Decreased serum selenium in alcoholics as related to liver structure and function

Serum selenium was evaluated in relation to hepatic structure and function in 46 alcoholics with diagnostic liver biopsy classified into 4 groups by hepatic histology. Their serum selenium concentration varied from 12 to 88 micrograms/l and was lower (p less than 0.001) in all groups of alcoholics, ie patients with normal liver (53.0 +/- 20.7 micrograms/l, mean +/- SD), fatty liver (55.8 +/- 21.2 micrograms/l), alcoholic hepatitis (46.0 +/- 14.1 micrograms/l), and cirrhosis (41.1 +/- 12.8 micrograms/l), than in 25 healthy controls (88.7 +/- 11.0 micrograms/l). Serum selenium level was related to the severity of liver disease, and most reduced in subjects with decompensated alcoholic cirrhosis. Their serum selenium level (29.2 +/- 13.7 micrograms/l) was below (p less than 0.05) that obtained in alcoholics with normal liver and fatty liver respectively. Both inadequate dietary selenium intake and alcohol-induced changes in hepatic structure and function may have contributed to the decrease of serum selenium in the subjects studied.     

Blood-lead levels in patients with chronic liver diseases

Blood-lead concentrations (Pb-B) were measured in 318 adult inpatients with chronic liver diseases. The Pb-B was highest (387 +/- 96 micrograms/l) in 102 patients with alcoholic liver disease without cirrhosis. The Pb-B was still high, but significantly lower in 60 patients with compensated alcoholic cirrhosis (342 +/- 100 micrograms/l) and in 72 patients with decompensated alcoholic cirrhosis (312 +/- 97 micrograms/l). This difference was in part due to a significant decrease of the hematocrit which fell from 44.4 +/- 4.9% to 42.4 +/- 27.2% and to 39.2 +/- 7.4% respectively. In patients with viral or cryptogenic liver diseases the Pb-B was 211 +/- 69 micrograms/l in 11 patients with chronic persistent hepatitis, 219 +/- 72 micrograms/l in 19 with chronic active hepatitis, 206 +/- 94 micrograms/l in 28 with compensated cirrhosis, and 226 +/- 98 micrograms/l in 26 with decompensated cirrhosis, without any significant difference. The Pb-B of the male patients showed no correlation to age, with the exception of 25 male patients with chronic persistent and active hepatitis (r = 0.626, P less than 0.001).     

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.     

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.     

Experimental carnitine depletion in rats

We studied tissue carnitine concentrations after long-term peroral feeding with carnitine-free parenteral nutrient solutions in rats. Group I (n = 22) was fed perorally for 6 weeks with the carnitine free experimental diet. The control group (group II, n = 22) was pair-fed a standard laboratory pellet diet containing carnitine 60 nmol/g. The carnitine free experimental diet caused approximately 50% depletion of carnitine in serum, muscle, and liver while the concentrations in the pair-fed rats were normal. The free and total carnitine concentrations in serum were 25.5 +/- 7.8 and 32.9 +/- 9.3 mumol/l (group I), and 69.3 +/- 13.7 and 84.1 +/- 16.5 mumol/l (group II, p < 0.001), in muscle 2.1 +/- 0.3 and 2.3 +/- 0.4 mumol/g dry weight (group I), and 3.8 +/- 0.6 and 4.3 +/- 0.8 mumol/g dry weight (group II, p < 0.001), and in liver 0.5 +/- 0.1 and 0.6 +/- 0.1 mumol/g dry weight (group I), and 1.2 +/- 0.1 and 1.3 +/- 0.1 mumol/g dry weight (group II p < 0.001). Daily supplementation of the experimental liquid diet with I-carnitine caused normal tissue carnitine concentrations, indicating the exclusion of dietary carnitine as the cause of carnitine depletion. We conclude that in rats carnitine depletion in serum, muscle, and liver can be induced by prolonged peroral feeding with carnitine free diet.     

High incidence of antibodies to hepatitis C virus in alcoholic cirrhosis: fact or fiction?

