Craig L Kien

Increased rates of whole body protein synthesis and breakdown in children recovering from burns.

The rates of whole body protein synthesis and breakdown were determined, with the aid of a constant administration of [15N]glycine, during recovery in 11 acutely burned children, involving a total of 24 studies. Eleven studies were also conducted in seven healthy children before and after reconstructive surgery. Rates of whole body protein synthesis and breakdown, expressed as g protein/kg body weight/day, were significantly (p less than 0.05) and positiviely correlated with per cent body surface area total burn, per cent third-degree burn, and per cent open wound. These rates (synthesis, 7.1 +/- 2.1 g protein/kg/day; breakdown, 6.3 +/- 1.8 g protein/kg/day) were 80 to 100% greater (p less than 0.05) in patients with total burns greater than or equal to 60%, as compared to patients with less than 25% total burns or to the surgical patients. Because of the high energy cost of protein synthesis, it is proposed that an increased whole body protein turnover is partly responsible for the reported elevations in rates of heat production occurring in patients recovering from thermal injury.

Dressing Changes by Specialized Personnel Reduce Infection Rates in Patients Receiving Central Venous Parenteral Nutrition

In 60 pediatric patients, 75 central venous catheters representing 1866 patient days were placed to provide parenteral nutrition. During the 21-month study period, surgical residents were responsible for dressing changes during the first 16 months and a specially trained nurse was responsible during the final 5 months. Twenty percent of the lines became infected. The infection rate was significantly higher in the lines cared for by residents, 28.8% compared to 3.3% in the lines cared for by the nurse. This occurred in spite of the lines being in place significantly longer in the nurse group (31.7 vs 20.3 patient days/line). These data indicate that a specially trained person using aseptic techniques can reduce infection rates in patients receiving central venous parenteral nutrition.

Whole-body protein synthesis and breakdown rates in children before and after reconstructive surgery of the skin

The effects of minor surgery on dynamic aspects of whole-body nitrogen metabolism were explored in healthy children aged 4--15 yr. A continuous administration of 15N-glycine was used to estimate rates of whole-body protein synthesis and breakdown both before reconstructive surgery of the skin and 5 days afterward. Mean preoperative values for protein synthesis and protein breakdown were 3.9 and 3.4 g protein/kg body weight/day, respectively. Protein synthesis decreased by 15% (p less than 0.05) postoperatively, but body weight, intake of protein and calories, nitrogen balance, and protein breakdown did not differ significantly between the two periods. Protein synthetic rate correlated (p less than 0.05) with protein (r = +0.75) and calorie (r = +0.58) intake. These results indicate that minor surgery causes a small decrease in the rate of whole-body protein synthesis even though calorie and nitrogen balance are maintained.

Quantitative contribution by skeletal muscle to elevated rates of whole-body protein breakdown in burned children as measured by Nτ-methylhistidine output

Abstract To investigate the distribution of whole-body protein breakdown in children suffering from severe burn injury, the rates of skeletal muscle and whole-body protein breakdown were estimated in a total of 13 studies on 7 children, ages 4–13 yr, with body burns ranging from 36% to 83% of body surface area. Results were compared with values reported for healthy children. Whole-body protein breakdown was determined using 15N-glycine, and muslcle protein breakdown was estimated from measurements of urinary excretion of Nτ-methylhistidine. The children were receiving a flesh-free diet, free of exogenous Nτ-methylhistidine. The mean rate of whole-body protein breakdown was 5.7 ± 1.3 g protein/kg/day, which was higher than that found previously in healthy children of the same age group. The mean rate of Nτ-methylhistidine excretion was 4.3 μmoles/kg/day, or 205 μmoles/g creatinine; this was higher than the rate for healthy children as determined by interpolation of data reported in the literature. Estimating the rate of muscle protein breakdown from these data revealed that skeletal muscle accounts for 19.1% ± 7.6% of whole-body protein breakdown in burned children. When compared with published data for healthy subjects of varying ages, the present findings suggest that, although the rate of muscle protein breakdown is elevated in children recovering from burn injury, its percentage contribution to the rate of whole-body protein breakdown, also elevated in response to burn injury, remains within approximately normal limits.

Whole body protein synthesis in relation to basal energy expenditure in healthy children and in children recovering from burn injury.

