Electrical activation in the coronary sinus branches as a guide to cardiac resynchronisation therapy: rationale for a coordinate system

Background

For successful cardiac resynchronisation therapy (CRT) a spatial and electrical separation of right and left ventricular electrodes is essential. The spatial distribution of electrical delays within the coronary sinus (CS) tributaries has not yet been identified.

Objective

Electrical delays within the CS are described during sinus rhythm (SR) and right ventricular pacing (RVP). A coordinate system grading the mitral ring from 0° to 360° and three vertical segments is proposed to define the lead positions irrespective of individual CS branch orientation.

Methods

In 13 patients undergoing implantation of a CRT device 6±2.5, (median 5) lead positions within the CS were mapped during SR and RVP. The delay to the onset and the peak of the local signal was measured from the earliest QRS activation or the pacing spike. Fluoroscopic positions were compared to localizations on a nonfluoroscopic electrode imaging system.

Results

During SR, electrical delays in the CS were inhomogenous in patients with or without left bundle branch block (LBBB). During RVP, the delays increased by 44±32 ms (signal onset from 36±33 ms to 95±30 ms; p<0.001, signal peak from 105±44 ms to 156±30 ms; p<0.001). The activation pattern during RVP was homogeneous and predictable by taking the grading on the CS ring into account: (% QRS) = 78−0.002 (grade−162)², p<0.0001. This indicates that 78% of the QRS duration can be expected as a maximum peak delay at 162° on the CS ring.

Conclusion

Electrical delays within the CS vary during SR, but prolong and become predictable during RVP. A coordinate system helps predicting the local delays and facilitates interindividual comparison of lead positions irrespective of CS branch anatomy.     

Field of attention for instantaneous object recognition

Background

Instantaneous object discrimination and categorization are fundamental cognitive capacities performed with the guidance of visual attention. Visual attention enables selection of a salient object within a limited area of the visual field; we referred to as “field of attention” (FA). Though there is some evidence concerning the spatial extent of object recognition, the following questions still remain unknown: (a) how large is the FA for rapid object categorization, (b) how accuracy of attention is distributed over the FA, and (c) how fast complex objects can be categorized when presented against backgrounds formed by natural scenes.

Methodology/Principal Findings

To answer these questions, we used a visual perceptual task in which subjects were asked to focus their attention on a point while being required to categorize briefly flashed (20 ms) photographs of natural scenes by indicating whether or not these contained an animal. By measuring the accuracy of categorization at different eccentricities from the fixation point, we were able to determine the spatial extent and the distribution of accuracy over the FA, as well as the speed of categorizing objects using stimulus onset asynchrony (SOA). Our results revealed that subjects are able to rapidly categorize complex natural images within about 0.1 s without eye movement, and showed that the FA for instantaneous image categorization covers a visual field extending 20°×24°, and accuracy was highest (>90%) at the center of FA and declined with increasing eccentricity.

Conclusions/Significance

In conclusion, human beings are able to categorize complex natural images at a glance over a large extent of the visual field without eye movement.     

Priming and re-drying improve the survival of mature seeds of Digitalis purpurea during storage

Background and Aims

Most priming studies have been conducted on commercial seed lots of unspecified uniformity and maturity, and subsequent seed longevity has been reported to both increase and decrease. Here a seed lot of Digitalis purpurea L. with relatively uniform maturity and known history was used to analyse the effects of priming on seed longevity in air-dry storage.

Methods

Seeds collected close to natural dispersal and dried at 15 % relative humidity (RH), 15 °C, were placed into experimental storage (60 % RH, 45 °C) for 14 or 28 d, primed for 48 h at 0, −1, −2, −5, −10 or −15 MPa, re-equilibrated (47 % RH, 20 °C) and then returned to storage. Further seed samples were primed for 2 or 48 h at −1 MPa and either dried at 15 % RH, 15 °C or immediately re-equilibrated for experimental storage. Finally, some seeds were given up to three cycles of experimental storage and priming (48 h at −1 MPa).

