Cardiac resynchronization therapy: an updateimpaired left ventricular systolic function.

Cardiac resynchronization therapy has been shown to reduce hospitalization and mortality, and to improve heart failure symptoms, in patients with systolic dysfunction and ventricular dyssynchrony. We review the current guidelines for cardiac resynchronization therapy, the underlying evidence, the latest developments in the field and directions of future research.

A method to improve accuracy and precision of water surface identification for photon depth dose measurements.

The objective of this study is to present a method to reduce the setup error inherent in clinical depth dose measurements and, in doing so, to improve entrance dosimetry measurement reliability. Ionization chamber (IC) depth dose measurements are acquired with the depth scan extended into the air above the water surface. An inflection region is obtained in each resulting percent depth ionization (PDI) curve that can be matched against other measurements or to an inflection region obtained from an analogous Monte Carlo (MC) simulation. Measurements are made with various field sizes for the 6 and 18 MV photon beams, with and without a Pb foil in the beam, to determine the sensitivity of the dose inflection region to the beam conditions. The offset between reference and test data set inflection regions is quantified using two separate methods. When comparing sets of measured data, maxima in the second derivative of ionization are compared. When comparing measured data to MC simulation, the offset that minimizes the sum of squared differences between the reference and test curves in the ionization inflection region is found. These methods can be used to quantify the offset between an initial setup (test) position and the true surface (reference) position. The ionization inflection location is found to be insensitive to changes in field size, electron contamination, and beam energy. Data from a single reference condition should be sufficient to identify the surface location. The method of determining IC offsets is general and should be applicable to any IC and other radiation sources. The measurement method could reduce the time and effort required in the initial IC setup at a water surface as setup errors can be corrected offline. Given a reliable set of reference data to compare with, this method could increase the ability of quality assurance (QA) measurements to detect discrepancies in beam output as opposed to discrepancies in IC localization. Application of the measurement method standardizes the procedure for localizing cylindrical ICs at a water surface and thereby improves the reliability of measurements taken with these devices at all depths.

Comfort zone-design free stalls: do they influence the stall use behavior of lame cows?

The behavior of 59 cows in 4 herds, each with Comfort Zone-design free stalls with dimensions suitable for 700-kg, mature Holstein dairy cows, was filmed for a 48-h period. Comparison was made between nonlame, slightly lame, and moderately lame cows on either rubber-crumb-filled mattress stall surfaces bedded with a small amount of sawdust (2 herds) or a Pack Mat design, which consisted of a rubber-crumb-filled mattress pad installed 5 cm below a raised rear curb, bedded with 5 to 8 cm of sand bedding (2 herds). All other stall design components were similar. Despite adequate resting space and freedom to perform normal rising and lying movements, lame cows on mattresses stood in the stall for >2 h longer than nonlame cows. Although a significant increase in stall standing behavior was observed in lame cows on Pack Mat stalls, the mean (95% confidence interval) standing time in the stall was only 0.7 (0 to 3.0) h/d for nonlame cows and 1.6 (0 to 4.2) h/d for moderately lame cows, which was less than the 2.1 (0 to 4.4), 4.3 (1.6 to 6.9), and 4.9 (2.5 to 7.3) h/d spent standing in the stall for nonlame, slightly lame, and moderately lame cows on mattresses, respectively. This observation supports the hypothesis that it is the nature of the stall surface that dictates changes in stall standing behavior observed in lame cows, rather than other components of stall design. The finding that only 5 to 8 cm of sand over a mattress pad provides most of the benefits of deep sand-bedded stalls, along with other advantages related to stall maintenance and manure handling, gives farmers another useful housing alternative with which to improve cow comfort and well-being.

Effect of additives on stability of etoposide in PLGA microspheres.

