Identification of secretory component as an IgA receptor on rat hepatocytes.

Secretory component (SC) was found to be synthesized by isolated rat hepatocytes. SC was detected by radioimmunoassay and cultured hepatocytes were found to synthesize 0.078 microgram SC/10(6) hepatocytes in a 48-h period. SC was also present on the surface of hepatocytes as detected by the specific binding of radiolabeled anti-SC antibodies as well as by the detection of specific membrane staining in indirect immunofluorescence tests using specifically purified anti-SC antibodies. Rat SC was detected on hepatocytes and intestinal epithelial cells but not on peripheral blood lymphocytes, unfractionated spleen cells, or erythrocytes. Specific binding of radiolabeled rat dimeric IgA to rat hepatocytes was also observed and evidence was obtained to indicate that such binding was mediated by SC. Thus, prior incubation of hepatocytes with anti-SC prevented binding of radiolabeled IgA. Moreover, prior incubation of radiolabeled IgA with rat SC prevented binding of the IgA to isolated hepatocytes. Cells treated with 0.25% trypsin lost their ability to bind to radiolabeled dimeric IgA.

Successful management of the short bowel syndrome.

Intestinal failure manifests as diarrhoea, fluid and electrolyte imbalance and malabsorption caused due to surgical resection of small intestine or very rarely due to nonfunctioning of large segment of bowel. Management of short bowel syndrome is quite challenging which requires better understanding of the site and extent of resected segment, pathophysiology of the remaining segment and the time of adaptation. Initial management includes control of diarrhoea with adequate fluid and electrolyte management which is critical for stabilization of the patient. Multidisciplinary approach to the patient is needed.

Renal effects of long-term treatment with 5-aminosalicylic acid.

BACKGROUND: A number of case reports link the use of 5-aminosalicylic acid (5-ASA) to interstitial nephritis in patients with inflammatory bowel disease (IBD). OBJECTIVE: To investigate whether the long-term use of 5-ASA has harmful effects on renal function in patients with IBD. METHODS: A retrospective analysis of 171 consecutive outpatients with Crohn's disease or ulcerative colitis was conducted. Serum creatinine levels and body weight were measured before and after treatment to calculate the creatinine clearance (CrCl) rate. RESULTS: In 171 patients (93 women, 78 men), the mean (+/- SD) dose of 5-ASA was 3.65+/-0.85 g/day with a cumulative dose of 11+/-7.7 kg over an interval of 8.4+/-5.9 years. Serum creatinine concentrations increased from 76.8 micromol/L to 88.7 micromol/L (n=171; P<0.0001) and the CrCl rate fell significantly from 104.6 mL/min to 93.1 mL/min (n=81; P<0.0001). There was one case of interstitial nephritis reported. Treatment groups included mesalamine (74.3%), sulfasalazine (15.2%) and combination (sulfalsalazine/mesalamine [10.5%]) with treatment durations of 7.2+/-4.5, 12.3+/-8.7 and 11.2+/-6.7 years, respectively. The duration of treatment was the most important covariate for change in CrCl and when analyzed by treatment group, those treated with sulfasazine had a strong correlation (r=-0.54, P=0.0145), while nonsignificant in the mesalamine group (r=0.06, P=0.7017). The decline in CrCl was negatively correlated with the pretreatment CrCl rate (r=-0.34; P=0.0024) and positively correlated with the mean daily dose of 5-ASA (r=0.32; P=0.0034). CONCLUSION: The present study is the first to demonstrate a significant dose- and treatment duration-dependant decline in CrCl. The risks need to be further evaluated because 5-ASA is widely used for long-term maintenance therapy in patients with IBD.

Design and evaluation by nitrogen balance and blood aminograms of an amino acid mixture for total parenteral nutrition of adults with gastrointestinal disease.

