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Biomedical subjects

K C Fearon

Publications and source records attributed to K C Fearon.

At least 73 records · Page 4Linked to original sources
PubMed1995

Outcome of patients with abdominal sepsis treated in an intensive care unit.

A group of 125 patients with abdominal sepsis admitted to the intensive therapy unit between January 1990 and June 1993 were reviewed to determine outcome. Mean(s.d.) age was 66(12) years and admission Acute Physiology And Chronic Health Evaluation (APACHE) II score 23(9). The hospital mortality rate was 63 per cent. Factors associated with mortality included age, APACHE II score, occurrence of septic shock, chronic ill health, female sex, sepsis of upper gastrointestinal origin and failure to clear the source of sepsis (all P < 0.05). Delay to surgery, anastomotic leakage and presence of malignancy did not influence survival significantly. Quality of life (measured by the World Health Organization performance score) at 15 months after discharge showed 24 of 32 survivors to be independent, ambulatory and capable of self care. No patient survived to become completely disabled. The factors associated with survival did not predict subsequent quality of life. Accurately defining the characteristics of this heterogeneous group of patients is a prerequisite for improved treatment, patient selection and research.

APACHE↗
PubMed1995

A prospective study of tumor recurrence and the acute-phase response after apparently curative colorectal cancer surgery.

BACKGROUND: Approximately 70% of patients who are going to develop tumor recurrence following curative colorectal surgery do so within 24 months of surgery. PATIENTS AND METHODS: The relationship was prospectively examined between an ongoing acute-phase response and subsequent clinical relapse in 36 colorectal cancer patients who had undergone a curative resection. Approximately 4 months after their operation, patients were grouped according to the presence (n = 15) or absence (n = 21) of an acute-phase response (C-reactive protein > 5 mg/L) and were followed-up for a minimum of 24 months. RESULTS: Age, tumor site, and serum carcinoembryonic antigen concentrations were similar in both groups. There was a significantly higher recurrence rate in patients with an acute-phase response (11 of 15) compared to those with no acute-phase response (2 of 21, P < 0.01). CONCLUSIONS: These results are consistent with the presence of an acute-phase response being an important predictive factor in the early stages of tumor recurrence in patients who have had apparently curative colorectal surgery.

Acute-Phase Reaction↗
PubMed1995

Ibuprofen reduces energy expenditure and acute-phase protein production compared with placebo in pancreatic cancer patients.

The aim of this study was to investigate the effect of the cyclo-oxygenase inhibitor ibuprofen on the acute-phase protein response and resting energy expenditure (REE) of weight-losing patients with pancreatic cancer. Patients with irresectable pancreatic cancer (n = 16) were treated with either ibuprofen (1200 mg day-1 for 7 days (n = 10) or placebo (n = 6). A group of 17 age-related non-cancer subjects were also studied. Indirect calorimetry, anthropometry, multifrequency bioelectrical impedence analysis and serum C-reactive protein (CRP) estimation were performed immediately before and after treatment. Before treatment, total REE was significantly elevated in the pancreatic cancer patients compared with healthy controls (1499 +/- 71 vs 1377 +/- 58 kcal) (P < 0.02). Following treatment the mean REE of the ibuprofen group fell significantly (1386 +/- 89 kcal) compared with pretreatment values (1468 +/- 99 kcal) (P < 0.02), whereas no change was observed in the placebo group. Serum CRP concentration was also reduced in the ibuprofen-treated group (pre-ibuprofen, 51 mg l-1; post-ibuprofen, 29 mg l-1; P < 0.05). These results suggest that ibuprofen may have a role in abrogating the catabolic processes which contribute to weight loss in patients with pancreatic cancer.

Acute-Phase Proteins↗
PubMed1995

Comparison of bio-impedance spectroscopy and multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients.

