P.A.M. van Leeuwen

Differences in immune status between well-nourished andmalnourished head and neck cancer patients

Malnutrition is reported to occur in approximately 30% of head and neck cancer patients. Also, impaired immunocompetence is described as a common phenomenon in this patient group. The purpose of this study was to assess the possible relationship between malnutrition and some prognostically important immune parameters in head and neck cancer patients. Thirty-two malnourished (recent weight loss >/= 10%) and 34 well-nourished patients undergoing curative treatment for advanced head and neck cancer were studied prospectively, and six parameters of their immune status (leucocytes, lymphocytes, lymphocyte phenotyping, monocytes, HLA-DR expression on monocytes and serum interleukin-10) were determined on the day of panendoscopy. Reference values for monocytes, HLA-DR expression and interleukin-10 were obtained from 43 healthy controls. Although the number of monocytes was elevated in both patient groups, the HLA-DR expression on these monocytes was significantly lower in the malnourished than in the well-nourished and control groups. Tumor stage, tumor localization, recurrence after initial radiotherapy, age and gender were not correlated to HLA-DR expression. No relationships emerged between nutritional status and lymphocyte subsets. Malnourished head and neck cancer patients show a significantly lower HLA-DR expression on monocytes than well-nourished ones and healthy controls. According to the literature this would imply an increased risk for postoperative complications. Indeed, postoperative complications occur more frequently in malnourished than in well-nourished patients.

Use of a mixture of medium-chain triglycerides and long-chaintriglycerides versus long-chain triglycerides in critically ill surgical patients: a randomized prospective double-blind study

Twenty critically-ill surgical patients who needed total parenteral nutrition were randomly enrolled in a double-blind study comparing two intravenous fat emulsions: one containing a mixture of 50% medium-chain triglycerides and 50% long-chain triglycerides and another containing 100% longchain triglycerides. The purpose of this study was to investigate metabolic and biochemical differences between both emulsions with special reference to liver enzymes. After a baseline period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added continuously during 24 h over 5 days. The parenteral nutrition was administered in mixture bags containing amino-acids, glucose and lipids together. Two-thirds of the non-protein calories were administered as glucose 40% and one third as either long-chain triglycerides or a mixture of medium-chain triglycerides and long-chain triglycerides. The total amount of non-protein calories received was the measured energy expenditure during the baseline period plus 10% and was fixed during the study. Plasma substrate concentrations, energy expenditure, and nitrogen balance were determined and arterial blood samples were taken. No toxic effects or complications attributable to one of the two emulsions were observed. There was no significant difference in energy expenditure, nitrogen balance, liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol, triglycerides and free fatty acids. The only parameter that showed a different pattern of reaction between the two emulsions was serum bilirubin concentration. In this study no evidence of any advantageous effect of a mixture of medium-chain triglycerides and long-chain triglycerides was seen.

Dietary glutamine supplementation reduces plasma nitrate levels in rats

It was recently shown that L-glutamine inhibits vascular nitric oxide (NO) production in vitro. The present study investigated the effect of glutamine enriched enteral diets on in vivo NO production in the rat. Nitrate, the stable end-product of NO production, was measured in plasma and 24 h urine collections in glutamine supplemented rats (6.25%, 12.5% and 25% w/w) and compared to the effect of isocaloric, nitrogenous control diets. Glutamine supplementation increased plasma levels of glutamine (up to 91%), arginine (up to 17%) and citrulline (up to 54%). After 1 week of glutamine supplementation plasma nitrate levels were significantly reduced by 50% compared to control (P < 0. 0001); irrespective of the amount of supplementation. No further decrease was observed after 2 weeks of feeding. No differences in daily urinary losses were found between the groups. These results point to an in vivo inhibitory effect of glutamine supplemented enteral feeding on NO production.

Hepatic failure and coma following liver resection is reversed by manipulation of gut contents: the role of endotoxin

Despite significant improvements in the surgical care of patients, hepatic failure after extensive liver resection continues to be associated with a high morbidity and death. We postulated that hepatic failure after liver resection was related to gut-derived endotoxemia. Rats were randomized to receive oral gavage twice daily with one of the following preparations: (1) 0.9% saline; (2) neomycin sulfate and cefazolin; (3) cholestyramine; (4) lactulose. After 7 days of gavage, animals underwent either a two-thirds partial hepatectomy or sham operation. At time 0 (preresection), 10, 20, and 30 hours after resection, aortic blood was obtained for determination of ammonia, glutamine, and endotoxin levels. In selected animals, portal vein or inferior caval blood was obtained simultaneously with the aortic sample to evaluate the glutamine and ammonia exchange across the intestine and hind limb. Germ-free rats also underwent a partial hepatectomy or sham operation, and blood was obtained for glutamine and ammonia exchange at 0 and 20 hours after resection. Hepatectomy in the saline-pretreated rats resulted in a sixfold increase in plasma glutamine, increased uptake of glutamine and release of ammonia by the gut, increased release of glutamine by the hind-limb, and a high mortality rate. Pretreatment with agents that altered gut contents reduced the endotoxemia, maintained normal glutamine and ammonia levels, and reduced the mortality rate. Germ-free rats had a similar response to that seen in treated animals. Altering the gut contents in this model reduced the level of endotoxemia, blunted the catabolic response, and enhanced survival.

Influence of L-Glutamine on the cytotoxicity of humanmonocytes against the SW948, a coloncarcinoma cell line

L-Glutamine is a non-essential amino-acid, which may become conditionally essential in certain clinical states (cancer, trauma, surgery) (1). Adding L-Glutamine to the diet might benefit these patient groups. Although it has recently been confirmed that L-Glutamine is an important nutrient for the cells of the immune system, especially the macrophage and monocyte, no experiments are yet done with respect to the cytotoxicity of the monocyte or macrophage against tumour cells (2). In this study we investigated the cytotoxicity of monocytes in vitro and of macrophages in vivo against colon carcinoma cell lines.