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This study assessed the effects of ambient UV light on the development of two native species of anurans, Rana blairi and Hyla chrysoscelis, during their normal breeding season in Oklahoma. Additionally, the effects of ambient UV light and water contaminated with landfill leachate in Rana blairi were examined. Embryos were collected from the field and distributed equally among replicates of four filter treatments of ambient UV light in experimental tubs filled with either FETAX solution or landfill leachate diluted to 25, 10, and 5%concentrations. Three endpoints (mortality, teratogenesis, and growth) were compared between filter treatments. By itself, UV-B caused no significant effects. Leachate at 10 and 25% concentrations caused 100% mortality across all filter treatments. There was a significant interaction between filter treatment and water toxicity at leachate concentrations of 5% for both malformation and growth. Increased UV-B exposure decreased the malformation rate and increased growth in the leachate treatments. [Copyright &y& Elsevier]

The objective of the present study was to compare the effects of two diets on the atherogenic potential of two VLDL subfractions harvested from fasting subjects by measuring the number and composition of particles and the amount of esterified cholesterol accumulated in macrophages. A high (25%) monounsaturated fatty acid (Mono) diet and a high (61%) carbohydrate (CHO) diet were provided for 4 wk in a randomized crossover design to 19 normolipidemic, nonobese patients with type 1 diabetes. The two diets were matched for protein, polyunsaturated/saturated fatty acids, cholesterol and fiber content. The number of circulating big VLDL (S:(f) 100-400) particles was greater during the high Mono than during the high CHO diet based on the levels of apolipoprotein B (means +/- SEM): 31.4 +/- 7.4 versus 20.0 +/- 3.8 mg/L (P: < 0.025, paired t test). The following variables did not differ during the diet periods: number of small VLDL (S:(f) 20-100) particles, esterified cholesterol accumulated in THP-1 macrophages incubated with the same number of big and small VLDL particles and particle composition. We conclude that a high CHO diet might be preferable to a high Mono diet, on the basis of the premise that more big VLDL particles could increase the atherosclerotic risk in patients with diabetes. [ABSTRACT FROM AUTHOR]

As expected on the basis of published research in both humans and animals, treatment with phentermine/fenfluramine lowers plasma 5-hydroxytryptamine [corrected], whereas treatment with phentermine had no significant effect. In light of these findings, future research should focus on mechanisms other than increased plasma 5-hydroxytryptamine [corrected] to explain how fenfluramine increases the risk of primary pulmonary hypertension and valvular heart disease. [ABSTRACT FROM AUTHOR]

Background: About 9% of average dietary energy intake in the United States comes from fructose. Such a high consumption raises concern about the metabolic effects of this sugar., Objective: The objective of this study was to determine the effect of dietary fructose on plasma lipids., Design: The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center. The participants were 24 healthy adult volunteers (12 men and 12 women; 6 of each sex were aged <40 y and 6 of each sex were aged >/=40 y). All subjects received 2 isoenergetic study diets assigned by using a randomized, balanced crossover design. One diet provided 17% of energy as fructose. The other diet was sweetened with glucose and was nearly devoid of fructose. Each diet was fed for 6 wk. Both diets were composed of common foods and contained nearly identical amounts of carbohydrate, protein, fat, fiber, cholesterol, and saturated, monounsaturated, and polyunsaturated fatty acids. All meals were prepared in the metabolic kitchen of the General Clinical Research Center., Results: The responses to the study diets differed by sex. In men, the fructose diet produced significantly higher fasting, postprandial, and daylong plasma triacylglycerol concentrations than did the glucose diet. The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32% greater in men than the corresponding concentration during the glucose diet (P: < 0.001). The fructose diet had no significant effect on fasting or postprandial plasma triacylglycerol concentrations in women. The fructose diet also had no persistent effect on fasting plasma cholesterol, HDL cholesterol, or LDL cholesterol in either men or women., Conclusions: Dietary fructose was associated with increased fasting and postprandial plasma triacylglycerol concentrations in men. Diets high in added fructose may be undesirable, particularly for men. Glucose may be a suitable replacement sugar.

