Update on vitamin supplements for the prevention of coronary disease and stroke.

Dietary antioxidants and folic acid may play a role in the pathophysiology of coronary disease and stroke. We review patient-oriented evidence on the effectiveness of supplementation with antioxidants and/or folic acid in the prevention of myocardial infarction and stroke. Observational data suggest cardiovascular benefit of vitamin E supplementation, but results of controlled clinical trials are inconsistent regarding the effect on nonfatal myocardial infarction. Moreover, studies have not shown a protective effect of vitamin E against fatal myocardial infarction and have not addressed stroke. For vitamin C and folic acid supplementation, observational data are inconsistent and controlled clinical trials are lacking. Thus, the available evidence is insufficient to recommend the routine use of vitamin E, vitamin C or folate supplements for the prevention of myocardial infarction or stroke. The evidence argues against the use of beta carotene supplements for this purpose. The costs and risks associated with these supplements are low, however, and physicians may choose to recommend vitamin E, folate and/or vitamin C supplementation pending conclusive evidence from clinical trials.

Acute phase response and plasma carotenoid concentrations in older women: findings from the nun study.

This cross-sectional study investigated whether the acute phase response was associated with suppressed circulating levels of antioxidants in a population of 85 Catholic sisters (nuns) ages 77-99 y. Fasting blood was drawn to determine the presence of an acute phase response, as defined by an elevation in the serum concentration of C-reactive protein. Serum concentrations of albumin, thyroxine-binding prealbumin, zinc, copper, and fibrinogen were determined as were plasma concentrations of carotenoids and alpha tocopherol. Results showed that the presence of an acute phase response was associated with (1) an expected significant decrease in the serum concentrations of albumin (p < 0.001) and thyroxine-binding prealbumin (p < 0.001); (2) an expected significant increase in copper (p < 0.001) and fibrinogen (p = 0.003); and (3) a significant decrease in the plasma concentrations of lycopene (p = 0.03), alpha carotene (p = 0.02), beta carotene (p = 0.02), and total carotenoids (p = 0.01). The acute phase response was associated with decreased plasma levels of the antioxidants lycopene, alpha carotene, and beta carotene. This decrease in circulating antioxidants may further compromise antioxidant status and increase oxidative stress and damage in elders.

Nutritional assessment in the elderly: biochemical analyses.

OBJECTIVE: To describe briefly the anthropometric, biochemical, clinical, and dietary components of a complete nutritional assessment and to examine four common nutritional concerns in the elderly and the biochemical tests that aid in the identification and treatment of these disorders. DATA SOURCES: Clinical expertise/practice, recent professional journals, and textbooks. STUDY SELECTION: Not applicable. DATA EXTRACTION: Clinical practice and literature review. DATA SYNTHESIS: Biochemical assays are one aspect of a complete nutritional assessment that provides valuable information in the determination of an individual's nutritional status and the identification of any nutrient deficiencies or excesses. As part of this nutritional assessment, specific biochemical tests are ordered to substantiate further or to rule out nutrient deficiencies or excesses gleaned from the clinical, dietary, and anthropometric components of the complete nutritional assessment. CONCLUSION: Given the increased potential for nutritional problems in the elderly, a comprehensive nutritional assessment should be performed as a routine part of elderly care. This assessment includes anthropometric measurements, biochemical assays, a clinical examination for signs of deficiencies or excesses, and a complete dietary evaluation to determine current intake and make necessary recommendations.

Case report of zinc deficiency in an elderly woman.

Zinc deficiency is not an uncommon nutritional disorder in the elderly. It should be suspected in patients who have conditions associated with zinc deficiency (Table 1) or who have one of the potential causes of zinc deficiency (Table 2). A low serum-zinc level indicates zinc deficiency unless an acute phase response is present. The acute-phase response should be suspected in a patient with an acute illness. A C-reactive protein level is helpful in identifying the acute-phase response. Our initial treatment of zinc deficiency centers on increasing dietary zinc. Often, however, because of other common problems of geriatric patients such as dementia or depression, the patient is unable to alter his or her diet. Then, zinc supplementation may be required. Copper, iron, and lipoprotein status should be monitored if long-term zinc supplementation is needed because they may be effected by the zinc supplementation.

Cholecystokinin and satiety: effect of hypothalamic obesity and gastric bubble insertion.

