Zusammenfassung
Hintergrund
Adipositas bei Schwangeren stellt ein zunehmendes Problem dar, das mit z. T. gravierenden geburtshilflichen Problemen einhergeht. Betroffene Frauen mit Kinderwunsch ...sollten hierüber aufgeklärt werden, um sie zur Gewichtsabnahme vor der Schwangerschaft zu motivieren.
Risiken von Übergewicht bei Kinderwunsch
Sie nehmen mit dem BMI (Body-Mass-Index) der Frauen zu. Die Fertilität ist bei Adipositas reduziert. Bei adipösen Schwangeren ist das Risiko für einen Abort und kongenitale Fehlbildungen erhöht. Im Lauf der Schwangerschaft kommen Hypertonus, Gestationsdiabetes und hohe Frühgeburtenrate hinzu. Zudem steigt das Risiko, makrosome Kinder zu gebären. Häufig wird eine Entbindung per Sectio erforderlich.
Präventive Maßnahmen
Eine Gewichtsabnahme vor der Schwangerschaft ist wünschenswert. Vorbestehende Begleiterkrankungen müssen präkonzeptionell erfasst und behandelt werden. Schwangere nach bariatrischen Operationen haben einen signifikant günstigeren Schwangerschaftsverlauf als Frauen mit vergleichbarem BMI vor der Operation. Die Schwangerschaft muss jedoch engmaschig überwacht werden.
European chemical policy in general and the REACH initiative in particular will increase the number of chemical substances submitted to toxicological evaluation by several orders of magnitude ...compared to the current status. To limit animal exposure the resulting enormous increase in testing, however, asks for validated in vitro test systems. While the OECD favours in vitro testing for cutaneous absorption using viable human and animal skin (Guideline 428) the availability of viable human skin is already limited today.
We present a comparison of various in vitro techniques suitable for routine skin absorption studies including commercially available reconstructed human epidermis which may be a reliable alternative to excised human and animal skin. In order to develop a protocol for the subsequent transfer to partner laboratories the experimental set-up was analysed stepwise using the OECD reference compounds caffeine and testosterone. Franz cell type, the donor and receptor media for hydrophilic/lipophilic substances, albumin and tensid addition, and storage conditions of the excised skins were systematically varied. A protocol has been developed which now allows to proceed to the pre-validation process.
Objectives:
Following CE mark approval, MitraClip is increasingly performed in Europe. The ACCESS-EU registry provides a snapshot of real-world clinical demographics and outcomes. We herein report ...early and mid-term outcomes of the ACCESS-EU Study, a European prospective, multicenter, non-randomized post-approval study of the MitraClip device.
Methods:
From April, 2009 through April 2011, total of 567 patients with significant MR underwent MitraClip therapy at 14 European centers. Mean logistic EuroSCORE I at baseline was 23.0 ± 18.3; 84.9% patients were in NYHA Class III or IV, and 52.7% patients had an EF ≤ 40%.
Results:
The MitraClip implant rate was 99.6%. A total of 19 patients (3.4%) died within 30 days after the MitraClip procedure. The Kaplan-Meier survival at 1 year was 81.8%. Intensive care unit and hospital length of stay was 2.5 ± 6.5 days and 7.7 ± 8.2 days, respectively. Single leaflet device attachment was reported in 27 patients (4.8%). There were no MitraClip device embolization. Thirty-six subjects (6.3%) required mitral valve surgery within 12 months post the MitraClip implant procedure. There was improvement in the severity of MR at 12 months compared to baseline (p < 0.0001), with 78.9% of patients free from MR severity of >2+ at 12 months. At 12 months, 71.4% of patients had NYHA Functional Class II or Class I. Six-minutes-walk-test improved 59.5 ± 112.4 meters and Minnesota-living-with-heart-failure score improved 13.5 ± 20.5 points.
Conclusions:
In a real world scenario, post-approval experience in Europe, patients undergoing the MitraClip therapy are high risk, elderly patients, mainly affected by functional MR. In this patient population, the MitraClip procedure is effective with low rates of hospital mortality and adverse events.
