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Biomedical subjects

H J Burns

Publications and source records attributed to H J Burns.

At least 19 recordsLinked to original sources

Report on consensus conference on colorectal cancer: Royal College of Surgeons of Edinburgh 1993.

Colorectal cancer is the second commonest cause of death from cancer in Scotland. Recent developments in molecular biology, pre-symptomatic diagnosis, surgery and adjuvant treatment suggest that a substantial reduction in mortality is achievable. Some fear that major changes to the organisation of the NHS could undermine future attempts to coordinate major cancer screening studies or multicentre adjuvant trials. In contrast, others argue that a sharp focus on cost and benefits could encourage the development of clear guidelines based on a consensus of good practice. Thus, the time seems right for a consensus conference and this article summarises the outcome of such a recent conference held in Scotland. A group of 80 surgeons, radiation oncologists and medical oncologists were invited as a representative cross-section of clinicians with an interest in colorectal cancer. Seventy per cent of those attending were surgeons. A series of expert presentations were used to lead discussion in four sessions devoted respectively to epidemiology and screening, influence of surgical factors and outcome, the role of adjuvant therapy and planning for the future. Full discussion from delegates was encouraged and computer-collated, key-pad responses allowed documentation of the opinions of the audience in respect of pre-defined questions. For statistical purposes we have assumed that a consensus had been reached when there was a statistically significant difference (Chi-square) between the observed response from clinicians and the null hypothesis, i.e. a 50/50 split.

Aftercare↗

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↗

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↗

Effects of cardiac surgery and intraoperative hypothermia on energy expenditure as measured by doubly labelled water.

Total energy expenditure (TEE) was measured over two 10-day periods, before and after operation in 16 patients undergoing coronary artery surgery and randomized to have cardiopulmonary bypass with an intraoperative blood temperature of either 28 or 20 degrees C. TEE was measured with doubly labelled water containing stable isotopes of hydrogen and oxygen to allow calculation of TEE over fixed periods from the differential rate of excretion of the two isotopes. Results were available for eight patients in the 28 degrees C group but for only seven in the 20 degrees C group (one patient in this group was excluded as the temperature allocated was not achieved). The groups were similar with respect to body-weight and lean body mass. The 20 degrees C group received more grafts than the 28 degrees C group, resulting in an increase in cross-clamp and bypass times. Mean preoperative TEE was similar in both groups. The mean difference in fractional turnover rates of hydrogen and oxygen was not significantly different in the postoperative period. There was a non-significant increase in the mean 10-day postoperative TEE, calculated in total calories, of 4.7 per cent in the 28 degrees C and 5.1 per cent in the 20 degrees C group. When changes in postoperative TEE were calculated according to lean body mass, the mean increases were respectively 3.7 and 3.2 per cent. Cardiac surgery utilizing cardiopulmonary bypass and intraoperative hypothermia results in only a modest increase in postoperative TEE. In this study a more profound level of intraoperative hypothermia did not influence the change in postoperative TEE.

Adult↗

Effect of surgical injury and intraoperative hypothermia on whole body protein metabolism.

Whole body protein turnover and urinary nitrogen and 3-methyl-L-histidine (3-MH) excretion were measured before and after cardiac surgery using cardiopulmonary bypass in 20 male patients randomized to an intraoperative blood temperature of 28 or 20 degrees C. Rates of whole body protein synthesis (WBPS) and breakdown (WBPB) were determined from the 15N isotopic enrichment of urinary urea, ammonium, and from a calculated end-product average (EPA) after a primed 24-h infusion of [15N]glycine. In the postoperative period, there was a 40% increase in median nitrogen excretion in the 28 degrees C group (P less than 0.03) and a 22% increase in the 20 degrees C group (P = 0.10). There was a 79% increase in the median postoperative 3-MH excretion in the 28 degrees C group (P = 0.01) and a 66% increase in the median postoperative 3-MH excretion in the 20 degrees C group (P less than 0.01). Postoperatively, there was a 23% fall in the median value of WBPS in the 28 degrees C group (P less than 0.01) and an 11% fall in the 20 degrees C group [not significant (NS)] measured by 15N enrichment of urinary urea. In contrast, when WBPS was measured from isotopic enrichment of urinary ammonium, there was an increase in the median value of the postoperative rates of WBPS in both groups, by 20% in the 28 degrees C group (P = NS) and 29% in the 20 degrees C group (P = 0.03). There was no significant change in the rate of WBPS and WBPB, judged by the postoperative EPA in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Palmitate turnover and its response to glucose infusion in weight-losing cancer patients.