This study was undertaken to assess the efficacy of an amino acid mixture formulated for intravenous use from estimates of requirements for essential amino acids of human adults, and from data previously derived from a study using casein hydrolysate as the amino acid source. This mixture contained 39.4% essential amino acids, with glycine, alanine, arginine, histidine, and proline selected to supply the nonessential nitrogen. Nitrogen balance and blood aminograms were measured in six adult patients with gastrointestinal disease, fed intravenously for 1 wk at each of three levels of amino acid intake, while all other nutrients were constant and adequate in relation to body weight. Four of the patients were then fed 1.0 g/kg of egg or meat protein orally for 1 wk at the end of the 3 wk study, while all nutrients other than the amino acids were fed intravenously. Average nitrogen balances of -0.8, 0.5, and 2.2 g/day were observed when the amounts of amino acids infused were 0.25, 0.5, and 1.0 g/kg, respectively. Fasting levels of threonine, glycine, cystine, methionine, isoleucine, tryptophan, and arginine, but not of the other amino acids, increased with the increment in input, although the levels were generally lower than normal. The increase in blood concentration observed during infusion was similar for each of the essential amino acids, indicating that the supply of each of the amino acids was much better balanced for utilization than casein hydrolysate. However the blood aminograms did suggest that some changes in composition of the mixture for the malnourished adult were desirable, such that the amino acid mixture resembled that needed by the normal growing child. Nitrogen balance in the four patients fed orally with high-quality protein averaged 2.0 g/day, showing that an amino acid mixture given intravenously, provided it is well-balanced, can be utilized as efficiently as protein given orally. It is concluded that the prediction of oral requirements for amino acids should be combined with observations on changes in blood aminograms during infusion over a range of amino acid input in the development of amino acid mixtures for intravenous feeding.

Effect of dietary manipulations (fasting, hypocaloric feeding, and subsequent refeeding) on rat muscle energetics as assessed by nuclear magnetic resonance spectroscopy.

31P nuclear magnetic resonance (NMR) spectroscopy in vivo and fluorometry were used to measure muscle ATP, total creatine, pH, and Mg2+ in vivo; and to calculate creatine phosphate (CrP), the ratios of CrP/inorganic phosphate (Pi), CrP/ATP, free ADP levels, and the free-energy change in ATP hydrolysis so nutritional effects could be ascertained. These parameters were determined in vivo in resting control, 2-d-fasted, and hypocalorically fed rats and in animals similarly hypocalorically fed and then refed. The ATP, Pi, and intracellular Mg2+ levels were comparable in the four groups. When the fasted and underfed animals were compared with the control and refed animals, there were falls in the ratios of CrP/Pi and CrP/ATP, in the calculated CrP, and the free-energy change of ATP hydrolysis, but a rise in the calculated free ADP. In the hypocaloric group, intracellular pH fell significantly and a large peak was noted in the phosphodiester region. The data are consistent with the hypothesis that ATP levels are maintained at the cost of CrP, suggesting that ATP production is disturbed by aerobic and anaerobic mechanisms.

Effect of fasting, hypocaloric feeding, and refeeding on the energetics of stimulated rat muscle as assessed by nuclear magnetic resonance spectroscopy.

A previous study suggested that muscles from hypocalorically fed rats were limited in their ability to rephosphorylate ADP. During muscle contraction hydrolysis of ATP results in an increase in phosphorus, free ADP, delta GATP, and a reduction in phosphocreatine levels that is reversed during rest by rephosphorylation of ADP to ATP and the resynthesis of phosphocreatine by ATP. We therefore hypothesized that these changes would be restored more slowly during postcontraction rest in hypocalorically fed rats as compared with controls. We compared controls fed ad lib to 2-d fasted and hypocalorically fed rats, losing 20% of their weight. We also compared hypocalorically fed rats that had been refed ad lib for 7 d with age-matched controls fed ad lib. The results showed that ATP, muscle pH, and total muscle creatine levels were not different in all groups. The raised phosphorus and delta GATP levels and lower phosphocreatine/phosphorus ratio at the end of contraction changed more slowly during rest in the hypocaloric rats. These abnormalities were partially corrected by refeeding. The data taken as a whole support the concept of impaired rephosphorylation of ADP in malnourished muscle that is not completely restored by refeeding in stimulated muscle.

Effects of total parenteral nutrition and chemotherapy on the metabolic derangements in small cell lung cancer.