Starting in 2014, the LHC will collide bunches of protons at up to 14 TeV with aninstantaneous luminosity increasing above the design value of 1 x 10 super(34) cm super(-2)s super(-1). Even thoughthe ...resulting higher event rate will challenge the existing ATLAS data acquisition system, thetrigger rate can be reduced by selecting channels based on their expected decay topology andthus reducing background. This will be achieved by introducing a new FPGA based module inthe Level-1 Trigger: the Topological Processor (L1Topo). With L1Topo it will be possible toconcentrate detailed information from the entire calorimeters and the muon detector into a single module. L1Topo will receive a total aggregate bandwidth of approximately 1 Tb/s. High density optical I/O and state of the art FPGAs with embedded multi-Gb/s transceivers will be required. For a typicalalgorithm, the topology data will be processed in less than 100 ns. This paper focuses on thedesign of the first L1Topo prototype and results from a full-size, full-function demonstrator module. Implementation details of a topological algorithm and latency figures are presented.
The sources and measurement of reactive oxygen species (ROS) in intact organs are largely unresolved. This may be related to methodological problems associated with the techniques currently employed ...for ROS detection. Electron spin resonance (ESR) with spin trapping is a specific method for ROS detection, and may address some these technical problems.
We have established a protocol for the measurement of intravascular ROS release from isolated buffer-perfused and ventilated rabbit and mouse lungs, combining lung perfusion with the spin probe 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) and ESR spectroscopy. We then employed this technique to characterize hypoxia-dependent ROS release, with specific attention paid to NADPH oxidase-dependent superoxide formation as a possible vasoconstrictor pathway.
While perfusing lungs with CPH over a range of inspired oxygen concentrations (1-21 %), the rate of CP* formation exhibited an oxygen-dependence, with a minimum at 2.5 % O2. Addition of superoxide dismutase (SOD) to the buffer fluid illustrated that a minor proportion of this intravascular ROS leak was attributable to superoxide. Stimulation of the lungs by injection of phorbol-12-myristate-13-acetate (PMA) into the pulmonary artery caused a rapid increase in CP* formation, concomitant with pulmonary vasoconstriction. Both the PMA-induced CPH oxidation and the vasoconstrictor response were largely suppressed by SOD. When the PMA challenge was performed at different oxygen concentrations, maximum superoxide liberation and pulmonary vasoconstriction occurred at 5% O2. Using a NADPH oxidase inhibitor and NADPH-oxidase deficient mice, we illustrated that the PMA-induced superoxide release was attributable to the stimulation of NADPH oxidases.
The perfusion of isolated lungs with CPH is suitable for detection of intravascular ROS release by ESR spectroscopy. We employed this technique to demonstrate that 1) PMA-induced vasoconstriction is caused "directly" by superoxide generated from NADPH oxidases and 2) this pathway is pronounced in hypoxia. NADPH oxidases thus may contribute to the hypoxia-dependent regulation of pulmonary vascular tone.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Four in vitro test systems were used to study the reservoir capacity of porcine stratum corneum (SC) for flufenamic acid and its drainage via penetration into the deeper skin layers: Franz diffusion ...cell using full thickness skin and split skin of 300 μm; Saarbruecken penetration model (SB) and intact porcine tissue (IP). Each skin sample was segmented 1, 4 and 21 h after application of an ‘infinite dose’ of flufenamic acid. The lipophilic drug was extracted from the SC and the deeper skin layers (viable epidermis and dermis) and determined using high-performance liquid chromatography (HPLC). For each test system, an increase in the drug amount in the deeper skin layers and the acceptor fluid, respectively, was observed in combination with a decreased amount in the SC with increasing time after application. The drainage of the SC reservoir was only reflected by a linear correlation of the drug amount in the SC with the amount in the deeper skin layers in the case of IP. The absolute drug concentrations previously detected in human skin in vivo and in vitro were compared with the present data, affording the best accordance in the case of IP.