Key Results

Priming at −1 MPa had a variable effect on subsequent survival during experimental storage. The shortest lived seeds in the control population showed slightly increased life spans; the longer lived seeds showed reduced life spans. In contrast, seeds first stored for 14 or 28 d before priming had substantially increased life spans. The increase tended to be greatest in the shortest lived fraction of the seed population. Both the period of rehydration and the subsequent drying conditions had significant effects on longevity. Interrupting air-dry storage with additional cycles of priming also increased longevity.

Conclusions

The extent of prior deterioration and the post-priming desiccation environment affect the benefits of priming to the subsequent survival of mature seeds. Rehydration–dehydration treatments may have potential as an adjunct or alternative to the regeneration of seed accessions maintained in gene banks for plant biodiversity conservation or plant breeding.Key words: Digitalis purpurea, priming, re-drying, seed longevity, seed storage, ageing     

Evaluation of combining bony anatomy and soft tissue position correction strategies for IMRT prostate cancer patients

Background

Radiotherapy treatment requires delivering high homogenous dose to target volume while sparing organs at risk. That is why accurate patient positioning is one of the most important steps during the treatment process. It reduces set-up errors which have a strong influence on the doses given to the target and surrounding tissues.

Aim

The aim of this study was to investigate the efficiency of combining bony anatomy and soft tissue imaging position correction strategies for patients with prostate cancer.

Materials and methods

The study based on pre-treatment position verification results determined for 10 patients using kV images and CBCT match. At the same patients’ position, two orthogonal kV images and set of CT scans were acquired. Both verification methods gave the information about patients’ position changes in vertical, longitudinal and lateral directions.

Results

For 93 verifications, the mean values of kV shifts in vertical, longitudinal and lateral directions equaled: −0.11 ± 0.54 cm, 0.26 ± 0.38 cm and −0.06 ± 0.47 cm, respectively. The same values achieved for CBCT matching equaled: 0.07 ± 0.62 cm, 0.22 ± 0.36 cm and −0.02 ± 0.45 cm. Statistically significant changes between the values of shifts received during the first week of treatment and the rest time of the irradiation process were found for 2 patients in the lateral direction and 2 patients in vertical direction among kV results and for 3 patients in the longitudinal direction among CBCT results. A significant difference between kV and CBCT match results was found in the vertical direction.

Conclusions

In clinical practice, CBCT combined with kV or even portal imaging improves precision and effectiveness of prostate cancer treatment accuracy.     

Fructose modulates cardiomyocyte excitation-contraction coupling and Ca²⁺ handling in vitro

Background

High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated.

Objective

The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting.

Methods and Results

The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca²⁺ handling were evaluated under physiological conditions (37°C, 2 mM Ca²⁺, HEPES buffer, 4 Hz stimulation) using video edge detection and microfluorimetry (Fura2) methods. Compared with control glucose (11 mM) superfusate, 2-deoxyglucose (2 DG, 11 mM) substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05) and this effect was completely abrogated with fructose supplementation (11 mM). Similarly, fructose prevented the Ca²⁺ transient delay induced by exposure to 2 DG (time to peak Ca²⁺ transient: 2 DG: 29.0±2.1 ms vs. glucose: 23.6±1.1 ms vs. fructose +2 DG: 23.7±1.0 ms; p<0.05). The presence of the fructose transporter, GLUT5 (Slc2a5) was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT-PCR.

Conclusion

This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function.     

Intra-examiner and inter-examiner reproducibility of paraspinal thermography

Objective

The objective of this study was to evaluate the intra-examiner and inter-examiner reproducibility of paraspinal thermography using an infrared scanner.

Materials and Methods

The thermal functions of a commercially available infrared scanner (Insight Subluxation Station®) were evaluated for clinical reliability. Two practicing clinicians conducted the measures on 100 subjects. Intra class correlation coefficients (ICCs) and concordance correlation coefficients (CCCs) were calculated from the collected data.

Results

Mean bilateral paraspinal skin temperature was 89.78° F and ranged from 88.77° F to 91.43° F. Intra class correlation coefficients (ICCs) for agreement and consistency ranged from 0.959 to 0.976. Concordance correlation coefficients (CCCs) ranged from 0.783 to 0.859 with tight confidence intervals indicating robust estimates of these quantities.