An enzyme immunoassay (Ortho-HCV ELISA) for antibodies against the hepatitis C virus was used to test serum samples from 39 patients with alcoholic cirrhosis and 34 patients with alcoholic hepatitis or fatty liver. The frequency of a positive result in the cirrhotics was significantly higher than in the alcoholics without cirrhosis (38.5% vs 8.8%, P less than 0.01). However, the positive results in the cirrhotics were associated with high gammaglobulin concentrations, and optical density values in the assay correlated closely with serum globulin (r = 0.73, P less than 0.01). The findings suggest that serum from patients with alcoholic cirrhosis may contain a component that give false-positive results in the assay.     

Coagulation factors V and VIII in relation to severity and outcome in acute alcoholic hepatitis.

The relationship between levels of coagulation Factors V and VIII and disease severity was evaluated in 33 patients with alcoholic liver disease, and related to outcome in the 23 with severe acute alcoholic hepatitis. Factor V levels in acute alcoholic hepatitis were significantly lower than in inactive alcoholic liver disease (median 28% vs 74%), and both results were lower than values in 10 control subjects (median 101%; P less than 0.001 and P less than 0.002, respectively). Plasma Factor VIII concentrations were not significantly higher in alcoholic hepatitis than in inactive alcoholic liver disease, although both results significantly exceeded control values (median 163% and 151% vs 104%; P less than 0.005 and P less than 0.05, respectively). In the 18 in-patients with alcoholic hepatitis who survived, admission factor V (median 32%) was higher, and admission serum bilirubin (65 mumol/l) and discriminant function score (derived from prothrombin time and bilirubin: median 31) were lower than in the four who died and one who received a liver transplant (median 16%, 527 mumol/l and 113; P less than 0.005, P less than 0.005, P less than 0.05, respectively). An admission Factor V level less than 15% correctly predicted outcome in a greater number (87%) of cases than admission discriminant function greater than 100 (83%), bilirubin greater than 300 mumol/l (83%) or prothrombin ratio greater than 1.5 (78%). This predictive accuracy increased to 100% for minimum Factor V less than 15% and was again superior to maximum discriminant function greater than 100 or greater than 300 mumol/l (both 83%) or maximum prothrombin ratio greater than 1.5 (78%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum zinc, retinol and retinol-binding protein levels in cirrhotics with hypogonadism

Levels of serum zinc, retinol and retinol-binding protein (RBP) were measured in 16 male hypogonadal cirrhotics and compared with 13 male cirrhotic patients without evidence of hypogonadism. Their ages ranged from 20 years to 76 years with a mean of 40.06 +/- 15.6 years (+/- s.e.m.) while non-hypogonadal patients had an age range of 30-55 years with a mean of 41.23 +/- 7.2 years. Mean testicular volume for hypogonadal patients was 6.69 +/- 3.5 cm3 (+/- s.e.m.) while for non-hypogonadal ones it was 12.15 +/- 6.0 cm3. Mean serum zinc level in hypogonadal patients was 4.43 +/- 0.05 mumol/l which was significantly lower than for those without hypogonadism (6.8 +/- 0.09 mumol/l). Similarly serum retinol was lower in hypogonadal patients (0.40 +/- 0.07 mumol/l) than in patients without hypogonadism (0.53 +/- 0.12), although this difference was not statistically significant. RBP was also lower in the hypogonadal patients (0.79 +/- 0.49 mumol/l) than in those without (1.36 +/- 0.74 mumol/l, P less than 0.05). It is concluded that hypogonadal cirrhotics have lower levels of serum zinc and RBP than those without hypogonadism. These deficiencies may contribute to the genesis of hypogonadism in cirrhosis of the liver and supplementation of zinc alone or with vitamin A early in the disease may retard the development of this feature of the disease.     

