Low blood selenium levels in patients with cystic fibrosis compared to controls and healthy adults

Frank clinical selenium deficiency has been described in cystic fibrosis (CF), and a relative deficiency has been proposed as contributing to the pathogenesis of the disease. Because of these possibilities, we investigated the relationship between overall nutritional status in CF with measures of selenium nutriture. Fifteen stable outpatients with CF (group I) were compared to 13 age-matched controls (group II) and 27 healthy adults (group III). Whole blood, plasma, and red blood cell selenium levels were reduced by 31%, 29%, and 33%, respectively, in CF patients vs controls (all p less than 0.001). In addition, both groups I and II showed significantly lower blood selenium levels than healthy adults (p less than 0.005). Nutritional assessment revealed CF patients to be undernourished, with significant decreases in serum albumin (p less than 0.025), weight-for-height deficit (p less than 0.01), and weight-for-age (p less than 0.025) vs controls. However, only the triceps skinfold (TSF) measurement correlated significantly with selenium status (r = 0.56: p less than 0.05 for whole blood selenium vs TSF). We conclude, based on the magnitude of decrement in blood selenium, that it is unlikely that selenium plays a significant primary pathogenic role in cystic fibrosis. However, these patients are at high risk for developing clinical selenium deficiencies. The measurement of blood selenium levels using appropriate age-matched normal standards should be mandatory in all CF patients with malnutrition, or in those requiring parenteral nutritional support.     

Reduced cardiac selenium content in the acquired immunodeficiency syndrome

Selenium deficiency has been implicated in the pathogenesis of a dilated congestive cardiomyopathy in areas of China (Keshan disease) and in several patients on long-term total parenteral nutrition. Recently a clinically and pathologically similar cardiomyopathy has been described in AIDS. Since blood selenium levels are low in AIDS, we assayed cardiac selenium status by a spectrofluorometric method in eight AIDS patients at autopsy compared to nine age-matched, non-AIDS autopsy controls with histologically normal hearts. We found (mean +/- SD) a cardiac selenium level of 0.327 +/- 0.082 microgram/g dry weight in AIDS vs 0.534 +/- 0.184 microgram/g dry weight in controls (p less than 0.01; Student's t test). There were no significant differences between the groups for heart weight, serum CPK, or other laboratory parameters. No specific chest x-ray or electrocardiographic abnormalities were present. Histologically, all AIDS hearts were abnormal; mostly with mild degrees of muscle hypertrophy or fibrosis. Foci of myocytolysis and myocyte necrosis and fibrous replacement of myocytes and monocytic infiltration were present in two AIDS cases. We conclude that heart tissue in AIDS demonstrates a significant selenium deficit. These data provide a potential link between selenium deficiency and cardiomyopathy in AIDS.     

Insulin-like growth factor-I in human malnutrition: relationship with some body composition and nutritional parameters

The insulin-like growth factor-I (IGF-I) plasma concentration was evaluated as a nutritional parameter in 18 patients affected with chronic malnutrition secondary to biliopancreatic bypass and compared with albumin, transferrin, and with body composition parameters: total body water (TBW), total body sodium (TBNa), total body potassium (TBK). Subjects were studied in malnutritional conditions and after 20 to 30 days of parenteral and enteral refeeding treatment. Immunoreactive IGF-I concentration was 0.35 U/ml +/- 0.07 (mean +/- SEM), significantly lower (p less than 0.01) than in age-matched controls (1.14 +/- 0.07 U/ml, n = 29) and rose significantly (0.84 +/- 0.12 U/ml; p less than 0.01) in parallel with the improvement of nutritional status. The ratios TBNa/TBW, TBNa/TBK, and TBK/TBW were then considered as reference parameters for definition of malnutritional state, and compared with IGF-I as well as with the most commonly used parameters, albumin and transferrin. Before treatment, IGF-I evidenced higher specificity (true negative ratios 0.63, 0.43, and 0.40 with regard to TBNa/TBW, TBNa/TBK, and TBK/TBW, respectively) than albumin (0.13, 0.14, and 0.10) and transferrin (0 in all cases), and slightly less sensitivity (true positive ratios for IGF-I 0.80, 0.67, and 0.67; always one for albumin and transferrin). Moreover, IGF-I resulted definitely more sensitive in assessing the effectiveness of the refeeding treatment and, on the basis of the likelihood ratio, it appeared a good discriminator of the nutritional status. The data indicate that different nutritional factors regulate IGF-I, albumin, and transferrin, and suggest that IGF-I can be used as a reliable and specific nutritional parameter, complementary to the others currently used.     