Conclusion

This study revealed excellent intra-examiner and inter-examiner reproducibility of paraspinal thermography using a commercially available unit.     

The effect of sample handling on cross sectional HIV incidence testing results

Objective(s)

To determine if mishandling prior to testing would make a sample from a chronically infected subject appear recently infected when tested by cross-sectional HIV incidence assays.

Methods

Serum samples from 31 subjects with chronic HIV infection were tested. Samples were subjected to different handling conditions, including incubation at 4°C, 25°C and 37°C, for 1, 3, 7 or 15 days prior to testing. Samples were also subjected to 1,3, 7 and 15 freeze-thaw cycles prior to testing. Samples were tested using the BED capture enzyme immuno assay (BED-CEIA), Vironostika-less sensitive (V-LS), and an avidity assay using the Genetic Systems HIV-1/HIV-2 plus O EIA (avidity assay).

Results

Compared to the sample that was not subjected to any mishandling conditions, for the BED-CEIA, V-LS and avidity assay, there was no significant change in test results for samples incubated at 4°C or 25°C prior to testing. No impact on test results occurred after 15 freeze-thaw cycles. A decrease in assay results was observed when samples were held for 3 days or longer at 37°C prior to testing.

Conclusions

Samples can be subjected up to 15 freeze-thaw cycles without affecting the results the BED-CEIA, Vironostika-LS, or avidity assays. Storing samples at 4°C or 25°C for up to fifteen days prior to testing had no impact on test results. However, storing samples at 37°C for three or more days did affect results obtained with these assays.     

Evaluation of transmitral pressure gradients in the intraoperative echocardiographic diagnosis of mitral stenosis after mitral valve repair

Objective

Acute mitral stenosis (MS) following mitral valve (MV) repair is a rare but severe complication. We hypothesize that intraoperative echocardiography can be utilized to diagnose iatrogenic MS immediately after MV repair.

Methods

The medical records of 552 consecutive patients undergoing MV repair at a single institution were reviewed. Post-cardiopulmonary bypass peak and mean transmitral pressure gradients (TMPG), and pressure half time (PHT) were obtained from intraoperative transesophageal echocardiographic (TEE) examinations in each patient.

Results

Nine patients (9/552 = 1.6%) received a reoperation for primary MS, prior to hospital discharge. Interestingly, all of these patients already showed intraoperative post-CPB mean and peak TMPGs that were significantly higher compared to values for those who did not: 10.7±4.8 mmHg vs 2.9±1.6 mmHg; p<0.0001 and 22.9±7.9 mmHg vs 7.6±3.7 mmHg; p<0.0001, respectively. However, PHT varied considerably (87±37 ms; range: 20–439 ms) within the entire population, and only weakly predicted the requirement for reoperation (113±56 vs. 87±37 ms, p = 0.034). Receiver operating characteristic curves showed strong discriminating ability for mean gradients (AUC = 0.993) and peak gradients (area under the curve, AUC = 0.996), but poor performance for PHT (AUC = 0.640). A value of ≥7 mmHg for mean, and ≥17 mmHg for peak TMPG, best separated patients who required reoperation for MS from those who did not.

Conclusions

Intraoperative TEE diagnosis of a peak TMPG ≥17 mmHg or mean TMPG ≥7 mmHg immediately following CPB are suggestive of clinically relevant MS after MV repair.     

Low efficacy of cardioversion of persistent atrial fibrillation with the implantable cardioverter-defibrillator

Aims

Atrial fibrillation (AF) and heart failure are conditions that often coexist. Consequently, many patients with an implantable cardioverter-defibrillator (ICD) present with AF. We evaluated the effectiveness of internal cardioversion of AF in patients with an ICD.

Methods

Retrospectively, we included 27 consecutive ICD patients with persistent AF who underwent internal cardioversion using the ICD. When ICD cardioversion failed, external cardioversion was performed.