The purpose of this article was to determine the shelf life of etoposide in poly(lactic-co-glycolic acid) (PLGA) microspheres prepared with and without additives (i.e., tricaprin and isopropyl myristic acid ester [IPM]). The microspheres were prepared by a single-emulsion solvent extraction technique with and without 25% w/w additive. The batches of microspheres were subjected to an accelerated stability study at two elevated temperatures (70 degrees C and 80 degrees C or 80 degrees C and 90 degrees C). Samples were taken at 7, 14, 21, 28, and 35 days for estimation of drug content by high-performance liquid chromatography (HPLC). The drug stability in the microspheres was determined by plotting the log percentage drug remaining versus time to obtain the degradation rate constant k of etoposide at the measured temperature. This degradation rate constant was then used in the Arrhenius equation to obtain the activation energy of etoposide, which was utilized to determine the shelf life of the microspheres at room temperature. The results showed that all three microsphere formulations had good long-term stability at room temperature (6.62-8.86 years at 25 degrees C). The plain microspheres were shown to possess a shelf life of 6.62 years, and the IPM and tricaprin were the most stable with shelf lives of 8.25 and 8.86 years, respectively.

Tetrapeptide derivatives of [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) lacking an N-terminal tyrosine residue are agonists at the mu-opioid receptor.

The Phe(1) cyclic tetrapeptide Phe-c[D-Cys-Phe-D-Pen]NH(2) (Et) (JH-54) has been shown previously to exhibit high affinity and selectivity for the mu-opioid receptor. To examine the role of the Phe(1) residue in the unexpected high affinity of this peptide, 11 analogs of JH-54 have been synthesized and evaluated for opioid ligand binding and for efficacy using the [(35)S]GTPgammaS assay. Alteration of the bridging groups between the D-Cys(2) and D-Pen(4) residues of JH-54 from dithioether to disulfide revealed the importance of the relative position of the aromatic rings of the first and third residues in determining mu- and delta-affinities. The one carbon distance between the alpha carbon and phenyl ring in the N-terminal residue was critical. Additional steric bulk in the N-terminal Phe(1) residue was accommodated without large reductions in affinity in two naphthyl analogs, but not with 3, 3-(diphenyl)alanine. Conformational restriction of the Calpha-Cbeta and/or Cbeta-Cgamma bonds had little effect on affinities in two peptides with 2-amino-2-carboxytetralin in position 1, but it abolished activity in an isoquinoline analog and differentially altered activity in four phenylproline(1)-containing peptides. Most surprisingly, replacement of the Phe(1) aromatic ring with cyclohexyl resulted in a peptide of moderate affinity (K(i) = 32.5 nM) and potency (EC(50) = 58.8 nM). Thus, the tyrosyl para-hydroxyl substituent and even aromaticity in the N-terminal amino acid of these tetrapeptides are shown to be important, but not critical, features for mu-opioid receptor affinity, agonist potency, and efficacy.

Effect of isopropyl myristic acid ester on the physical characteristics and in vitro release of etoposide from PLGA microspheres.

The purpose of this paper was to study the effect of the isopropyl myristic acid ester (IPM) on the physicochemical characteristics of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres-specifically, the effects on the size and drug loading of the microspheres, the polymer matrix and surface morphology, and the release of etoposide from the microspheres. The experiment was structured to examine 2 IPM concentrations (25% and 50%) and 1 control (no IPM) at 2 different etoposide-loading percentages (10% and 5%). The microspheres were prepared using a single-emulsion solvent-extraction procedure. Samples from each batch of microspheres were then analyzed for size distribution, drug-loading efficiency, surface characteristics, in vitro release, and in vitro microsphere degradation. The incorporation of 50% IPM significantly increased (P <.05) the size of the microspheres when compared with the control and 25% IPM microspheres. However, incorporation of 25% or 50% IPM did not change (P >.05) the drug-loading efficiency in comparison with the microspheres prepared without IPM. The microspheres containing 50% IPM were shown to significantly increase (P <.05) the release of etoposide from the microspheres at both etoposide concentrations. The microspheres prepared incorporating 25% IPM and 5% etoposide increased the in vitro release (P <.05) in comparison with the microspheres prepared without IPM. The 5% etoposide-PLGA microspheres showed a smooth, nonporous surface that changed to a dimpled, nonporous surface after addition of 25% IPM. During the in vitro degradation study, the IPM-containing microspheres slowly became porous but retained their structural integrity throughout the experiment.

An integrated approach to developing administrators and organizations.

Can administrators increase their administrative capabilities in isolation from the rest of the institution? The authors of this article contend that administrative competency can be defined only in terms of contributions to organizational performance and that the motivation to achieve a high level of competency must be supported and reinforced at the institutional level. They establish a basis for the interdependency of administrators and institutions and outline an approach to their simultaneous development.