Biomedical subjects
Publications and source records attributed to H H Sandstead.
Some of the toxic and nutritional aspects of trace elements in patients with renal failure are reviewed. Data are presented that tend to disprove the hypothesis that aluminum poisoning alone is responsible for dialysis encephalopathy. Possible dietary restrictions imposed in uremic patients may impair iron, zinc, copper, manganese, or chromium nutritive.
Trace metals, vitamins, and other biochemical parameters were measured in 30 female patients hospitalized for anorexia nervosa with the aim of relating them to taste function, biochemical changes, and clinical signs found in this illness. Plasma zinc (71.9 +/- 14 microgram/100 ml; P < 0.01), urinary zinc (129.5 +/- 121 microgram/24 hr), and copper (84 +/- 17 microgram/100 ml; P < 0.001), were depressed, whereas zinc and copper content of hair was normal. Anorexia nervosa patients showed hypogeusia, with the bitter and sour taste most severely affected, however plasma zinc levels did not correlate with taste recognition scores. Patients showed hypercarotenemia (214 +/- 129 microgram/100 ml; P < 0.01) with normal plasma vitamin A and retinol-binding protein levels. Total iron binding capacity was depressed (261 +/- 62 microgram/100 ml; P < 0.001) in contrast to plasma iron, ceruloplasmin and folic acid, which were normal. In nine patients, who were retested before discharge, taste function improved; plasma zinc, copper, and total iron binding capacity levels increased whereas plasma carotene and cholesterol decreased to normal levels. It is concluded that the observed zinc, copper, and iron binding protein deficiencies, and hypogeusia, reflect the self-imposed nutritional restriction of anorexia nervosa patients. Zinc and other micronutrients released from catabolized tissue along with vitamin intake may mitigate against more severe deficiency states in anorexia nervosa.
At 100 days of age rats, whose dams suffered severe zinc deficiency and/or undernutrition throughout lactation, were tested in two learning tasks. One test was an original discrimination learning task and the other test was a more difficult reverse discrimination learning task. In the reverse learning test, performance differed significantly between rehabilitated malnourished rats and normal rats. Difference in motivation, and not learning ability, was the explanation for the differences in performance between the malnourished and normal rats.
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This study was conducted to characterize nitrogen retention in response to marginal dietary zinc during gestation. Long-Evans rats were randomly assigned to one of two dietary groups on day 1 of gestation. The dams were fed a basal diet supplemented with either restricted or control levels of zinc. Feces and urine were collected for 24 h on day 20 of pregnancy, and their nitrogen and zinc contents were determined. Urinary and fecal nitrogen excretions were similar for zinc-restricted and control dams, whereas fecal zinc excretions were depressed by feeding the zinc-restricted diet. Mean zinc and nitrogen retentions were negative for the zinc-restricted and positive for the control groups. Multiple stepwise regression analysis showed that nitrogen retention on day 20 depended on both dietary nitrogen and zinc intakes. Zinc-restricted offspring weighed 12% less and the maternal plasma zinc concentrations were reduced by 66% when compared with the control group values on day 22. Marginal dietary zinc and the associated anorexia limited fetal growth without causing excessive nitrogen excretion or severe weight loss.
Hematologic indices and iron balance data were obtained on 22 normal male volunteers who were subjected to a mean +/- SD phlebotomy of 164 +/- 34 ml whole blood/mo while living in a controlled environment. Over an average stay of 5 mo, volunteers did not develop anemia, but did display a reduction in iron stores that was quantitated by measurement of serum ferritin and iron balance. The percent saturation of transferrin and the usual erythrocyte parameters did not reflect changes in iron status. Loss of iron, which was calculated from quantitative phlebotomy and iron balance data, showed that a decrease of 1 ng of serum ferritin represented a loss of 4.5 +/- 5.3 mg of iron in 10 men whose initial serum ferritins were greater than 25 ng/ml, and 25.3 +/- 58.8 mg of iron in 7 men whose initial serum ferritins were less than 25 ng/ml. The period required for 3 volunteers who consumed a self-selected mixed diet at home to replace their depleted iron stores to prephlebotomy levels was about 4.5 mo. The sensitivity of serum ferritin as an index of iron stores was affirmed. In addition it was found that normal men who were consuming a mixed diet containing about 15 mg of iron daily and losing blood at a rate of 164 +/- 34 ml/mo did not increase their iron absorption sufficiently to compensate for the iron loss.