Results

Patients were predominantly male (89 %) with a mean (SD) age of 65 ± 9 years and left ventricular ejection fraction of 36 ± 17 %. Only nine (33 %) patients had successful internal cardioversion after one, two or three shocks. The remaining 18 patients underwent external cardioversion after they failed internal cardioversion, which resulted in sinus rhythm in all. A smaller left atrial volume (99 ± 36 ml vs. 146 ± 44 ml; p = 0.019), a longer right atrial cycle length (227 (186–255) vs. 169 (152–183) ms, p = 0.030), a shorter total AF history (2 (0–17) months vs. 40 (5–75) months, p = 0.025) and dual-coil ICD shock (75 % vs. 26 %, p = 0.093) were associated with successful ICD cardioversion.

Conclusion

Internal cardioversion of AF in ICD patients has a low success rate but may be attempted in those with small atria, a long right atrial fibrillatory cycle length and a short total AF history, especially when a dual-coil ICD is present. Otherwise, it seems reasonable to prefer external over internal cardioversion when it comes to termination of persistent AF.     

New-onset atrial fibrillation and prognosis in nonagenarians after acute myocardial infarction

Background

The influence of new-onset atrial fibrillation (AF) on the long-term prognosis of nonagenarians who survive acute myocardial infarction (AMI) has not been demonstrated.

Objective

Our aim was to study the association between new-onset AF and long-term prognosis of nonagenarians who survive AMI.

Methods

From a total of 96 patients aged ≥89 years admitted during a 5-year period, 64 (67 %) were discharged alive and are the focus of this study.

Results

Mean age was 91.0 ± 2.0 years, and 39 patients (61 %) were women. During admission, 9 patients (14 %) presented new-onset AF, 51 (80 %) did not present AF, and 4 (6 %) had chronic AF. During follow-up (mean 2.3 ± 2.6 years; 6.6 ± 3.6 years in survivors), 58 patients (91 %) died, including the 9 patients with new-onset AF. Cumulative survival at 6, 12, 18, 24, and 30 months was 68.3 %, 57.2 %, 49.2 %, 47.6 %, and 31.8 %, respectively. The only two independent predictors of mortality in the multivariate analysis were age (hazard ratio [HR] 1.14; 95 % confidence interval [CI] 1.01–1.28; p = 0.04) and new-onset AF (HR 2.3; 95 % CI 1.1–4.8; p = 0.02).

Conclusion

New-onset AF is a marker of poor prognosis in nonagenarians who survive AMI.     

Prevalence of psychological distress in elderly hypertension patients in primary care

Background

Recent guidelines on cardiovascular disease prevention advocate the importance of psychological risk factors, as they contribute to the risk of developing cardiovascular disease. However, most previous research on psychological distress and cardiovascular factors has focused on selected populations with cardiovascular disease.

Aim

The primary aim was to determine the prevalence of depression, anxiety, and Type D personality in elderly primary care patients with hypertension. Secondary aim was to examine the relation between elevated systolic blood pressure and depression, anxiety, and Type D personality.

Design and Setting

A cross-sectional study in primary care practices located in the south of the Netherlands.

Method

Primary care hypertension patients (N = 605), between 60 and 85 years (45 % men, mean age = 70 ± 6.6), were recruited for this study. All patients underwent a structured interview including validated self-report questionnaires to assess depression (PHQ-9), anxiety (GAD-7), and Type D personality (DS14) as well as blood pressure assessment.

Results and Conclusion

Depression was prevalent in 5 %, anxiety in 5 %, and Type D personality in 8 %. None of the distress measures were associated with elevated systolic blood pressure of >160 mmHg (all p-values >0.05). This study showed no relation between psychological distress and elevated systolic blood pressure in elderly primary care patients with hypertension.     

Implementation of guidelines for implantable cardioverter-defibrillator therapy in clinical practice: Which patients do benefit?

Purpose

Based on multiple large clinical trials conducted over the last decades guidelines for implantable cardioverter-defibrillator (ICD) implantations have been evolving. The increase in primary prophylactic ICD implantations challenges us to be critical towards the indications in certain patient populations.

Methods

We retrospectively collected patient characteristics and rates of appropriate and inappropriate ICD therapy, appropriate and inappropriate ICD shock and mortality of all patients who received an ICD in the University Medical Center Utrecht (UMCU) over the years 2006–2011.

