001).

CONCLUSIONS

Although albuterol, but not the two placebo interventions, improved FEV1 in these patients with asthma, albuterol

provided no incremental benefit with respect to the self-reported outcomes. Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma. However, from a clinical-management and research-design perspective, patient self-reports can be unreliable. An assessment of untreated responses in asthma may be essential in evaluating patient-reported outcomes. (Funded by the National Center for Complementary and Alternative Medicine.)”
“BACKGROUND

The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused Necrostatin-1 purchase by bacille Calmette-Guerin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained.

METHODS

We evaluated an infant presenting with features of severe immunodeficiency, including early-onset disseminated BCG disease, who required

hematopoietic stem-cell selleck compound transplantation. We also studied two otherwise healthy subjects with a history of disseminated but curable BCG disease in childhood. We characterized the monocyte and dendritic-cell compartments in these three subjects and sequenced candidate genes in which mutations could plausibly confer susceptibility to BCG disease.

RESULTS

We detected two distinct disease-causing

mutations affecting interferon regulatory factor 8 (IRF8). Both K108E and T80A mutations impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA. The K108E variant was associated with an autosomal recessive severe immunodeficiency with a complete lack of circulating monocytes and dendritic cells. The T80A variant was associated with an autosomal dominant, milder immunodeficiency and a selective depletion Selleckchem JNJ-64619178 of CD11c+CD1c+ circulating dendritic cells.

CONCLUSIONS

These findings define a class of human primary immunodeficiencies that affect the differentiation of mononuclear phagocytes. They also show that human IRF8 is critical for the development of monocytes and dendritic cells and for antimycobacterial immunity. (Funded by the Medical Research Council and others.)”
“Studies relating sensory hearing impairment to lead (Pb) exposure in children have presented inconsistent results. The objective of this study was to measure distortion product otoacoustic emissions (DPOAE), sounds emanating from the outer hair cells of the inner ear, in Pb-exposed children to determine the effects of Pb poisoning on the inner ear.