Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (−9.4 mmHg/min per litre and −14.7 mmHg/min per litre), mean arterial pressure (−2.8 mmHg and −8.4 mmHg) and LAP (left atrial pressure; −2.6 mmHg and −5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF

Learning a Sport through Video Gaming: A Mixed-Methods Experimental Study

This study examined the impact of playing a sport video game on learning the sport as well as how the game may influence future intentions of watching or playing the sport. Utilizing American university students with little prior knowledge of cricket, this study employed a mixed-methods pre/post intervention design with randomized experimental (EG; n = 43) and control (CG; n = 46) groups. Results indicated that cricket knowledge significantly increased for the EG pre-test to post-test (p < .05, n^2 = 0.19; particularly regarding cricket rules, terminology, player positions, and field layout), while the CG did not significantly differ. A significant difference was also found between the EG and CG for interest in playing cricket (p < .05, n^2 = 0.9). Qualitative findings supported that video gaming motivated intentions to watch and play cricket. Sport video games can facilitate increased sport knowledge, sport appreciation, and intentions for future physical activity

122Outcome of unrelated umbilical cord-blood transplants (UCBT) in pediatric patients: Experience of one center

This item contains two issues of the Take One newsletter: September 8, and 22, 1977.Take One was published every two weeks and focused on short news items and announcements "for the people of University Hospital.

Space--time fluctuations and the spreading of wavepackets

Using a density matrix description in space we study the evolution of wavepackets in a fluctuating space-time background. We assume that space-time fluctuations manifest as classical fluctuations of the metric. From the non-relativistic limit of a non-minimally coupled Klein-Gordon equation we derive a Schr\"odinger equation with an additive gaussian random potential. This is transformed into an effective master equation for the density matrix. The solutions of this master equation allow to study the dynamics of wavepackets in a fluctuating space-time, depending on the fluctuation scenario. We show how different scenarios alter the diffusion properties of wavepackets.Comment: 11 page

Design of a Prostate Cancer Patient Navigation Intervention for a Veterans Affairs Hospital

Patient navigation programs have been launched nationwide in an attempt to reduce racial/ethnic and socio-demographic disparities in cancer care, but few have evaluated outcomes in the prostate cancer setting. The National Cancer Institute-funded Chicago Patient Navigation Research Program (C-PNRP) aims to implement and evaluate the efficacy of a patient navigation intervention for predominantly low-income minority patients with an abnormal prostate cancer screening test at a Veterans Affairs (VA) hospital in Chicago

Evaluation of Dynamic Models of Distillation Columns with Emphasis on the Initial Response

The flow dynamics (tray hydraulics) are of key importance for the initial dynamic response of distillation columns. The most important parameters are the liquid holdup, the liquid hydraulic time constant and the vapor constant representing the initial effect of a change in vapor flow on liquid flow. In the paper we present methods for determining these parameters experimentally, and compare the results with estimates from available correlations such as the Francis Weir formula

Development and internal validation of a prediction model for the presence of tinnitus in a Dutch population-based cohort

OBJECTIVES: In this study we aim to develop and internally validate a prediction model on tinnitus experience in a representative sample of the Dutch general population. METHODS: We developed a multivariable prediction model using elastic net logistic regression with data from the Dutch Lifelines Cohort Study. This is a multigenerational cohort study on adults who are located in the northern parts of the Netherlands. The model was internally validated using 10-fold cross-validation. The outcome of the model was tinnitus presence, for which we used 24 candidate predictors on different domains (among others demographic, hearing specific, and mental health variables). We assessed the overall predictive performance, discrimination, and calibration of the model. RESULTS: Data on 122.884 different participants were included, of which 7,965 (6.5%, 0 missing) experienced tinnitus. Nine variables were included in the final model: sex, hearing aids, hearing limitations, arterial blood pressure, quality of sleep, general health, symptom checklist of somatic complaints, cardiovascular risk factors, and age. In the final model, the Brier score was 0.056 and 0.787 in internal validation. CONCLUSION: We developed and internally validated a prediction model on tinnitus presence in a multigenerational cohort of the Dutch general population. From the 24 candidate predictors, the final model included nine predictors

Monitoring of heart failure: comparison of left atrial pressure with intrathoracic impedance and natriuretic peptide measurements in an experimental model of ovine heart failure

Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1–5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P<0.001) levels. All impedance vectors decreased in proportion to HF severity (all P<0.001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P<0.001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P<0.001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful

Urocortin 2 Infusion in Healthy Humans Hemodynamic, Neurohormonal, and Renal Responses

ObjectivesWe sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans.BackgroundUrocortin 2 is a vasoactive and cardioprotective peptide belonging to the corticotrophin-releasing factor peptide family. Recent reports indicate the urocortins exert important effects beyond the hypothalamo-pituitary-adrenal axis upon cardiovascular and vasohumoral function in health and cardiac disease.MethodsWe studied 8 healthy unmedicated men on 3 separate occasions 2 to 5 weeks apart. Subjects received placebo, 25-μg low-dose (LD), and 100-μg high-dose (HD) of UCN 2 intravenously over the course of 1 h in a single-blind, placebo-controlled, dose-escalation design. Noninvasive hemodynamic indexes, neurohormones, and renal function were measured.ResultsThe administration of UCN 2 dose-dependently increased cardiac output (mean peak increments ± SEM) (placebo 0.5 ± 0.2 l/min; LD 2.1 ± 0.6 l/min; HD 5.0 ± 0.8 l/min; p < 0.001), heart rate (placebo 3.3 ± 1.0 beats/min; LD 8.8 ± 1.8 beats/min; HD 17.8 ± 2.1 beats/min; p < 0.001), and left ventricular ejection fraction (placebo 0.6 ± 1.4%; LD 6.6 ± 1.5%; HD 14.1 ± 0.8%; p < 0.001) while decreasing systemic vascular resistance (placebo −128 ± 50 dynes·s/cm5; LD −407 ± 49 dynes·s/cm5; HD −774 ± 133 dynes·s/cm5; p < 0.001). Activation of plasma renin activity (p = 0.002), angiotensin II (p = 0.001), and norepinephrine (p < 0.001) occurred only with the higher 100-μg dose. Subtle decreases in urine volume (p = 0.012) and natriuresis (p = 0.001) were observed.ConclusionsBrief intravenous infusions of UCN 2 in healthy humans induced pronounced dose-related increases in cardiac output, heart rate, and left ventricular ejection fraction while decreasing systemic vascular resistance. Subtle renal effects and activation of plasma renin, angiotensin II, and norepinephrine (at high-dose only) were observed. These findings warrant further investigation of the role of UCN 2 in circulatory regulation and its potential therapeutic application in heart disease