was a molar excess of retinol binding protein to both vitamin A and prealbumin as compared with normal individuals. Renal transplantation significantly reduces serum vitamin A and retinol binding protein concentrations but has no effect on prealbumin concentrations. The reduction in vitamin A and retinol binding protein is variable in individual patients and cannot be predicted either by the allograft function or time since transplantation. Several years after transplantation, with normal serum creatinine, both serum vitamin A and retinol binding protein levels may still be greatly increased. Despite the very high vitamin A and retinol binding protein concentrations, the close correlation between the two seen in normal individuals is well maintained. The continuing high vitamin A and retinol binding protein levels in patients with satisfactorily functioning transplants is unexplained.

Creatinine↗

Sequential changes in NK and ADCC effector cell function after organ transplantation in man.

Antibody-dependent cellular (K cell) cytotoxicity (ADCC) and cellular cytotoxicity against natural killer (NK) targets exerted by the same cells were both measured sequentially in ten patients after renal transplantation using conventional immunosuppression. Cytotoxicity against NK targets appeared to correlate more closely with rejection episodes than did assays of ADCC activity during the same period. An apparent rise in NK activity was frequently accompanied by a fall in ADCC activity. Collectively these data suggest that the previously reported increase in NK activity during rejection episodes may represent a manifestation of the appearance of non-clonally activated T-cells in peripheral blood during rejection.

Antibody-Dependent Cell Cytotoxicity↗

HLA antigens in relationship to duodenal ulceration, gastric acid secretion and the clinical result following vagotomy.

The distribution of 20 HLA antigens was measured in 100 patients with a duodenal ulcer. An increase (P less than 0.05) in the incidence of the HLA-BW35 antigen was identified which conferred an increased risk factor of developing a duodenal ulcer of 2.7. The preoperative acid output in patients who had the BW35 antigen was significantly lower than that found in all other patients prior to surgery. The clinical outcome from definitive surgical treatment did not appear to be influenced by the HLA status of the patients.

Adult↗

Urinary pseudouridine/creatinine ratio as an indicator of gastrointestinal cancer.

Urinary pseudouridine/creatinine ratio was determined in 74 patients with gastrointestinal tumours and 34 patients with no known malignant disease. The reproducibility of a single random urine sample was demonstrated. The mean ratio for control patients was 26.9 +/- 7.7 nmol/mumol and no control patient exceeded the mean by 2 standard deviations. There was no difference in the ratio between the sexes. Sixty-five per cent of colon cancer patients and 37.5 per cent of gastric and rectal cancer patients exceeded this upper limit of normality. There was no correlation between pseudouridine/creatinine ratio and histological differentiation, liver involvement or stage in either colorectal or gastric cancer patients. Urinary pseudouridine/creatinine ratio is one of the better non-specific cancer markers and may be particularly useful for detecting colonic cancer.

Colonic Neoplasms↗

Changes in human natural killer activity early and late ater renal transplantation using conventional immunosuppression.

The natural killer (NK) cell activity of human peripheral blood lymphocytes falls following major surgical procedures including renal transplantation but in non-immunosuppressed individuals returns to normal levels within the first 72 hr after operation. In renal allograft recipients, if this early postoperative fall is excluded from the analysis, NK cell function appears to follow changes in allograft function, suggesting that in vivo, as has been reported in vitro, NK activity is generated during activation of the alloreactive process. In an additional group of patients whose grafts were functioning for between 3 and 102 months after cadaveric renal transplantation using conventional immunosuppression, NK function was depressed in comparison with that of control subjects. However, some patients who were more than 48 months post-transplant had normal NK cell activity. Collectively, these results suggest that NK cell function may recover despite the continued administration of conventional immunosuppressive agents.

Adolescent↗

Pyrimidine nucleoside phosphorylase activity in tumour and matched normal gastrointestinal mucosa.

5-Fluorouracil (5-FU) requires activation to the metabolites FdUMP and FUTP for its cytotoxic effect. This activation involves the intracellular enzymes uridine and thymidine phosphorylase. We have assayed the levels of these enzymes in colorectal and gastric cancers and have shown that, in the majority of cases, the enzyme levels were higher than in the adjacent normal mucosa. It is suggested that, while the ratio tumour/normal mucosa enzyme activity may give some indication of the relative toxicity of 5-FU in these tissues, the absolute activities of the phosphorylases in tumour tissue could give a better indication of tumour responsiveness.

Adult↗

Does osmotic control of gastric emptying persist after truncal vagotomy?

Gastric emptying of 5 per cent and 10 per cent glucose test meals has been measured in 43 patients with a duodenal ulcer prior to surgery and in 52 patients with an unsatisfactory result following truncal vagotomy and a drainage procedure. Seventeen patients had a recurrent ulcer and incomplete vagotomy while 35 patients were symptomatic with complete vagotomy. In both the preoperative and postoperative patients the 10 per cent glucose test meal emptied significantly more slowly than the 5 per cent glucose test meal regardless of the completeness of vagotomy. Thus, osmotic control of gastric emptying persists after vagotomy.

Adult↗

Bile reflux and gastric emptying in patients with combined gastric and duodenal ulceration.

Measurements of duodenogastric reflux of bile and gastric emptying of a 5 per cent glucose liquid test meal have been made in 8 patients with combined gastric and duodenal ulcers and the results compared with those found in 21 patients with a diagnosis of uncomplicated duodenal ulceration. It was not possible to demonstrate any differences between the two groups of patients in respect of these studies and it is suggested that gastric stasis and duodenogastric reflux may not be important factors in the aetiology of combined ulcer disease.

Adolescent↗