Cholecystokinin (CCK) is a gut peptide whose proposed effect on satiety is thought to be related to gastric volume and to be signaled through vagal afferent fibers to the medial hypothalamus. To test these hypotheses we infused CCK C-terminal octapeptide (CCK-8) or saline in a random double-blind fashion in three groups of subjects: 17 obese subjects, 6 of whom subsequently received a gastric bubble, and 5 obese subjects whose obesity was due to hypothalamic injury. The number of sandwich canapes eaten after saline or CCK-8 infusion was recorded during three consecutive 10-min eating periods. Each subject served as his/her own control. The prior infusion of CCK-8 significantly decreased the consumption of sandwich canapes in the first eating period in both the control obese subjects and the subjects with obesity due to hypothalamic injury. Insertion of a gastric bubble did not enhance the satiety effect of CCK-8. These studies support the hypothesis that CCK produces satiety in a time-dependent manner that is not enhanced after the insertion of a gastric bubble but is operative in obese subjects with hypothalamic injury.

The acute phase response in autologous bone marrow transplantation.

Due to the stress imposed by the process of bone marrow transplantation (BMT), we hypothesized that individuals receiving such a transplant underwent an acute phase response (APR). Circulating levels of C-reactive protein (CRP), haptoglobin (HAP), alpha-1 acid glycoprotein (AAG), ceruloplasmin (CER), zinc (Zn), copper (Cu), interleukin-6 (IL-6), albumin (ALB), and thyroxine-binding prealbumin (TBPA), were measured at baseline (Day -7), Day -4, Day 0 (Transplant Day), Day +2, +7, and weekly until day 28 in 14 adults receiving an autologous bone marrow transplant as Phase 1 treatment for various hematologic or solid tumor malignancies. Ten of 14 recipients survived, 9 of which had a significant increase in CRP (p = 0.012), HAP (p = 0.011), AAG (p = 0.002), and decrease in ALB (p = 0.002) and TBPA (p = 0.004) on Day +7, but not Day 0, after bone marrow reinfusion. These findings document the presence of an APR and suggest that the bone marrow transplant process (post reinfusion) initiates a stress response in the recipient.

Increased urinary zinc excretion after thermal injury.

Urinary zinc excretion normally plays a minor role in zinc homeostasis; however, urinary zinc excretion is markedly elevated after trauma or surgery, and mechanism(s) for this zinc loss are poorly defined. In this study we evaluated multiple potential mechanisms for increased urinary zinc excretion in patients with thermal injury. We documented that patients with severe thermal injury had markedly elevated urinary zinc excretion. Above 20% total body surface area burn, however, the severity of thermal injury did not correlate with urinary zinc excretion. Serum zinc concentrations were depressed on initial evaluation and gradually increased during the hospital course, whereas peak urinary zinc excretion occurred 2 to 5 weeks after injury. Thus the depression in serum zinc concentration did not temporally relate to the observed pattern of hyperzincuria. Increased urinary zinc excretion also did not temporally relate to urinary excretion of the amino acids cysteine and histidine (both of which tightly bind zinc) nor to urinary 3-methylhistidine excretion, a marker of muscle breakdown. Urinary amylase excretion, a marker of renal tubular dysfunction, did follow the pattern of urinary zinc loss to some extent, although this correlation was not perfect. Increased oral intake of zinc via zinc supplements resulted in significantly increased urinary zinc excretion. Patients receiving total parenteral nutrition (TPN) did not have significantly increased urinary zinc excretion when compared with people receiving their total nutrient intake by mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Phase I study of combination recombinant interleukin-2 and interferon gamma in patients with advanced malignancies.

A phase I trial of interleukin-2 and interferon gamma combination treatment in patients with advanced malignancies was performed based on preclinical in vitro and in vivo data which demonstrated synergistic antitumor effect. The toxicities, immune parameters, and tumor responses are described. The clinical and biologic maximal tolerated doses were extrapolated from these data.

Relationship of visceral proteins to nutritional status in chronic and acute stress.

Visceral protein levels are used as indicators of prognosis, severity of injury, and nutritional status in hospitalized patients. Clinicians often use visceral protein levels to assess efficacy of nutritional support. The purpose of this study was to test the validity of such practices. Visceral protein levels were determined in patients in a medical ICU, head injury unit, and burn unit. The serum albumin and thyroxine-binding prealbumin (TBPA) levels correlated significantly with mortality in the medical ICU patients. Burn patients had depressed albumin and TBPA concentrations over the duration of hospitalization that related to the severity of thermal injury but not to adequacy of nutritional support. Head-injured patients had depressed admission albumin and TBPA levels, with neither protein level adequately related to caloric or protein supplementation. We conclude that visceral proteins may reflect severity of injury and prognosis in critically ill hospitalized patients, but they often do not accurately reflect nutritional status or adequacy of nutritional support.