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The hypothesis that dietary fiber lowers serum cholesterol was tested in 10 healthy men, 19 to 54 years old, who ate a mixed diet similar to the diets of many American adult males, that contained 16% of calories as protein (70% from animal), 40% as fat (P/S = 0.3), 44% as carbohydrate (9% of calories as sucrose) and 3 g of crude fiber. The energy intake ranged from 2700 to 3500 kcal adjusted to their height and weight. Weight and fitness were held constant. After 30 days of equilibration on the basal diet, they ate 26 g of either soft white wheat bran, corn bran (CB), soybean hulls (SH), textured vegetable protein, or hard red spring wheat bran (HRS) for periods of 28 to 30 days each in no particular sequence. Each fiber was fed to four to six subjects. The dietary fiber contents of soft white wheat bran, CB, SH, and HRS were: 44, 92, 87, and 51%, respectively. Mean daily fecal weight increased (P less than or equal to 0.01) from 72.4 to 144, 68 to 128, and 81 to 151 g when CB, SH, and HRS were fed respectively. No effects were noted with soft white wheat bran or textured vegetable protein. Total plasma cholesterol decreased 12% with HRS (P less than or equal to 0.05) and 14.0% with SH (P less than or equal to 0.05). Low density lipoprotein cholesterol decreased 21% with HRS (P less than or equal to 0.05). High density lipoprotein cholesterol did not change with any of the dietary fiber sources nor did the ratio of high density lipoprotein cholesterol to total cholesterol. Some triglyceride lowering effect was seen with all sources of dietary fiber (P less than or equal to 0.01). There was a significant direct correlation between the area under the oral glucose tolerance curves and the levels of total cholesterol (r = 0.57, P less than or equal to 0.0001) and low density lipoprotein cholesterol (r = 0.49, P less than or equal to 0.0007), and between fasting plasma glucose and triglycerides (r = 0.32, P less than or equal to 0.03). Results were replicated when subjects were fed the same fiber source on two occasions at 2 to 4 month intervals.
The cellular immune response of a 17-year-old decerebrate male with acquired zinc deficiency was studied. He had been fed a commercial formula which contained 7.6 mg zinc per kilogram. His caloric intake had been inadequate as judged by his cachexia. A detailed pretreatment nutritional assessment (five separate observations) which included total serum protein and globulins, albumin, folate, vitamins A, B2, C, ceruloplasmin, and plasma zinc, copper, iron, and total iron binding capacity revealed that the patient was deficient only in zinc and calories. His plasma zinc was 41 +/- 5 microgram/d1 compared with our laboratory norm of 89 +/- 9 microgram/d1 for young adult males. Cellular immunity was assessed by delayed skin reactivity to dinitrochlorobenzene and by in vitro lymphocyte transformation studies. Before zinc therapy the patient rendered a negative skin reaction to dinitrochlorobenzene, and the ability of his lymphocytes to undergo blast transformation in response to mitogen stimulation was significantly depressed with a stimulation index of 4.7 +/- 0.8 as compared with 139.1 +/- 77.3 for controls. Within 3 weeks after zinc therapy (22.7 mg zinc per day) he demonstrated a positive delayed skin reaction to dinitrochlorobenzene and a normal lymphocyte response stimulation index = 205.5 +/- 42.6 versus 199.3 +/- 58.2 for control). In addition, a pretreatment facial seborrhea and a decubitus ulcer rapidly healed.
Because zinc apparently has a role in amino acid utilization, we have studied possible consequences of zinc deficiency on the metabolism of amino acids in the intestinal mucosa by examining proteins transported via the mesenteric lymph in zinc-deficient and zinc-supplemented rats. Mesenteric lymph ducts were cannulated under pentobarbital, and on recovery the animals were fed [14C]leucine as a pulse dose by duodenal infusion. Protein output via intestinal lymph was generally constant over the infusion range studied. Total lymph protein output was not affected by zinc deficiency or supplementation. The electrophoretic pattern of the lymph protein revealed a protein band that migrated with the alpha2-globulins coincidental to zinc deficiency; the band disappeared after zinc supplementation. There was an inverse zinc-copper relationship in mesenteric lymph; duodenal infusion of zinc to deficient rats was followed by a decrease in lymph copper. Deficiency of zinc seems to have little influence on the quantitative aspect of protein carried in mesenteric lymph but seems to be involved with the nature of the protein in this body fluid.