1. Measurements of extracellular and total body water provide useful information on the nutritional status of surgical patients and may be estimated from whole-body bio-impedance measurements at different frequencies. 2. Resistance and reactance were measured at 50 frequencies from 5kHz to 1MHz in 29 surgical patients (17 males, 12 females) with a wide range of extracellular to total body water ratios. 3. A fit to the spectrum of reactance versus resistance data gave predicted resistances at frequencies zero and infinity. Values of extracellular and total body water determined by this bio-impedance spectroscopy technique were regressed against values obtained from radioisotope dilution. The standard errors of the estimate were 1.8931 and 3.2591 respectively. 4. Resistance indices (height2/resistance) at selected frequencies gave the highest correlations with extracellular and total body water at 5kHz and 200kHz respectively, and prediction equations derived from multiple stepwise regressions also showed these to be the optimum frequencies. The standard errors of the estimate for this multi-frequency bio-impedance analysis method were 1.9371 and 2.6061 for extracellular and total body water respectively. 5. To assess the ability of the two methods to measure changes in extracellular and total body water, reproducibility was assessed from repeat measurements 10 min apart in a subgroup of 15 patients. Bio-impedance spectroscopy gave mean coefficients of variation for extracellular and total body water of 0.9% and 3.0% respectively. For multi-frequency bio-impedance analysis the corresponding coefficients of variation were 0.9% and 0.6%. 6. It is concluded that a simple impedance analyser operating at only two frequencies compares favourably with the more complex spectroscopy technique for the determination of extracellular and total body water in surgical patients.

Biometry↗
PubMed1995

Interleukin-4 and interleukin-10 increase endotoxin-stimulated human umbilical vein endothelial cell interleukin-8 release.

The aim of this study was to determine the effect of interleukin-4 (IL-4) and interleukin-10 (IL-10) on interleukin-8 (IL-8) release from endothelial cells. Confluent monolayers of human umbilical vein endothelial cells (HUVECs) were incubated in the absence or presence of 10 ng/ml of bacterial lipopolysaccharide (LPS), with 5% human AB serum and recombinant human IL-4 or IL-10 over a dose range from 50 fg/ml to 50 ng/ml (final concentration). IL-4 and IL-10 had no effect on HUVEC IL-8 release in the absence of LPS. In the presence of LPS, IL-4 and IL-10 enhanced IL-8 release by approximately 300% compared with LPS-stimulated cells alone, IL-8 release increasing from 2594 +/- 493 pg/ml (no IL-4 or IL-10) to 7892 +/- 320 pg/ml (IL-4, 5 pg/ml; p = 0.001) and 8359 +/- 712 pg/ml (IL-10, 50 pg/ml; p = 0.002). IL-8 release in response to IL-4 or IL-10 plateaued above 5 and 50 pg/ml, respectively. This study suggests that IL-4 and IL-10 may be involved in the complex regulation of endothelial cell cytokine production during the response to endotoxin.

Cells, Cultured↗
PubMed1995

Insulin and counterregulatory hormones influence acute-phase protein production in human hepatocytes.

After trauma or sepsis, the liver undergoes a reprioritization of export protein synthesis with elevated production of some acute-phase reactants and reduced production of others. We have examined the effects of combinations of insulin and the counterregulatory hormones (dexamethasone, glucagon, and epinephrine), in the presence or absence of interleukin (IL)-6, on the production by isolated hepatocytes of the positive acute-phase proteins C-reactive protein, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, and haptoglobin, and the negative acute-phase proteins prealbumin and transferrin. The effect of IL-6 on the production of the above proteins was influenced significantly by insulin and all of the counterregulatory hormones. Significant three-way interactions as well as higher order interactions between the stress hormones and insulin were seen in the case of C-reactive protein. The results indicate that both positive and negative acute-phase proteins respond differently to insulin and the counterregulatory hormones and that the potential exists for the regulation of synthesis of individual acute-phase reactants by interaction between the cytokine network and the classical endocrine hormones.

Acute-Phase Proteins↗
PubMed1994

Clofazimine alters the energy metabolism and inhibits the growth rate of a human lung-cancer cell line in vitro and in vivo.

