The relationship between delayed hypersensitivity response, nutritional status and clinical outcome in surgical patients referred for nutritional support

Delayed hypersensitivity responses to recall antigens were measured in 125 surgical patients referred for nutritional assessment and support. On initial testing 57 patients were skin test positive and 68 were anergic each of these patient groups being closely matched in terms of surgical conditions. There was a mortality of 4 in the skin test positive group and 26 in the anergic group. The anergic patients were significantly older and in biochemical and anthropometric terms were in poorer nutritional status than the skin test positive group. Of 33 anergic patients who were repeat tested, 15 remained anergic and 18 converted to a positive response. Conversion from anergy to a positive response was not associated with changes in the measured indices of nutritional status and did not improve clinical outcome. The value of repeat skin testing is therefore in doubt.     

Effects of surgery and nutritional support on some lymphocyte and PMN leucocyte functions in man

The purpose of the present study was to evaluate the effect on some leucocyte functions of 1) an elective surgical procedure; 2) nutritional repletion provided by parenteral alimentation (TPN). The rates of cellular proliferation and protein synthesis in lymphocyte cultures were measured by the incorporation of respectively 3H-thymidine and 3H-leucine; both measures were performed without and with additions of mitogenic agents. Random migration and chemotaxis of PMN leucocytes were measured under agarose. In 10 well-nourished patients, both lymphocyte proliferation and protein synthesis in stimulated cultures decreased after elective surgery, respectively by 50% (p < 0.01) and by 32% (p < 0.05) while random migration of PMN leucocytes was increased by 50% (p < 0.02). Stimulated lymphocyte proliferation and protein synthesis measured in 10 nutritionally depleted non-cancer patients prior to TPN were lower in comparison to the values obtained in a control population (respectively p < 0.006 and p < 0.04). These parameters rose progressively during TPN and reached the normal range after 3 weeks. Before TPN, PMN leucocyte random migration was slower in depleted patients than in control subjects; this parameter reached normal values after one week of TPN, while chemotaxis tended to decrease. Both parameters were in the normal range after 3 weeks of TPN. Conclusions 1) an elective operation depresses lymphocyte functions but stimulates PMN leucocyte random migration in well-nourished patients; 2) in depleted patients, previously depressed leucocyte responses are restored within 3 weeks of adequate nutritional support.     

The effect of continuous enteral tube feeding on various nutritional parameters in patients with disseminated malignant melanoma during intensive chemotherapy

In a prospective study the effect of continuous enteral tube feeding was evaluated on various nutritional parameters in patients with disseminated malignant melanoma during 13 chemotherapy courses employing bleomycin, DTIC, vindesine and actinomycin D. The patients received a quantity of calories according to their pretreatment intake, but complete metabolic equilibrium could not be obtained during chemotherapy. Although the weight/height index remained unchanged, a decrease of serum albumin and prealbumin level occurred during all 13 treatment courses. Transferrin level decreased during 11 of these courses and cholinesterase level during 12. Triceps skinfold thickness and arm muscle circumference diminished equally. Serum prealbumin was the first nutritional parameter to fall during chemotherapy and seems to be a very sensitive indicator of the occurrence of nutritional imbalance. The plasma vitamin C level was low before treatment while during treatment both vitamin C and vitamin A level fell quickly even though the nutritional intake of these vitamins was adequate. We conclude that continuous enteral tube feeding, which is a feasible method of feeding, can to some extent fulfill the nutritional needs of patients treated with intensive chemotherapy.     

Metabolic effects of four intravenous nutritional regimens in patients undergoing elective surgery II.--Muscle amino acids and energy-rich phosphates

Muscle amino acids and energy-rich phosphates have been determined in 28 patients before and after resection of a carcinoma of colon or rectum. Before operation the patients received a synthetic diet (Vivasorb for four days and postoperatively four different intravenous regimens with different amounts and proportions of amino acids were given for six days, the energy intake being the same for all groups. When compared with age-matched healthy controls the patients showed only slight increases in phenylalanine and isoleucine concentration in muscle and plasma with elevated plasma glutamate during the four days prior to the operation. Vivasorb treatment increased the concentration of alanine, glycine and methionine in both muscle and plasma while increases of threonine and histidine were seen only in muscle. Decreased concentrations of valine were found in muscle and plasma, while lysine and leucine decreased only in plasma. As an effect of operation, but independent of the nutritional regimen, muscle asparagine increased and muscle glutamine and glutamate decreased in all groups. The unique pattern of amino acid changes in postoperative trauma was confirmed in the present investigation but few differences in amino acid concentrations could be related to the various nutritional intakes. Alterations in the individual amino acid concentrations were not influenced by the intake of amino acids and seemed to have little relationship to the composition of any solution infused. Prior to operation there were low levels of ATP in muscle possibly due to immobilisation and chronic semistarvation but no changes in the energy rich phosphates could be attributed to trauma or nutrition. The content of muscle glycogen increased as a result of the Vivasorb supply indicating that the preoperative carbohydrate administration promotes muscle glycogen synthesis and postoperatively muscle glycogen was reduced significantly indicating enhanced glycogenolysis in the postoperative state. This finding emphasizes the importance of providing the patients with ample amount of glucose before and after surgery.     

