Aldosterone and aldosterone receptor antagonists in patients with chronic heart failure

Aldosterone is a mineralocorticoid hormone synthesized by the adrenal glands that has several regulatory functions to help the body maintain normal volume status and electrolyte balance. Studies have shown significantly higher levels of aldosterone secretion in patients with congestive heart failure compared with normal patients. Elevated levels of aldosterone have been shown to elevate blood pressure, cause left ventricular hypertrophy, and promote cardiac fibrosis. An appreciation of the true role of aldosterone in patients with chronic heart failure did not become apparent until the publication of the Randomized Aldactone Evaluation Study. Until recently, the use of aldosterone receptor antagonists has been limited to patients with severe heart failure and patients with heart failure following myocardial infarction. The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) study added additional evidence to support the expanded use of aldosterone receptor antagonists in heart failure patients. The results of the EMPHASIS-HF trial showed that patients with mild-to-moderate (New York Heart Association Class II) heart failure had reductions in mortality and hospitalizations from the addition of eplerenone to optimal medical therapy. Evidence remains elusive about the exact mechanism by which aldosterone receptor antagonists improve heart failure morbidity and mortality. The benefits of aldosterone receptor antagonist use in heart failure must be weighed against the potential risk of complications, ie, hyperkalemia and, in the case of spironolactone, possible endocrine abnormalities, in particular gynecomastia. With appropriate monitoring, these risks can be minimized. We now have evidence that patients with mild-to-severe symptoms associated with systolic heart failure will benefit from the addition of an aldosterone receptor antagonist to the standard therapies of angiotensin-converting enzyme inhibitors and beta-blockers. This review will address the pharmacologic basis of aldosterone receptor antagonists in patients with heart failure and the clinical impact of this therapy

Basic pathophysiology and options of treatment for surgical management of functional tricuspid regurgitation: a systematic review

Background: Functional tricuspid regurgitation (TR) appears frequently in the presence of left-sided heart valve diseases, combined with symptoms of heart failure, worsens if left untreated, and is associated with poor patient survival. Correct indications for surgery and the choice of suitable technique, which should be based on pathophysiology of disease are of utmost importance to ensure longevity and durability of repair; particularly given the risky nature of reoperations due to residual/recurrent TR. Methods: A systematic review was performed using Embase, Ovid Medline, Cochrane, Web of Science, and Google to deepen knowledge of major and controversial aspects of the subject. Results: A total of 1,579 studies were reviewed, and 32 of these were enclosed in the final review: 13 studies were primarily focused on pathophysiology and preoperative assessment of functional TR; 19 studies on surgical treatment of functional TR. A total of 15,509 patients were included. Conclusions: Indications for treatment of TR are based on the severity of regurgitation (grading), as well as on the presence of signs and symtoms of right-sided heart failure and on the extent of tricuspid annular dilation, leaflet tethering, and pulmonary hypertension (staging of disease). Despite improved knowledge of the underlying pathophysiology of TR, issues regarding indications for treatment and options of repair remain present. There is no consensus within the scientific community, for the preferred method to quantify the severity of TR; the recently introduced 5-grade TR classification based on objective quantitative parameters has not yet become common practice. The assessment of TR during stress exercise is rarely performed, though it takes into account the changes in severity of regurgitation that occur under different physiological conditions. Magnetic resonance imaging, which is the gold standard for the right heart evaluation is occasionally carried out before surgery. The threshold beyond which the tricuspid annular dilation should be repaired is unclear and recent studies put forward the idea that it may be lower than current recommendations. Tricuspid valve annuloplasty is the most adopted surgical option today. However, the ideal annuloplasty device remains elusive. In addition, as severe leaflet tethering cannot be addressed by annuloplasty alone, the addition of new techniques further increasing leaflet coaptation might optimize long-term valve continence. Further investigations are needed to address all these issues, alongside the potential of percutaneous options

Final tests of the CsI-based ring imaging detector for the ALICE experiment

We report on the final tests performed on a CsI-based RICH detector equipped with 2 C$_6$F$_{14}$ radiator trays and 4 photocathodes, each of 64$\times$38 cm$^2$ area. The overall performance of the detector is described, using different gas mixtures, in view of optimizing the photoelectron yield and the pad occupancy. Test results under magnetic field up to 0.9 T, photocathode homogeneity and stability are presented

Relationship Between Vancomycin Trough Concentrations and Nephrotoxicity: A Prospective Multicenter Trial

Several single-center studies have suggested that higher doses of vancomycin, aimed at producing trough concentrations of \u3e15 mg/liter, are associated with increased risk of nephrotoxicity. We prospectively assessed the relative incidence of nephrotoxicity in relation to trough concentration in patients with documented methicillin-resistant Staphylococcus aureus (MRSA) infections at seven hospitals throughout South Carolina. Adult patients receiving vancomycin for at least 72 h with at least one vancomycin trough concentration determined under steady-state conditions were prospectively studied. The relationship between vancomycin trough concentrations of \u3e15 mg/ml and the occurrence of nephrotoxicity was assessed using univariate and multivariate analyses, controlling for age, gender, race, dose, length of therapy, use of other nephrotoxins (including contrast media), intensive care unit (ICU) residence, episodes of hypotension, and comorbidities. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a ≥ 50% increase from the baseline for two consecutive measurements. MICs of vancomycin for the MRSA isolates were also determined. A total of 288 patients were studied between February 2008 and June 2010, with approximately one-half having initial trough concentrations of ≥ 15 mg/ml. Nephrotoxicity was observed for 42 patients (29.6%) with trough concentrations \u3e15 mg/ml and for 13 (8.9%) with trough concentrations of ≤ 15 mg/ml. Multivariate analysis revealed vancomycin trough concentrations of \u3e15 mg/ml and race (black) as risk factors for nephrotoxicity in this population. Vancomycin trough concentrations of \u3e15 mg/ml appear to be associated with a 3-fold increased risk of nephrotoxicity

