BACKGROUND:There is an association between cryptogenic stroke and patent foramen ovale (PFO). The optimal treatment strategy for secondary prevention remains unclear. The purpose of this study was to analyze aggregate data examining the safety and efficacy of transcatheter device closure versus standard medical therapy in patients with PFO and cryptogenic stroke.METHODS:A search of published data identified 3 randomized clinical trials for inclusion. The primary outcome was a composite end-point of death, stroke and transient-ischemic attack (TIA). Pre-defined subgroup analysis was performed with respect to baseline characteristics including age, sex, atrial septal aneurysm and shunt size. Data was synthesized using a random effects model and results presented as hazard ratios (HRs) with 95% confidence intervals (CIs).RESULTS:A cohort of 2,303 patients with a history of cryptogenic stroke and PFO were randomized to device closure (n=1150) and medical therapy (n=1153). Mean follow-up was 2.5years. Transcatheter closure was not superior to medical therapy in the secondary prevention of stroke or TIA in intention-to-treat analysis (HR: 0.66, 95% CI: 0.43 to 1.01 / p=0.056). However, the results were statistically significant using per-protocol analysis (HR: 0.64, 95% CI: 0.41 to 0.98 / p=0.043). Males had significant benefit with device closure (HR: 0.48, 95% CI: 0.24 to 0.96 / p=0.038).CONCLUSIONS:In this meta-analysis, using intention-to-treat analysis, transcatheter device closure of PFO was not superior to standard medical therapy in the secondary prevention of cryptogenic stroke. Transcatheter closure was superior using per-protocol analysis.

Este trabalho objetivou a construção de um resistor shunt dedicado a medir correntes impulsivas com valores de 2 kA a 100 kA. Esse resistor possui características gerais similares aos resistores shunt coaxiais convencionais descritos na literatura. No entanto, ele difere dos demais já desenvolvidos, por apresentar inúmeras inovações tecnológicas. Quando comparado com um resistor shunt Haefely® padrão, apresentou excelente estabilidade em toda a faixa de freqüência requerida, até 10 MHz, bem como, excelente resposta temporal. / The aim of this work was to construct a shunt resistor to measure impulsive currents with values from 2 kA to 100 kA, with general features similar to conventional coaxial resistors as described in the literature. However, it differs from resistors already developed because it shows many offers technological innovations. When compared to a should stand Haefely® shunt resistor, it presented great stability in all required frequency band to 10 MHz, as well as excellent temporal response.

