Physiological Phenomenology of Neurally-Mediated Syncope with Management Implications

BACKGROUND: Due to lack of efficacy in recent trials, current guidelines for the treatment of neurally-mediated (vasovagal) syncope do not promote cardiac pacemaker implantation. However, the finding of asystole during head-up tilt -induced (pre)syncope may lead to excessive cardioinhibitory syncope diagnosis and treatment with cardiac pacemakers as blood pressure is often discontinuously measured. Furthermore, physicians may be more inclined to implant cardiac pacemakers in older patients. We hypothesized that true cardioinhibitory syncope in which the decrease in heart rate precedes the fall in blood pressure is a very rare finding which might explain the lack of efficacy of pacemakers in neurally-mediated syncope. METHODS: We studied 173 consecutive patients referred for unexplained syncope (114 women, 59 men, 42 ± 1 years, 17 ± 2 syncopal episodes). All had experienced (pre)syncope during head-up tilt testing followed by additional lower body negative suction. We classified hemodynamic responses according to the modified Vasovagal Syncope International Study (VASIS) classification as mixed response (VASIS I), cardioinhibitory without (VASIS IIa) or with asystole (VASIS IIb), and vasodepressor (VASIS III). Then, we defined the exact temporal relationship between hypotension and bradycardia to identify patients with true cardioinhibitory syncope. RESULTS: Of the (pre)syncopal events during tilt testing, 63% were classified as VASIS I, 6% as VASIS IIb, 2% as VASIS IIa, and 29% as VASIS III. Cardioinhibitory responses (VASIS class II) progressively decreased from the youngest to the oldest age quartile. With more detailed temporal analysis, blood pressure reduction preceded the heart-rate decrease in all but six individuals (97%) overall and in 10 out of 11 patients with asystole (VASIS IIb). CONCLUSIONS: Hypotension precedes bradycardia onset during head-up tilt-induced (pre)syncope in the vast majority of patients, even in those classified as cardioinhibitory syncope according to the modified VASIS classification. Furthermore, cardioinhibitory syncope becomes less frequent with increasing age

Liver Afferents Contribute to Water Drinking-Induced Sympathetic Activation in Human Subjects: A Clinical Trial

Water drinking acutely increases sympathetic activity in human subjects. In animals, the response appears to be mediated through transient receptor potential channel TRPV4 activation on osmosensitive hepatic spinal afferents, described as osmopressor response. We hypothesized that hepatic denervation attenuates water drinking-induced sympathetic activation. We studied 20 liver transplant recipients (44±2.6 years, 1.2±0.1 years post transplant) as model of hepatic denervation and 20 kidney transplant recipients (43±2.6 years, 0.8±0.1 years post transplant) as immunosuppressive drug matched control group. Before and after 500 ml water ingestion, we obtained venous blood samples for catecholamine analysis. We also monitored brachial and finger blood pressure, ECG, and thoracic bioimpedance. Plasma norepinephrine concentration had changed by 0.01±0.07 nmol/l in liver and by 0.21±0.07 nmol/l in kidney transplant recipients (p<0.05 between groups) after 30–40 minutes of water drinking. While blood pressure and systemic vascular resistance increased in both groups, the responses tended to be attenuated in liver transplant recipients. Our findings support the idea that osmosensitive hepatic afferents are involved in water drinking-induced sympathetic activation in human subjects

Effect of Acute Ozone Induced Airway Inflammation on Human Sympathetic Nerve Traffic: A Randomized, Placebo Controlled, Crossover Study

Background: Ozone concentrations in ambient air are related to cardiopulmonary perturbations in the aging population. Increased central sympathetic nerve activity induced by local airway inflammation may be one possible mechanism. Methodology/Principal Findings: To elucidate this issue further, we performed a randomized, double-blind, cross-over study, including 14 healthy subjects (3 females, age 22-47 years), who underwent a 3 h exposure with intermittent exercise to either ozone (250 ppb) or clean air. Induced sputum was collected 3 h after exposure. Nineteen to 22 hours after exposure, we recorded ECG, finger blood pressure, brachial blood pressure, respiration, cardiac output, and muscle sympathetic nerve activity (MSNA) at rest, during deep breathing, maximum-inspiratory breath hold, and a Valsalva maneuver. While the ozone exposure induced the expected airway inflammation, as indicated by a significant increase in sputum neutrophils, we did not detect a significant estimated treatment effect adjusted for period on cardiovascular measurements. Resting heart rate (clean air: 59 +/- 62, ozone 60 +/- 62 bpm), blood pressure (clean air: 121 +/- 3/71 +/- 2 mmHg; ozone: 121 +/- 2/71 +/- 2mmHg), cardiac output (clean air: 7.42 +/- 0.29 mmHg; ozone: 7.98 +/- 0.60 l/min), and plasma norepinephrine levels (clean air: 213 +/- 21 pg/ml; ozone: 202 +/- 16 pg/ml), were similar on both study days. No difference of resting MSNA was observed between ozone and air exposure (air: 2362, ozone: 2362 bursts/min). Maximum MSNA obtained at the end of apnea (air: 44 +/- 4, ozone: 48 +/- 4 bursts/min) and during the phase II of the Valsalva maneuver (air: 64 +/- 5, ozone: 57 +/- 6 bursts/min) was similar. Conclusions/Significance: Our study suggests that acute ozone-induced airway inflammation does not increase resting sympathetic nerve traffic in healthy subjects, an observation that is relevant for environmental health. However, we can not exclude that chronic airway inflammation may contribute to sympathetic activation