Palmitate turnover in weight-stable control subjects (n = 4) and weight-losing patients with progressive malignant disease (n = 4) has been determined. Measurements were made after an overnight fast and during glucose infusion (3.5 mg/kg/min). Turnover rates were calculated from plateau isotopic enrichment of palmitate in plasma during a continuous infusion of 1-13C palmitate. Palmitate turnover was higher in the cancer group before (180%) and during glucose loading (170%) compared with the control group. Palmitate turnover was reduced during glucose administration by approximately 34% in both groups. Plasma concentration of insulin was decreased and of cortisol was increased in the cancer group compared with the control group before and during glucose infusion. We conclude that cancer patients with weight loss have increased rates of fatty acid turnover indicative of enhanced mobilisation of body fat stores. Altered plasma concentrations of insulin and cortisol may mediate this effect. Nonetheless, even at more advanced stages of cachexia cancer patients have normal control mechanisms for inhibiting fatty acid turnover following administration of carbohydrate.

Journal Article↗

Response of serum interleukin-6 in patients undergoing elective surgery of varying severity.

1. Recent studies have suggested that interleukin-6 is a major mediator of the acute-phase protein response in man. The aim of the present study was to investigate the relationships between the response of serum interleukin-6 to surgery, the type of surgical procedure performed and the response of serum C-reactive protein. 2. Timed venous blood samples were taken from 26 patients in five broad surgical categories (minor surgery, cholecystectomy, hip replacement, colorectal surgery and major vascular surgery). C-reactive protein and interleukin-6 were measured in each sample. 3. Serum interleukin-6 rose within 2-4 h of incision in all patients and the magnitude of the response differed among the various surgical groups. The response of interleukin-6 correlated (r = 0.80, P less than 0.001) with the duration of surgery. In contrast, serum C-reactive protein was not detectable after minor surgery (less than 10 mg/l) and the response of C-reactive protein did not differ among the more major surgical groups. The response of interleukin-6 showed a weak, but significant, correlation with the response of C-reactive protein (r = 0.67, P less than 0.001). 4. We conclude that serum interleukin-6 is a sensitive, early marker of tissue damage. In general, the greater the surgical trauma, the greater the response of serum interleukin-6 and the greater the peak serum concentration of interleukin-6. Our results are consistent with a role for interleukin-6 in the induction of C-reactive protein synthesis.

C-Reactive Protein↗

Effect of nutritional status on acute phase protein response to elective surgery.

The aim of this study was to assess the effect of nutritional status on the acute phase protein response to elective surgery. Matched pairs of patients with gastric or colorectal cancer were studied. Undernourished patients (body-weight less than 80 per cent of ideal and triceps skinfold thickness less than 65 per cent of standard) were matched with controls (body-weight greater than 95 per cent of ideal and triceps skinfold thickness greater than 80 per cent of standard) for age, sex, type of pathology and surgery. Blood samples taken preoperatively and on days 1-5 after operation were analysed for C-reactive protein, alpha 1-antitrypsin, alpha 1-acid glycoprotein, albumin, prealbumin and transferrin. There was no significant difference in any of the preoperative protein concentrations between the two groups although undernourished patients tended to have lower transferrin concentrations (mean +/- s.e.m., 2.2 +/- 0.3 g/l) than the control group (2.9 +/- 0.1 g/l). C-reactive protein response was significantly smaller in the undernourished group than in the control group (P = 0.05, Mann-Whitney U test). The responses of the other acute phase proteins did not differ between the two groups. There was no difference in the length of hospital stay after operation when undernourished patients (mean +/- s.e.m., 17.7 +/- 3.0 days) were compared with controls (14.3 +/- 3.6 days). Undernourished patients therefore have an attenuated C-reactive protein response to elective surgery. The significance of this in relation to morbidity and mortality in severely ill patients requires further investigation.

Acute-Phase Proteins↗

The utilisation of peripherally-administered intravenous nutrient solutions.

The utilisation of three peripherally-administered intravenous nutritional regimens has been evaluated in 42 patients on the first four days following surgery for colorectal cancer. A standard dextrose-saline (DS) regimen (n = 16) has been compared with an amino-acid (AA) regimen (n = 12) and a regimen consisting of glucose, amino-acid and fat (GAF) (n = 14). Fat and carbohydrate oxidation was calculated pre- and post-operatively using indirect calorimetry. Patients receiving AA showed a fall in carbohydrate oxidation (p < 0.01) and a rise in fat oxidation (p < 0.05) post-operatively, whereas no significant changes in fat and carbohydrate oxidation occurred in the DS and GAF groups. Cumulative nitrogen balance (NB) for the first four post-operative days was significantly better (p < 0.01) in the AA group (-10.3 +/- 3.8 g; mean +/- s.e.m.) than in the DS group (-25.3 +/- 3.1 g), due to an improved NB in the AA group on the first and second days only. Cumulative NB in the GAF group (+7.7 +/- 2.3 g) was significantly better (p < 0.01) than in the other two groups. Where the provision of peripheral intravenous nutritional support is desired, the use of a combination of glucose, amino-acid and fat is recommended.