Changes in energy metabolism, substrate use, and hormone profiles were prospectively studied in 31 patients with small cell lung cancer receiving chemotherapy. Patients were randomized to receive either 4 weeks of total parenteral nutrition (n = 15) or to continue self-regulated p.o. diet (control group; n = 16). The initial actual resting energy expenditure measured by indirect calorimetry was 31% higher than the predicted resting energy expenditure determined by the Harris-Benedict formula. The p.o. calorie intake was inappropriately low for these hypermetabolic patients. Total parenteral nutrition resulted in a significant positive net energy balance, but in follow-up was associated with prolonged anorexia and a negative energy balance. Complete response to therapy reduced resting energy expenditure and increased calorie intake, whereas the contrary was true in nonresponders. Elevated plasma-free fatty acids (800 +/- 62 microM; S.E.) and a low respiratory quotient (0.74 +/- 0.02) indicate that the dominant energy source in patients with small cell lung cancer is fat, and that increased fat oxidation continues despite tumor response. Elevated fasting plasma catecholamines and insulin resistance may contribute to continued fat mobilization. Initially, there was a significant increase in blood lactate (1118 +/- 95 microM) suggesting either increased tumor or tumor-mediated glycolytic activity. Response to therapy was associated with a fall in blood lactate levels. The most effective way of improving the metabolic derangements in patients with small cell lung cancer was to achieve tumor response to therapy.

Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer.

During a randomized trial of total parenteral nutrition (TPN) in patients with small cell lung cancer, we evaluated the short- and long-term effects of 4 weeks of TPN on nutritional assessment parameters. All 119 patients who were accrued to the study received the same chemotherapy and radiotherapy protocol which extended over a 1-year period: 57 patients received TPN; and 62 served as controls. At base line, patients with greater than 5% pretreatment weight loss had significantly lower levels of serum albumin, total iron-binding capacity, and creatinine/height index. TPN administration led to a significant increase in mean caloric intake and weight compared with controls (P less than 0.0001). In the short-term study, body fat, as measured by triceps skinfold thickness, was maintained, and there was a small increase in arm muscle circumference. Serum albumin and hematocrit decreased but promptly returned to pretreatment levels when TPN was stopped. There were no long-term differences in any of the nutritional assessment parameters between the two groups.

Increased oxidative stress in patients with congestive heart failure.

OBJECTIVES: We sought to study the markers of lipid peroxidation and defenses against oxidative stress in patients with varying degrees of heart failure. BACKGROUND: Despite advances in other areas of cardiovascular disease, the morbidity and mortality from congestive heart failure (CHF) are increasing. Data mainly from animal models suggest that free radical injury may promote myocardial decompensation. However, there are no studies in humans correlating the severity of heart failure with increased free radical injury and antioxidants. METHODS: Fifty-eight patients with CHF and 19 control subjects were studied. In addition to complete clinical and echocardiographic evaluations, the prognosis of these patients was established by measuring the levels of soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2). Oxidative stress was evaluated by measuring plasma lipid peroxides (LPO), malondialdehyde (MDA), glutathione peroxidase (GSHPx) and vitamin E and C levels. RESULTS: The patients' age range, cause of heart failure and drug intake were comparable across the different classes of heart failure. Heart failure resulted in a significant increase in LPO (p < 0.005), MDA (p < 0.005), sTNF-R1 (p < 0.005) and sTNF-R2 (p < 0.005). There was a significant positive correlation between the clinical class of heart failure and LPO, MDA, sTNF-R1 and sTNF-R2 levels. There was an inverse correlation between GSHPx and LPO. With increased lipid peroxidation in patients with CHF, the levels of vitamin C decreased, but vitamin E levels were maintained. CONCLUSIONS: These data demonstrate a progressive increase in free radical injury and encroachment on antioxidant reserves with the evolution of heart failure; they also suggest that oxidative stress may be an important determinant of prognosis. The therapeutic benefit of administering antioxidant supplements to patients with CHF should be evaluated.

L-thyroxine absorption in patients with short bowel.

Because the exact site of thyroid hormone absorption in man is not known, we assessed the absorption of oral [125I]Na-L-T4 in patients with varying lengths of intact bowel and correlated this absorption with bowel length. Two normal subjects and five patients with surgical bowel resections, all of whom were euthyroid, were studied. Each received a tracer dose of [125I]Na-L-T4 orally, and serial samples of serum were assayed for radioactivity both with and without butanol extraction. The peak serum radioactivity in normal subjects occurred 2 h post ingestion and was 15% and 17% of the administered dose per liter serum and 11% and 13%/liter serum in butanol-extracted serum, respectively. In patients with shortened bowel, the peak radioactivity both in serum and butanol extracted serum was decreased, ranging from 2%-7% and 0%-5%/liter, respectively. There was no absorption of labeled T4 in the patient with a duodenum only. No consistent relationship was found between absorption and bowel length distal to the duodenum.

