No abstract

An interferon-'y, tumor necrosis factor, and interleukin-1-inducible, high-output pathway synthesizing nitric oxide (NO) from L-arginine was recently identified in rodents. High-dose interleukin-2 (IL-2) therapy is known to induce the same cytokines in patients with advanced cancer. Therefore, we examined renal cell carcinoma (RCC; n = 5) and malignant melanoma (MM; n = 7) patients for evidence of cytokine-inducible NO synthesis. Activity of this pathway was evaluated by measuring serum and urine nitrate (the stable degradation product of NO) during IL-2 therapy. IL-2 administration caused a striking increase in NO generation as reflected by serum nitrate levels (10-and 8-fold increase IP < 0.001, P < 0.0031 for RCC and MM patients, respectively) and 24-h urinary nitrate excretion (6.5-and 9-fold increase [both P < 0.0011 for RCC and MM patients, respectively). IL-2-induced renal dysfunction made only a minor contribution to increased serum nitrate levels. Metabolic tracer studies using L-[guanidino-5N2Jarginine demonstrated that the increased nitrate production was derived from a terminal guanidino nitrogen atom of L-arginine. Our results showing increased endogenous nitrate synthesis in patients receiving IL-2 demonstrate for the first time that a cytokine-inducible, highoutput L-arginine/NO pathway exists in humans. (J. Clin. Invest. 1992. 89:867-877.) Key words: acute renal failure * malignant melanoma * nitrate * nitrite * renal cell carcinoma

No abstract

Contrary to expectations, the ad libitum, low-fat, high-fiber diet promoted weight loss in patients with type 2 diabetes without causing unfavorable alterations in plasma lipids or glycemic control.

The mineral status in phenylketonuria (PKU) was measured by single-photon densitometry of the distal radius and plasma concentrations in 26 subjects. Bone mineral content increased normally with age in the younger children despite strict dietary restrictions. Subjects aged greater than 8 y, however, were frequently below the normal curve for bone mineral content. Blood phenylalanine concentrations were significantly higher in the older group of subjects and this correlated with decreased compliance with dietary prescriptions. PKU children had significantly decreased plasma concentrations of alkaline phosphatase, magnesium, and parathyroid hormone. Subnormal concentrations of plasma zinc and plasma and red blood cell (RBC) copper were common, but RBC zinc was normal. We conclude that compliance with dietary therapy for PKU is associated with normal bone mineral development in young children. Older patients with PKU who follow the diet less carefully are at risk for low bone mineral content.