Journal Article↗

Comparison of various predictive formulae for the estimation of resting energy expenditure.

The accuracy of the Harris-Benedict (HB), Kleiber and Robertson-Reid predictive formulae and the Fleisch tables in estimating resting energy expenditure (REE) has been assessed in 114 cancer patients and 54 patients with nonmalignant illness. The effects of weight status and disease on the predictive ability of the formulae were assessed by comparison of the estimated REE value with that measured by indirect calorimetry. Underestimation of measured REE by greater than 10% occurred in 6-62% of patients, depending on the formula used. Weight loss did not affect predictive ability, whereas the presence of cancer resulted in inaccurate prediction of REE in female patients. Using a multiple comparison procedure, the Fleisch tables were the most accurate in all groups, while the HB formula was least accurate in male patients, irrespective of weight status or disease status. The use of predictive formulae and tables are inappropriate for the accurate estimation of REE in individual patients.

Journal Article↗

The serum interleukin 6 response to elective surgery.

We have investigated changes in serum interleukin 6 (IL-6) in patients undergoing elective cholecystectomy. Serum IL-6 increased in all patients within 1.5 hour of incision, reaching a maximum between 1.5-4 hours after incision (median 50 U/ml; range 22-79 U/ml). The maximum serum IL-6 correlated with the length of the operation (r = 0.95). Serum C-reactive protein was not detectable until 8-12 hours post-incision, but maximum serum C-reactive protein did not correlate with maximum serum IL-6 concentration or length of operation. There was no consistent increase in plasma interleukin 1 or tumour necrosis factor following surgery. Serum IL-6 is an early marker of tissue damage and may be of value in the study of the metabolic response to injury.

C-Reactive Protein↗

Influence of whole body protein turnover rate on resting energy expenditure in patients with cancer.

Whole body protein turnover and resting energy expenditure are measured simultaneously in weight stable and weight losing patients with lung (n = 22) or colorectal cancer (n = 38). These results were compared with those from weight stable and weight losing non-cancer controls (n = 22). Rates of whole body protein turnover were calculated from the plateau isotopic enrichment of urinary ammonia and urea following a primed, continuous, 24-h infusion of [15N]glycine. Resting energy expenditure was measured by indirect calorimetry. All groups of cancer patients had significantly elevated rates of whole body protein turnover (P less than 0.05) and synthesized, on average, 1.9 g/kg/day more protein compared with weight stable non-cancer controls. In contrast, the resting energy expenditure of cancer patients and controls was similar. Moreover, there was no correlation between individual rates of whole body protein turnover. Thus, although cancer patients had rates of whole body protein turnover which were 50-70% greater than controls, this did not result in a measurable increase in resting energy expenditure. The assumption that elevation of whole body protein turnover or resting energy expenditure causes weight loss in cancer patients must be an oversimplification. An acute phase protein response was observed in the majority of cancer patients. Although the presence of such an inflammatory response did not correlate with the rate of whole body protein turnover, the role of inflammatory mediators in the pathogenesis of disturbed protein metabolism in cancer patients merits further investigation.

Aged↗

Improving prognosis of Hodgkin's disease in Scotland.

Time trends in mortality from Hodgkin's disease have been studied in Great Britain for the 70-year period, 1911-1980, and incidence in Scotland since 1959. In both Scotland and England and Wales, in each sex, mortality from Hodgkin's disease rose steadily from 1911 until 1970 and thereafter dropped substantially; the greatest fall was apparent in Scottish males. While mortality rates continue to decline in Scotland the incidence has remained fairly constant over the last 25 years suggesting a major change in prognosis for this disease. The introduction of effective chemotherapy and improved techniques of radiotherapy appear to have improved prognosis sufficiently, and to have been made adequately widely available, as to influence overall mortality rates at a national level as well as at the level of the clinical trial. No such improvement in prognosis, however, explains the declines observed in mortality rates among children of each sex in both areas which have taken place since the 1930s. In view of the current knowledge of the aetiology of Hodgkin's disease this fall may have been brought about by changes in socioeconomic factors.

Age Factors↗

The metabolic and nutritional effects of injury and sepsis.

