Establishing an Indicator of Hypokalemia in Patients Receiving Anti-Epidermal Growth Factor Receptor Antibodies.

Risk factors for hypokalemia were analyzed in patients who received anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs) at Gifu Municipal Hospital between February 2010 and March 2013. Subjects were 51 patients (27 men and 24 women) with the median age (interquartile range) of 66 (63-72) years. The study period started from the initiation of anti-EGFR MoAbs administration and ended 4 weeks after administration was completed. Patients were categorized into the side effect group if both minimum serum potassium (Min S-K) grade and b grade (pre-treatment S-K grade-Min S-K grade) were B1; otherwise, they were placed into the no side effect group. Univariate analysis for factors to prevent the side effect identified the "concomitant use of hyperkalemia-inducing drugs" to be statistically significant (p=0.010). Multivariate analysis was conducted on factors with a p value of <0.25 in the univariate analysis and on "concomitant use of hyperkalemia-inducing drugs," which was likely to clinically affect S-K decrease, although its p value was >0.25. It showed that "concomitant use of hyperkalemia-inducing drugs" was a significant risk-prevention factor (odds ratio: 0.138, 95% confidence interval[CI]: 0.033-0.581, p=0.007). In conclusion, "concomitant use of hyperkalemia-inducing drugs" is a factor associated with preventing hypokalemia accompanying anti-EGFR MoAbs administration.

Delayed-type asthmatic response induced by repeated intratracheal exposure to toluene-2,4-diisocyanate in guinea pigs.

BACKGROUND: A toluene-2,4-diisocyanate (TDI)-induced asthma model, in which delayed-type hypersensitivity-like asthmatic airway obstruction is elicited restrictively in the lung, has never been developed. METHODS: Guinea pigs were percutaneously sensitized with TDI. For the challenges, once every 2 weeks for a total of 5 times, TDI mists were delivered directly to the lung through an oral cannula, with its tip being positioned in the opening of the trachea. Time-course changes in specific airway resistance (sRaw) were measured by double-flow plethysmography. Basic mechanisms underlying TDI-induced asthma were analyzed. RESULTS: After the 2nd-5th challenges, induction of both an early increase in sRaw that peaked at 10 min and a delayed-type sRaw elevation that peaked at 22 h were observed. Interestingly, in the sensitized/challenged animals, baseline sRaw was elevated by repeated challenge as compared to that seen for non-sensitized animals. Intratracheal administration of a bronchodilator, salbutamol, strongly suppressed the early asthmatic response (EAR) but not the delayed-type asthmatic response (DAR). During DAR, both albumin leakage and fucose secretion into the bronchoalveolar lavage fluid were increased. The cysteinyl leukotriene antagonist pranlukast failed to inhibit either EAR or DAR while the corticosteroid dexamethasone significantly suppressed DAR, without significantly affecting EAR. CONCLUSIONS: Effective delivery of TDI to the lung may induce reproducible DAR in sensitized guinea pigs with chronicity that is reflected by an increase in the sRaw baseline. DAR is not mediated by constriction of airway smooth muscles and is probably due to the concurrent presence of mucosal edema and mucus hypersecretion in the airways.