Low serum selenium and glutathione peroxidase activity in patients receiving short-term total parenteral nutrition

Selenium status was determined in 15 consecutive postoperative patients receiving short-term total parenteral nutrition (TPN) using both serum selenium concentration and glutathione peroxidase (GSH-Px) activity as an indicator of body selenium status. The serum selenium concentration was significantly (p less than 0.001) lower in TPN patients (0.52 +/- 0.16 mumol/l, mean +/- SD) than in age- and sex-matched controls (1.08 +/- 0.17 mumol/l). Serum selenium in TPN patients ranged from 0.28 to 0.79 mumol/l and was associated with the duration of TPN. The lowest selenium values was found in patients who had received TPN over 3 weeks (0.35 +/- 0.06 mumol/l) as compared to patients receiving TPN for 1-3 weeks (0.61 +/- 0.13 mumol/l; p less than 0.01). Serum GSH-Px activity in TPN patients was also low (116 +/- 21 U/l) and ranged from 75 to 159 U/l. A significant positive correlation was found between serum selenium and GSH-Px activity (r = 0.520; p less than 0.05) whereas serum selenium and GSH-Px activity did not correlate significantly with liver function tests and body mass index. This study suggests that also short-term TPN patients may be at risk of selenium deficiency.     

The interactions of insulin-like growth factor I(IGF-I) with protein-calorie malnutrition in patients with alcoholic liver disease: V.A. Cooperative Study on Alcoholic Hepatitis VI

Plasma concentrations of insulin-like growth factor I (IGF-I) were measured in 95 alcoholic men with a spectrum of alcoholic liver injury and protein-calorie malnutrition (PCM). Circulating levels of IGF-I were depressed in the alcoholic patients (0.23 +/- 0.02 U/ml; mean +/- S.E.M.) compared to controls (1.0 +/- 0.07, P less than 0.0001). Plasma IGF-I levels declined progressively with falling indices of PCM (P less than 0.001) and correlated especially with the parameters relating to protein deficiency. While the severity of liver dysfunction and histopathologic alterations in the liver also related to plasma IGF-I concentration, partial correlation analysis showed that only PCM correlated significantly with IGF-I levels independent of the other factors. These findings indicate that IGF-I levels reflect nutritional status even in the presence of alcoholic liver disease.     

Selenium status prior to and during one month total parenteral nutrition in gastroenterological patients: A randomised study of two dosages of Se supplementation

13 consecutive adult gastroenterological patients with non-malignant disease who were candidates for total parenteral nutrition (TPN), and who had mild protein-energy malnutrition (82 +/- 3% of ideal body weight, serum albumin 32 +/- 2 g/l, mean +/- SEM) were found to have, prior to TPN, a Selenium level 50% less than controls (p < 0.001) as assayed by Se and glutathione peroxidase (GSHPx) in plasma and erythrocytes. Compared with other trace metals and minerals, eg, Mn, Zn and Cu, depletion of Selenium was the most marked in this population. Patients were randomised to be supplemented with either 100 or 200 mug/d of sodium-selenite, equal to 32 mug (0.4 mumol) or 64 mug (0.8 mumol) of selenium, in two cross-over periods of TPN, each of two weeks. In this short term study, significant increases in the four measurements of Se status (p < 0.05) were seen in all patients, but there was no difference between those receiving the high or low dose of the element. GSHPx in plasma was normalised within 1 month whereas the increase seen in the erythrocyte pool was consistent with a 4-month half-life. Pooled Se values for patients and controls showed logarithmic correlations between Se and GSHPx in erythrocytes (p < 0.001) and plasma (p < 0.01). Changes in GSHPx provided further evidence of Se depletion in our patients. This study suggests that malnourished gastroenterological patients receiving TPN require Se supplements and that 100 mug (0.4 mumol)/d of sodium-selenite is adequate for most patients since there was no additional benefit from the higher dose of 200 mug (0.8 mumol).     