A large area CsI RICH Detector in ALICE at LHC

A 1m2 CsI RICH prototype has been successfully tested in a hadron beam at CERN SPS. The prototype, fully equipped with 15k electronic channels, has been used to identify particles coming from pi-Be interactions. Track reconstruction has been performed by using a telescope consisting of four gas pad chambers. A detailed description of the detector will be presented and results from the test will be discussed.List of figuresFigure 1 Expected proton and antiproton yields including jet quenching mechanism in central Pb-Pb collisions at LHC.Figure 2 Schematic view of the HMPID CsI-RICHFigure 3 Experimental layout used at the SPS/H4 test beamFigure 4 Distributions of the mean number, per ring, of pad hits (Npad), electrons (Ntot) and Cherenkov photoelectrons (Nres) as a function of the single-electron mean pulse heightFigure 5 Mean single-electron pulse height as a function of high voltage measured at the centre of each of the four photocathodesFigure 6 Evaluation of the uniformity of the chamber gain for the photocathode PC32Figure 7 Azimuthal distribution of the photon pad hits in the Cherenkov fiducial zone (HV=2050 V)Figure 8 Photon angle (a) and track Cherenkov angle (b) distributions for beam events at the SPSFigure 9 Track density on the HMPID cathode plane in real 350 GeV/c pi--Be eventsFigure 10 Three dimensional display of an SPS 350 GeV/c pi--Be event. Eleven tracks are reconstructed in the telescope by requiring one hit on each pad chamber to reconstruct a track</UL

The Present Development of CsI Rich Detectors for the ALICE Experiment at CERN

The ALICE Collaboration plans to implement a 12m^2 array consisting of 7 proximity focussed C6F^14 liquid radiator RICH modules devoted to the particle identification in the momentum range: 1 GeV/c - 3.5 GeV/c for pions and kaons. A large area CSI-RICH prototype has been designed and built with the aim to validate the detector parameter assumptions made to predict the performance of the High Momentum Particle Identification System (HMPID) of the ALICE Experiment. The main elements of the prototype will be described with emphasis on the engineering solutions adopted. First results from the analysis of multitrack events recorded with this prototype exposed to hadron beams at the CERN SPS will be discussedList of FiguresFigure 1 General view of the ALICE lay-outFigure 2 Schematic layout of the fast CsI-RICHFigure 3 Perspective view of the HMPID layout with the seven RICH modules tilted according to their position with respect to the interaction vertex. The frame that supports the detectors is also shownFigure 4 Top view of the photodetector anode plane with the wire support spacer. One CsI board, out of six forming the pad cathode plane, is also shown.Figure 5 Perspective view of the HMPID honeycomb panel with the three radiator vesselsFigure 6 Cut away view of the HMPID CsI-RICH showing separately each detector component. Kapton buses that carry signals from the pads to the readout electronics are also shownFigure 7 a)number of resolved photoelectrons per event, b)reconstructed Cherenkov angle per photonFigure 8 C6F14 transmission plots before and after the molecular sieve purificationFigure 9 Display plot showing an SPS event. Three tracks are reconstructed by using the tracking chamber telescope, the associated rings are shown in the HMPID prototypeThis publication also appears as INT-98-20

SPECIAL ARTICLES Benchmarking in Academic Pharmacy Departments

Benchmarking in academic pharmacy, and recommendations for the potential uses of benchmarking in academic pharmacy departments are discussed in this paper. Benchmarking is the process by which practices, procedures, and performance metrics are compared to an established standard or best practice. Many businesses and industries use benchmarking to compare processes and outcomes, and ultimately plan for improvement. Institutions of higher learning have embraced benchmarking practices to facilitate measuring the quality of their educational and research programs. Benchmarking is used internally as well to justify the allocation of institutional resources or to mediate among competing demands for additional program staff or space. Surveying all chairs of academic pharmacy departments to explore benchmarking issues such as department size and composition, as well as faculty teaching, scholarly, and service productivity, could provide valuable information. To date, attempts to gather this data have had limited success. We believe this information is potentially important, urge that efforts to gather it should be continued, and offer suggestions to achieve full participation

A progress report on the development of the CsI-RICH detector for the ALICE experiment at LHC

The particle identification in ALICE (A Large Ion Collider Experiment) at LHC will be achieved by two complementary systems based on time of flight measurement, at low $p_t$, and on the Ring Imaging Cherenkov (RICH) technique, at $p_t$ ranging from 2 to 5 GeV/$c$, respectively. The High Momentum PID (HMPID) system will cover $\sim$5\% of the phase space, the single arm detector array beeing composed by seven 1.3$\times$1.3 m$^2$ CsI-RICH modules placed at 4.7 m from the interaction point where a density of about 50 particles/m$^2$ is expected.\\ A 1 m$^2$ prototype, 2/3 of HMPID module size, has been successfully tested at the CERN/PS beam where 18 photoelectrons per event have been obtained with 3 GeV/c pions and 10 mm liquid $\mathrm{C}_6\mathrm{F}_{14}$ radiator. Mechanical problems related to the liquid radiator vessel construction have been solved and the prototype, fully equipped, will be tested at the CERN/SPS to investigate the PID capability in high particle density events.\\ In this report, after an introductory discussion on the requirements for PID in ALICE, the HMPID prototype is described and the main results of beam tests on large area CsI photocathodes, operated in RICH detectors, are given