Delayed gastric emptying and improvement with domperidone in a patient with anorexia nervosa.

A woman with anorexia nervosa who displayed severe bloating after eating was treated with domperidone, a novel compound with prokinetic properties. Both subjective ratings of satiety and assessment of gastric emptying documented improvement.

In vivo breath alkane as an index of lipid peroxidation.

Interaction of active oxygen species with polyunsaturated fatty acids (PUFA) results in a series of reactions called lipid peroxidation. During the process of peroxidation of polyunsaturated fatty acids there is a scission of an alkane fragment extending from the methyl end of the fatty acid to the double bond. Thus, with a w-6 polyunsaturated fatty acid pentane is released, and with a w-3 polyunsaturated fatty acid ethane is released. These hydrocarbons are distributed in the body, partly metabolized, and excreted in the breath, making it possible to estimate the magnitude of in vivo lipid peroxidation by measuring pentane and ethane exhaled in breath. Advantages of this method are discussed as well as limitations and possible sources of error.

Total parenteral nutrition: potion or poison?

The role of nutritional support in clinical care has burgeoned over the past 40 y. Initially, total parenteral nutri-tion (TPN) was considered to be the standard of care. Later, the concept that enteral nutrition (EN) promoted gut function and prevented the translocation of intestinal bacteria resulted in EN becoming the standard of care. Furthermore, TPN was consid-ered to be a dangerous form of therapy. Critical review of the data suggests that, in humans, TPN does not cause mucosal atrophy or increase bacterial translocation. Increased sepsis with TPN can be ascribed to overfeeding; the dangers of TPN-induced complications have been exaggerated. TPN is an equally effective alternative to EN when a risk of malnutrition is present and EN is not tolerated or when gut failure is present.

Changes in body composition and dietary intake induced by tumor necrosis factor alpha and corticosterone--individually and in combination.

Previous studies have shown that anorexia and reduced food intake are the main causes of weight loss in rats infused with tumor necrosis factor alpha (TNF-alpha), with no influence on corticosterone concentrations. In contrast, in clinical sepsis, muscle wasting due to increased catabolism is associated with increased corticosteroid concentrations. We hypothesized that in the rat model, corticosterone potentiates the catabolic effect of TNF-alpha in amounts that by itself does not influence muscle catabolism. Orally fed rats were divided into 3 treatment groups: continuous infusion of TNF-alpha (TNF; 100 microg x kg(-1) x d(-1)), corticosterone (Cort; 50 microg x g(-1) x d(-1)), or both (TNF+Cort). Each group was compared with a respective pair-fed (PF) group. In addition an ad libitum (AL)-fed group receiving an infusion of physiologic saline was studied to observe unrestricted food intake and weight gain. After 4 d of infusion, dietary intake and weight gain were significantly higher in the Cort and AL groups than in the TNF and TNF+Cort groups. Although wet liver weights and protein contents were significantly higher in the Cort, TNF, and TNF+Cort groups than in their respective PF group, the TNF and TNF+Cort groups had lower relative carcass weights. The weight and protein content of the diaphragm were lower and nitrogen excretion was higher in the TNF+Cort group than in the respective PF group. The results suggest that TNF-alpha plus corticosterone had a specific catabolic effect on the diaphragm. In addition, together they increased overall nitrogen excretion.

Effect of hypoenergetic feeding and refeeding on muscle and mononuclear cell activities of mitochondrial complexes I--IV in enterally fed rats.