Blood selenium and glutathione peroxidase activity in normal subjects and in surgical patients with and without cancer in New Zealand.

This study was carried out in Otago, South Island, where most arable land has a low soil selenium content (less than 0.5 microgram/g) and where selenium (Se) responsive diseases in livestock are common. Se concentration in whole blood, erythrocytes and plasma, and activity of glutathione peroxidase (EC 1.11.1.9) were measured in blood from 104 healthy Otago residents, 80 patients with cancer and 66 noncancer surgical patients. The older residents over 60 years had lower blood Se levels (0.047 +/- 0.010 microgram Se/ml blood) than the young and middle-aged (0.060 +/- 0.012 microgram Se/ml). Blood Se levels of cancer patients were no lower than those of elderly subjects and patients without cancer, and were less than half comparable United States values. Blood Se levels were decreasing in two cancer patients, and the lowest values (less than 0.03 microgram Se/ml blood) were obtained for five cancer patients, and two noncancer patients after a long period of inanition; these were similar to values for patients on parenteral nutrition with negligible intakes. Lower blood Se levels were associated with lower serum albumin and enzyme activities. It is suggested that low Se status of cancer patients was more likely a consequence of their illness than the cause of the cancer.     

Response to total parenteral nutrition in the extremely malnourished patient

Changes in serum albumin levels and body weight are often used as indicators of the efficiency of a nutritional support regimen. Patients with moderate nutritional depletion demonstrate two distinct patterns of response during refeeding. The first is characterized by a decrease in the previously expanded extracellular fluid space with a rise in serum albumin and a loss of weight and the second by continued fluid retention with weight gain and no rise in serum albumin concentration. The second pattern has been observed in patients with ongoing stress such as infection. This study examines severely malnourished patients with no apparent inflammatory complications and demonstrates that this group responds to nutritional support in a pattern similar to that seen in the stressed patient. Eight patients with profound malnutrition were studied during the 1st week of nutritional support. Nitrogen balance was measured and the findings confirmed that all patients were anabolic. Sodium balances were used as an indicator of changes in the extracellular fluid compartment. Body weight and serum albumin were assessed daily. Body weight increased from 59 +/- 4 to 62 +/- 4% of normal (p less than 0.01) while serum albumin changed insignificantly (3.00 +/- 0.27 to 2.85 +/- 0.23 g/100 ml, NS) during the initial week of an adequate nutritional support regimen (nitrogen balance was +21.0 +/- 4.3 g, p less than 0.05). These changes were associated with a positive sodium balance (+215 +/- 20 mEq, p less than 0.05). These data confirm that some extremely malnourished patients do not experience a diuresis during the initial phase of nutritional support but rather may retain water and increase body weight.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nutritional status of diabetic and nondiabetic patients after renal transplantation

To assess whether there was improvement in the nutritional status of Type I insulin-dependent diabetics treated with renal transplantation as compared with dialysis, 24 diabetics and 21 nondiabetics were studied 22.6 +/- 23.8 mo after transplantation. Nutritional assessment included weight, height, triceps skinfold thickness, midarm muscle circumference (MAMC), serum albumin, and transferrin. Mean age of the 28 males and 17 females was 37.1 +/- 9.4 yr. Weight of diabetics increased from 55.6 +/- 8.4 kg to 61.5 +/- 9.5 kg (p less than 0.05); weight for height, from 81 +/- 8% to 95 +/- 9% (p less than 0.001); and serum albumin, from 3.8 +/- 0.5 gm/dl to 4.3 +/- 0.4 gm/dl (p less than 0.001). Weight also increased significantly in nondiabetics from 64.5 +/- 10.5 kg to 72.1 +/- 13.5 kg (p = 0.05); weight for height, from 96 +/- 15% to 108 +/- 16% (p less than 0.05); but not albumin, 4.1 +/- 0.7 gm/dl to 4.4 +/- 0.6 gm/dl (p greater than 0.05). Serum transferrin was 210 +/- 62 mg/dl in diabetics and 226 +/- 52 mg/dl in nondiabetics. Forty-two percent of diabetics and 29% of nondiabetics had a MAMC less than 5th percentile, indicating protein-calorie malnutrition. Results suggest a significant improvement in nutritional status after transplantation in both diabetics and nondiabetics, but particularly in the diabetic group.     

