Publications

We studied the interaction between airway drying (cooling) and inhalation of sulfur dioxide (SO2) causing bronchoconstriction in 8 subjects with mild asthma. On 3 separate days, we measured specific airway resistance (SRaw) before and after the subject performed voluntary eucapnic hyperpnea at a constant minute ventilation (30 to 40 L/min) for successive 3-min periods with doubling concentrations of SO2 in dry cold air (-20 degrees C, 0% relative humidity), in dry warm air (22 degrees C, 0% relative humidity), and in partially humidified warm air (22 degrees C, 70% relative humidity). On another day, we measured SRaw before and after the subject performed each of 6 successive 3-min periods of voluntary eucapnic hyperpnea at the same minute ventilation breathing dry cold air without SO2. The concentration of SO2 that caused a 100% increase in SRaw was significantly lower in dry cold air and in dry warm air than it was in humidified warm air. Repeated hyperpnea with dry cold air without SO2 at the same ventilation had no effect on SRaw. We then had the same subjects perform voluntary eucapnic hyperpnea at successively increasing levels of ventilation on 3 different days with dry air alone, dry air with 0.1 ppm SO2, or dry air with 0.25 ppm SO2. The minute ventilation that caused an 80% increase in SRaw was significantly lower for hyperpnea with 0.1 and with 0.25 ppm SO2 than for dry air without SO2, but these differences were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent theoretical work has suggested that radiochemical impurities can significantly alter the binding results for highly protein-bound drugs. We compared protein binding of warfarin by ultrafiltration and equilibrium dialysis with 98% radiochemically pure [14C]warfarin. Ultrafiltration and equilibrium dialysis were performed at 37 degrees C and pH 7.45 on the plasma of patients receiving chronic warfarin therapy. Binding to plasma from seven patients were measured in duplicate by both a nonspecific radioisotopic technique and a specific HPLC technique. The nonspecific technique gave percentage of free warfarin values of 1.84 +/- 0.11 (mean +/- SD) and 1.59 +/- 0.14 for ultrafiltration and equilibrium dialysis, respectively. The HPLC procedure yielded a percentage of free warfarin by ultrafiltration of 0.969 +/- 0.203 and a value of 0.690 +/- 0.095 by equilibrium dialysis (p less than 0.05). The HPLC procedure for protein binding was performed on plasma samples from 12 additional patients and yielded a percentage of free warfarin of 1.01 +/- 0.69 by ultrafiltration and 0.44 +/- 0.34 by equilibrium dialysis (p less than 0.05). It can be concluded that radiochemical impurities may lead to significant overestimation of the percentage of free warfarin. Ultrafiltration yielded a higher percentage of free warfarin than did equilibrium dialysis, but the ability to distinguish binding differences among patients was similar.