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The effect of dextroamphetamine sulfate (Dexedrine) on plasma opioid peptides, hormones, and other metabolites was studied in eight female subjects with idiopathic (orthostatic) edema and five healthy females. All subjects were given 20 mg of dextroamphetamine sulfate, a drug widely used in the treatment of this disorder, and blood samples were collected before and 30, 60, and 90 minutes after treatment. Patients with idiopathic (orthostatic) edema had significantly lower plasma sodium levels but higher blood urea nitrogen, aldosterone, and renin levels. D-amphetamine decreased aldosterone and renin levels in both groups. Plasma adrenocorticotropin levels were lower whereas met-enkephalin levels were higher in idiopathic (orthostatic) edema subjects compared to control subjects. D-amphetamine had no significant effect on plasma beta-endorphin, adrenocorticotrophic hormone, or enkephalins. Our data indicate that opioid peptides, especially enkephalins, and adrenocorticotrophic hormone may be involved in the pathogenesis of idiopathic (orthostatic) edema syndrome, but they seem uninvolved in the aldosterone- and renin-lowering action of amphetamine. It is possible that amphetamine is acting further down the chain, either directly on the adrenal and kidney or the microvasculature, rather than at hypothalamus-pituitary axis.

Carbon dioxide production, water production, and energy expenditure (EE) determined with 2H2(18)O were validated using a room calorimeter. Nine human subjects (5 males, 4 females) resided in the calorimeter for five to seven consecutive 23.5-h days. Daily carbon dioxide and water production and EE were averaged from calorimeter data and compared with 2H2(18)O results for the same period and for the following week. Isotope concentrations were measured by isotope ratio mass spectroscopy (18O) and infrared spectrophotometry (2H). Isotope clearance rates and pool sizes were determined by two multipoint methods and the two-point method. No significant differences were measured between calorimetry and 2H2(18)O results for the period within the chamber [multipoint A.M. urine 1.55% +/- 2.57 (SD) %, multipoint A.M. + P.M. urine 0.98% +/- 8.19%, two-point 1.59% +/- 4.50%]. Free-living EE was 13% +/- 7% greater. The results indicate that the 2H2(18)O method as applied is a valid technique for measuring EE, that multipoint calculation methods can be as precise as the two-point method, and that EE was greater in free-living than in calorimeter-confined conditions.

Young female obese (cp/cp) and lean littermates (?/+) of the recently developed congenic strain, SHR/NIH-corpulent (SHR/N-cp), were fed for 6.5 months isocaloric diets containing 54 percent carbohydrate as either sucrose or starch. Glycemic, lipidemic and renal parameters were determined after 1, 3 and 6 months. Systolic blood pressure and plasma corticosterone levels were determined after 3 months. After 6.5 months rats were killed for histological examination. Obese rats were hyperglycemic following an oral glucose challenge (1 hour response greater than 11.1 mmol/l) (200 mg/dl), hyperinsulinemic, hypertriglyceridemic, and developed proteinuria and mild hypertension. Feeding sucrose, as compared to starch, further increased serum glucose, insulin and triglyceride levels and urinary protein excretion in obese rats and serum triglyceride levels in lean rats. An amelioration of glucose intolerance was observed in sucrose-fed obese rats by 6 months. In contrast to serum insulin levels, serum triglyceride levels increased with age in obese rats. Obese rats exhibited hypertrophy of the kidney and adrenal cortex with abnormal histology. The study demonstrates that obese female SHR/N-cp rats exhibit some of the metabolic and histopathological changes associated with NIDDM in humans and that feeding sucrose, as the source of dietary carbohydrate, further magnifies the expression of diabetes in this model.

Forty-nine ostensibly healthy men consumed either patties of all-beef or beef extended with soy-isolate, -concentrate or -flour as the principal protein source in 1 to 2 meals daily for 180 days. Iron status was monitored by absorption of radioiron from a reference dose of ferrous ascorbate and by serum ferritin concentration. In addition, nonheme iron absorption from a test meal of the respective beef pattie consumed for the 180 days was estimated by the extrinsic tag procedure. There was no detrimental effect on iron stores as indexed by reference ferrous ascorbate absorption or serum ferritin concentration. Absorption of nonheme iron from the test meals was low except for individuals having indices of low iron stores. When adjusted for the effect of level of iron stores the relative absorption of nonheme iron from soy-isolate and -flour containing meals was greater than from the all-beef meal, indicating marked differences in the effect on iron absorption by different soy products. Consumption of soy-extended beef should have no detrimental effect on iron status of adult men if consumed in mixed diets at the level used in this study.

Analysis of a series of 200 surgically treated cases of primary hyperparathyroidism was carried out in an effort to identify not only the changing clinical patterns and improved diagnostic methods but also to assess the long term results of our conventional operative methods in light of recent reports of a high incidence of diffuse hyperplasia and a high recurrence rate when surgery is restricted to removal of the adenoma. As reported by others the "chemical diagnosis" of primary hyperparathyroidism, the clinical setting in which unsuspected hypercalcemia is demonstrated on routine blood analysis, accounts for the majority of diagnoses today. Impending or actual "parathyroid crisis" has been observed with alarming frequency. The use of the thiazide challenge test provides a useful diagnostic aid in many instances. The incidence of diffuse hyperplasia was 6% in this series while an adenoma was present in 88%. No instance of recurrence was observed in either the cases of adenomas or diffuse hyperplasia.

In an investigation of the effects of fiber and oxalic acid on weekly mineral balances, 12 men consumed two diets consisting of natural foods for 6 wk each in a crossover design. One diet contained about 25 g neutral detergent fiber (NDF) in fruits and vegetables and included 100 g spinach, which is high in oxalic acid, every other day. The second diet was a low fiber diet that contained about 5 g NDF and the same amount of spinach as the first diet. On the basis of mean values for 6 wk, balances for calcium, magnesium, iron, zinc or manganese were not significantly different due to diet. Copper balances were significantly lower when the low fiber diet was consumed than when the diet containing fiber in fruits and vegetables and consequently a higher level of copper was consumed. Mineral balances were significantly different due to week. When results of both diets were considered together, mean mineral balances decreased at some time after wk 1 and returned to the wk 1 level during wk 6. Balances for wk 1 and 6 were not significantly different for any of the six minerals. These results demonstrate the importance of determining weekly balances for several weeks when conducting a human metabolic study.

A patient suspected of having adrenal hyperfunction was scanned with 131I-iodocholesterol. Intense gallbladder activity persisted for several days and was eliminated by a fatty meal. The possibility of confusion with unilateral adrenal localization is discussed.

Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed a typical American diet containing 20% of calories either as fructose or as high-amylose cornstarch for 5 wk in a crossover design to determine their effects on indices of glucose tolerance. Blood glucose, insulin, and fructose were determined before and 30, 60, 90, 120 and 180 min after breakfast, lunch, and dinner. Glucose responses were significantly lower 60 and 120 min and the insulin response lower 60 min after the meals containing fructose. Hyperinsulinemic men showed a tendency toward decreased insulin sensitivity after consuming fructose on the basis of an increased insulin-to-glucose ratio and decreased insulin binding to erythrocytes. These results generally show a beneficial effect of fructose on glucose tolerance; however, recommendations for including large amounts of fructose in the diet should also be based on a complete evaluation of the effect on other metabolic risk factors.

The effect of propranolol on the surgical course of 84 thyrotoxic patients undergoing partial thyroidectomy or extrathyroidal surgery was evaluated. Seventy-two patients (group 1) underwent surgery with propranolol as their sole preparatory medication, whereas in 12 (group 2) surgery was carried out after a rather prolonged period of thionamide preparation with the addition of propranolol preoperatively as an adjunctive therapeutic agent. Preoperative pulse rate and systolic blood pressure levels fell in both groups, and the clinical features of thyrotoxicosis were rapidly ameliorated with an average dose of propranolol of 330 mg (range 40 to 1,280 mg) daily. Maximal clinical response occurred within 48 to 72 hours of starting propranolol therapy. In 14 patients in group 1, paired serum calcium levels were reduced by the administration of propranolol preoperatively; serum thyroxine levels were unchanged. Serum thyroxine decay, evaluated postoperatively in the patients in group 1, was decreased. The half life of thyroxine was inversely related to the initial thyroxine levels. Analysis of these data indicates that the administration of propranolol alone provides rapid, safe and effective preparation of thyrotoxic patients for emergency or for elective thyroidal or extrathyroidal surgical procedures.

Twenty men, 19 premenopausal and 14 postmenopausal women consumed a diet for 13 weeks that supplied 35% of the calories from fat, 50% from carbohydrate, and 15% from protein. The diet was low in cholesterol, saturated fat, and salt, and high in complex carbohydrate and fiber. The 7-day menu was composed of common well-accepted foods prepared in a simple attractive manner. Plasma total cholesterol, LDL cholesterol, and VLDL cholesterol were reduced, but triglyceride levels were not different than after self-selected diets. When 20% of the complex carbohydrate was replaced by simple carbohydrate and other diet components remained optimal, triglyceride and VLDL cholesterol levels increased in men and premenopausal women and total cholesterol increased in premenopausal women. These results suggest that beneficial effects on the blood lipids and lipoprotein distribution of men and women may be obtained by minimal modification of a typical U.S. diet.