Metabolic effects of four intravenous nutritional regimens after elective surgery. I. Clinical data and biochemistry

Biochemical variables have been determined in 28 patients before and after resection of carcinoma of colon or rectum. A synthetic oral diet was given for four days before operation, (0.1 gN.kg/day and 165 kJ.kg/day) and four isocaloric intravenous regimens with different amounts and proportions of amino acids were given for six days after operation. During the preoperative diet the serum urea, glucose, urate, inorganic phosphate and cholesterol concentration decreased while those of triglyceride, iron and alanine amino-transferase increased. After operation the serum triglyceride, protein, albumin, iron, TIBC and urate concentrations decreased. The serum calcium fell in all groups receiving amino acids after operation while magnesium increased in all groups except the one receiving the highest amount of amino acids. The urea concentration decreased when no amino acids were given but increased when amino acids were administered whereas the reverse situation occurred with cholesterol. The highest increase in glucose level was observed when the highest amount of amino acids were given.     

Current status of human rabies transmitted by dogs in Latin America

Latin American countries made the political decision to eliminate human rabies transmitted by dogs by the year 2005. The purpose of the current study is to evaluate to what extent this goal has been reached. The epidemiological situation and control measures were analyzed and broken down within the countries by georeferencing. The 27 human cases reported in 2003 occurred in some 0.2% of the second-level geopolitical units (municipalities or counties) in the region, suggesting that the disease is a local problem. Several areas within the countries reported no more transmission of rabies in dogs. Nearly 1 million people potentially exposed to rabies received treatment. On average, 34,383 inhabitants per health post receive anti-rabies treatment (range: 4,300-148,043). Nearly 42 million dogs are vaccinated annually. Surveillance is considered fair according to the epidemiological criteria adopted by the study. Samples sent for rabies testing represent 0.05% of the estimated canine population (range: 0.001 to 0.2%). The countries are quite close to achieving the goal.     

Nasogastric tube substitution for nutritional support in patients with oesophageal cancer: A simple method

A simple method is described allowing an easy and rapid substitution of nasogastric tubes for enteral nutrition in patients with stenosing oesophageal cancer, using the Seldinger technique.     

Absorption of magnesium chloride solution in small bowel disease

The absorption of a magnesium chloride solution has been observed by balance studies in three patients with ileal resections and in one patient with idiopathic steatorrhoea and biliary cirrhosis. All patients were depleted of magnesium because of malabsorption. The mean net absorption of magnesium increased to 4.5, 4.9, 5.8 and 16.4 mmol magnesium per day, when a supply of 25 mmol magnesium was given. The result was encouraging with positive magnesium balances in all patients.     

Effects of malnutrition on the acute phase response of plasma proteins in patients undergoing total gastrectomy

The serum level of six acute phase proteins (APP) has been evaluated preoperatively and for a few days in the postoperative period. Thirty patients undergoing total gastrectomy for gastric cancer have been studied in two subgroups according to their nutritional status. Those with gastric cancer had significantly higher baseline serum levels of alpha 1 acid glycoprotein (alpha1AGP) and C-reactive protein (CRP) than a control group. Malnourished patients also had reduced acute phase response for alpha1AGP and alpha 1 antitrypsin (alpha1AT) a higher increase of CRP and fibrinogen, and a lower decrease for transferrin and retinol binding protein (RBP).     