Utilizing selenious acid to reverse selenium deficiency in total parenteral nutrition patients

The ability of selenious acid to reverse selenium deficiency in eight adult home TPN patients was assessed. Initially, deficiency was documented by comparing both plasma selenium levels in patients (means = 0.035 micrograms/g) to those of 10 controls (means = 0.117 micrograms/g) (p less than 0.001) and by comparing erythrocyte glutathione peroxidase (GSHPx) activity, as mumol NADPH oxidized/g Hb/min, in patients (means = 8.93) to controls (means = 31.76) (p less than 0.002). Subsequently, patients added 100 micrograms/day of selenious acid to their total parenteral nutrition solutions. Postsupplementation selenium status demonstrated a mean plasma level of 0.101 micrograms/g and a mean erythrocyte GSHPx activity of 17.56. Statistically, patients' plasma selenium levels were significantly different (p less than 0.001) when compared to pretreatment levels. Additionally, there was no significant difference between the restored levels and the levels of the controls. Postsupplementation erythrocyte GSHPx activity (means = 17.56) was not significantly different from the initial patient values, although activity did double. Additionally, there existed a significant difference between the postsupplementation enzyme activity and the controls (p less than 0.03). We conclude that selenious acid is able to normalize deficient plasma levels but not deficient erythrocyte GSHPx activity.     

Vitamin E deficiency in phrynoderma cases from Sri Lanka

Phrynoderma cases were identified in a village close to Colombo in Sri Lanka. The alpha-tocopherol level in plasma was 3.3 +/- 0.6 mumol/L among the phrynoderma patients (n = 11) and 13.0 +/- 2.3 mumol/L among the control subjects (p less than 0.002). A test on glutathione reductase activity in erythrocytes revealed a stronger riboflavin deficiency among patients than among control subjects (p less than 0.005). No significant differences were found between the groups with regard to plasma levels of retinol, retinol-binding protein, vitamin B-12, folic acid, thiamin, selenium, zinc, or essential fatty acid pattern. Primary malnutrition may partly explain the deficiency of alpha-tocopherol and riboflavin observed in phrynoderma cases.     

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin - ALB, transferrin - TRF, transthyretin - TTR, retinol binding protein - RBP, fibronectin), inflammation (C-reactive protein - CRP, alpha(1) glycoprotein acid - alpha(1)GPA) and catabolism (plasma phenylalanine - PHE, urinary 3-methylhistidine - 3-MH). Values were expressed as mean +/- SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 +/- 5 vs 42 +/- 3 g.l(-1); TTR = 118 +/- 75 vs 251 +/- 43 mg.l(-1); RBP = 23 +/- 12 vs 46 +/- 8 mg.l(-1); p < 0.001), were hypercatabolic (3-MH Cr = 31 +/- 12 vs 22 +/- 7 mumol.mmol Cr (-1); PHE = 62 +/- 27 vs 46 +/- 10 mumol.l(-1); p < 0.001) and inflamed (CRP = 68 +/- 50 vs 12 +/- 5 mg.l(-1); alpha(1)GPA = 1.2 +/- 0.4 vs 0.5 +/- 0.1 g.l(-1); p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.     

