ObjectiveTo examine the effects of cholestatic jaundice on gut barrier function. Summary Background DataGut barrier failure occurs in animal models of jaundice. In humans, the presence of endotoxemia indirectly implicates failure of this host defense, but this has not previously been investigated in jaundiced patients. MethodsTwenty-seven patients with extrahepatic obstructive jaundice and 27 nonicteric subjects were studied. Intestinal permeability was measured using the lactulose-mannitol test. Small intestinal morphology and the presence of mucosal immunologic activation were examined in endoscopic biopsies of the second part of the duodenum. Systemic antiendotoxin core IgG antibodies and serum interleukin-6 and C-reactive protein were also quantified. Intestinal permeability was remeasured in 9 patients 5 weeks after internal biliary drainage.
Autologous blood transfusion in surgery for cancer has been avoided because of the metastatic potential of reinfused malignant cells. This study determined whether viable tumour cells remain in the red cell concentrate after separation and whether blood transfusion filters remove these tumour cells before reinfusion. Units of banked blood were inoculated with tumour cell lines: breast cancer SKBr3; colon cancer COLO 320; lymphoma Daudi; erythroleukaemia K562. After processing with the Cell Saver, aliquots of the red cell concentrate and waste saline wash were examined for tumour cells and cultured. Tumour cells from all four cell lines were identified in the red cell concentrate but not in the waste saline wash. All the cell lines except Daudi grew from the red cell concentrate. Experiments on two of the cell lines (SKBr3 and COLO 320) were performed in which the red cell concentrate was either unfiltered (control) or filtered with SQ40S blood transfusion filter or RC100 leucocyte depletion filter. Both cell lines were present in the control samples and after filtration with SQ40S filters, and cells from these samples grew normally in culture. No tumour cells were evident after filtration with the RC100 filters and no growth of either cell line was found after 1 week in culture. The Cell Saver in combination with RC100 filters may be suitable for use during the surgical treatment of malignant disease.
A prospective randomized study of the immunological effects of three total parenteral nutrition (TPN) regimens in patients undergoing preoperative parenteral nutrition was conducted. In one regimen the calories were derived solely from glucose. The others were identical except that 50 per cent of the calories were provided as lipid emulsion, in one as long-chain triglycerides (LCT) only while the other contained half the fat as medium-chain triglycerides (MCT) and half as LCT (MCT/LCT). Natural killer (NK) activity and lymphokine-activated killer (LAK) activity were significantly higher after TPN with the MCT/LCT solution. A significant fall in LAK activity occurred after TPN with the LCT solution. The interleukin 2 content in supernatants from activated T lymphocytes was significantly higher after TPN with the LCT-containing solution. Solutions containing LCT and those containing MCT perturb cytokine interactions, but this is less with MCT-containing solutions, which may augment certain responses. These observations may have implications for the design of TPN regimens.
Mitogen-stimulated basal and maximal interleukin-2 production has been measured in 60 control subjects and 45 patients with gastrointestinal cancer (14 localized and 31 advanced). Peripheral blood T cell subsets in these subjects were also measured. In patients with advanced gastrointestinal cancer interleukin-2 production (mean +/- s.e.m. units/ml) is impaired when compared with that of control subjects (26.5 +/- 7 versus 61.1 +/- 9, P less than 0.0001) or patients with localized cancer (26.5 +/- 7 versus 59.4 +/- 13, P less than 0.02). This cannot be restored to normal by in vitro irradiation of the lymphocytes, suggesting that the impaired function is not due to IL-2 suppressor cells. Using monoclonal antibodies the percentages of T cell subsets were similar in all groups and we therefore conclude that the reduced production of IL-2 in these patients is due to deficient helper T cell function. These results provide a rational basis for the administration of exogenous IL-2 in the future management of patients with advanced gastrointestinal cancer.
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