Results

A total of 1075 patients were included in this analysis (74 % male, mean age 61 ± 13 years, left ventricular ejection fraction 30 ± 13 %); 61 % had a primary indication and 58 % had ischaemic heart disease. During a mean follow-up period of 31 ± 17 months, 227 of the patients (21 %) received appropriate ICD therapy (149 (14 %) patients received an appropriate ICD shock). Females, patients with a primary prophylactic indication and patients with non-ischaemic heart disease experienced significantly less ICD therapy. Only a few patients (54, 5 %) received inappropriate ICD therapy; 33 (3 %) patients received an inappropriate ICD shock. Fifty-five patients died within one year after ICD implantation and were therefore, in retrospect, not eligible for ICD implantation.

Conclusion

Our study confirms the benefit of ICD implantation in clinical practice. Nevertheless, certain patients experience less benefit than others. A more patient-tailored risk stratification based on electrophysiological parameters would be lucrative to improve clinical benefit and cost-effectiveness.     

The flexibility of nonconsciously deployed cognitive processes: evidence from masked congruence priming

Background

It is well accepted in the subliminal priming literature that task-level properties modulate nonconscious processes. For example, in tasks with a limited number of targets, subliminal priming effects are limited to primes that are physically similar to the targets. In contrast, when a large number of targets are used, subliminal priming effects are observed for primes that share a semantic (but not necessarily physical) relationship with the target. Findings such as these have led researchers to conclude that task-level properties can direct nonconscious processes to be deployed exclusively over central (semantic) or peripheral (physically specified) representations.

Principal Findings

We find distinct patterns of masked priming for “novel” and “repeated” primes within a single task context. Novel primes never appear as targets and thus are not seen consciously in the experiment. Repeated primes do appear as targets, thereby lending themselves to the establishment of peripheral stimulus-response mappings. If the source of the masked priming effect were exclusively central or peripheral, then both novel and repeated primes should yield similar patterns of priming. In contrast, we find that both novel and repeated primes produce robust, yet distinct, patterns of priming.

Conclusions

Our findings indicate that nonconsciously elicited cognitive processes can be flexibly deployed over both central and peripheral representations within a single task context. While we agree that task-level properties can influence nonconscious processes, our findings sharply constrain the extent of this influence. Specifically, our findings are inconsistent with extant accounts which hold that the influence of task-level properties is strong enough to restrict the deployment of nonconsciously elicited cognitive processes to a single type of representation (i.e. central or peripheral).     

Assessment of left ventricular ejection fraction in patients eligible for ICD therapy: Discrepancy between cardiac magnetic resonance imaging and 2D echocardiography

Objective

Implantable cardioverter defibrillators (ICD) and cardiac resynchronisation therapy (CRT) have substantially improved the survival of patients with cardiomyopathy. Eligibility for this therapy requires a left ventricular ejection fraction (LVEF) <35 %. This is largely based on studies using echocardiography. Cardiac magnetic resonance imaging (CMR) is increasingly utilised for LVEF assessment, but several studies have shown differences between LVEF assessed by CMR and echocardiography. The present study compared LVEF assessment by CMR and echocardiography in a heart failure population and evaluated effects on eligibility for device therapy.

Methods

152 patients (106 male, mean age 65.5 ± 9.9 years) referred for device therapy were included. During evaluation of eligibility they underwent both CMR and echocardiographic LVEF assessment. CMR volumes were computed from a stack of short-axis images. Echocardiographic volumes were computed using Simpson’s biplane method.

Results

The study population demonstrated an underestimation of end-diastolic volume (EDV) and end-systolic volume (ESV) by echocardiography of 71 ± 53 ml (mean ± SD) and 70 ± 49 ml, respectively. This resulted in an overestimation of LVEF of 6.6 ± 8.3 % by echocardiography compared with CMR (echocardiographic LVEF 31.5 ± 8.7 % and CMR LVEF 24.9 ± 9.6 %). 28 % of patients had opposing outcomes of eligibility for cardiac device therapy depending on the imaging modality used.

Conclusion

We found EDV and ESV to be underestimated by echocardiography, and LVEF assessed by CMR to be significantly smaller than by echocardiography. Applying an LVEF cut-off value of 35 %, CMR would significantly increase the number of patients eligible for device implantation. Therefore, LVEF cut-off values might need reassessment when using CMR.     