Serum osteoprotegerin and RANKL levels in chronic alcoholic liver disease

OBJECTIVES: Osteoprotegerin (OPG) is a decoy receptor that binds RANK-ligand (RANKL) and prevents osteoclast activation. Oestrogens, androgens, corticosteroids, parathyroid hormone (PTH), vitamin D, and several cytokines exert their effects on bone modulating the OPG/RANKL system. Since these substances become altered in chronic alcoholic liver disease, we investigated the OPG/RANKL system in alcoholic liver disease, its relation with bone mineral density (BMD) and with several hormones and cytokines. METHODS: Serum OPG, RANKL, C-terminal cross-linking telopeptide of type 1 collagen, osteocalcin, insulin-like growth factor 1 (IGF-1), 1,25 dihydroxyvitamin D, IL-6, tumour necrosis factor (TNF)-alpha, PTH, estradiol, free testosterone and corticosterone were measured in 77 male alcoholic patients, 25 of them cirrhotics. All these patients underwent assessment of BMD at lumbar spine and left hip by a Hologic QDR-2000 (Waltham, MA) bone densitometer. Nineteen non-drinkers male sanitary workers of similar age served as controls. RESULTS: Serum OPG levels were higher in patients (12.66 +/- 6.44 pmol/l) than in controls (6.59 +/- 1.58 pml/l, P < 0.005), especially in cirrhotics (15.97 +/- 7.03 pmol/l) vs non-cirrhotics (10.96 +/- 5.45 pmol/l, P < 0.001). Patients also showed higher telopeptide levels (0.60 +/- 0.36 vs 0.20 +/- 0.10 nmol/100 ml, P < 0.001), less IGF-1 [median = 192, interquartile range (IQR) = 46.7-175.99 ng/ml vs 150, IQR = 118.8-239.4 ng/ml, P < 0.001], vitamin D (25.5, IQR = 18.25-35 pg/ml vs 77.89, IQR = 57.48-98.53 pg/ml, P < 0.001) and osteocalcin (1.8, IQR = 1-3.6 ng/ml vs 6.04, IQR = 4.63-8.20 ng/ml, P < 0.001) than controls, but no differences in PTH and RANKL. Patients also showed lower Z-scores than controls at trochanter (-0.36 +/- 1.10 vs 0.26 +/- 0.87 in controls, P = 0.026), intertrochantereal area (-0.56 +/- 1.16 vs 0.46 +/- 1.01, P = 0.001), and total hip (-0.44 +/- 1.12 vs 0.42 +/- 1, P = 0.003). TNF-alpha levels were higher in patients (7.40, IQR = 4.30-17.80 pg/ml) than in controls (5.10, IQR = 4.40-8 pg/ml, P = 0.009), especially in cirrhotics (median = 13.90, IR = 6.10-21.10 pg/ml). OPG levels showed strong correlations with TNF-alpha (rho = 0.57, P < 0.001) and IL-6 (r = 0.62, P < 0.001), but not with BMD. Estradiol levels (31.83 +/- 13.11 pg/ml) were higher and free testosterone lower (13.62 +/- 11.96 pg/ml) in patients than in controls (20.36 +/- 3.08 and 18.19 +/- 4.68 pg/ml, respectively, P < 0.001 in both cases). CONCLUSION: OPG is raised in alcoholics, especially in cirrhotics, showing no relationship with decreased BMD. Also, raised TNF and IL-6 were observed, and were strongly, directly related with OPG levels. Since TNF and IL-6 enhance bone resorption, their relation with OPG suggests a protective effect of raised OPG on bone loss.     

Vitamin E (tocopherols) in human cerebrospinal fluid

Cerebrospinal fluid (CSF) and blood were obtained at the time of myelographic examinations from 40 adult, male, human subjects with no neurologic or metabolic abnormalities. Vitamin E (tocopherols) concentrations were determined by liquid chromatography. In subjects with normal concentrations of CSF protein (n = 22), the alpha- and gamma-tocopherol concentrations were 29.2 +/- 9.5 (mean +/- SD) and 6.5 +/- 3.6 nmol/L, respectively, in CSF and 26.0 +/- 8.1 and 6.0 +/- 3.6 mumol/L, respectively, in serum. The concentrations of alpha-tocopherol in CSF correlated significantly (P less than 0.001) with both total protein and albumin concentrations, suggesting that tocopherol transport into CSF is linked with that of plasma proteins. In vitro oxidation of vitamin E in CSF by the free-radical generator 2,2'-azobis-(2-amidinopropane) hydrochloride showed a measurable induction (lag) period. This is due to the presence of other antioxidants in human CSF.     