The existence of a co-ordinated response to stress of a variety of causes has clearly been established. Basically, this consists of an elevation in energy expenditure and an increased breakdown of skeletal muscle protein. In addition, glucose level in the plasma increases as a result of increased synthesis and decreased uptake of glucose into cells. Release of fatty acid into the plasma is also increased, and an elevation in the proportion of energy derived from oxidation of fatty acids is observed. This response is qualitatively very different from that seen in simple starvation, where a progressive reduction in energy expenditure and a reduction in the synthesis of glucose allows fat to become the major energy-producing substrate and also allows sparing of body protein stores. The mechanisms responsible for this altered pattern of metabolism are probably primarily hormonal in nature, with adrenaline, cortisol and glucagon being the major catabolic stimulants. Some evidence exists, however, for alteration in intracellular pathway metabolism. Within the past decade a new class of mediators of the stress response, the cytokines, has been recognized. These substances are protein products of circulating monocytes and the way in which they integrate into the control of the stress response has not been completely elucidated. At present there is evidence that they can stimulate production of catabolic hormones, and also they may well have direct effects in enhancing protein catabolism in muscle. At present the main method for modification of the stress response remains the provision of energy and amino acid, either intravenously or enterally. In the present state of our knowledge, 30-40 kcal kg-1 day-1 would appear to be adequate for most patients, with half provided as fat. Amino acids 3 g kg-1 day-1 will provide adequate nitrogen. It must be said, however, that the most effective method of modifying the stress response is removal of the source of stress by surgery, antibiotics or other primary therapy.

Energy Metabolism↗

Regulation of muscle protein turnover: possible implications for modifying the responses to trauma and nutrient intake.

The physiological control of muscle protein balance has been reviewed. In addition to trauma, fasting and reduced activity have been shown to cause muscle protein loss through changes in synthesis and breakdown. Many of the effects of these states are mediated by alterations in the concentrations of insulin, glucagon, steroids and catecholamines. Branched-chain amino acids also appear to have specific effects in improving protein synthesis. Recently, prostaglandins have been identified as having a central role as mediators in the control of protein metabolism by many hormones and pathological states. Identification of factors which control muscle protein synthesis leads to the possibility that the metabolic response to illness and injury and its attendant muscle protein loss could be open to pharmacological manipulation. Inhibition of prostaglandin synthesis by non-steroidal anti-inflammatory drugs can improve muscle protein turnover, but their clinical usefulness may be limited by side-effects. Hormonal manipulation may offer the possibility of abolishing the metabolic response. For example, inhibition of adrenal secretion in surgical patients by spinal anaesthesia appears to modify many of the metabolic effects of injury. A variety of other treatments have been used to minimize the metabolic derangements of injury. Some of these have considerable potential, but as yet clinical benefits from their use have not been positively identified. It is likely that a pharmacological approach to the nutritional disorders of stress and injury will prove to be of major interest in the future.

Energy Metabolism↗

Reduction of the growth rate of the Walker 256 tumor in rats by rhodamine 6G together with hypoglycemia.

Previous attempts to use tumor energy metabolism as a target for antineoplastic therapy have used single agents aimed at inhibiting either glycolysis or oxidative phosphorylation. Since most tumor cells use both pathways for energy production, this approach is unlikely to succeed. The aim of this study was to simultaneously manipulate both sources of intracellular ATP to achieve more selective control of tumor growth. Rhodamine 6G (R6G) is a fluorochrome mitochondrial dye which inhibits oxidative phosphorylation. 3-Mercaptopicolinic acid inhibits gluconeogenesis and is a potent hypoglycemic agent in the fasting state. Dose-response relationships were established for R6G and 3-mercaptopicolinic acid, and a nontoxic dose of the compounds was selected for subsequent experiments. Thereafter, groups of rats (n = 7 per group) underwent s.c. implantation of Walker 256 carcinosarcoma. Following a 24-h fast each group received either saline, R6G (0.8 mg/kg), 3-mercaptopicolinic acid (40 mg/kg), or the combination given i.p. Seven days after tumor implantation animals were sacrificed, and tumors were exercised and weighed. Administration of R6G during a period of hypoglycemia significantly reduced the tumor growth rate when compared to control experiments (3.6 +/- 0.3 g cf. 7.1 +/- 0.7 g, mean +/- SE; P less than 0.05). In contrast, neither R6G nor the period of hypoglycemia alone significantly affected tumor growth. These results suggest that simultaneous manipulation of oxidative phosphorylation and glycolysis may be used to selectively inhibit tumor growth in vivo.

Adenosine Triphosphate↗