We have isolated and characterized the will die slowly (wds) gene of Drosophila melanogaster, formerly known as l(1)zw8 or l(1)3Ad. The gene codes for a 2.0-kb RNA that is transcribed at all stages ...of development. The RNA has been localized by in situ hybridization to imaginal discs, larval brain, to nurse cells in the ovary, and to spermatogonia and spermatocytes in the testis. The putative translation product contains seven WD-repeats and is, therefore, a new member of the family of WD-proteins. Clear homologues of the Drosophila WDS protein exist in three other fully sequenced higher eukaryotes - human, Caenorhabditis elegans and Arabidopsis. A genomic fragment containing the wds transcription unit is able to rescue two different lethal wds alleles, thus proving that we have indeed isolated the wds gene.
The development of Silicon Photomultipliers (SiPM) is very dynamic and a large variety of types exists. Important SiPM characteristics include the size and number of pixels, the gain, the photon ...detection efficiency (PDE), the recovery time, and correlated noise. SiPMs are particularly suitable for single-photon detection and low-intensity exposures. For photon numbers (PDE corrected) reaching the number of pixels, however, the sensors saturate. In this work, we present comprehensive response measurements for state-of-the-art SiPMs using an experimental setup based on a tunable picosecond laser. Several models are applied to the measured response curves, taking particularly correlated noise and saturation effects into account. Sensors with different numbers of pixels and different design are compared, some of which exhibit an over-saturation behavior. The results are discussed in the context of high-granularity calorimeters developed for future particle physics experiments employing millions of SiPMs. For these projects the full dynamic range of the sensors has to be exploited, thus an understanding and calibration of the saturation behavior is crucial.
•Experimental method to compare the response of different SiPMs using the same setup.•Observation of over-saturation for certain SiPM models.•SiPMs with many small pixels (here 2668 pixels with 25 μm pitch) and trenches are best suitable for calorimeter applications.
Zusammenfassung
Der vorliegende Beitrag geht auf die Besonderheiten der Insulintherapie bei schwangeren Diabetespatientinnen ein, da sich sowohl Zielwerte, Modus der Blutzucker(BZ)-Kontrollen als ...auch die Dynamik der notwendigen Insulinanpassung maßgeblich unterscheiden. Vorangestellt ist die Bedeutung der präkonzeptionellen Stoffwechseloptimierung, da der HbA
1c
-Wert bei Konzeption entscheidend für den gesamten Verlauf der Schwangerschaft ist. Nach Datenlage sind die Insulintherapie mithilfe einer Pumpe und die intensivierte konventionelle Insulintherapie (ICT) bezüglich des perinatalen Outcomes als gleichwertig anzusehen. Das Gleiche gilt für Humaninsulin im Vergleich zu Insulinanaloga; auch Langzeitanaloga werden inzwischen als unbedenklich eingestuft. Die BZ-Zielwerte liegen weit tiefer als außerhalb der Schwangerschaft, das Erreichen muss jedoch im Verhältnis zur Gefährdung der Mutter durch schwere Hypoglykämien stehen. Eine engmaschige persönliche Betreuung mit Anpassung der Insulindosierung ist nötig, um auf den sich schnell ändernden Insulinbedarf zu reagieren. Das Wachstum des Fetus als Parameter für eine mögliche Über- oder Unterversorgung muss mitberücksichtigt werden. Unter der Geburt und postpartal bedarf es eines Klinikstandards für die Stoffwechselführung. Für Frauen mit Typ-2-Diabetes gelten die gleichen Prinzipien der Insulintherapie. Im 3. Trimenon kann der Insulinbedarf sehr hoch werden; eventuell ist zusätzlich als „off label use“ Metformin nötig. Auf orale Antidiabetika („oral antidiabetic agents“, OADS) eingestellte Frauen sollten optimalerweise vor der Konzeption auf Insulin umgestellt werden. Dies sollte auch beim Stillen beibehalten werden.
PDF