There is little information comparing the effects of a high-monounsaturated (Mono)-fat versus a high-carbohydrate (CHO) diet in patients with type 1 diabetes mellitus. In the present study, the effects of these diets on a number of metabolic parameters were compared. Seventeen normolipidemic, nonobese patients with type 1 diabetes were provided with the diets for 4 weeks each in a randomized, crossover design. The percentages of Mono fat of the two diets were 25 Mono versus 9 CHO, with a corresponding total fat content of 40% versus 24% and a total CHO content of 45% versus 61%. At the end of each dietary period, parameters of glycemic control, coagulation factors, and fasting and postprandial lipoproteins were assessed. There were no differences in weight, glycemia, insulin dose, fasting lipid profile, or coagulation factors between the two diets. However, the metabolism of postprandial lipoproteins after a fat load differed; viz, after the Mono diet compared with the CHO diet, mean plasma triglyceride levels over 10 hours were higher (P=.0025, by repeated-measures ANOVA). The levels of triglyceride (P=.0045) and retinyl esters (P=.0046) in chylomicrons (Sf>400) and chylomicron remnants (Sf 100 to 400) (P=.0047 and P=.043, respectively), and the total particle number (apolipoprotein B levels) in chylomicron remnants (P=.001) and small, very low density lipoprotein (Sf 20 to 100, P=.016) were also higher. Our data suggest that in patients with type 1 diabetes, a CHO diet might be preferable to a Mono diet, since adherence to the former results in a lower number of circulating postprandial lipoprotein particles that are potentially atherogenic.

Although measurement of capillary blood glucose remains the standard method of self-monitoring for persons with diabetes mellitus, a less-invasive method of monitoring would be desirable. Measurement of dermal interstitial fluid glucose might meet this need. To test this possibility, plasma glucose, capillary blood glucose (current standard), and dermal interstitial fluid glucose were measured in 17 subjects with type I diabetes during a 5-hour pre- and postprandial period when plasma glucose was changing rapidly. The objective was to assess the ability of dermal interstitial fluid glucose to accurately predict plasma glucose over a wide range of potential glucose concentrations. Dermal interstitial fluid glucose was highly correlated with plasma glucose (r = 0.95, p < 0.0001). The mean absolute and percent differences between dermal interstitial fluid glucose and plasma glucose were 1.2 mmol/L (21 mg/dl) and 10.6%, respectively. The kinetics of dermal interstitial fluid glucose and plasma glucose were similar. There was no significant difference between dermal interstitial fluid glucose and plasma glucose in mean glucose excursion, peak glucose concentration, or time to peak glucose concentration. The correlation between dermal interstitial fluid glucose and plasma glucose was as strong as the correlation between capillary blood glucose and plasma glucose. In conclusion, dermal interstitial fluid glucose can be used to estimate plasma glucose, and has the potential to be used for monitoring patients with diabetes mellitus.

Objective: To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non-insulin-dependent diabetes mellitus (NIDDM)., Design: A four-center randomized crossover trial., Setting: Outpatient and inpatient evaluation in metabolic units., Patients: Forty-two NIDDM patients receiving glipizide therapy., Interventions: A high-carbohydrate diet containing 55% of the total energy as carbohydrates and 30% as fats was compared with a high-monounsaturated-fat diet containing 40% carbohydrates and 45% fats. The amounts of saturated fats, polyunsaturated fats, cholesterol, sucrose, and protein were similar. The study diets, prepared in metabolic kitchens, were provided as the sole nutrients to subjects for 6 weeks each. To assess longer-term effects, a subgroup of 21 patients continued the diet they received second for an additional 8 weeks., Main Outcome Measures: Fasting plasma glucose, insulin, lipoproteins, and glycosylated hemoglobin concentrations. Twenty-four-hour profiles of glucose, insulin, and triglyceride levels., Results: The site of study as well as the diet order did not affect the results. Compared with the high-monounsaturated-fat diet, the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24% (P < .0001) and 23% (P = .0001), respectively, and increased daylong plasma triglyceride, glucose, and insulin values by 10% (P = .03), 12% (P < .0001), and 9% (P = .02), respectively. Plasma total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels remained unchanged. The effects of both diets on plasma glucose, insulin, and triglyceride levels persisted for 14 weeks., Conclusions: In NIDDM patients, high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable.

Objective: Subcutaneous insulin is absorbed at different rates from different anatomical regions, but it is not clear how much the varying rates of absorption affect plasma glucose concentrations in diabetic subjects. To address this issue, subcutaneous injections of insulin in the abdomen were compared with subcutaneous injections of insulin in the thigh., Research Design and Methods: In a crossover trial, 22 type I diabetic subjects received, in random order, a test dose of regular insulin injected subcutaneously in the abdomen on one morning and in a thigh on another morning. The subjects also received, in random order, usual morning doses of NPH and regular insulins injected subcutaneously in the abdomen on one morning and in a thigh on another morning. The study was performed in the University of Minnesota General Clinical Research Center. Main outcome measures were plasma glucose and serum free insulin., Results: After injections of regular insulin in the abdomen, the peak postprandial increment in plasma glucose was 3.1 mM or 29% lower (P < 0.001), the peak increment in serum free insulin was 54 pM or 38% higher (P = 0.017), and the length of time required to achieve peak serum free insulin was significantly shorter than after injections of regular insulin in the thigh. After injections of NPH and regular insulins in the abdomen, the morning peak increment in plasma glucose was 2.5 mM or 18% lower (P = 0.008) than after injections of NPH and regular insulins in a thigh. However, no significant difference was observed in the afternoon peak increment in plasma glucose., Conclusions: A subcutaneous injection of regular insulin in the abdomen produced a substantially greater reduction in plasma glucose than an injection of regular insulin in the thigh. Changing the injection site of regular insulin from the abdomen to the thigh had an effect equivalent to reducing the dose administered. With injections of NPH and regular insulin in combination, the influence of the region used for injection was less but still potentially important.

One hundred and two patients (81 females, 21 males) suffering from thyrotoxicosis as diagnosed clinically and confirmed by laboratory investigations including the estimation of thyroid hormones in blood were treated with radioiodine (I-131) at the University of Minnesota Hospital between 1976 and 1986. Nine (9%) patients needed two and 3 (3%) patients needed three therapeutic doses of I-131. The age range of the patients was 17-82 years (mean 43, SD 17). The doses of I-131 administered ranged from 3.9 to 100 mCi (mean 13.7). Twenty of these patients received a relatively high dose from 20 to 100 mCi. The others were given smaller calculated doses based on radioiodine uptake and thyroid size is determined by palpation and nuclear scans. Of the 73 patients for whom follow-up information was available, 66 (90%) eventually became hypothyroid as judged by clinical criteria. These data also suggest that the incidence of hypothyroidism is quite independent of the dose (microCi/g thyroid) administered.

To evaluate whether cyclosporine nephrotoxicity is progressive, glomerular filtration rate and renal plasma flow were determined by isotopic techniques in 24 cyclosporine-treated organ transplant recipients (12 heart, 1 pancreas, and 11 kidney recipients). The cyclosporine group demonstrated reductions in glomerular filtration rate and renal plasma flow, with higher renal vascular resistance and mean arterial pressure as compared with an azathioprine-treated control group. However, longitudinal studies over a mean time period of 23 months in eight cyclosporine-treated renal transplant recipients showed renal function to remain stable. In the entire group of 24 cyclosporine-treated patients, longer duration of cyclosporine treatment was associated with decreased but stable glomerular filtration rate, increased renal plasma flow, decreased renal vascular resistance, and lower daily doses of cyclosporine. Evaluation of intrarenal resistances demonstrated a greater decrease in efferent than afferent arteriolar resistance, consistent with the fall in plasma renin activity that occurred with time. Short-term treatment of 12 patients with prazosin produced no beneficial effect on renal function, whereas treatment of nine patients with captopril produced a 20% increase in renal plasma flow, with a significant reduction in renal vascular resistance. We conclude that although cyclosporine treatment produces decreased renal function, the loss in renal function is not necessarily progressive. Treatment with captopril may improve the abnormal renal hemodynamics of cyclosporine-treated patients.

Abnormal serum creatinine (1.6 mg/dL) and creatinine clearance (33 mL/min) levels found in a 50-year-old woman during fasting were corrected with refeeding. Five healthy subjects who fasted for 96 hours demonstrated an increase in their mean serum creatinine level from 1.0 +/- 0.08 to 1.7 +/- 0.11 mg/dL as determined by Jaffé's method. This increase was probably an artifact caused by the rise in the serum acetoacetate level during fasting. The serum creatinine level determined by an enzymatic method and serum urea nitrogen level did not change substantially during the fast. We conclude that fasting may cause an artifactual increase in the serum creatinine level determined by Jaffé's method, the method used by most clinical laboratories.

Bulimia is a disorder characterized by episodes of binge-eating. Patients with this problem consume large amounts of food when binge-eating and, subsequently, to avoid weight gain, usually self-induce vomiting or induce diarrhea with laxatives. Metabolic and endocrine investigations in six bulimic subjects of normal weight are reported. Normal fasting plasma glucose concentrations and glucose tolerance were present in all. Five subjects had normal serum T4 and T3 concentrations. Only one subject had depressed serum T4 and T3 concentrations and this subject had a normal serum TSH level. Menstrual irregularities were present in all patients and, in three, were associated with modestly elevated serum prolactin levels. In four subjects there was an abnormal increase in serum growth hormone following TRH administration and in three, growth hormone failed to suppress normally after oral glucose. Two subjects were found to have a hypokalimic metabolic alkalosis, presumably due to vomiting. Urinary 17-OH steroid excretion and urinary concentrating ability were normal or nearly so in all subjects.

