Pathologic water loss from sickle erythrocytes concentrates the abnormal hemoglobin and promotes sickling. The Ca 2 ϩ -activated K ϩ channel (Gardos channel) contributes to this deleterious dehydration in vitro, and blockade of K ϩ and water loss via this channel could be a potential therapy in vivo. We treated five subjects who have sickle cell anemia with oral clotrimazole, a specific Gardos channel inhibitor. Patients were started on a dose of 10 mg clotrimazole/kg/d for one week. Protocol design allowed the daily dose to be escalated by 10 mg/kg each week until significant changes in erythrocyte density and K ϩ transport were achieved. Blood was sampled three times a week for hematological and chemical assays, erythrocyte density, cation content, and K ϩ transport. At dosages of 20 mg clotrimazole/kg/d, all subjects showed Gardos channel inhibition, reduced erythrocyte dehydration, increased cell K ϩ content, and somewhat increased hemoglobin levels. Adverse effects were limited to mild/moderate dysuria in all subjects, and a reversible increase in plasma alanine transaminase and aspartic transaminase levels in two subjects treated with 30 mg clotrimazole/kg/d. This is the first in vivo evidence that the Gardos channel causes dehydration of sickle erythrocytes, and that its pharmacologic inhibition provides a realistic antisickling strategy. ( J. Clin. Invest. 1996. 97:1227-1234.)

High-flow nasal cannula used early in the development of pediatric ARI is associated with a decreased the need for intubation and mechanical ventilation.

A CHr of less than 27.5 pg is a more accurate hematological indicator of iron deficiency compared with hemoglobin of less than 11 g/dL in these healthy 9- to 12-month-old infants. Further studies are warranted to determine whether CHr should be the preferred screening tool in the early detection of iron deficiency in infants.

Pediatric poisonings are a significant percentage of admissions to the PICU. The majority of poisonings are non-fatal, require supportive care, close monitoring, and some specific treatment. Drug classes causing poisonings have changed to a higher percentage of opioids in younger patients and atypical antidepressants in adolescents.

We investigated cation transport and cell volume regulation in erythrocytes of CD1 and C57/B6 mice. Swelling of cells from either strain stimulated K+ efflux that was insensitive to ouabain, bumetanide, and clotrimazole. Seventy-five percent of swelling-induced K+ efflux was Cl- dependent (inhibited by sulfamate or methanesulfonate, partially by NO3-, but not by SCN-) and was inhibited by okadaic acid (OA; 50% inhibitory concentration = 18 +/- 6 nM in CD1 and 10 +/- 4 nM in C57/B6). In both strains, K+ efflux into isotonic medium was stimulated by staurosporine or by N-ethylmaleimide, and the latter was partially blocked by pretreatment of cells with OA. When cells of either strain were incubated in hypotonic medium or preswollen isosmotically with nystatin, OA-sensitive regulatory volume decrease (RVD) and K+ loss were observed. RVD produced by hypotonic swelling was prevented by Cl- replacement with sulfamate or methanesulfonate. These properties suggest the presence in outbred and inbred mouse erythrocytes of RVD mediated by K(+)-Cl- cotransport.