Outcome of stand-alone thoracoscopic epicardial left atrial posterior box isolation with bipolar radiofrequency energy for longstanding persistent atrial fibrillation

Introduction

Catheter ablation of longstanding (> 1 year) persistent atrial fibrillation (AF) is associated with poor outcome. This might be due to remodelling and fibrosis formation, mainly located in the posterior left atrial (LA) wall. Therefore, we adopted a thoracoscopic epicardial box isolation of the posterior left atrium using bipolar RF energy with intraoperative testing of conduction block.

Methods and results

Bilateral thoracoscopic box isolation was performed with a bipolar RF clamp. Entrance block was defined as absence of a conducted electrogram within the box, while exit block was confirmed by pacing at 10.0 V/2 ms. Ablation outcome was evaluated after 3, 6, 12 and 24 months with 12-lead ECGs and 24-hour Holter recordings.Twenty-five consecutive patients were included (58 ± 7 years, persistent AF duration 1.8 ± 0.9 years). Entrance block was achieved in all patients and exit block confirmed if sinus rhythm was achieved. After 17 ± 7 months, 76 % of the patients (n = 19) were free of AF recurrence. One patient died within 1 month and was considered an ablation failure. Four patients with AF recurrences regained sinus rhythm with additional catheter ablation or antiarrhythmic drugs.

Conclusions

Treatment of longstanding persistent AF with thoracoscopic epicardial LA posterior box isolation using bipolar RF energy with intraoperative testing of conduction block is feasible and highly effective.     

Oral administration of γ-aminobutyric acid affects heat production in a hot environment in resting humans

Background

Central administration of γ-amino butyric acid (GABA) induces lower body temperature in animals in hot ambient air. However, it is still unknown whether oral GABA administration affects temperature regulation at rest in a hot environment in humans. Therefore, in the present study, we specifically hypothesized that systemic administration of GABA in humans would induce hypothermia in a hot environment and that this response would be observed in association with decreased heat production.

Methods

Eight male participants drank a 200-ml sports drink with 1 g of GABA (trial G) or without GABA (trial C), then rested for 30 minutes in a sitting position in a hot environment (ambient air temperature 33°C, relative humidity 50%).

Results

We found that changes in esophageal temperature from before drinking the sports drink were lower in trial G than in trial C (-0.046 ± 0.079°C vs 0.001 ± 0.063°C; P < 0.05), with lower heat production calculated by oxygen consumption (41 ± 5 W/m² vs 47 ± 8 W/m²; P < 0.05).

Conclusions

In this study, we have demonstrated that a single oral administration of GABA induced a larger decrease in body core temperature compared to a control condition during rest in a hot environment and that this response was concomitant with a decrease in total heat production.     

The effect of prolonged physical activity performed during extreme caloric deprivation on cardiac function

Background

Endurance exercise may induce transient cardiac dysfunction. Data regarding the effect of caloric restriction on cardiac function is limited. We studied the effect of physical activity performed during extreme caloric deprivation on cardiac function.

Methods

Thirty-nine healthy male soldiers (mean age 20±0.3 years) were studied during a field training exercise lasted 85–103 hours, with negligible food intake and unlimited water supply. Anthropometric measurements, echocardiographic examinations and blood and urine tests were performed before and after the training exercise.

Results

Baseline VO₂ max was 59±5.5 ml/kg/min. Participants'' mean weight reduction was 5.7±0.9 kg. There was an increase in plasma urea (11.6±2.6 to 15.8±3.8 mmol/L, p<0.001) and urine osmolarity (692±212 to 1094±140 mmol/kg, p<0.001) and a decrease in sodium levels (140.5±1.0 to 136.6±2.1 mmol/L, p<0.001) at the end of the study. Significant alterations in diastolic parameters included a decrease in mitral E wave (93.6 to 83.5 cm/s; p = 0.003), without change in E/A and E/E′ ratios, and an increase in iso-volumic relaxation time (73.9 to 82.9 ms, p = 0.006). There was no change in left or right ventricular systolic function, or pulmonary arterial pressure. Brain natriuretic peptide (BNP) levels were significantly reduced post-training (median 9 to 0 pg/ml, p<0.001). There was no elevation in Troponin T or CRP levels. On multivariate analysis, BNP reduction correlated with sodium levels and weight reduction (R = 0.8, p<0.001).