Summary: Dynamic aspects of whole body nitrogen metabolism in children recovering from burn injury have been examined in relation to basal metabolic rate (BMR). A continuous administration of [15N]glycine was used to estimate the rates of whole body protein synthesis (S) and breakdown (C) in five acutely burned children (ages 5–16 years) and in nine healthy subjects (ages 9–18 years). S (grams of protein per kg body wt per day) and BMR were significantly correlated (r = +0.73; P < 0.01). There was no significant correlation of C with BMR. The ratio of S (grams of protein per day) to BMR (kilocalories per day) was the same in burned and healthy children; the mean value for all children was 0.10 ± 0.03 g protein synthesis/basal kcal. Calorie intake and S were significantly correlated (r = +0.70; P < 0.01). There were significant correlations between BMR and percentage of total body surface area burned (r = +0.66; P < 0.01), and BMR and age (r = −0.57; P < 0.05). Age did not correlate significantly with percent of total body surface burned.Speculation: A significant proportion of basal energy expenditure is directly associated with energy needs for whole body protein synthesis and breakdown. The results of the present study demonstrated an increase in BMR in children recovering from burn injury, and the statistical correlations between the rate of S and BMR suggest that body protein synthesis accounts for approximately 50% of the variation in resting energy expenditure in the burned child. If more extensive data on the correlation between rates of S and energy expenditure can be obtained, it should be possible to exploit this relationship to estimate the energy intake required to support a rate of S that would equal or exceed the rate of C and result, therefore, in net tissue protein gain.

THE CLOSE ASSOCIATION BETWEEN ACCELERATED RATES OF WHOLE BODY PROTEIN SYNTHESIS(S) AND BASAL METABOLIC RATE (BMR) IN CHILDREN WITH NEWLY DIAGNOSED ACUTE LYMPHOCYTIC LEUKEMIA (ALL)

Using a single dose [15N]-glycine technique in 15 newly diagnosed ALL patients, we confirmed our previous data which showed increased rates of S and whole body protein breakdown in comparison to healthy controls (independent of prior prednisone treatment; 8 so treated) (Cancer Res 43:5586). In 8 patients we assessed basal oxygen consumption (BMR; assume 4.83 kcal/1 O2); there was a significant linear regression between BMR (kcal/d) (Y) and S (g protein/d) (X): Y=3.7 X + 850 (R=0.925, p<0.001). Individual values (Y,X) for the 8 patients were: 835, 36; 1085, 87; 1252, 121; 1273, 134; 1614, 124; 1551, 179; 2087, 394; 2212, 308. Excluding the 2 highest values for Y and X, there was still a significant correlation (R=0.87, p<0.05), and there was a positive rank correlation for all 8 values (R=0.905, p<0.01). There were also significant positive correlations between BMR and body weight (Wt) (R=0.75, p<0.05) or age (R=0.83, p<0.05) and between S and Wt or age (both, R=0.86, p<0.01). Multiple regression analysis revealed that BMR was much more highly related to S than to Wt. These data suggest that increased energy costs of S account, at least in part, for increased energy requirements in patients with ALL. (Support: Nutrition Foundation, Inc.; Leukemia Soc. of America, Inc.; MACC Fund).

HIGH DIETARY PROTEIN/ENERGY (P/E) RATIO SPARES TISSUE NITROGEN (N) ASCITES TUMOR-BEARING MICE TREATED WETH ACINETOBACTER GLUTAMINASE-ASPARAGINASE (AGA)

Previously, we showed that a high protein (58g%; HP) diet caused marked N sparing of liver (L), intestine (I), thymus (T), and carcass (C) compared to an isocaloric, normal protein diet (20g%; NP) in normal mice treated with AGA (Pediatr Res 17: 192A). In the present study, 32 mice previously innoculated with Ehrlich Ascites tumor were randomized into 2 treatments: AGA (600 IU/kg/d, 7d) and 0.9% NaCl controls and into 2 diets HP or NP. In both diet groups, AGA resulted in markedly lower (p<0.01) tumor burdens as characterized by ascites volume, cell count, or tumor N content, but HP did not increase tumor burden. In the AGA group: HP resulted in significant N sparing in the following tissues (% increase from NP; P value): L (18%; P=0.05), I (25%; p<0.05), T (164%; p<0.01); HP completely prevented the N depleting effect of AGA on L and T; HP resulted in significantly (p< 0.05) higher hematocrit (42%) and serum total protein (5.5 g/dl) compared to NP (33% and 5.0 respectively) but in lower total food intake and insignificant differences in blood counts. Our conclusion may be relevant to man, to other cancers, and to those forms of chemotherapy which affect Nutilization: an increased dietary P/E ratio, even without energy supplementation, may improve N content of T, L, and I without antagonizing anti-cancer therapy. (Support: NIH Grant CA20061)