Os shunts vasculares temporários (SVT) são utilizados como uma técnica eficaz para reestabelecer rapidamente o fluxo sanguíneo em casos de lesão vascular com isquemia do membro ou órgão acometido, no qual a revascularização deverá ser postergada. Habitualmente, o SVT é inserido dentro dos cotos proximal e distal do vaso lesado através de uma abertura na pele, visando restaurar a perfusão e interromper a isquemia. O objetivo deste estudo é comparar a pressão arterial média (PAM em mmHg) e o fluxo sanguíneo (em ml/min) em dois modelos de SVT, um habitual e outro implantado por punção, bem como o tempo para a inserção destes dispositivos e suas patências primária e secundária. Realizamos experimentos em 30 suínos, somando 60 intervenções de revascularização arterial temporária dos membros posteriores: trinta SVT habituais e trinta por punção. Analisamos a PAM durante os procedimentos nos membros posteriores e o fluxo através dos dois tipos de SVT. A análise de fluxo mostrou uma diferença significativa entre os SVT testados (p=0,001), sendo menor no grupo SVT por punção. No entanto, o tempo decorrido (min) para inserção do SVT habitual foi maior do que o tempo para inserção do SVT por punção (15,32 ± 3,08 vs. 10,37 ± 1,7, p=0,001). Além disso, observamos uma recuperação da PAM nos membros submetidos aos dois tipos de SVT próxima à PAM sistêmica em 100% dos experimentos. Os resultados revelaram patência primária, secundária, e taxa de complicações similares entre os dois tipos de SVT. Concluímos que o fluxo foi menor no SVT por punção, mas a recuperação da PAM foi semelhante e com menor tempo de inserção do SVT por punção / Temporary vascular shunts (TVS) are used as an effective technique to rapidly restore blood flow in cases of vascular injury with ischemia of the affected limb or organ, in which revascularization shall be postponed. Usually, TVS is positioned within the proximal and distal stumps of the injured vessel, through an opening of the skin, in order to restore perfusion and stop the ischemia. We sought to compare mean blood pressure (MBP in mmHg) and blood flow (ml/min) between two types of TVS, a standard one and a puncture one, as well as the time spent to insert these devices. We performed an experimental study on 30 pigs, including 60 vascular interventions in posterior limbs: thirty standard TVS and thirty puncture TVS. MBP was analyzed during the interventions in both posterior limbs and the flow through both types of TVS. Flow analysis revealed a significant difference between the two types of TVS (p=0,001), being lower in the puncture TVS. However, the time spent during standard TVS insertion was greater than that of the puncture shunt (15,32 ± 3,08 min vs.10,37 ± 1,7 min, p=0,001). In addition, we observed a limb MBP recovery close to systemic MBP in 100% of the experiments. The results show similar primary and secondary patency and complication rate in both TVS types. Therefore, we conclude that the flow was lower in the puncture TVS, but the MBP recovery was similar and it took less time to be inserted

Dendritic cells (DCs) are the most potent professional antigen presenting cells (pAPCs) of the immune system and play a fundamental role in coordinating innate and adaptive immune responses. Through the expression of a wide array of pattern recognition receptors (PRRs), such as toll-like receptors (TLRs), DCs recognize a variety of microbial pathogens and infectious stimuli. Stimulation of DCs through TLR ligation results in a rapid series of activation-associated events, termed "maturation," which include the upregulation of surface co-stimulatory molecule expression, inflammatory cytokine secretion, and stimulation of naïve T cells via antigen presentation by MHC molecules. Activation of DCs through TLRs is coupled with an increased metabolic demand fulfilled by a rapid change in DC glucose metabolism and characterized by increased aerobic glycolysis rates. TLR-driven glycolytic reprogramming plays an essential role in generating building blocks required for high level protein synthesis associated with maturation. Although glucose imported from extracellular environments has been broadly considered as the major driver of glycolytic metabolism in immune cells, the contributions of intracellular glucose stores to these processes are not well-defined. The role of intracellular stores of glucose, in the form of glycogen, is widely appreciated in non-immune systems. However, very little is known about the implication of glycogen metabolism in DC immune responses. This work unveils the role and potential regulatory mechanisms of glycogen metabolism in support of DC effector function. The first part of this work primarily focuses on our characterization of the role of glycogen metabolism in early DC activation responses; while in the last chapter, we describe a potential regulatory mechanism of DC glycogen metabolism by activation-associated nitric oxide (NO) production. In this work, we tested the overarching hypothesis that DC-intrinsic glycogen metabolism supports the early glycolytic reprogramming required for effector responses and that nitric oxide can regulate this metabolism. We demonstrate that DCs possess the enzymes required for glycogen metabolic machinery and that glycogen metabolism supports DC immune effector response, particularly during early activation and in nutrient-limited environments. More importantly, we uncover a very intriguing metabolic phenomenon, in which DCs engage in the differential metabolic pathways driven by carbons derived distinctively from glycogen and free glucose. Our studies present the fundamental role and regulatory mechanisms of DC-intrinsic glycogen metabolism and underline the differential utilization of glycogen and glucose metabolism to support their effector responses. Overall, this work adds to a growing field of immuno-metabolism an improved understanding of an intricate layer of metabolic mechanisms that immune cells undertake in response to immune stimuli.