Increased plasma lipid peroxidation in riboflavin-deficient, malaria-infected children

Plasma lipid peroxides were measured as malonyldialdehyde (MDA) by the thiobarbituric acid (TBA) method in 75 children suffering from Plasmodium falciparum malaria. Their riboflavin status was assessed by measuring erythrocyte glutathione reductase activation coefficients (EGRACs), and values greater than 1.40 were regarded as indicating biochemical deficiency. Plasma MDA was higher (p less than 0.001) in patients than in control subjects; the concentrations were 3.65 +/- 0.70 and 1.77 +/- 0.45 mumol/L (means +/- SD), respectively. The riboflavin-deficient group had higher plasma MDA values (3.98 +/- 0.70 mumol/L) than did the nondeficient group (3.30 +/- 0.68 mumol/L, p less than 0.001). Plasma MDA concentrations correlated with EGRACs (r = 0.46, p less than 0.01) in the patients. It is proposed that riboflavin deficiency restricts regeneration of reduced glutathione making the parasitized erythrocytes more vulnerable to destructive lipid peroxidation and increasing plasma lipid hydroperoxides.     

Fever and malnutrition: endogenous pyrogen/interleukin-1 in malnourished patients

The effect of protein-calorie malnutrition on the release of endogenous pyrogen/interleukin-1 (EP/IL-1), the protein responsible for the induction of fever, was investigated in 18 hospitalized patients with chronic malnutrition. Monocytes from the 18 patients and from 19 healthy controls were cultured overnight after stimulation with Staphylococcus epidermidis. The presence of EP/IL-1 was tested by injecting culture supernatants into rabbits and measuring the maximum febrile response (delta Tmax). Malnourished patients produced significantly less EP/IL-1 than controls (delta Tmax = 0.27 +/- 0.04 degrees C for patients vs 0.49 +/- 0.03 degrees C for controls, p less than 0.001). The poor febrile response in the malnourished patients was related to low serum albumin and retinol-binding protein, but not to thyroxine-binding albumin or lymphocyte number. This abnormality may help explain the poor febrile response often noted in hospitalized debilitated patients.     

Body composition studies in patients with the acquired immunodeficiency syndrome

Body composition studies were performed in 33 patients suffering from the acquired immunodeficiency syndrome (AIDS). Studies included measurements of total body potassium, fat, and total body and extracellular water volumes plus serum retinol binding protein concentration, iron binding capacity, and albumin concentration. AIDS patients were underweight (p less than 0.001) and were depleted of potassium (p less than 0.001) with the lowest values occurring in patients close to death at the time of study. Body fat contents also were reduced. Intracellular water volumes were decreased in the AIDS patients (p less than 0.001) with a relative increase in extracellular water volume (p less than 0.001). Serum protein concentrations were decreased in the AIDS patients. Longitudinal studies did not demonstrate tissue repletion in patients with AIDS, despite apparent clinical stability. These studies demonstrate that severe, progressive malnutrition occurs in patients with AIDS. If malnutrition can be shown to have a deleterious effect upon the disease course, therapy of malnutrition may play an important role in the treatment of this disorder.     

Natural killer cell activity in alcoholic cirrhosis: influence of nutrition

Forty-five patients with alcoholic cirrhosis, 20 chronic alcoholics with normal liver function tests and 36 healthy subjects were investigated. A combined index of nine anthropometric and biochemical parameters (triceps skinfold, arm muscle circumference, mid-arm muscle area, body fat percentage, creatinine-height index, serum albumin, plasma transferrin, prealbumin and retinol-binding protein levels) was used to evaluate nutritional status, allowing a distinction to be made between those patients with adequate nutrition (group I: 40 per cent of cirrhotics and 55 per cent of alcoholics), those with slight malnutrition (group II: 37.7 per cent of cirrhotics and 45 per cent of alcoholics) and those with severe malnutrition (group III: 22.2 per cent of cirrhotics and none alcoholic). Natural Killer (NK) cell activity of peripheral blood lymphocytes was determined using a 51Cr releasing cytotoxicity assay against K562 target cells. This was significantly lower in the cirrhotics than in the controls and chronic alcoholics (P less than 0.001 and P less than 0.01 respectively), but there was no difference between the latter two groups. Natural Killer activity was significantly lower in samples obtained from cirrhotics with severe malnutrition than in those with adequate nutrition, suggesting that malnutrition may play a role in the onset of the immunological disorder. No relationship could be established between nutritional status, NK activity and the clinical activity of the disease using Orrego's index on the liver function tests.     