For decades, the preparation of a hyperthyroid patient for surgery took several weeks or months utilizing thyroid blocking agents and iodine. In 1973, a preliminary report of 20 patients with hyperthyroidism treated with propranolol and thyroidectomy was presented. It was found that a thyrotoxic patient could be prepared for surgery, in an emergency, by intravenous propranolol in less than an hour, or electively by oral propranolol within 24 hours. Since then, 140 additional patients have been similarly treated. It continues to be true at this institution that propranolol, a beta-adrenergic blocking agent, effectively neutralizes the symptoms of autonomic hyperactivity, including sweating, tremor, fever, dilation of blood vessels, and increased pulse rate without significantly affecting thyroid function. An average dose of 160 mg/day was used, with a range of 40 to 320 mg/day. In none of these patients was iodine used; in fact, its use with propranolol is considered unnecessary. A subtotal, near total, or total thyroidectomy was done in all patients, resulting in a 55% incidence of hypothyroidism. There was no postoperative thyroid storm, nerve injury, or permanent hypoparathyroidism. It is believed that the administration of propranolol alone provides a rapid, safe, and effective preparation of the thyrotoxic patient for thyroidal or extrathyroidal surgical procedures during the perioperative period.

A study was conducted to evaluate the effects on blood lipids and lipoproteins of feeding 21 healthy volunteers, 40-60 yr old, foods commonly eaten in the United States for two 40-day periods. Activities of lactate dehydrogenase (LDH) and LDH isoenzymes, lactate, and pyruvate were monitored. Results showed that LDH activity was significantly lower in all subjects at the end of the 25% fat-calorie period (period I) than at the beginning of the study, but rose above initial levels at the end of the 35% fat-calorie period (period II). While total LDH fell during period I, relative activity of M type subunits of LDH rose significantly in relation to H type in both sexes. This rise is probably indicative of an increase in glycolytic activity as a consequence of the increased intake of dietary carbohydrate. In period I, lactate and pyruvate decreased significantly in males (pyruvate greater than lactate) but not in females. Values for males returned to near initial levels in period II. The ratio of lactate/pyruvate was elevated in both sexes after period I. The greater change in pyruvate relative to lactate with increased dietary carbohydrate suggests increased Krebs Cycle activity. There was a statistically significant positive correlation between lactate, pyruvate, and serum triglyceride for males after they ate the 25% and 35% fat-calorie diets and for females after they ate the 35% fat-calorie diet, but not between lactate, pyruvate, and serum cholesterol for either sex.

Twenty-three apparently healthy volunteers aged 35 to 60 years consumed closely monitored self-selected (SS) diets for five weeks followed by two low fat controlled diets (25% energy) for two six-week periods followed by another five-week SS diet. The two low fat diets, fed in a crossover design to one-half of the subjects per controlled diet period, had a polyunsaturated/saturated (P/S) fat ratio of either 0.3 or 1.0. Results are reported for bi-weekly measurements of energy and nutrients; blood profiles and plasma fatty acids; and for end-of-period values for stool characteristics. Blood chemistry profiles differed in the two groups. The low P/S diet produced significant increases not only in cholesterol, but in 16:0, 16:1, and percent saturated fatty acids and decreases in 18:2 and omega 6 fatty acids. The reverse was seen with the high P/S diet. The essential fatty acid (EFA) linoleic acid returned in the poststudy period to prestudy levels (all subjects), but arachidonic acid did not. The explanation for negative correlation between magnesium intake or excretion and percent plasma linoleic acid must await further research.

The iron status of men, women and children consuming beef extended with soy protein was evaluated by measuring serum ferritin and clinical parameters of iron status during a six-month study. Fifty-two families (245 participants) were randomly assigned to consume, for 180 days, 1 of 7 beef products: all beef, beef extended with either soy isolate, soy concentrate or soy flour (20% reconstituted soy product, 80% beef), or beef extended with each of the three soy products fortified with 60 mg Fe and 25 mg Zn/100 g protein. The beef product was consumed by the subjects as their principal source of protein for 1 meal a day (children 1-18 yr) or 1-2 meals a day (11 per week; adult men and women). A control group consumed their usual self-selected diets. No evidence was found that consumption of beef extended with soy protein deleteriously affected the iron status of men, women or children. Consumption of beef extended with soy protein, at the levels used in this study, by military men and women and by school lunch participants would not appear to impose a risk in these population groups.

Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed for 5 wk each in a cross-over design a diet, similar to one currently consumed in the United States, with 20% of the kilocalories from either fructose or high-amylose cornstarch to determine the effects of the two diets on various blood metabolites considered to be risk factors associated with heart disease. In the hyperinsulinemic men the intake of fructose as compared with cornstarch significantly increased total triglycerides and their lipoprotein distribution; total and very-low-density lipoprotein cholesterol; apoproteins B-100, C-II, C-III; and uric acid. In the nonhyperinsulinemic men total triglycerides, total and low-density lipoprotein cholesterol and uric acid were significantly greater after the consumption of fructose than after cornstarch. The results indicate that in a diet high in saturated fatty acids and cholesterol, fructose increases the levels of risk factors associated with heart disease, especially in hyperinsulinemic men.

This study demonstrates that a three-week stabilization period, in which all subjects eat an identical diet, produced a more uniform but different baseline of metabolic parameters than the subject's self-selected or "habitual" diets. Subjects required more food energy to maintain initial body weights during the stabilization period than when they ate their reported self-selected diets; average intakes of almost all nutrients were higher from the stabilization than from the self-selected diet. The switch to the stabilization diet produced small but significant reductions in blood pressure, in some serum enzymes, urine volume, and sodium; and statistically significant increases in serum LDL cholesterol, potassium, aldosterone, protein, albumin, phosphorus, BUN, and in urine potassium. The findings indicate that results must be interpreted with caution from studies in which the baseline for measuring metabolic variables is established by feeding subjects a standardized diet that differed markedly from their regular, self-selected diets.

The effect of long-term consumption, under practical conditions, of beef extended with soy protein on serum zinc levels of men, women and children was studied. Fifty-two families were randomly assigned to consume for 180 days 1 of 7 beef products: all beef, beef extended with either soy isolate, soy concentrate or soy flour (20% reconstituted soy product, 80% beef), or beef extended with each of the 3 soy products fortified with 60 mg Fe and 25 mg Zn/100 g protein. The beef product was consumed by the subjects as their principal source of protein for 1 meal a day (children 1-8 yrs) or 1-2 meals a day (11 per week) for adult men and women. A control group consumed their usual self-selected diet. Diet records (4-day) of all foods and beverages consumed by the subjects were obtained pre-study and 63 +/- 7 and 126 +/- 7 days for calculation of nutrient intakes. No deleterious effects were found on the serum zinc levels when subjects consumed beef extended with soy protein for 180 days.

The effect of propranolol on the hypermetabolism of thyrotoxicosis was investigated in eight subjects with diffuse toxic goiter. After equilibration on a constant nitrogen, calcium, and hydroxproline intake, nitrogen balance was determined before and during propranolol therapy prior to subtotal thyroidectomy and compared to similar data obtained in seven of the patients following surgically induced euthyroidism. Propranolol administration was associated with clinical amelioration and a rapid, statistically significant, improvement in nitrogen retention. A slight additional improvement in retention was noted in the postoperative euthyroid state. Oxygen consumption, measured serially in four patients, was not significantly changed by propranolol. Urinary loss of calcium, phosphorus, and hydroxyproline was unaffected by propranolol, but excretion of these substances was sharply reduced in the subjects restudied postoperatively. These data offer a evidence of a previously unreported nitrogen sparing effect of oral propranolol during its short-term administration in thyrotoxic man.

This study proposed to determine whether the stimulation of insulin secretion observed in humans infused with fructose when glucose levels were elevated could be observed when fructose was consumed during postprandial hyperglycemia. At 2-wk intervals, healthy volunteers consumed drinks containing glucose, starch, glucose followed 20 min later by fructose, starch followed 20 min later by fructose, and water followed 20 min later by fructose. Fructose consumption following glucose or starch drinks produced significantly higher levels of plasma insulin, but not plasma glucose, as compared to corresponding drinks consumed without fructose. Ten subjects whose blood glucose response levels were above 155 mg% after a glucose-containing drink appeared to be particularly responsive to the effects of fructose with increases in insulin levels of 60-288%. Results indicate that oral fructose can be insulinogenic in humans when blood glucose levels are elevated.

To determine if chromium (Cr) is involved in hypoglycemia, eight female patients with symptoms of hypoglycemia were supplemented with 200 micrograms of Cr as chromic chloride for three months in a double-blind crossover experimental design study. Chromium supplementation alleviated the hypoglycemic symptoms and significantly raised the minimum serum glucose values observed two to four hours following a glucose load. Insulin binding to red blood cells and insulin receptor number also improved significantly during Cr supplementation. These data suggest that impaired Cr nutrition and/or metabolism may be a factor in the etiology of hypoglycemia.