BACKGROUND: Previous studies suggested that cell energetics are altered by malnutrition. OBJECTIVE: We hypothesized that nutritional manipulations influence mitochondrial enzyme activities of the electron transport chain in both skeletal muscle and blood mononuclear cells. DESIGN: After a gastrostomy tube was inserted, 44 rats were randomly assigned to 1 of 4 experimental groups: control fed (CF; 364 kJ/d for 7 d), hypoenergetic fed (HF; 92 kJ/d for 7 d), hypoenergetic protein refed (HPR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d), and hypoenergetic glucose refed (HGR; 92 kJ/d for 7 d and then 129 kJ/d for 1 d). The protein and glucose contents of the liquid formulas were different for the HPR and HGR groups. After mitochondria were isolated from the soleus muscle, the activities of complexes I--IV were measured spectrophotometrically. Because of the lack of available tissue, only the activity of complex I was measured in the mononuclear cell extract. RESULTS: The recovery of complex activities in the CF and HF groups was not significantly different in the mitochondrial fraction of the soleus muscle. Compared with that in the CF group, the activities of complexes I--III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly lower in the HF group. The activities of complexes I--III in the mitochondrial fraction of the soleus muscle and the activity of complex I in mononuclear cells were significantly higher in the HPR than in the HF group. The activity of complex IV was generally not affected by nutritional manipulations. CONCLUSION: Malnutrition decreases activities of mitochondrial complexes, which are restored by protein but not glucose refeeding.

Effect of hypoenergetic feeding and high-carbohydrate refeeding on muscle tetanic tension, relaxation rate, and fatigue in slow- and fast-twitch muscles in rats.

Studies using nuclear magnetic resonance have shown that undernutrition affects muscle performance and energetics. It is unclear to what extent underfeeding and refeeding influence the availability of muscle glycogen, net glycogenolysis, skeletal muscle wasting, and recovery. We hypothesized that muscle performance is independent of muscle size and weight, is specific to muscle type, and is unrelated to muscle glycogen concentrations. Slow- and fast-twitch muscles were studied in three groups of adult male Wistar rats: well-fed controls, hypoenergetically fed (Hypo) rats, and rats refed for 4 d after the hypoenergetic diet. Glycogen concentrations and net glycogenolysis; serum glucose, insulin, and protein concentrations; and muscle weight, protein, and cross-sectional area were studied relative to the performance of both types of muscles. Our study controlled for muscle size, weight, and type and electrolyte-micronutrient deficiency. Undernutrition affected muscle performance in five ways. First, compared with controls, fatigue increased only in the soleus muscles of Hypo rats yet the maximal relaxation rate (MRR) decreased in both the soleus and extensor digitorum longus (EDL) muscles. Second, muscle glycogen concentrations did not significantly correlate with fatigue in either the soleus or the EDL although net glycogenolysis was significantly correlated with fatigue in the soleus (r = -0.64; P > 0.01 < 0.05). Third, lower glycogen concentrations did not hinder net glycogenolysis in the EDL of Hypo rats or the soleus of refed rats. Fourth, muscle weight, size, and protein were dissociated from function. Fifth, refeeding did not restore muscle endurance; however, the MRR of the soleus normalized. In conclusion, glycogen values and muscle performance did not correlate but net glycogenolysis correlated with fatigue in the soleus. Also, there was a dissociation between muscle weight, size, and protein and muscle function during hypoenergetic feeding and refeeding.

Nutritional and metabolic effects of the endotoxin bacterial lipopolysaccharide in orally and parenterally fed rats.

BACKGROUND: Animals treated with tumor necrosis factor alpha (TNF-alpha) developed severe metabolic abnormalities despite receiving sufficient protein and energy by total parenteral nutrition (TPN). OBJECTIVE: We sought to investigate the nutritional and metabolic effects of bacterial lipopolysaccharide (LPS) in rats. DESIGN: Rats were randomly allocated to 5 groups: oral nutrition (ON control; n = 7), TPN control (n = 7), ON+LPS (n = 6), TPN+LPS (n = 9), and pair fed (PF) in relation to ON+LPS (n = 6). RESULTS: Body weight decreased significantly as diet consumption decreased in the ON+LPS and PF groups compared with the ON control group. Relative carcass weights were significantly lower in the TPN+LPS and ON+LPS groups than in their respective control groups. Diaphragm and extensor digitorum longus weights were significantly lower in the ON+LPS and PF rats, but not in the TPN+LPS rats, compared with their respective controls. Biochemical abnormalities and plasma corticosterone concentrations were greater in the TPN+LPS group than in the other groups. CONCLUSIONS: These data suggest that provision of sufficient protein and energy by TPN does not prevent general carcass wasting induced by LPS but may protect individual muscles. However, compared with an oral ad libitum diet, TPN providing sufficient protein and energy worsens the biochemical abnormalities induced by LPS. More rapid clearance of TNF-alpha and low corticosterone concentrations in weight-losing animals may help reduce the severity of the metabolic effects of LPS.