Causes of anergy in the surgical patient and its relationship to postoperative sepsis

Between June 1981 and June 1983 the delayed hypersensitivity response (DHR) was studied in 401 patients considered for major surgical procedure: 320 of these patients underwent surgery. The incidence of sepsis and postoperative mortality was higher in anergic and relative anergic patients than in normal responders (p<0.001). To evaluate whether DHR depression in cancer patients was due to the direct effect of cancer or to tumour-linked malnutrition, the 401 patients were divided into 4 groups: 1) 140 malnourished cancer patients, 2) 51 malnourished non-cancer patients, 3) 120 well-nourished cancer patients and 4) 90 well-nourished non-cancer patients. The mean age was not significantly different for the 4 groups. The results showed a relationship between DHR and nutritional status (p<0.001). The tumour-related DHR impairment disappeared when the cancer and non-cancer patient groups were homogeneous with regard to their nutritional status. Therefore, the tumour was able to determine the DHR depression because of the cancer-linked malnutrition. We did not observe any relationship between local extension of the tumour and lymph node involvement and DHR depression. In 90 well-nourished non-cancer patients the relation between DHR and age was investigated. The incidence of anergy and relative anergy was higher in patients over 59 years than in patients under 60 years (p<0.001).     

Nitrogen sparing effects and mechanisms of branched-chain amino acids in the injured rat

A series of experiments in a rat injury model were designed to elucidate the role and mechanisms of branched-chain amino acids in the post-injury catabolism. Our results suggest that: 1. Nutritional support can maintain nitrogen equilibrium in the early post-operative state. 2. Branched chain amino acids exert a nitrogen sparing effect and thus prevent or minimise post-operative catabolism. 3. Increasing the amount of infused branched chain amino acids results in nitrogen retention. 4. A balanced amino-acid mixture containing 45 per cent branched chain amino acids seems to be optimal for nutritional support in the post-injury state.     

Plasma amino acid pattern in burn subjects: influence of septicemia

A comparison of plasma amino acid levels was made between two groups of burn subjects, septic and non-septic. On day 4 after injury, results do not show any differences between patients who later went on to develop sepsis on day 7 and those who remained non-septic. Similarly, no differences between these two groups were discernable on day 7. Thus metabolic variations induced by septicemia do not seem to modify the usual burn-induced amino acid variations; consequently, plasma amino acid determination in burn patients do not appear to predict septicemia.     

Prolonged impairment of cell-mediated immunity after major abdominal surgery in malnourished patients

The effect of the nutritional status on postoperative impairment of the immune response was studied in adults undergoing major abdominal surgery. The immune function was evaluated by measuring in vitro the lymphocytic response to phytohaemagglutinin (PHA), concanavalin A (Con A) and the purified protein derivative of tuberculin (PPD) in whole blood cultures, and in vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD. Nutritional assessment was carried out by evaluating recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and the serum concentration of albumin and prealbumin. The patient was considered malnourished, if at least three of these criteria were abnormal. The immune parameters were measured preoperatively, at the end of the surgery and five days after operation. Before the operation both malnourished and well-nourished patients had normal lymphocytic responses, but the malnourished patients had a slower recovery of immune responses after the operation and they had an increased number of postoperative complications. No significant differences in the incidence of anergy were observed between the well and malnourished patients pre or postoperatively.     

Effects of preoperative parenteral nutrition on cell-mediated immunity in malnourished patients

Cell-mediated immunity was studied in 19 malnourished patients admitted for major abdominal surgery. Nine of them received total parenteral nutrition (TPN) before operation (the TPN group), while ten (the control group) were operated on without a period of TPN. In vitro lymphocyte proliferative responses to phytohaemagglutinin (PHA), concanavalin A (Con A) and purified protein derivative of tuberculin (PPD), were measured in whole blood cultures preoperatively, at the end of surgery and 5 days after operation. In vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD was studied preoperatively and 5 days after operation. Complications in both groups were observed and recorded. Nutritional assessment was carried out by evaluating the extent of recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and serum albumin and prealbumin concentrations. The patient was considered to be malnourished and was included in the study, if at least three of these criteria were abnormal. In the TPN group changes in mitogen induced lymphocyte proliferative responses caused by surgery were not significant. By contrast, responses in the control group decreased significantly (P < 0.01) during surgery and most of these responses differed from the preoperative values even at the fifth postoperative day. Anergy was equally common in both groups before and after surgery. The number of infectious complications was lower in the TPN group.     