Serum zinc response in thermal injury.

Zinc is an essential trace element required for RNA and DNA synthesis and the function of over 200 zinc metalloenzymes. After surgery or trauma, the serum zinc concentration usually decreases. The magnitude and duration of this hypozincemia after thermal injury are unclear, as are mechanisms for this hypozincemia. In this study we evaluated, over the duration of their hospital course, serum zinc concentrations in 23 thermal injury patients. The initial mean serum zinc concentration was significantly depressed (42 +/- micrograms/dl; normal 66-110 micrograms/dl). By the second week of hospitalization, serum zinc concentrations gradually increased into the normal range in the majority of patients. Mechanisms for this hypozincemia were evaluated. Decreases in the serum zinc concentration did not correlate with increased urinary zinc excretion; thus increased urinary zinc excretion was an unlikely mechanism for the observed hypozincemia. Values for albumin, the major zinc binding protein in serum, generally were inversely correlated with the serum zinc concentration. Thus, hypoalbuminemia could not explain the decreased serum zinc concentration. Certain cytokines such as interleukin-1 are known to cause a decrease in the serum zinc concentration as part of the acute phase response. Therefore, we measured serum C reactive protein concentrations as an indicator of the acute phase response. Thermally injured patients initially had markedly elevated C-reactive protein levels which gradually decreased during hospitalization. We suggest that the initial hypozincemia observed in thermally injured patients may be a reflection of interleukin-1 mediated acute phase response. Whether one should vigorously attempt to correct this initial marked hypozincemia requires further investigation.

Serum and urinary silver levels in thermal injury patients.

Although silver sulfadiazine has been used extensively as an effective topical antimicrobial agent in thermal injury patients, little is known about the cutaneous absorption of the silver moiety in these patients. Therefore, we longitudinally evaluated both serum silver concentration and 24-hour urinary excretion of silver in 23 patients with second- and third-degree thermal burns. Mean serum silver concentrations were modestly elevated throughout the patients' hospital course. Urinary excretion of silver was markedly elevated, especially in those patients with more severe burns. Indeed, in patients who had burns covering more than 60% of the total body surface area mean peak silver excretion was 1100 micrograms/24 hr (normal, less than 1 micrograms/24 hr). Thus, silver ion is absorbed across the burn wound in thermal injury patients treated with silver sulfadiazine. The 24-hour urinary excretion of silver appears to be a very sensitive indicator of cutaneous absorption in these patients. Possible implications of this cutaneous silver absorption warrant further evaluation.

Serum copper and ceruloplasmin levels and urinary copper excretion in thermal injury.

Conflicting reports regarding copper status in thermal injury patients have been published. We determined serial serum-copper and serum-ceruloplasmin levels and 24-h urinary excretion of copper in 23 patients with second- and third-degree thermal burns. Throughout hospitalization, mean serum-copper concentration was significantly depressed; lowest levels were found in patients with greater than 40% total body surface area burns. Serum ceruloplasmin was also depressed, an unexpected finding because this protein is a positive acute-phase reactant poststress. Mean urinary excretion of copper was elevated, reaching 2.5 times the upper limit of normal 2 wk postburn. Depressed serum-copper levels paralleled the serum-ceruloplasmin levels rather than the increased urinary-copper losses. Further studies are required to determine the mechanism(s) of this altered copper metabolism and whether physiological or biochemical evidence of copper deficiency accompanies the observed hypocupremia.

Serum and urinary selenium levels in thermal injury.

Information concerning selenium status in thermal injury patients is limited. Therefore, both serum selenium concentration and 24 h urinary excretion of selenium were evaluated throughout the hospital course for 23 patients with partial and full skin thickness thermal burns. Serum selenium levels were depressed throughout the hospital course in the majority of patients, and only two patients' serum selenium levels had reached the normal range by discharge. Urinary selenium losses were essentially within normal range throughout the same period and thus were not responsible for the observed depression in serum selenium levels. A possible antagonistic relationship between selenium and silver is discussed.

Population Dynamics of Sugar Beets, Rhizoctonia solani, and Laetisaria arvalis: Responses of a Host, Plant Pathogen, and Hyperparasite to Perturbation in the Field.