Implantation of a left ventricular assist device (LVAD) is a potential treatment in terminal heart failure. Right ventricular (RV) failure is a severe complication in these patients and sometimes requires additional placement of a right ventricular assist device (RVAD). RVAD implantation, however, is an invasive treatment associated with both increased mortality and morbidity. The aim of this thesis was to study whether partial volume exclusion of the RV through a modified Glenn shunt or cavoaortic shunt could treat severe RV failure. The ultimate goal would be to use it as an alternative to a RVAD in RV failure during LVAD therapy. Swine were used as the model animal in all studies. In Study I, experimental RV failure was induced by ischemia, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis and improved hemodynamics in general. In Study II, experimental RV failure was induced by the same method as in Study I. Treatment with a cavoaortic shunt in addition to LVAD therapy proved to reduce venous stasis and improved hemodynamics in general, which was feasible with preserved oxygen delivery despite cyanotic shunting. In Study III, experimental RV failure was induced by pulmonary banding, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis but did not improve hemodynamics in general compared with a control group. In Study IV, the effects of LVAD therapy and subsequent treatment with a modified Glenn shunt on the normal RV function were studied. It demonstrated that LVAD therapy can put strain on the RV by increasing stroke work and end-diastolic volume, and that these effects can be reversed by treatment with a modified Glenn shunt during LVAD therapy. In conclusion, partial volume exclusion through a modified Glenn shunt or cavoaortic shunt is a feasible treatment of experimental RV failure. Thus, it could potentially be used as an alternative treatment to a RVAD in severe RV failure during LVAD therapy.

When spontaneous breathing (SB) is allowed during mechanical ventilation (MV), atelectatic lung areas are recruited and oxygenation improves thereby. Whether unsupported SB at its natural pattern (without PEEP and at low pressure/small tidal volume) equally recruits and improves oxygenation, and if so by which mechanism, has not been studied. A porcine lung collapse model was designed to study this question. The cardiac output dependency of the pulmonary shunt was investigated with healthy lungs and with major shunt (during one-lung ventilation) and with SB, MV and continuous positive airway pressure (CPAP). The hypoxic pulmonary vasoconstriction (HPV) was blocked with sodium nitroprusside (SNP) to see whether HPV is the only mechanism available for ventilation/perfusion (VA/Q) matching during MV and SB. In all experiments, respiratory rate and tidal volume during MV were matched to SB. Oxygenation was assessed by serial blood gas measurements, recruitment by thoracic CTs; pulmonary shunt was assessed by multiple inert gas elimination or venous admixture. SB attained better oxygenation and lower pulmonary shunt compared with MV, although it did not recruit collapsed lung. Pulmonary shunt did not correlate with cardiac output during SB, whereas a correlation was found during MV and CPAP. With blocked HPV, pulmonary shunt was considerably lower during SB than MV. In conclusion, SB improves VA/Q matching as compared with MV, even when no recruitment occurs. In contrast to MV and CPAP, cardiac output has no major effect on pulmonary shunt during SB. The improved VA/Q matching during SB despite a blocked HPV might indicate the presence of a SB-specific mechanism that improves pulmonary blood flow redistribution towards ventilated lung regions independent of or supplementary to HPV.

Ulm, Univ., Diss., 2000.

Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist as part of the normal pulmonary vasculature for over 50 years but have been underappreciated by physiologists and clinicians. Using a technique called saline contrast echocardiography we and others have demonstrated that during exercise or when breathing low oxygen gas mixtures IPAVA open, but breathing 100% oxygen during exercise prevents them from opening. However, the mechanism(s) for this dynamic regulation and the role IPAVA play in affecting pulmonary gas exchange efficiency remain unknown. In Chapter IV the infusion of epinephrine and dopamine into resting subjects opened IPAVA. While it is possible this opening was due to the direct vasoactive action of these catecholamines, the opening may simply be due to increases in cardiac output and pulmonary artery systolic pressure secondary to the cardiac effects of these drugs. In Chapter V I used Technetium-99m labeled macroaggregated albumin (99mTc-MAA) to quantify blood flow through IPAVA in exercising healthy humans. Initial attempts to correct for attenuation of the emitted signal were unsuccessful due to the time necessary for data acquisition and the resulting accumulation of free-99mTc. However, I used a blood sample to calculate freely circulating 99mTc which could be subtracted from the shunt fraction. Using this procedure I demonstrated for the first time using filtered solid particles that breathing 100% oxygen reduces blood flow through IPAVA during exercise. Finally, in Chapter VI I tackled the elephant in the room surrounding IPAVA in healthy humans: do these vessels play a role in pulmonary gas exchange efficiency? Our data suggest that the efficiency of pulmonary gas exchange is dependent on the driving pressure gradient for oxygen and the distance to blood flowing through the core of IPAVA. As such, with increases in exercise intensity the diffusion distance and transit time of blood at the core of IPAVA prevent complete gas exchange, thus blood flow through IPAVA acts as a shunt. This dissertation includes previously unpublished co-authored material.

Este trabalho objetivou a construção de um resistor shunt dedicado a medir correntes impulsivas com valores de 2 kA a 100 kA. Esse resistor possui características gerais similares aos resistores shunt coaxiais convencionais descritos na literatura. No entanto, ele difere dos demais já desenvolvidos, por apresentar inúmeras inovações tecnológicas. Quando comparado com um resistor shunt Haefely® padrão, apresentou excelente estabilidade em toda a faixa de freqüência requerida, até 10 MHz, bem como, excelente resposta temporal. / The aim of this work was to construct a shunt resistor to measure impulsive currents with values from 2 kA to 100 kA, with general features similar to conventional coaxial resistors as described in the literature. However, it differs from resistors already developed because it shows many offers technological innovations. When compared to a should stand Haefely® shunt resistor, it presented great stability in all required frequency band to 10 MHz, as well as excellent temporal response.

<p align="justify">Many different active control techniques can be used to control the vibrations of a mechanical structure: they however require at least a sensitive signal amplifier (for the sensor), a power amplifier (for the actuator) and an analog or digital filter (for the controller). The use of all these electronic devices may be impractical in many applications and has motivated the use of the so-called shunt circuits, in which an electrical circuit is directly connected to a transducer embedded in the structure. The transducer acts as an energy converter: it transforms mechanical (vibrational) energy into electrical energy, which is in turn dissipated in the shunt circuit. No separate sensor is required, and only one, generally simple electronic circuit is used. The stability of the shunted structure is guaranteed if the electric circuit is passive, i.e. if it is made of passive components such as resistors and inductors.</p><p><p><p align="justify">This thesis compares the performances of the electric shunt circuits with those of classical active control systems. It successively considers the use of piezoelectric transducers and that of electromagnetic (moving-coil) transducers.</p><p><p><p align="justify">In a first part, the different damping techniques are applied on a benchmark truss structure equipped with a piezoelectric stack transducer. A unified formulation is found and experimentally verified for an active control law, the Integral Force Feedback (IFF), and for various passive shunt circuits (resistive and resistive-inductive). The use of an active shunt, namely the negative capacitance, is also investigated in detail. Two different implementations are discussed: they are shown to have very different stability limits and performances.</p><p><p><p align="justify">In a second part, vibration isolation with electromagnetic (moving-coil) transducers is introduced. The effects of an inductive-resistive shunt circuit are studied in detail; an equivalent mechanical representation is found. The performances are compared with that of resonant shunts and with that of active isolation with IFF. Next, the construction of a six-axis isolator based on a Stewart Platform is presented: the key parameters and the main limitations of the system are highlighted.</p> / Doctorat en Sciences de l'ingénieur / info:eu-repo/semantics/nonPublished