The anti-leprosy drug Clofazimine is known to inhibit respiratory function and hence energy metabolism in yeast and in transformed fibroblasts. The aim of this study was to examine the effect of Clofazimine on the energy metabolism of a chemoresistant human non-small-cell bronchial-carcinoma cell line (WIL) and to determine whether this agent might inhibit the growth rate of this cell line in vitro and in vivo. Oxidative phosphorylation was estimated in vitro by measuring oxygen consumption polarographically and glycolysis was estimated from lactate production. In cells that had been pre-treated with an ATP synthetase inhibitor (oligomycin), the addition of Clofazimine resulted in an increase in oxygen consumption similar to that observed with 2,4-dinitrophenol, a classical inhibitor of oxidative phosphorylation. This inhibition of mitochondrial function was associated with an increase in lactate production. Cellular ATP levels were maintained, possibly indicating a compensatory increase in ATP production via glycolysis. Clofazimine was shown to have a direct cytotoxic effect in vitro with an ID50 of 10.2 microM. When Clofazimine was administered to athymic mice bearing WIL as a subcutaneous xenograft, tumour growth rate was significantly reduced, so that after 3 weeks, tumour size was one third that of controls (p < 0.01). These results suggest that selective inhibition of tumour energy metabolism with agents such as Clofazimine is a potential novel approach to cancer treatment.

Adenosine Diphosphate↗
PubMed1994

Relationship between weight loss, reduction of body cell mass and inflammatory response in patients with cancer.

Reduced food intake is a major cause of continuing weight loss in patients with cancer. Previous work has suggested that an ongoing inflammatory response may also contribute to weight loss and alter the nature of body tissue loss. To examine this, body cell mass was estimated using measurements of total body potassium (TBK) in 31 patients with gastrointestinal cancer and weight loss with or without an inflammatory response (C-reactive protein level above 5 mg/l). Albumin levels, total body water and 24-h urinary creatinine clearance were also measured. When measured TBK was expressed as a percentage of predicted normal values there was a significant reduction in TBK for patients with an inflammatory response compared with that of those without (P = 0.04). However, when a different prediction equation for TBK was used this difference was not significant (P = 0.29). Therefore, it remains uncertain whether an ongoing inflammatory response in patients with cancer and weight loss contributes to loss of body cell mass.

Aged↗
PubMed1994

Effect of megestrol acetate on weight loss, body composition and blood screen of gastrointestinal cancer patients.

Reduced food intake is probably the major cause of continuing weight loss in cancer patients. Therefore, agents which stimulate food intake may be of significant benefit to such patients. To examine this, a randomized double-blind placebo controlled study of megestrol acetate was carried out. 38 gastrointestinal cancer patients with weight loss (8-43% of pre-illness stable weight) were entered into the study. 26 were evaluable at 6 weeks and 21 at 12 weeks. Clinical details, serum biochemistry and haematology were examined at 6 and 12 weeks and total body water, total body potassium at 12 weeks after the baseline assessment. There was no significant weight change in either group over the 6 or 12 weeks. Furthermore, there was no significant difference in total body water, total body potassium, blood biochemistry or haematology between the groups over the study period. It does not appear that megestrol acetate at a dose of 480 mg/day results in weight gain in advanced gastrointestinal cancer patients with weight loss.

Journal Article↗
PubMed1994

Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines.

A number of polyunsaturated fatty acids have been shown to inhibit the growth of malignant cells in vitro. To investigate whether fatty acids modify the growth of human pancreatic cancer, lauric, stearic, palmitic, oleic, linoleic, alpha-linolenic, gamma-linolenic, arachidonic, docosahexaenoic and eicosapentaenoic (EPA) acids were each incubated with the cells lines MIA PaCa-2, PANC-1 and CFPAC at concentrations ranging from 1.25 microM to 50 microM and the effect of each fatty acid on cell growth was examined. All the polyunsaturated fatty acids tested had an inhibitory effect, with EPA being the most potent (ID50 2.5-5 microM). Monounsaturated or saturated fatty acids were not inhibitory. The action of EPA could be reversed with the anti-oxidant vitamin E acetate or with oleic acid. The cyclo-oxygenase inhibitors indomethacin and piroxicam had no effect on the action of EPA. The action of EPA appeared to be associated with the generation of lipid peroxides, although the level of lipid peroxidation did not always appear to correlate directly with the extent of cell death. The ability of certain fatty acids to inhibit significantly the growth of three human pancreatic cancer cell lines in vitro at concentrations which could be achieved in vivo suggests that administration of such fatty acids may be of therapeutic benefit in patients with pancreatic cancer.

