Heterogeneous Response (heterogeneous + response)

Distribution by Scientific Domains


Selected Abstracts


Endurance Exercise Training in Older Patients with Heart Failure: Results from a Randomized, Controlled, Single-Blind Trial

JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2009
Peter H. Brubaker PhD
OBJECTIVES: To test the hypothesis that exercise training (ET) improves exercise capacity and other clinical outcomes in older persons with heart failure with reduced ejection fraction (HfrEF). DESIGN: Randomized, controlled, single-blind trial. SETTING: Outpatient cardiac rehabilitation program. PARTICIPANTS: Fifty-nine patients aged 60 and older with HFrEF recruited from hospital records and referring physicians were randomly assigned to a 16-week supervised ET program (n=30) or an attention-control, nonexercise, usual care control group (n=29). INTERVENTION: Sixteen-week supervised ET program of endurance exercise (walking and stationary cycling) three times per week for 30 to 40 minutes at moderate intensity regulated according to heart rate and perceived exertion. MEASUREMENTS: Individuals blinded to group assignment assessed four domains pivotal to HFrEF pathophysiology: exercise performance, left ventricular (LV) function, neuroendocrine activation, and health-related quality of life (QOL). RESULTS: At follow-up, the ET group had significantly greater exercise time and workload than the control group, but there were no significant differences between the groups for the primary outcomes: peak exercise oxygen consumption (VO2 peak), ventilatory anaerobic threshold (VAT), 6-minute walk distance, QOL, LV volumes, EF, or diastolic filling. Other than serum aldosterone, there were no significant differences after ET in other neuroendocrine measurements. Despite a lack of a group "training" effect, a subset (26%) of individuals increased VO2 peak by 10% or more and improved other clinical variables as well. CONCLUSION: In older patients with HFrEF, ET failed to produce consistent benefits in any of the four pivotal domains of HF that were examined, although the heterogeneous response of older patients with HFrEF to ET requires further investigation to better determine which patients with HFrEF will respond favorably to ET. [source]


Focal Atrial Fibrillation: Experimental Evidence for a Pathophysiologic Role of the Autonomic Nervous System

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2001
PATRICK SCHAUERTE M.D.
Focal AF and Autonomic Nerves.Introduction: Focal paroxysmal atrial fibrillation (AF) was shown recently to originate in the pulmonary veins (PVs) and superior vena cava (SVC). In the present study, we describe an animal model in which local high-frequency electrical stimulation produces focal atrial activation and AF/AT (atrial tachycardia) with electrogram characteristics consistent with clinical reports. Methods and Results: In 21 mongrel dogs, local high-frequency electrical stimulation was performed by delivering trains of electrical stimuli (200 Hz, impulse duration 0.1 msec) to the PVs/SVC during atrial refractoriness. Atrial premature depolarizations (APDs), AT, and AF occurred with increasing highfrequency electrical stimulation voltage. APD/AT/AF originated adjacent to the site of high-frequency electrical stimulation and were inducible in 12 of 12 dogs in the SVC and in 8 of 9 dogs in the left superior PV (left inferior PV: 7/8, right superior PV: 6/8; right inferior PV: 4/8). In the PVs, APDs occurred at 13 ± 8 V and AT/AF at 15 ± 9 V (P < 0.01; n = 25). In the SVC, APDs were elicited at 19 ± 6 V and AT/AF at 26 ± 6 V (P < 0.01; n = 12). High-frequency electrical stimulation led to local refractory period shortening in the PVs. The response to high-frequency electrical stimulation was blunted or prevented after beta-receptor blockade and abolished by atropine. In vitro, high-frequency electrical stimulation induced a heterogeneous response, with shortening of the action potential in some cells (from 89 ± 35 msec to 60 ± 22 msec; P < 0.001; n = 7) but lengthening of the action potential and development of early afterdepolarizations that triggered APD/AT in other cells. Action potential shortening was abolished by atropine. Conclusion: High-frequency electrical stimulation evokes rapid ectopic beats from the PV/SVC, which show variable degrees of conduction block to the atria and induce AF, resembling findings in patients with focal idiopathic paroxysmal AF. The occurrence of the arrhythmia in this animal model was likely due to alterations in local autonomic tone by high-frequency electrical stimulation. Further research is needed to prove absolutely that the observed effects of high-frequency electrical stimulation were caused by autonomic nerve stimulation. [source]


Reproducible fashion of the HSP70B' promoter-induced cytotoxic response on a live cell-based biosensor by cell cycle synchronization

BIOTECHNOLOGY & BIOENGINEERING, Issue 3 2010
Satoshi Migita
Abstract Live cell-based sensors potentially provide functional information about the cytotoxic effect of reagents on various signaling cascades. Cells transfected with a reporter vector derived from a cytotoxic response promoter can be used as intelligent cytotoxicity sensors (i.e., sensor cells). We have combined sensor cells and a microfluidic cell culture system that can achieve several laminar flows, resulting in a reliable high-throughput cytotoxicity detection system. These sensor cells can also be applied to single cell arrays. However, it is difficult to detect a cellular response in a single cell array, due to the heterogeneous response of sensor cells. The objective of this study was cell homogenization with cell cycle synchronization to enhance the response of cell-based biosensors. Our previously established stable sensor cells were brought into cell cycle synchronization under serum-starved conditions and we then investigated the cadmium chloride-induced cytotoxic response at the single cell level. The GFP positive rate of synchronized cells was approximately twice as high as that of the control cells, suggesting that cell homogenization is an important step when using cell-based biosensors with microdevices, such as a single cell array. Biotechnol. Bioeng. 2010;107: 561,565. © 2010 Wiley Periodicals, Inc. [source]


Cluster analysis of BOLD fMRI time series in tumors to study the heterogeneity of hemodynamic response to treatment

MAGNETIC RESONANCE IN MEDICINE, Issue 6 2003
Christine Baudelet
Abstract BOLD-contrast functional MRI (fMRI) has been used to assess the evolution of tumor oxygenation and blood flow after treatment. The aim of this study was to evaluate K-means-based cluster analysis as a exploratory, data-driven method. The advantage of this approach is that it can be used to extract information without the need for prior knowledge concerning the hemodynamic response function. Two data sets were acquired to illustrate different types of BOLD fMRI response inside tumors: the first set following a respiratory challenge with carbogen, and the second after pharmacological modulation of tumor blood flow using flunarizine. To improve the efficiency of the clustering, a power density spectrum analysis was first used to isolate voxels for which signal changes did not originate from noise or linear drift. The technique presented here can be used to assess hemodynamic response to treatment, and especially to display areas of the tumor with heterogeneous responses. Magn Reson Med 49:985,990, 2003. © 2003 Wiley-Liss, Inc. [source]