Rhizoctonia solani causes crown rot of sugar beets, a severe disease that has destroyed up to 60% of the plants in a test field in western Nebraska. Laetisaria arvalis, a natural hyperparasite of Rhizoctonia spp., was isolated from fields in western Nebraska. To test for the potential for biological control of R. solani, in November 1980 (following harvest) we applied various combinations of a nematicide (Telone II; Dow Chemical Co.), a nutrition source (sugar beet pulp), and an inoculum of L. arvalis in a randomized block design. Populations of R. solani, L. arvalis, and sugar beets were monitored monthly through October 1981 (just after harvest). In control and nematicide plots, the R. solani population did not change significantly through time. In plots inoculated with L. arvalis, the R. solani populations declined through March, concomitant with an increase in L. arvalis. L. arvalis then declined with a corresponding increase in the R. solani populations. Beet plant numbers declined significantly in all treatments. We suggest that reduction of the R. solani populations with the hyperparasite L. arvalis is possible but that a stable equilibrium naturally exists.

Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung cancer.

Patients with bronchogenic carcinoma often have low serum zinc concentrations and sometimes have markedly elevated renal zinc losses. Since normal zinc metabolism is critical for the proper function of T lymphocytes and natural killer cells, the effect of zinc status on T cell phytohemagglutinin response and peripheral blood lymphocyte natural killer cell activity was studied in patients with lung cancer. Mean (+/- SEM) serum zinc concentration in 75 patients with cancer was 67.4 +/- 2.2 micrograms/dl versus 96.0 +/- 8.0 micrograms/dl for normal subjects. Patients with low serum zinc levels (less than 70 micrograms/dl) had significantly higher urine zinc excretion than patients with normal serum zinc levels (1,385 +/- 240 micrograms per 24 hours versus 392 +/- 107 micrograms per 24 hours) (p less than 0.001). This pattern of zinc concentrations (i.e., low serum zinc in combination with high urine zinc) is typical of patients with mild zinc deficiency, and suggests that a mild chronic zinc deficiency state was present in some of these patients. When lymphocyte data were analyzed according to serum zinc concentrations and urinary zinc excretion, low serum zinc concentration and high urine zinc excretion both correlated with depressed T cell phytohemagglutinin response (p less than 0.005 and p less than 0.001, respectively). For instance, mean maximal phytohemagglutinin response in patients with urinary zinc excretion of more than 700 micrograms per 24 hours was 22,132 +/- 3,201 cpm (n = 14) compared with 68,130 +/- 6,850 cpm for patients with normal zinc excretion (n = 7). Peripheral blood lymphocyte natural killer cell activity did not correlate with either serum or urine zinc values. Oral zinc sulfate (220 mg, three times daily for six weeks) was then administered to patients with hyperzincuria (mean = 992 micrograms per 24 hours). Zinc-supplemented patients had normalization of T cell phytohemagglutinin response after zinc therapy, whereas control patients demonstrated continued T cell dysfunction. Natural killer cell activity did not change in either group during the study period. These data suggest that a mild subclinical zinc deficiency state may exist in some patients with lung cancer and may be an important cause of abnormal T cell function. Furthermore, zinc supplementation may be useful to improve lymphocyte function in selected patients. Whether zinc supplementation would alter the course of the disease or the patient's prognosis is presently unknown.

Impaired handling of orally administered zinc in pancreatic insufficiency.

Five patients with pancreatic insufficiency were evaluated for presence of impaired handling of orally administered zinc. Six hospital employees, eight alcoholic cirrhotics, and four patients with small bowel disease served as healthy or chronically ill controls. Two zinc tolerance tests (ZTT) were performed on each subject, one test using zinc sulfate and the other using zinc dipicolinate, a putative zinc binding ligand. Healthy controls demonstrated normal ZTT curves, with no significant difference between the two forms of zinc. Chronically ill controls had significantly depressed ZTT curves compared to healthy controls with both forms of zinc administered. In contrast, pancreatic insufficiency patients had significantly depressed ZTT curves with zinc sulfate but not with zinc dipicolinate, demonstrating a 40% reduction in the area under the curve with zinc sulfate compared to healthy controls. Our study shows impaired handling of orally administered zinc sulfate but not zinc dipicolinate in patients with pancreatic insufficiency and suggests normal pancreatic function may play a role in zinc metabolism in man.