Cell Division↗
PubMed1994

Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients.

1. Multi-frequency bio-impedance analysis has been used to estimate extracellular and total body water in a heterogeneous group of 43 surgical patients (23 males, 20 females). 2. Radioisotope-dilution methods were used for the measurement of extracellular and total body water. 3. Resistance and reactance were measured between wrist and ankle at frequencies from 5 kHz to 1 MHz. 4. Extracellular and total body water were estimated by multiple stepwise regression using the radioisotope values as the dependent variables. The parameters included in the regression were: resistance and reactance at each frequency, body habitus parameters, plasma albumin and plasma sodium. 5. The standard errors of the estimates between the measured and estimated values were 1.73 litres (coefficient of variation 9.6%) and 2.17 litres (coefficient of variation 6.0%) for extracellular and total body water, respectively. 6. These errors represent a useful improvement relative to those obtained from anthropometric estimates. However, the improvements relative to the use of a single frequency (50 kHz) are not clinically significant.

Body Composition↗
PubMed1994

Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer.

OBJECTIVE: To determine whether resting energy expenditure (REE) is increased in cachectic patients with pancreatic cancer and to define the relation of tumor necrosis factor (TNF) and interleukin-6 (IL-6) production to the acute-phase response and to REE. METHODS: Measurement of REE (indirect calorimetry) and assessment of body composition (bioelectrical impedance analysis) were done in 21 patients with unresectable pancreatic cancer and on 16 age-related controls. The systemic inflammatory response in peripheral blood of the cancer patients was assessed using the acute-phase protein, C-reactive protein, and the cytokines TNF and IL-6. Production of these cytokines by peripheral blood mononuclear cells in vitro was also measured. RESULTS: Patients with pancreatic cancer had an elevated REE when compared with controls (73.4 +/- 5.0 vs. 53.5 +/- 1.6 kcal/kg body cell mass; p < 0.003). Resting energy expenditure was significantly greater in cancer patients with an acute-phase response (C-reactive protein > 10 mg/L) than in those who did not have such a response (85.5 +/- 10.0 [n = 9] vs. 64.3 +/- 3.0 [n = 12] kcal/kg body cell mass; p < 0.04). Tumor necrosis factor was not detected in the serum of any of the cancer patients. Serum IL-6 was detected but levels were not significantly different among cancer patients with or without an acute-phase response. In contrast, spontaneous production of TNF and IL-6 by isolated peripheral blood mononuclear cells was significantly greater in cancer patients with an acute-phase response that in those without (TNF: 1231 +/- 244 vs. 210 +/- 54 pg/ml/10(5) cells; p < 0.001; IL-6: 11.5 +/- 1.7 vs. 3.6 +/- 1.4 ng/mL/10(5) cells; p < 0.003). CONCLUSIONS: In pancreatic cancer at least a component of weight loss is due to increased REE. Furthermore, the presence of an acute-phase response identifies a group of patients who are markedly hypermetabolic. The serum concentration of TNF of IL-6 does not correlate with the presence of an acute-phase response, whereas rates of cytokine production by peripheral blood mononuclear cells are significantly greater in patients with such a response. This suggests that local rather than systemic cytokine production may be important in regulating the acute-phase response.

Acute-Phase Proteins↗
PubMed1994

Glutamine-supplemented total parenteral nutrition enhances T-lymphocyte response in surgical patients undergoing colorectal resection.