Plasma vitamin E and selenium and breath pentane in home parenteral nutrition patients.

Because both vitamin E and selenium protect against lipid peroxidation, we evaluated the relationship between breath pentane, evolved from the peroxidation of linoleic acid, and plasma levels of alpha-tocopherol (vitamin E), Se, and Se-dependent glutathione peroxidase (Se-GSHPx). Nine home parenteral-nutrition (HPN) patients received added Se in intravenous solutions and were compared with 10 normal control subjects. The excretion of pentane (pmol.kg-1.min-1, means +/- SEM) in control subjects (6.34 +/- 0.96) was significantly lower than in HPN patients (15.02 +/- 1.12, p less than 0.001). alpha-Tocopherol (mumol/L), Se (mumol/L), and Se-GSHPx (U) values were, respectively, 18.13 +/- 1.70, 1.70 +/- 0.05, and 5.34 +/- 0.27 in control subjects and 10.21 +/- 1.66, 1.35 +/- 0.14, and 7.01 +/- 0.31 in HPN patients. All differences were statistically significant. Significant negative correlations were observed between plasma alpha-tocopherol levels and HPN duration and between pentane output and plasma alpha-tocopherol levels (r = -0.58, p less than 0.01). In HPN patients with reduced plasma alpha-tocopherol levels associated with increased pentane output, there is, inferentially, increased lipid peroxidation despite normal plasma Se and Se-GSHPx levels.

Dose-response relationships between amino acid intake and blood levels in newborn infants.

The objective of the present investigation was to investigate the nature of the blood amino acid response with amino acid intake in newborn infants. Forty-nine newborn infants of 640 to 4020 g birth weight and 26 to 40 weeks gestational age were placed on one of the following regimes within 48 hr of birth: intravenous dextrose with intravenous feeding of three levels of crystalline amino acid mixture, or of one level of casein hydrolysate, or with oral feeding of two levels of milk formula. Blood amino acid levels at 132 hr after feeding of graded levels of the intravenous amino acid solution were evaluated by regression analyses and compared to blood levels when casein hydrolysate was fed intravenously or milk formula was fed orally. At low levels of amino acid intake, such as were achieved with formula feeding, blood levels were relatively unchanged. However, with higher intakes, as were obtained with intravenous feedings, blood levels increased at rates which could be defined for each amino acid. This observation suggests that if the composition and rate of delivery of an amino acid solution is known, blood levels may be predicted.

Skeletal muscle function in malnutrition.

Skeletal muscle function was studied in 10 malnourished patients with various gastrointestinal disorders and in 22 normal subjects. The function of the adductor pollicis muscle was assessed by electrical stimulation of the ulnar nerve. The objective parameters of muscle function measured were: 1) Force of contraction expressed as a percentage of the maximal force obtained with electrical stimulation at 10, 20, 30, 50 and 100 Hz. 2) Maximal relaxation rate expressed as percentage force loss/!10 ms. 3) Endurance expressed as percentage force loss/30 s. The force of contraction at 10 Hz was higher in malnourished patients compared with normal subjects, with a mean +/- SEM (n) of 43.0 +/- 4.2% (n = 10) and 28.8 +/- 1.2% (n = 22), respectively, (p less than 0.001). The maximal relaxation rate was slower in patients compared with normals with a mean +/- SEM (n) of 7.2 +/- 0.4% (n = 9) ad 9.6 +/- 0.2% (n = 22), respectively, (p less than 0.001). Muscle endurance testing showed an increased force loss with prolonged tetanic stimulation in patients compared with normals, with a mean +/- SEM (n) of 29.1 +/- 4.0% (n = 7) and 3.5 +/- 0.8% (n = 22), respectively, (p less than 0.001). Four patients were restudied after a 4-wk period of total parenteral nutrition, with a significant improvement in muscle function parameters. Malnutrition results in both increased muscle fatiguability and an altered pattern of muscle contraction and relaxation which are reversible by nutritional supplementation. This technique promises to be valuable in assessing the functional effects of malnutrition and the response to nutritional support.