Conclusions

Exposure to prolonged physical activity performed under caloric deprivation resulted in minor alterations of left ventricular diastolic function. BNP levels were significantly reduced due to negative water and sodium balance.     

Assessment of LV ejection fraction using real-time 3D echocardiography in daily practice: direct comparison of the volumetric and speckle tracking methodologies to CMR

Aims

This study is the first to directly compare two widely used real-time 3D echocardiography (RT3DE) methods of cardiac magnetic resonance imaging (CMR) and assess their reproducibility in experienced and less experienced observers.

Methods

Consecutive patients planned for CMR underwent RT3DE within 8 h of CMR with Philips (volumetric method) and Toshiba Artida (speckle tracking method). Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) were measured using RT3DE, by four trained observers, and compared with CMR values.

Results

Thirty-five patients were included (49.7 ± 15.7 years; 55 % male), 30 (85.7 %) volumetric and 27 (77.1 %) speckle tracking datasets could be analysed. CMR derived LVEDV, LVESV and LVEF were 198 ± 58 ml, 106 ± 53 ml and 49 ± 15 %, respectively. LVEF derived from speckle tracking was accurate and reproducible in all observers (all intra-class correlation coefficients (ICC) > 0.86). LVEF derived from the volumetric method correlated well to CMR in experienced observers (ICC 0.85 and 0.86) but only moderately in less experienced observers (ICC 0.58 and 0.77) and was less reproducible in these observers (ICC = 0.55). Volumes were significantly underestimated compared with CMR (p < 0.001).

Conclusion

This study demonstrates that both RT3DE methodologies are sufficiently accurate and reproducible for use in daily practice. However, experience importantly influences the accuracy and reproducibility of the volumetric method, which should be considered when introducing this technique into clinical practice.     

Prevention of ocular scarring post glaucoma filtration surgery using the inflammatory cell and platelet binding modulator saratin in a rabbit model

Clinical Relevance

Late complications can occur with use of current antimetabolites to prevent scarring following glaucoma filtration surgery (GFS). Safer, more targeted, anti-fibrosis agents are sought.

Objectives

The protein saratin has been shown to exhibit anti-fibrotic and anti-thrombotic properties in response to injury, but had not been used for glaucoma surgery. The goal of this study was to compare the efficacy of saratin with that of the widely accepted mitomycin-C (MMC) in prolonging bleb survival following GFS in the rabbit model. Two saratin delivery routes were compared; a single intraoperative topical application versus a combination of intraoperative topical application with two additional postoperative injections.

Methods

Twenty-four New Zealand White rabbits underwent GFS and received either intraoperative topical saratin, intraoperative topical saratin plus two injections on post-operative days 4 and 8, balanced saline solution (BSS), or MMC. The bleb tissues and their elevation durations were compared based on clinical and histological findings.

Results

Rabbits receiving topical+injections of saratin had a mean bleb survival of 33.6±8.5 days, significantly higher than the negative BSS controls, which averaged 17.4±6.0 days (p = 0.018). No improvement over BSS was seen for rabbits receiving topical saratin only (15.5±4.8 days, p = 0.749). Rabbits receiving saratin did not develop bleb avascularity and thinning associated with MMC treatment and there were no apparent clinical signs of toxicity.

Conclusions

Treatment with a single intraoperative topical application plus two additional postoperative injections significantly prolonged bleb elevation comparable to MMC, but without toxicity; however, topical application alone was ineffective.     

In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses,Revealing Rapid Loss of Virus Reactive CD4+ T Cells in Acute HIV-1 Infection

Background

The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission.

Methodology

The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited.

Findings

Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naïve T cells. Responses included several CD4⁺ and CD8⁺ T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4⁺ T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4⁺ T cell depletion which renders the newly activated HIV-specific CD4⁺ T cells prime targets for elimination.

Conclusion

Our studies highlight the ability of DCs to efficiently prime naïve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.