Electrocardiographic and echocardiographic findings in malnourished children

OBJECTIVE: To compare heart abnormalities in a group of malnourished children with a control group and to describe their predictive variables. METHODS: Thirty children with malnutrition were matched with thirty healthy children. Anthropometry, plasma levels of albumin and electrolytes were determined. Among others, corrected QT interval (QTc) and QT dispersion (QTd: difference between the maximum and the minimum QT) were measured in 12-lead electrocardiogram; and left ventricular mass (LVm) and left ventricular mass index (LVmi) were measured by echocardiography. Regression analyses were performed with cardiac findings as dependent variables and anthropometric and biochemical data as independent variables. RESULTS: Plasma levels of albumin, potassium and calcium were lower in malnourished children. QTc and QTd were significantly greater in patients with malnutrition than in controls (QTc: 445.9 +/- 31.4 vs. 400.9 +/- 17.7 ms, p = 0.000; QTd: 76.4 +/- 34.1 vs. 47.9 +/- 10.2 ms, p = 0.000). LVm and LVmi were significantly lower in malnourished children (LVm: 55.3 +/- 10.3 vs. 71.4 +/- 6.9 g, p = 0.000; LVmi: 46.5 +/- 6.6 vs. 60.5 +/- 4.9 g/m2, p = 0.000). The body mass index (kg/m2) was the most powerful predictor of the variability in QTc (39.1%), LVm (48.1%) and LVmi (51.2%). CONCLUSIONS: Important electrocardiographic and echocardiographic abnormalities have been found in malnourished children associated with their nutritional status. Special precaution must be taken about the possibility of occurrence of arrhythmias and sudden death related with malnutrition.     

The response of fibronectin to differing parenteral caloric sources in normal man

The relationship between circulating fibronectin concentration and nutritional status was examined in eight healthy male (31 +/- 1 yr old) volunteers in three nutritional states: the postabsorptive state, after 10 days of protein-caloric starvation, and during the 10th day of refeeding by total parenteral nutrition. Plasma fibronectin was significantly decreased from 330 +/- 22 to 154 +/- 11 micrograms/ml (p less than 0.001) from the postabsorptive to starved state which was accompanied by appropriate changes in body weight, anthropometric measurements, and nitrogen balance. Plasma fibronectin levels were restored to 402 +/- 39 micrograms/ml following 10 days of total parenteral nutrition. The plasma fibronectin response was greater (p less than 0.05) during total parenteral nutrition with dextrose as the nonprotein calorie source as compared to a 50% dextrose/50% lipid regimen. These results suggest that the calorie source must be considered during interpretation of plasma fibronectin levels in patients undergoing parenteral nutrition.     

Changes in nutritional status associated with obstructive jaundice and biliary drainage in rats

Effect of bile duct ligation (BDL) and internal biliary drainage on food intake and nutritional status was studied in rats and compared with sham and pair-fed animals. During week 1, food intake of BDL animals was reduced (p less than 0.05), resulting in weight loss (p less than 0.05). In weeks 2 and 3, food intake, nitrogen balance, and weight gain were similar in all groups. Internal biliary drainage or sham operation after 3 wk produced transient changes in food intake and N2 balance. Serum albumin fell in all groups, returned to normal in sham (3.2 +/- 0.1 g/dl) and pair-fed (3.1 +/- 0.1 g/dl), but persisted in BDL rats (2.4 +/- 0.2 g/dl, p less than 0.001). Jaundice was associated with anemia. Although BDL produces transient changes in food intake, weight gain, and N2 balance, anorexia and malnutrition are not features of this animal model. Nutritional risk factors associated with hyperbilirubinemia are probably due to changes in intermediary metabolism.