Serum beta-carotene before and after beta-carotene supplementation.

A two-month double-blind, placebo-controlled supplementation study of oral beta-carotene (20 mg daily) was conducted. Two hundred and twenty two 30-69 year old men were randomized into either a beta-carotene or placebo group, and serum samples were obtained at baseline, follow-up (2 months), and up to 12 weeks post-supplementation. Serum beta-carotene increased on average 10-fold in the beta-carotene group, from 0.53 +/- 0.32 mumol/l (mean +/- SD) at baseline to 4.99 +/- 2.47 mumol/l at follow-up (P less than 0.0001), and beta-carotene levels remained elevated up to 12 weeks post-supplementation (0.61 +/- 0.15 mumol/l). No changes in serum retinol, alpha-tocopherol, or total cholesterol were observed. At baseline, serum beta-carotene levels were positively correlated with dietary beta-carotene (r = 0.29) and inversely correlated with body mass index and serum gamma-glutamyltransferase (r = -0.33 and r = -0.40, respectively). The inverse association with body mass index and serum gamma-glutamyltransferase persisted during active supplementation, whereas the positive association with dietary beta-carotene disappeared. In multivariate analysis, serum cholesterol was also positively associated with serum beta-carotene levels both before and after supplementation. Baseline serum beta-carotene was the factor most strongly associated (positively) with serum beta-carotene after supplementation. Our study highlights the importance of several factors which affect serum beta-carotene.     

Blood lead concentration, renal function, and blood pressure in London civil servants.

Blood lead concentration was measured in 398 male and 133 female London civil servants not subject to industrial exposure to heavy metals. The relation between blood lead and serum creatinine concentrations and blood pressure were examined. Blood lead concentration ranged from 0.20 to 1.70 mumol/l with a geometric mean concentrations of 0.58 mumol/l in men and 0.46 mumol/l in women (p less than 0.001). In women blood lead concentration increased with age (r = +0.27; p = 0.002). In the two sexes blood lead concentration was positively correlated with the number of cigarettes smoked a day (men r = +0.17 and women r = +0.22; p less than or equal to 0.01), with the reported number of alcoholic beverages consumed a day (men r = +0.34 and women r = 0.23; p less than 0.01), and with serum gamma-glutamyltranspeptidase (men r = +0.23 and women r = +0.14; for men p less than 0.01). Blood lead concentration was not correlated with body weight, body mass index, and employment grade. In men 14% of the variance of blood lead concentration was explained by the significant and independent contributions of smoking and alcohol intake and in women 16% by age, smoking, and alcohol consumption. In men serum creatinine concentration tended to rise by 0.6 mumol/l (95% confidence interval from -0.2 to +1.36 mumol/l) for each 25% increment in blood lead concentration. In men and women the correlations between blood lead concentration and systolic and diastolic blood did not approach statistical significance. In conclusion, in subjects not exposed to heavy metals at work gender, age, smoking, and alcohol intake are determinants of blood lead concentration. At a low level of exposure, lead accumulation may slightly impair renal function, whereas blood pressure does not seem to be importantly influenced. Alternatively, a slight impairment of renal function may give rise to an increase in blood lead concentration.     