EFFECT OF pH on RECOVERY OF ENERGY (E) DERIVED FROM SHORT CHAIN FATTY ACIDS (SCFA) IN FECES: RELEVANCE TO STUDIES OF CARBOHYDRATE ENERGY (CE) ABSORPTION IN PREMATURE INFANTS (PI)

Our previous studies of PI suggested that there is minimal fecal excretion of CE derived from lactose or glucose polymer (Am J Clin Nutr 36:910). To further assess our methodology (loss of SCFA via volatilization), the following SCFA were added to fecal homogenates in sufficient quantities to raise the energy density by 18-27%: acetic (A), propionic (P), valeric (V), and butyric (B). The pKas of these acids are respectively 4.75, 4.87, 4.82, and 4.81. Fecal samples were then either alk-alinized (Alk) (pH 7.9-8.7), acidified (2.8-3.2) or left unchanged (UNC) (4.0-4.8). After storage on dry ice for 24 hrs, the samples were lyopholized and bomb calorimetry performed. There was an approximate 20% loss of SCFA in the Alk and UNC groups (Table). The potential clinical significance of this error during E balance studies will be small (<5% CE intake) unless the actual fecal excretion of SCFA exceeds 24% of CE intake. (Support: NIH Grant HD17401).

SPECIALIZED NURSES REDUCE INFECTION RATES IN CENTRAL VENOUS PARENTERAL NUTRITION (CVPN)

Although some institutions use a specially trained nurse to change CVPN dressings, the actual effect such an individual has on reducing infection rates and decreasing complications of CVPN has not been proven. During a 9 month period all children receiving CVPN were followed for both mechanical and infectious complications. For 4 months, surgical residents (group R) were responsible for the dressing changes and for the subsequent 5 months, two trained nurses were responsible for dressing changes (group N). The protocol for handling the lines was otherwise the same for the two groups. The two groups were comparable for most known confounding variables. These include primary illness, serum albumin, lymphocyte count, age, race and sex; however, lines from group N were in place longer (t=2.21,p<0.05). In group R, 49% of the lines were removed because of septic or mechanical complications. This rate compared to 20% in group N (X2=6.42,p<0.05). The infection rate alone was also higher in the R group, 31% compared to 3.3% in the N group (X2=8.7,p<0.01): relative risk (RR)=9.3. When patient days on CVPN was used as the denominator, the difference between the groups was greater, 1.42 infections/100 patient days in group R versus 0.11 in the N group (RR=12.9,p<0.01). These data indicate that the utilization of a highly trained individual using meticulous care for all dressing changes is an extremely important factor in lowering infection rates in CVPN lines.

445 LOW SERUM 3,3′,5′ TRIIODOTHYRONINE (REVERSE T 3 ) CONCENTRATION IN BURNED CHILDREN AND ITS RELATIONSHIP TO NUTRITIONAL STATE

We studied the correlation between protein turnover and serum thyroid hormone levels in 10 children, age 1-16 yrs., with severe burn injuries. Whole body protein synthesis (S) and breakdown (C) were determined using an (15N) glycine infusion technique. Patients were maintained in good nutritional status as evidenced by a net anabolism (S,C) in 14 of 21 studies. There was no change in mean levels of serum 3,3′,5′ triiodothyronine (T3), a decrease in serum thyroxine (T4) and a suppression of serum reverse T3 levels.The difference between protein synthesis and breakdown (S minus C) was negatively correlated with the rT3/T3 ratio (r=-.0.46,p .05). Thus, a decrease in N balance was associated with a rise in rT3/T3 ratio, similar to observations made in humans during fasting or severe stress. These studies suggest that the rT3/T3 ratio may be useful clinically as an indicator of relative dietary energy deficiency.