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Five adult male volunteers were fed a diet containing (as percent of calories) 16% protein, 40% fat, and 44% carbohydrate, a diet similar to that consumed by many American males. Twenty-six grams of soft white wheat bran or corn bran were added to the daily bread, and the effects on zinc, iron, and copper balance were assessed during the last 12 days of each 30-day study period. The soft white wheat bran appeared to decrease retention of zinc in four subjects but not significantly so. Iron retention was similar in all three treatments. Copper balance was improved by addition of soft white wheat bran and to a lesser degree by corn bran. An apparent copper requirement of 1.28 mg/day for the volunteers was calculated by regression analysis.
Zinc status and the retinol transport system were examined in 18 retinol supplemented cystic fibrosis (CF) patients and 40 age-matched controls. Plasma vitamin A was significantly lower in the CF group as compared to the controls and correlated positively with plasma retinol-binding protein (RBP) in both the CF and control groups. Plasma zinc of the CF group was not significantly lower than controls whereas hair zinc was. Plasma zinc was positively correlated with plasma RBP, vitamin A, and albumin in the CF group but not in the controls. Plasma concentrations of vitamin A, RBP, albumin, and zinc decreased with age in the CF group but not in the controls. The data support previous suggestions that low plasma vitamin A levels in CF are due to defects in the retinol transport system. The zinc status of the CF groups as a whole was judged to be low-normal however a subgroup of CF patients were in the marginal to deficient category. This subgroup also had lower levels of plasma vitamin A and RBP. The data suggest that zinc may be a contributing factor in the low plasma vitamin A/RBP levels of CF patients with marginal or deficient zinc status.
Zinc deprivation from day 110 to 150 of gestation in rhesus monkeys resulted in rash, alopecia, anorexia, decreased feed efficiency, and low plasma zinc in the mothers. Infants of the dams that had been deprived of zinc during gestation displayed a more rapid postnatal growth rate than infants of the control mothers. Infants of the zinc-deprived dams played and explored less than the control infants. They also associated with their mothers a greater percentage of the time and were less active. This study has shown that third trimester maternal zinc deprivation in nonhuman primates can impair behavioral development of offspring.
Reduced concentrations of plasma zinc associated with elevated levels of serum leukocytic endogenous mediator activity were found in 17 patients hospitalized with acute exacerbation of Crohn's disease. Neither the decrease in plasma zinc nor the increase in leukocytic endogenous activator activity in nine outpatients with quiescent disease was significant. Leukocytic endogenous mediator activity may be increased in inflammatory conditions as well as in microbial infections. Although zinc deficiency may be common in patients with Crohn's disease, exclusive reliance on circulating zinc levels to assess zinc nutriture in active Crohn's disease may be misleading.
Plasma concentrations of zinc and copper were measured in 15 obese patients before intestinal bypass surgery, in 27 patients after intestinal bypass surgery, and in 52 lean control subjects. Preoperatively, the obese patients had zinc concentrations that were significantly lower than in the lean control subjects (76 +/- 3 versus 89 +/- 2 microgram/dl) (+/- SEM) and copper levels that were significantly higher (147 +/- 10 versus 119 +/- 3 microgram/dl). After intestinal bypass, plasma zinc and copper concentrations were significantly lower (zinc, 62 +/- 2 microgram/dl; copper, 90 +/- 5 microgram/dl; P less than 0.001) than in prebypass patients. One patient developed leukopenia associated with a plasma copper concentration of 36 microgram/dl. Leukocyte count and plasma copper level rose with oral copper sulfate replacement therapy. Intestinal bypass surgery may produce clinically significant decreases in plasma concentrations of zinc and copper. Careful observation and replacement therapy are indicated in all patients who develop deficiences after intestinal bypass surgery.
Fetal malnutrition has emerged as a significant health problem over the past decade. Present evidence suggests that maternal environment plays the major etiologic role in fetal malnutrition. The association of fetal malnutrition in mothers with chronic hypertension is well known, but fetal malnutrition is associated with maternal hypertension in less than 25 per cent of cases. Among a group of 182 pregnant women studied at midpregnancy for blood levels of vitamins, trace metals, proteins, amino acids, and parameters of maternal leukocyte energy metabolism, it was found that the concentration of 10 amino acids, alpha-1-globulin, zinc, and total carotenes had a statistically significant relationship to fetal growth. Similarly significant correlations were found for maternal leukocyte adenosine disphosphate, phosphofructokinase activity, ribonucleic acid (RNA) synthesis, and cell size. Maternal cigarette smoking was correlated with reduced fetal growth. Analysis showed that there was a significant reduction in leukocyte RNA synthesis and phosphokinase activity and in the plasma levels of 14 amino acids, and carotene in smoking mothers. This information lends support to the hypothesis that factors which affect the growth of fetal cells also will affect maternal leukocytes in a definable way.