Blood lead concentration, renal function, and blood pressure in London civil servants

Blood lead concentration was measured in 398 male and 133 female London civil servants not subject to industrial exposure to heavy metals. The relation between blood lead and serum creatinine concentrations and blood pressure were examined. Blood lead concentration ranged from 0.20 to 1.70 mumol/l with a geometric mean concentrations of 0.58 mumol/l in men and 0.46 mumol/l in women (p less than 0.001). In women blood lead concentration increased with age (r = +0.27; p = 0.002). In the two sexes blood lead concentration was positively correlated with the number of cigarettes smoked a day (men r = +0.17 and women r = +0.22; p less than or equal to 0.01), with the reported number of alcoholic beverages consumed a day (men r = +0.34 and women r = 0.23; p less than 0.01), and with serum gamma-glutamyltranspeptidase (men r = +0.23 and women r = +0.14; for men p less than 0.01). Blood lead concentration was not correlated with body weight, body mass index, and employment grade. In men 14% of the variance of blood lead concentration was explained by the significant and independent contributions of smoking and alcohol intake and in women 16% by age, smoking, and alcohol consumption. In men serum creatinine concentration tended to rise by 0.6 mumol/l (95% confidence interval from -0.2 to +1.36 mumol/l) for each 25% increment in blood lead concentration. In men and women the correlations between blood lead concentration and systolic and diastolic blood did not approach statistical significance. In conclusion, in subjects not exposed to heavy metals at work gender, age, smoking, and alcohol intake are determinants of blood lead concentration. At a low level of exposure, lead accumulation may slightly impair renal function, whereas blood pressure does not seem to be importantly influenced. Alternatively, a slight impairment of renal function may give rise to an increase in blood lead concentration.     

Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes

BACKGROUND: Endogenous reactive oxygen species appear to contribute to aging and cancer and dietary antioxidants, present in fruit and vegetables, counteract these effects. OBJECTIVE: The objective was to examine the association between intracellular glutathione, ascorbate (vitamin C), and alpha-tocopherol (vitamin E) in human lymphocytes. DESIGN: The study group consisted of 240 healthy nonsmoking volunteers with an approximately equal number of male and female subjects subdivided into 3 age groups: 18-39, 40-59, and >/=60 y). Glutathione, glutathione disulfide, ascorbate, and alpha-tocopherol were measured in lymphocytes by HPLC. RESULTS: The average concentration of antioxidants in lymphocytes was 27 +/- 8 nmol/mg protein for glutathione, 21 +/- 8 nmol/mg protein for ascorbate, and 0.4 +/- 0.2 nmol/mg protein for alpha-tocopherol. There was a strong positive correlation between glutathione and ascorbate (r = 0.62, P < 0.001). No correlation was observed for glutathione and ascorbate with alpha-tocopherol. The concentration of glutathione in lymphocytes was inversely correlated with age (r = -0.19, P < 0.01), as was that of ascorbate (r = -0.22, P < 0.01), with 10-20% lower values in elderly than in young and elderly subjects. The concentrations of glutathione in lymphocytes were as much as 25% higher and those of ascorbate were as much as 38% higher during the summer than during the winter. The seasonal variation of ascorbate in lymphocytes was described by a linear function for age and a periodic sine function for season. CONCLUSION: Glutathione and ascorbate are directly correlated in human lymphocytes.     

The absorption of zinc from a standardized meal in alcoholics and in normal volunteers

The mean serum zinc in 30 normal volunteers was 12.8 mumol/l (SE +/- 0.3) and in 30 alcoholic subjects was 10.7 mumol/l (SE +/- 0.6) (p less than 0.005). Postprandial changes in serum zinc were studied in these volunteers and alcoholics who were divided into three groups. After a standardized meal with no added zinc there was a sustained postprandial fall in serum zinc in 10 normal volunteers (23%) and in 10 alcoholic subjects (19%). After a standardized meal supplemented with 25 mg zinc there was a similar rise in postprandial serum zinc concentration in 10 alcoholic subjects and 10 normal volunteers. After a standardized meal supplemented with 50 mg zinc there were lower serum zinc concentrations in 10 alcoholic subjects when compared with 10 normal volunteers. These lower postprandial serum zinc concentrations in alcoholics may suggest a reduced absorptive capacity for zinc in alcoholics.     

