Altered neuronal lineages in the facial ganglia of Hoxa2 mutant mice.

Neurons of cranial sensory ganglia are derived from the neural crest and ectodermal placodes, but the mechanisms that control the relative contributions of each are not understood. Crest cells of the second branchial arch generate few facial ganglion neurons and no vestibuloacoustic ganglion neurons, but crest cells in other branchial arches generate many sensory neurons. Here we report that the facial ganglia of Hoxa2 mutant mice contain a large population of crest-derived neurons, suggesting that Hoxa2 normally represses the neurogenic potential of second arch crest cells. This may represent an anterior transformation of second arch neural crest cells toward a fate resembling that of first arch neural crest cells, which normally do not express Hoxa2 or any other Hox gene. We additionally found that overexpressing Hoxa2 in cultures of P19 embryonal carcinoma cells reduced the frequency of spontaneous neuronal differentiation, but only in the presence of cotransfected Pbx and Meis Hox cofactors. Finally, expression of Hoxa2 and the cofactors in chick neural crest cells populating the trigeminal ganglion also reduced the frequency of neurogenesis in the intact embryo. These data suggest an unanticipated role for Hox genes in controlling the neurogenic potential of at least some cranial neural crest cells.

Combination of B-type natriuretic peptide levels and non-invasive hemodynamic parameters in diagnosing congestive heart failure in the emergency department.

This study aimed to assess whether the combination of a B-type natriuretic peptide (BNP) level with various noninvasive hemodynamic parameters can help physicians more quickly and accurately diagnose congestive heart failure and determine the type of left ventricular dysfunction present in patients presenting to the emergency department with dyspnea. Subjects were 98 men (aged 64.57+/-1.23 years) that presented to the VA San Diego Healthcare System. Hemodynamic parameters were measured using impedance cardiography, and BNP levels were quantified using a rapid immunoassay. All patients with a BNP <100 pg/mL (n=37) had no evidence of congestive heart failure 97% of the time. In those with a BNP >100 pg/mL (601+/-55 pg/mL; n=61), a cardiac index of 2.6 L/min/m2 is 65% sensitive and 88% specific in determining systolic dysfunction. In patients with a BNP >100 pg/mL, a multivariate model consisting of noninvasive hemodynamic measurements was able to predict cardiac deaths, readmissions, and emergency department visits within 90 days with 83% accuracy. The authors conclude that, in patients presenting to an emergency department with dyspnea, the addition of impedance cardiography measurements to BNP level measurements will more effectively diagnose congestive heart failure and determine both the type of heart dysfunction and the severity of illness.