In an attempt to compare the cholesterol-lowering effects of equivalent doses of D- and L-thyroxine, 10 euthyroid, hypercholesterolemic subjects were treated with graded doses of each medication in a cross-over design using thyrotropin suppression following thyrotropin-releasing hormone administration as the end-point. The mean thyrotropin-suppressive dose of D-thyroxine was 2.4 +/- 0.66 mg per day, which resulted in mean reductions of 10 percent in total plasma cholesterol, 10 percent in plasma low-density lipoprotein cholesterol, and 11 percent in plasma high-density lipoprotein cholesterol. The mean thyrotropin-suppressive dose of L-thyroxine was 135 +/- 46 micrograms per day, which resulted in mean reductions of 7 percent in total plasma cholesterol, 6 percent in plasma low-density lipoprotein cholesterol, and 14 percent in plasma high-density lipoprotein cholesterol. The reductions in total, low-density, and high-density cholesterol achieved with D-thyroxine were not significantly different from those achieved with L-thyroxine. Neither medication produced a significant increase in heart rate or ventricular ectopy as determined by Holter monitoring. These data do not support the belief that D-thyroxine has a preferential cholesterol-lowering effect in humans when compared with equivalent doses of L-thyroxine. In addition, both D- and L-thyroxine reduced plasma high-density lipoprotein cholesterol.

Of 11 patients with active acromegaly treated with transsphenoidal selective pituitary adenomectomy, four failed to show evidence of clinical improvement. An additional four patients showed clinical and biochemical improvement after the surgical procedure but, with more prolonged follow-up, showed a recurrence of acromegaly. Only three patients had prolonged clinical and biochemical evidence of improvement; they had glucose suppressed growth hormone concentrations of 1.0, 2.7, and 2.8 ng/mL 22, 40, and 24 months, respectively, after the surgical procedure. Two of these three patients, however, showed an increase in growth hormone concentration after thyrotropin-releasing hormone injection, a finding that suggests the possibility of eventual relapse. Our data also clearly indicated a need for more rigorous criteria for biochemical cure of acromegaly than those used previously. Study of 20 healthy volunteers showed that growth hormone concentration should normally be suppressible to less than 2.0 ng/mL after 100 g oral glucose.

The efficacy of clofibrate (CPIB) and nicotinic acid (NA) in the treatment of type III hyperlipoproteinemia was evaluated in 5 male subjects in a randomized cross-over study with clofibrate 1 g b.i.d. and NA 3 g/day (given either b.i.d. or t.i.d.). Following a baseline period of 6 weeks, each drug was given for 12 weeks with samples for lipid and lipoprotein determinations obtained at 6, 9, and 12 weeks. Both clofibrate and NA resulted in a significant reduction from baseline of total cholesterol (23% and 28%), VLDL cholesterol (49% and 56%), total triglycerides (40% and 43%), and VLDL triglycerides (46% and 48%), as well as a significant increase in HDL cholesterol (22% and 28%) and HDL/LDL ratio (31% and 62%). The HDL/LDL ratio was higher on NA than clofibrate (0.47 +/- 0.19 vs. 0.38 +/- 0.09, P less than 0.05). Four subjects were continued in the study and treated sequentially with NA 3.0 g/day (alternate to the previous schedule) and gemfibrozil 1.2 g/d in divided doses. Each of the 4 regimens resulted in a significant change from baseline of each of the measured lipid and lipoprotein determinations except LDL cholesterol. Comparison among the treatment regimens revealed no differences except for significantly higher HDL cholesterol and HDL/LDL ratio with NA given t.i.d.

Cyclosporine treatment is associated with hypertension and suppression of plasma renin activity, the causes of which are unclear. To determine whether suppressed plasma renin activity is due to extracellular fluid volume expansion, 10 cyclosporine-treated renal transplant recipients were compared with 10 azathioprine-treated renal transplant recipients and seven patients with renal insufficiency. Glomerular filtration rate and effective renal plasma flow were significantly lower in cyclosporine-treated patients than in azathioprine-treated patients. Upright plasma renin activity was suppressed in cyclosporine-treated patients (cyclosporine 2.9 +/- 0.9, azathioprine 4.7 +/- 0.9, renal insufficiency 5.2 +/- 1.9 ng/ml/hour) but could be stimulated by a four-day period of dietary sodium restriction and diuretic administration (cyclosporine 15.8 +/- 4.4 ng/ml/hour). Extracellular fluid volume tended to be higher in cyclosporine-treated patients (cyclosporine 30.7 +/- 2.3, azathioprine 26.7 +/- 2.5, renal insufficiency 25.5 +/- 1.4 percent lean body mass), although the difference between cyclosporine-treated and azathioprine-treated patients did not attain statistical significance. There were no differences in the urinary excretion of prostaglandin E2 or 6-keto prostaglandin F1 alpha between the two groups of renal transplant recipients. It is concluded that suppression of plasma renin activity by cyclosporine is physiologic and may reflect expansion of extracellular fluid volume, which can be reversed by sodium depletion.