Nutritional state after colon interposition for benign oesophageal disease

The nutritional state of 32 patients after (mean 66 months) colon interposition due to benign oesophageal disease was examined. Forty-four per cent of the patients had depleted iron stores (low serum ferritin concentration). Serum iron and blood haemoglobin concentrations were lower (P less than 0.001) in those with low than in those with normal serum ferritin concentration (115 +/- 12 g/l and 15 +/- 5 mumol/l vs 135 +/- 12 g/l and 23 +/- 9 mumol/l). Most very low blood haemoglobin concentrations (less than 110 g/l) were found in patients with depleted iron stores. Eighteen patients had serum albumin concentrations slightly below (35-39 g/l) the normal range, and two other patients had values less than 35 g/l. The patients had less dietary iron (13 +/- 6 mg/d) than age- and sex-matched controls (19 +/- 7 mg/d), but the intake of patients with depleted iron stores (12 +/- 5 mg/d) was similar to that of patients with normal iron stores (14 +/- 6 mg/d). Symptoms and/or the replacement of colon graft anti- or isoperistaltically did not have any significant association with the nutritional status, only slightly reduced blood haemoglobin and serum albumin concentration were found among the symptomatic patients and the patients with an antiperistaltic graft. Iron therapy and protein supplements, eg, from milk, egg, soy and meat, are recommended as the dietary treatment. To improve the nutritional status a short intra-abdominal colon graft loop anastomosed to the proximal stomach instead of long loop with an antral anastomosis of the present patients is suggested.     

Hypermetabolism in clinically stable patients with liver cirrhosis.

BACKGROUND: Hypermetabolism has a negative effect on prognosis in patients with liver cirrhosis. Its exact prevalence and associations with clinical data, the nutritional state, and beta-adrenergic activity are unclear. OBJECTIVE: We investigated resting energy expenditure (REE) in 473 patients with biopsy-proven liver cirrhosis. DESIGN: This was a cross-sectional study with a controlled intervention (beta-blockade) in a subgroup of patients. RESULTS: Mean REE was 7.12 +/- 1.34 MJ/d and correlated closely with predicted values (r = 0.70, P < 0.0001). Hypermetabolism was seen in 160 patients with cirrhosis (33.8% of the study population). REE was > 30% above the predicted value in 41% of the hypermetabolic patients with cirrhosis. Hypermetabolism had no association with clinical or biochemical data on liver function. REE correlated with total body potassium content (TBP; r = 0.49, P < 0.0001). Hypermetabolic patients had lower than normal body weight and TBP (P < 0.05). About 47% of the variance in REE could be explained by body composition whereas clinical state could maximally explain 3%. Plasma epinephrine and norepinephrine concentrations were elevated in hypermetabolic cirrhotic patients (by 56% and 41%, respectively; P < 0.001 and 0.01). Differences in REE from predicted values were positively correlated with epinephrine concentration (r = 0.462, P < 0.001). Propranolol infusion resulted in a decrease in energy expenditure (by 5 +/- 3%; P < 0.05), heart rate (by 13 +/- 4%; P < 0.01), and plasma lactate concentrations (by 32 +/- 12%; P < 0.01); these effects were more pronounced in hypermetabolic patients (by 50%, 33%, and 68%, respectively; each P < 0.05). CONCLUSIONS: Hypermetabolism has no association with clinical data and thus is an extrahepatic manifestation of liver disease. Increased beta-adrenergic activity may explain approximately 25% of hypermetabolism.     

