Digoxin did not reduce overall mortality, but it reduced the rate of hospitalization both overall and for worsening heart failure. These findings define more precisely the role of digoxin in the management of chronic heart failure.

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Summary• Cavitation of xylem elements diminishes the water transport capacity of plants, and quantifying xylem vulnerability to cavitation is important to understanding plant function. Current approaches to analyzing hydraulic conductivity (K) data to infer vulnerability to cavitation suffer from problems such as the use of potentially unrealistic vulnerability curves, difficulty interpreting parameters in these curves, a statistical framework that ignores sampling design, and an overly simplistic view of uncertainty.• This study illustrates how two common curves (exponential-sigmoid and Weibull) can be reparameterized in terms of meaningful parameters: maximum conductivity (k sat ), water potential (-P) at which percentage loss of conductivity (PLC) = X% (P X ), and the slope of the PLC curve at P X (S X ), a 'sensitivity' index.• We provide a hierarchical Bayesian method for fitting the reparameterized curves to K H data. We illustrate the method using data for roots and stems of two populations of Juniperus scopulorum and test for differences in k sat , P X , and S X between different groups.• Two important results emerge from this study. First, the Weibull model is preferred because it produces biologically realistic estimates of PLC near P = 0 MPa. Second, stochastic embolisms contribute an important source of uncertainty that should be included in such analyses.

Background information. Many neurons secrete classical transmitters from synaptic vesicles as well as peptide transmitters from LDCVs (large dense-core vesicles). Little is known about the mechanistic differences between these two secretory pathways. The soluble protein Munc18-1 is essential for synaptic vesicle secretion [Verhage, Maia, Plomp, Brussaard, Heeroma, Vermeer, Toonen, Hammer, van den Berg, Missler, et al. (2000) Science 287, 864-869.].Results. In the present study, we tested if Munc18 genes are also involved in peptidergic secretion from LDCVs using the anterior pituitary as a model system. We show that Munc18-1 is the dominant isoform expressed in the anterior pituitary. In Munc18-1 null mutant mice, the anterior pituitary developed normally and the five major endocrine cell types had a normal distribution. However, circulating peptide hormone levels were decreased by up to 50-fold in the null mutant, whereas the intracellular levels were significantly higher than that in controls. Ultrastructural analysis using the tannic acid method revealed striking differences in the distribution of secretory vesicles: (i) the number of exocytotic figures was mostly decreased in the null mutants and (ii) the LDCVs accumulated near but not at their target membrane. This is in contrast with the apparently normal distribution of synaptic vesicles in developing synapses in the null mutant (Verhage et al., 2000). Conclusions.We conclude that Munc18-1 is involved in the secretion of peptide hormones and in the docking of LDCVs. These results unmask an apparent mechanistic difference between LDCVs and synaptic vesicles.

Left ventricular ejection fraction (EF) is used to assess patients with heart failure (HF); however, frequent measurements are not cost-effective. Impedance cardiography (ICG) is a low-cost, noninvasive test that measures systolic time intervals and may be a method for detecting impaired vs intact EF. This study evaluated the relationship between EF by echocardiography or gated nuclear ventriculography and systolic time ratio (STR) by ICG in outpatients with chronic HF. A retrospective chart review identified 52 patients with EF and STR measured within 2 weeks. There was an inverse correlation between STR and EF (r=-0.54; P<.001). The area under the receiver operating characteristic curve for STR to identify reduced EF was 0.86. An EF < or =50% and STR > or =0.50 demonstrated 93% sensitivity and 85% specificity. STR was able to distinguish intact (>50%) from impaired EF (< or =50%). STR by ICG has the potential to be a reliable method to monitor ventricular function in chronic HF.