Delayed hypersensitivity. A critical evaluation of five recall antigens in a large reference population

The reactivity to five recall antigens, candida, mumps, PPD, varidase and trichophyton and the corresponding diluents was tested in 840 healthy persons aged between 17 and 101 years. Candida antigen was tested in a lower (l) and a higher (h) dose. The size of reactions did not follow a Gaussian distribution and we therefore used the 10th and 5th percentiles instead of standard deviation to define the limits between positive, weak and negative reactions. The number of positive reactions to each of candida-h, mumps, PPD and varidase was between 80 and 95 per cent in patients less than 60 years of age and above this age it varied between 0 and 85 per cent. The number of positive reactions to candida-l and trichophytin was low in all ages. The reactivity was regarded as normal if there was a positive reaction i.e.sum of right angle diameters >10 mm to atl east one antigen, relatively anergic if there was only a weak reaction (7-9 mm) and anergic if there was a negative reaction (0-6 mm) to all antigens. A normal reaction was found in 100 per cent of subjects up to 60 years of age, and in 95 per cent up to 30 years. Among those with normal reactivity, positive results were found with candida-h alone in between 67-93 per cent, candida-h + mumps between 92-100 per cent and candida + mumps + PPD in 100 per cent irrespective of age.     

Effects of intravenous infusion of a ten percent soybean emulsion on hormones, amino acids and other substrates in blood

Acute responses in hormone and substrate concentrations to intravenous administration of a fat emulsion were studied in metabolically normal subjects. Eight subjects were infused with either a fat emulsion or an aqueous solution of glycerol for 3 h. Serum triglycerides (TG), free fatty acids (FFA), glucose, glycerol, 3-hydroxybutyrate (3-OH butyrate), insulin, thyroid hormones, plasma glucagon, norepinephrine, and amino acids were measured. The infusion of a fat emulsion induced a 30% increase in glucose and a 22% decrease in alanine together with significant elevations of TG (> 10 mM) and FFA (> 1 mM). A small increase in insulin (4 microU/ml) and a reduction in glucagon (40 pg/ml) were observed. Eight-fold increases in glycerol occurred with both the fat emulsion and glycerol infusions. The administration of a fat emulsion resulted in a 4-fold increase in 3-OH butyrate, whereas glycerol infusion reduced its level by 50%. Glycerol infusion produced no measurable effects on the substrates other than glycerol or 3-OH butyrate. No significant changes were observed in thyroid hormones or norepinephrine after either solution was given. The data suggest that acute elevation of FFA by means of intravenous fat emulsions leads to preferential oxidation of FFA and stimulates hepatic ketogenesis with resulting glucose conservation as well as inhibition of alanine production without many alterations in hormonal concentrations.     

The metabolic effects of isotonic amino acid infusion in surgical sepsis

28 normally nourished adult male and female patients who had undergone major elective surgery were maintained on dextrose-free isotonic amino acid solutions as their sole nutritional support. In the 6 days after surgery, 15 patients had no septic complications, 9 developed superficial sepsis, and 4 developed a deep seated collection of pus or deep sepsis. Patients without infection developed and maintained a fasting metabolic fuel profile within the first 3 days and increasingly spared protein. Superficial sepsis caused a small depression in serum ketone body concentrations but did not otherwise alter the fasting profile. Moreover nitrogen balances and plasma albumin and transferrin concentrations were unaltered by superficial sepsis which is not the response usually recognised with infection. Metabolic adaptation to the fasting state was lost in patients with deep sepsis and nitrogen losses were increased with greater decreases in plasma albumin and transferrin.     

Fat elimination in acute renal failure

Lipid metabolism and elimination of parenterally administered fat were investigated in 15 patients with acute renal failure (ARF). The mean triglyceride level was elevated to 2.56 +/- 1.43 mmol/l and the mean cholesterol level was 3.32 +/- 0.66 mmol/l, which is slightly below the normal range. A type IV hyperlipoproteinaemia was present in 47 per cent of the patients. The triglyceride content of LDL and VLDL was elevated and the cholesterol concentration of HDL and of LDL was reduced markedly. The fractional removal rate of triglycerides (K2) evaluated by an intravenous fat tolerance test using a bolus technique was reduced to 2.44 +/- 1.56 per cent/min which is about half of normal and correspondingly the elimination half life was prolonged to 28.4 min. No correlation could be demonstrated between the impairment of fat elimination and residual renal function, basal and VLDL triglyceride concentration or HDL cholesterol content.     

The roles of lactose and Clostridium difficile in the pathogenesis of enteral feeding associated diarrhoea

This study investigated the influence of the disaccharide lactose on the incidence of clinically significant enteral feeding associated diarrhoea. In this double blind study both groups each of 25 patients were randomised to receive either a lactose containing diet Clinifeed 400 in 25 patients or a lactose free diet Ensure in 25 patients. Diarrhoea occurred with equal frequency in both treatment groups, even in those patients with symptomatic and biochemical evidence of impaired lactose handling. Although the onset of diarrhoea was significantly associated with antibiotic administration (p<0.01), Cl. difficile was not isolated from the stools of any patient with diarrhoea.