Selenium intake, age, gender, and smoking in relation to indices of selenium status of adults residing in a seleniferous area

Duplicate meals, serum, whole blood, and toenails were collected every 3 mo for 1 y from a group of 44 free-living adults residing in high-selenium areas of South Dakota and Wyoming to assess the relation of selenium intake to indices of selenium status. The average selenium values for the group were as follows: dietary intake, 174 +/- 91 micrograms/d (mean +/- SD), 2.33 +/- 1.08 micrograms/kg body wt; serum, 2.10 +/- 0.38 mumol/L; whole blood, 3.22 +/- 0.79 mumol/L; and toenails, 15.2 +/- 3.0 nmol/g. Selenium intake (micrograms/kg body wt) was strongly correlated (all values, P less than 0.01) with selenium concentration of serum (r = 0.63), whole blood (r = 0.62), and toenails (r = 0.59). Men and women had similar mean values of serum, whole blood, and toenail selenium despite higher selenium intakes in men. Smokers had lower tissue selenium concentrations than did nonsmokers due, at least in part, to lower selenium intake. Age was not associated with tissue selenium content. Of the variables examined selenium intake was clearly the strongest predictor of tissue selenium concentration.     

The concentration of thiamin and thiamin phosphate esters in patients with alcoholic liver cirrhosis.

The blood and plasma concentrations of thiamin and thiamin phosphate esters were determined concomitantly by high-performance liquid chromatography (HPLC) in 22 patients with alcoholic liver cirrhosis, and also in 10 of them 24 hr after a 100 mg thiamin i.m. injection. Sixteen patients were abstaining from alcohol at the time of the study, 6 were currently misusing alcohol. The control group included 30 healthy volunteers, of whom 10 were given the same thiamin injection as the patients. Blood thiamin diphosphate was the only compound decreased in the abstaining patients compared to controls (70.9 +/- 21.9 nmol/l vs. 84.4 +/- 19.0 nmol/l), but all thiamin compounds in blood and plasma were decreased in the misusing patients. All thiamin compounds (except blood monophosphate) were also significantly lower in the misusing than in the abstaining patients (plasma thiamin: 5.3 +/- 1.3 vs. 11.7 +/- 8.3 nmol/l; plasma monophosphate: 1.0 +/- 1.1 vs. 4.1 +/- 2.9 nmol/l; blood diphosphate: 45.7 +/- 18.3 vs. 70.9 +/- 21.9 nmol/l). Thiamin phosphorylation ratio was decreased in the patients after thiamin administration compared to controls (2.83 +/- 0.74 vs. 3.68 +/- 0.58). Plasma thiamin was higher in the abstaining patients than in the controls (11.7 +/- 8.4 nmol/l vs. 7.3 +/- 2.5 nmol/l), and above the mean + 2 SD of the controls in 31% of the abstaining patients. In conclusion, current ethanol misuse is associated with low thiamin concentrations, and liver cirrhosis is associated with a decreased thiamin diphosphate concentration and thiamin phosphorylation.     

Effects of prolonged, purine-free total parenteral and enteral nutrition on urate homeostasis in man

The influence on human urate homeostasis of prolonged, totally purine-free nutritional support, using total parenteral (TPN) or elemental enteral (EN) nutrition, is not well known. In a prospective study, we measured weekly serum uric acid, renal urate excretion and clearance, together with parameters of hydration, in 58 normally hydrated patients receiving prolonged (15 to 170 days) purine-free TPN (30 patients) or EN (28 patients) for various gastrointestinal disorders. A marked, early and sustained decrease (p less than 0.001) in serum uric acid was observed in TPN (155 +/- 9 mumol/l at day 7 versus 318 +/- 13 mumol/l before nutrition, mean +/- SEM) as well as in EN patients (192 +/- 11 mumol/l at day 7 versus 320 +/- 16 mumol/l before nutrition), together with a significant (p less than 0.01) rise in renal urate clearance. The urate clearance/glomerular filtration rate ratio increased significantly, while there was no significant change in natremia or plasma osmolarity. Serum urate and urate clearance returned to normal within 8 days of refeeding with a normally purine-containing diet. Replacement of TPN by EN or vice versa, or substitution of glucose by fructose resulted in no change in hypouricemia. A 4-day oral supply of purines (125 mg/day) in EN patients was associated with a 53% rise (p less than 0.01) in serum urate. We conclude that prolonged, purine-free TPN and elemental EN are a new cause of marked hypouricemia which is mainly due to increased urate clearance, the mechanism of the latter is still poorly known, but is not related to extracellular volume expansion.