Perioperative Strategien zur Regulierung des Sympathikotonus

Zusammenfassung: Obwohl für verschiedene therapeutische Konzepte zur Verminderung der kardialen perioperativen Morbidität und Mortalität zunehmend Evidenz vorliegt, bleibt die tatsächliche Umsetzung solcher Konzepte im klinischen Alltag oft aus. Zwar ist einem großen Teil der klinisch tätigen Ärzte die wachsende Literatur bekannt; dieses Wissen wird aber nur in einem Teil der Fälle angewendet, selbst wenn allgemein akzeptierte Indikationen bestehen. Die vorliegende Übersichtsarbeit hat deshalb zum Ziel, die Gründe für die mangelnde Umsetzung aufzuzeigen und nochmals die wesentlichen Grundlagen sowie die klinische Bedeutung einzelner Strategien einschließlich des α2-Agonismus, der β-adrenergen Blockade und der Regionalanästhesien zusammenzufassen. Dies insbesondere im Hinblick auf die klinische Anwendung dieser Konzepte in einem allgemeinanästhesiologischen Umfeld. Zudem wird ein Ausblick in die auf "gene profiling" basierende individualisierte Pharmakotherapie der perioperativen Medizin von morgen gegebe

Suppression of the 1 MHz beam current modulation in the LEDA/CRITS proton source

Earlier operation of a microwave proton source exhibited an approximate 1-MHz modulation in the beam current. This oscillation could cause instabilities at higher energies in the linac, as the low-level RF control for linac operation rolls off at 200 kHz. Tests on a dummy load show the modulation is created by the magnetron itself: at a typical power level required for the source operation (680W), the 1-MHz sideband level was as high as {minus}4 dB from carrier. Since the magnetron exhibited better behavior at higher levels, a RF power attenuator is inserted to force the magnetron to run at a 50% higher power level for the same final power in the load. This attenuator is made of two antennas plunged in the waveguide and connected to dummy loads by a coaxial line. As the antenna are separated by a quarter of the guided wavelength, mismatching effects approximately cancel each other. The antenna length is experimentally adjusted to obtain the {minus}1.8 dB attenuation required. Magnetron operation at the higher power level gives a beam current spectrum free of the 1-MHz modulation, showing the coherent beam noise is not generated by plasma chamber phenomena

Ischemic postconditioning protects remodeled myocardium via the PI3K-PKB/Akt reperfusion injury salvage kinase pathway

OBJECTIVE: We tested whether ischemic postconditioning (IPostC) is protective in remodeled myocardium. METHODS: Post-myocardial infarct (MI)-remodeled hearts after permanent coronary artery ligation and one kidney one clip (1K1C) hypertensive hearts of male Wistar rats were exposed to 40 min of ischemia followed by 90 min of reperfusion. IPostC was induced by six cycles of 10 s reperfusion interspersed by 10 s of no-flow ischemia. Activation of reperfusion injury salvage kinases was measured using Western blotting and in vitro kinase activity assays. RESULTS: IPostC prevented myocardial damage in both MI-remodeled and 1K1C hearts, as measured by decreased infarct size and lactate dehydrogenase release, and improved function. The reduction in infarct size and the recovery of left ventricular contractility achieved by IPostC was less in 1K1C hearts, but was unchanged in MI-remodeled hearts when compared to healthy hearts. In contrast, the recovery of inotropy was unaffected in 1K1C hearts, but was less in MI-remodeled hearts. Inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway with LY294002 abolished the protective effects of IPostC on both disease models and healthy hearts. Western blot analysis in conjunction with in vitro kinase activity assays identified protein kinase B (PKB)/Akt but not p42/p44 extracellular-signal regulated kinase 1/2 (ERK1/2) as the predominant kinase in IPostC-mediated cardioprotection in remodeled hearts. IPostC increased phosphorylation of the PKB/Akt downstream targets eNOS, GSK3beta, and p70S6K in remodeled hearts. CONCLUSION: Our results offer evidence that IPostC mediates cardioprotection in the remodeled rat myocardium primarily via activation of the PI3K-PKB/Akt reperfusion injury salvage kinase pathwa

Operation of a microwave proton source in pulsed mode

Initial beam operation of the cw radio-frequency-quadrupole (RFQ) built for the Low Energy Demonstration Accelerator (LEDA) project requires the injection into the RFQ of a 75-keV, pulsed, H{sup +} beam with a rise and fall time less than 10 microseconds and a pulse width from 0.1 to 1 millisecond at a repetition rate up to 10 Hz. The ion source for the accelerator is a microwave proton source driven by a 2.45-GHz magnetron. Pulsed beam for the RFQ is accomplished by modulation of the magnetron tube current. The magnetron provides microwave pulses to the ion source, and a medium-bandwidth, extraction power supply produces the H{sup +} ion beam using a four-electrode extractor. A similar ion source with a three-element extractor operating at 50 kV has also been tested with this magnetron modulator. The authors report the results of modulating the ion-source microwave power and extracting a pulsed proton beam using both a triode and a tetrode extractor

Explicit solution of the quantum three-body Calogero-Sutherland model

Quantum integrable systems generalizing Calogero-Sutherland systems were introduced by Olshanetsky and Perelomov (1977). Recently, it was proved that for systems with trigonometric potential, the series in the product of two wave functions is a deformation of the Clebsch-Gordan series. This yields recursion relations for the wave functions of those systems. In this note, this approach is used to compute the explicit expressions for the three-body Calogero-Sutherland wave functions, which are the Jack polynomials. We conjecture that similar results are also valid for the more general two-parameters deformation introduced by Macdonald.Comment: 10 page

Doppler-Shift Proton Fraction Measurement on a CW Proton Injector

A spectrometer/Optical Multi-channel Analyzer has been used to measure the proton fraction of the cw proton injector developed for the Accelerator Production of Tritium (APT) and the Low Energy Demonstration Accelerator (LEDA) at Los Alamos. This technique, pioneered by the Lawrence Berkeley National Laboratory (LBNL), was subsequently adopted by the international fusion community as the standard for determining the extracted ion fractions of neutral beam injectors. Proton fractions up to 95 {+-} 3% have been measured on the LEDA injector. These values are in good agreement with results obtained by magnetically sweeping the ion beam, collimated by a slit, across a Faraday cup. Since the velocity distribution of each beam species is measured, it also can be used to determine beam divergence. While divergence has not yet been ascertained due to the wide slit widths in use, non-Gaussian distributions have been observed during operation above the design-matched perveance. An additional feature is that the presence of extracted water ions can be observed. During ion source conditioning at 75 kV, an extracted water fraction > 30% was briefly observed

Comparison of beam simulations with measurements for a 1.25-MeV, CW RFQ

The Low-Energy Demonstration Accelerator (LEDA) injector is tested using the Chalk River Injector Test Stand (CRITS) radio-frequency quadrupole (RFQ) as a diagnostic instrument. Fifty-keV, dc proton beams are injected into the 1.25-MeV, CW RFQ and transported to a beamstop. Computer-simulation-code predictions of the expected beam performance are compared with the measured beam currents and beam profiles. Good agreement is obtained between the measurements and the simulations at the 75-mA design RFQ output current

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story

BACKGROUND A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence