Determinants of the recommended dietary allowance (RDA) for vitamin C include the relationship between vitamin C dose and steady-state plasma concentration, bioavailability, urinary excretion, cell concentration, and potential adverse effects. Because current data are inadequate, an in-hospital depletion-repletion study was conducted. Seven healthy volunteers were hospitalized for 4-6 months and consumed a diet containing <5 mg of vitamin C daily. Steady-state plasma and tissue concentrations were determined at seven daily doses of vitamin C from 30 to 2500 mg. Vitamin C steady-state plasma concentrations as a function of dose displayed sigmoid kinetics. The steep portion of the curve occurred between the 30-and 100-mg daily dose, the current RDA of 60 mg daily was on the lower third of the curve, the first dose beyond the sigmoid portion of the curve was 200 mg daily, and complete plasma saturation occurred at 1000 mg daily. Neutrophils, monocytes, and lymphocytes saturated at 100 mg daily and contained concentrations at least 14-fold higher than plasma. Bioavailability was complete for 200 mg of vitamin C as a single dose. No vitamin C was excreted in urine of six of seven volunteers until the 100-mg dose. At single doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1000 mg of vitamin C daily compared to lower doses. Based on these data and Institute of Medicine criteria, the current RDA of 60 mg daily should be increased to 200 mg daily, which can be obtained from fruits and vegetables. Safe doses of vitamin C are less than 1000 mg daily, and vitamin C daily doses above 400 mg have no evident value.The recommended dietary allowance (RDA) for vitamin C is 60 mg daily, based on threshold urinary excretion of the vitamin and on preventing the vitamin C deficiency disease scurvy with a margin of safety (1, 2).. Ingestion of 60 mg daily was proposed to prevent scurvy for 30-45 days if vitamin C intake ceased (1-7). Threshold urinary excretion of vitamin C was reported at the 60-mg daily dose (3,4,7,8 tTo whom reprint requests should be addressed.
Among volunteer blood donors, prior blood transfusion, intranasal cocaine use, intravenous drug use, sexual promiscuity, and ear piercing in men are risk factors for HCV infection. The high frequency of intravenous drug use was unexpected, because these donors had denied such use when questioned directly at the time of their blood donations.
Most blood donors with anti-HCV have chronic hepatitis C regardless of their serum alanine aminotransferase levels. Donors with normal alanine aminotransferase levels and no HCV RNA in their serum generally have normal liver histologic findings or minimal changes and have probably recovered from HCV infection.
Background Chimeric antigen receptor (CAR) T cells are a promising new immunotherapy. The first step in manufacturing is to collect autologous CD3+ lymphocytes by apheresis. Patients, however, are often leukopenic or have other disease-related complications. We evaluated the feasibility of collecting adequate numbers of CD3+ cells, risk factors for inadequate collections, and the rate of adverse events. Study Design Apheresis lymphocyte collections from patients participating in 3 CAR T cell clinical trials were reviewed. Collections were performed on the COBE Spectra by experienced nurses, with the goal of obtaining a minimum of 0.6×109 and a target of 2×109 CD3+ cells. Pre-apheresis peripheral blood counts, apheresis parameters, and product cell counts were analyzed. Results Of the 71 collections, 69 (97%) achieved the minimum and 55 (77%) achieved the target. Before apheresis, the 16 patients with yields below the target had significantly lower proportions and absolute numbers of circulating lymphocytes and CD3+ lymphocytes, and higher proportions of circulating blasts and NK cells than those who achieved the target (470 vs. 1340 lymphocytes/μL, p=0.008; 349 vs. 914 CD3+ cells/μL, p=0.001; 17.6% vs. 4.55% blasts, p=0.029). Enrichment of blasts in the product compared to the peripheral blood occurred in 4 patients, including the 2 patients whose collections did not yield the minimum number of CD3+ cells. Apheresis complications occurred in 11 patients (15%), and with one exception, were easily managed in the apheresis clinic. Conclusions In most patients undergoing CAR T cell therapy, leukapheresis is well-tolerated and adequate numbers of CD3+ lymphocytes are collected.
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