OBJECTIVE: The authors determined the effect of glutamine-supplementation of TPN on postoperative peripheral blood T-cell response and proinflammatory cytokine production in patients undergoing colorectal resection. SUMMARY BACKGROUND DATA: Several vital tissues, including the immune system, are very dependent on glutamine; however, this amino acid, which may be essential in conditions of stress, only now is becoming formulated suitably for incorporation into TPN. The effects of such supplementation on the immune function of stressed surgical patients is unknown. METHODS: Patients (n = 20) were randomized to receive conventional TPN (0.2 g nitrogen/kg/d) or an isonitrogenous/isocaloric regimen with 0.18 g of glutamine/kg/d from days 1 to 6 postoperatively. T-cell DNA synthesis and interleukin (IL)-2 production and peripheral blood mononuclear cell IL-6 and tumor necrosis factor (TNF) production were measured in vitro preoperatively and on days 1 and 6 postoperatively. RESULTS: T-cell DNA synthesis after 5 days of TPN was increased compared with preoperative values in the glutamine-supplemented group (median preoperative tritiated thymidine uptake: 78.3 x 10(3) cpm, day 6: 95.0 x 10(3) cpm, p < 0.05). There was no such increase in the control TPN group (preoperative: 89.0 x 10(3) cpm, day 6: 69.4 x 10(3) cpm, p > 0.05). Glutamine supplementation did not influence IL-2 production or the production of TNF or IL-6. CONCLUSIONS: Glutamine supplementation may be a method of enhancing T-cell function in the surgical patient receiving TPN.

Adolescent↗
PubMed1994

Interleukin-6, neutrophilia and the acute phase protein response in colorectal cancer patients.

White blood cell counts and circulating interleukin-6 concentrations were measured in male colorectal cancer patients with (n = 12) and without (n = 15) evidence of an acute phase protein response. In the group with an acute phase protein response circulating neutrophils were increased whereas serum interleukin-6 concentrations were not. These results suggest that in colorectal cancer patients although an acute phase protein response is associated with neutrophilia, both events can occur independent of circulating interleukin-6 concentrations.

Aged↗
PubMed1993

Role of serum endotoxin and antiendotoxin core antibody levels in predicting the development of multiple organ failure in acute pancreatitis.

It has been proposed that endotoxin contributes to the development of multiple organ failure (MOF) in acute pancreatitis. Endotoxaemia is transient and may not be detected by intermittent blood sampling. By contrast, not only can changes in the patient's endogenous antiendotoxin core antibody pool persist for many days, but depletion of this pool may be a key event in determining the physiological significance of endotoxaemia. A series of 33 patients with acute pancreatitis had daily measurement of Acute Physiology Score (APS) and levels of C-reactive protein, interleukin 6, endotoxin, immunoglobulin (Ig) G and IgM antiendotoxin core antibodies, and prospective documentation of complications. Endotoxin was detected in the serum of 13 patients, while a significant change in levels of endogenous antiendotoxin core antibodies was detected in all those with severe pancreatitis and in 28 overall. MOF developed in seven patients, five of whom died. The combination of a rising APS over the first 48 h of admission and a significant fall in endogenous IgG antibody level was observed in all patients who developed MOF (seven of seven), but in only one of 16 without MOF (P = 0.00003; overall predictive value 91 per cent). This study suggests that measuring the initial trend in APS and the concentration of endogenous IgG antiendotoxin core antibody provides a means of identifying patients with acute severe pancreatitis who are at high risk of developing MOF. This group might benefit from passive immunotherapy with antiendotoxin antibodies.

Acute Disease↗
PubMed1993

Audit of nutritional support provided to surgical patients by a nutrition team.

An audit was carried out over a 24 month period to assess the practice, safety and efficacy of nutritional support provided to surgical patients by a designated team. 135 patients received nutritional support: 51% were fed parenterally, 32% enterally and 17% via combined nutritional support. The duration of feeding ranged from 1-177 days with 23% being supported for < 7 days. The line infection rate for patients receiving intravenous nutrition was 6.5%. Nutritional outcome was assessed using weight, anthropometry and bioelectrical impedance analysis. Pre-and post-feeding results were available for 67% of patients. These patients were classified as either oedematous (n = 21), normally nourished (n = 23) or nutritionally depleted (n = 46). Overall, the oedematous patients lost water, the protein status of the normally nourished group deteriorated slightly and the nutritional status of the nutritionally depleted patients was maintained. Audit is a valuable means of defining the efficacy of a nutrition support service and has identified areas which require review.

Journal Article↗