In vivo imaging of pancreatic tumours and liver metastases using 7 Tesla MRI in a murine orthotopic pancreatic cancer model and a liver metastases model

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 Tesla MRI and evaluate its clinical relevance and applicability.</p> <p>Methods</p> <p>6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.</p> <p>Results</p> <p>MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm³+/-243 mm³) with MRI (mean 918 mm³+/-193 mm³) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm²+/-22.8 mm²versus 32.6 mm²+/-22.6 mm²(histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm³+/-56.7 mm³after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.</p> <p>Conclusions</p> <p>This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.</p

A judicialização das demandas por justiça social possibilidades e limites

O presente trabalho objetiva examinar a judicialização das demandas por justiça social, bem como seus limites e potencialidades para a efetivação de direitos e transformação social a partir do ponto de vista dos movimentos sociais. Inicialmente buscaremos apresentar algumas possíveis causas para o fenômeno, a partir do novo constitucionalismo latino-americano, apontando as possíveis causas institucionais e culturais do fenômenos, entre as quais se destacam o ordenamento jurídico introduzido pela Constituição Federal de 1988 bem como a mobilização jurídica vivenciada desde esse período. Posteriormente, serão apresentadas algumas considerações sobre possíveis usos emancipatórios da judicialização, a partir da perspectiva da prática da assessoria jurídica popular e da advocacia popular, bem como das teorias críticas do direito. Por fim, serão apresentadas possíveis limites para o caráter emancipatório da judicialização.This paper aims to examine judicialisation of the demands for social justice, as well as its limits and potential for the realization of rights and social transformation from the point of view of social movements. Initially we seek to present some possible causes for the phenomenon, from the new Latin American Constitutionalism, pointing out the possible institutional and cultural causes of phenomena, among which stand out the legal framework introduced by the Federal Constitution of 1988 as well as legal mobilization experienced since that time. After, will be presented some considerations about possible emancipatory uses of judicialization, from the perspective of Popular Legal Counseling, as well as the critical theories of law. Finally, they will be presented possible limits to the emancipatory character of judicialization

A judicialização das demandas por justiça social possibilidades e limites

O presente trabalho objetiva examinar a judicialização das demandas por justiça social, bem como seus limites e potencialidades para a efetivação de direitos e transformação social a partir do ponto de vista dos movimentos sociais. Inicialmente buscaremos apresentar algumas possíveis causas para o fenômeno, a partir do novo constitucionalismo latino-americano, apontando as possíveis causas institucionais e culturais do fenômenos, entre as quais se destacam o ordenamento jurídico introduzido pela Constituição Federal de 1988 bem como a mobilização jurídica vivenciada desde esse período. Posteriormente, serão apresentadas algumas considerações sobre possíveis usos emancipatórios da judicialização, a partir da perspectiva da prática da assessoria jurídica popular e da advocacia popular, bem como das teorias críticas do direito. Por fim, serão apresentadas possíveis limites para o caráter emancipatório da judicialização.This paper aims to examine judicialisation of the demands for social justice, as well as its limits and potential for the realization of rights and social transformation from the point of view of social movements. Initially we seek to present some possible causes for the phenomenon, from the new Latin American Constitutionalism, pointing out the possible institutional and cultural causes of phenomena, among which stand out the legal framework introduced by the Federal Constitution of 1988 as well as legal mobilization experienced since that time. After, will be presented some considerations about possible emancipatory uses of judicialization, from the perspective of Popular Legal Counseling, as well as the critical theories of law. Finally, they will be presented possible limits to the emancipatory character of judicialization

AROSICS: An Automated and Robust Open-Source Image Co-Registration Software for Multi-Sensor Satellite Data

Abstract Geospatial co-registration is a mandatory prerequisite when dealing with remote sensing data. Inter- or intra-sensoral misregistration will negatively affect any subsequent image analysis, specifically when processing multi-sensoral or multi-temporal data. In recent decades, many algorithms have been developed to enable manual, semi- or fully automatic displacement correction. Especially in the context of big data processing and the development of automated processing chains that aim to be applicable to different remote sensing systems, there is a strong need for efficient, accurate and generally usable co-registration. Here, we present AROSICS (Automated and Robust Open-Source Image Co-Registration Software), a Python-based open-source software including an easy-to-use user interface for automatic detection and correction of sub-pixel misalignments between various remote sensing datasets. It is independent of spatial or spectral characteristics and robust against high degrees of cloud coverage and spectral and temporal land cover dynamics. The co-registration is based on phase correlation for sub-pixel shift estimation in the frequency domain utilizing the Fourier shift theorem in a moving-window manner. A dense grid of spatial shift vectors can be created and automatically filtered by combining various validation and quality estimation metrics. Additionally, the software supports the masking of, e.g., clouds and cloud shadows to exclude such areas from spatial shift detection. The software has been tested on more than 9000 satellite images acquired by different sensors. The results are evaluated exemplarily for two inter-sensoral and two intra-sensoral use cases and show registration results in the sub-pixel range with root mean square error fits around 0.3 pixels and better.Peer Reviewe