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Find video protocols related to scientific articles indexed in Pubmed.
Plasmatic isoforms of cytokeratin 18 and RAGE after severe trauma: A longitudinal cohort study.
J Trauma Acute Care Surg
PUBLISHED: 09-25-2014
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Life-threatening traumatic injuries lead to a complex inflammation-driven pathophysiology. Receptor of advanced glycation end product (RAGE) is a multiligand receptor of several endogenous alarmins, while cytokeratin 18 is a structural component of the filament of epithelial cells. Both proteins can be frequently found in plasma of patients with different diseases, whereby they have distinct underlying mechanism of formation. In this prospective observational study, we wanted to shed light on the kinetic of plasmatic RAGE and cytokeratin 18 isoforms after severe trauma, thereby also addressing the association of these markers with inflammation and their potential use as biomarkers.
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Multilayer Fresnel zone plates for high energy radiation resolve 21 nm features at 1.2 keV.
Opt Express
PUBLISHED: 08-05-2014
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X-ray microscopy is a successful technique with applications in several key fields. Fresnel zone plates (FZPs) have been the optical elements driving its success, especially in the soft X-ray range. However, focusing of hard X-rays via FZPs remains a challenge. It is demonstrated here, that two multilayer type FZPs, delivered from the same multilayer deposit, focus both hard and soft X-rays with high fidelity. The results prove that these lenses can achieve at least 21 nm half-pitch resolution at 1.2 keV demonstrated by direct imaging, and sub-30 nm FWHM (full-pitch) resolution at 7.9 keV, deduced from autocorrelation analysis. Reported FZPs had more than 10% diffraction efficiency near 1.5 keV.
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Comparative study of prescribing patterns of tigecycline for trial patients versus non-trial patients.
In Vivo
PUBLISHED: 07-02-2014
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Comparing published trial patients and non-trial patients in clinical practice, clinicians often doubt whether critically ill patients are sufficiently represented in randomised clinical trials.
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Mechanisms of lidocaine's action on subtypes of spinal dorsal horn neurons subject to the diverse roles of Na(+) and K(+) channels in action potential generation.
Anesth. Analg.
PUBLISHED: 06-04-2014
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Superficial dorsal horn neurons of the spinal cord receive sensory information from A? and C fibers. According to their response to sustained depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting (AFN), and single spike firing (SSN) neurons. During spinal and systemic administration of lidocaine, these neurons are exposed to different concentrations of the local anesthetic lidocaine. In this study, we explored its effect on the excitability of sensory neurons.
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Sepsis varies arterial two-pore-domain potassium channel messenger RNA in mice.
J. Surg. Res.
PUBLISHED: 05-17-2014
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Hemodynamic changes are mainly responsible for organ failure and subsequently for the poor outcome of sepsis. Occurring macro- and micro-circulatory dysfunctions are not homogeneously distributed in the vessel beds. Especially mesenteric arterioles are subject to hypoperfusion during sepsis, and in consequence, a dysfunction of the downstream organs develops. Furthermore, impaired perfusion of the splanchnic area may cause intestinal barrier breakdown supporting the translocation of bacteria or toxins into the circulation aggravating a systemic infection and organ failure. The two-pore potassium channels (K2P channels) are responsible for setting the resting membrane potential of smooth muscle cells. Because of their sensitivity by various metabolic or humoral mediators, which are also varying during inflammatory processes, they can determine vascular resistance during sepsis. Dopamine receptors type 1 (D1R) and 2 (D2R) are assumed to be involved in the regulation of arterial tone under hypoxic conditions and are investigated too.
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Interleukin-6 contributes to the paracrine effects of cardiospheres cultured from human, murine and rat hearts.
J. Cell. Physiol.
PUBLISHED: 03-11-2014
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Cardiosphere-derived cells (CDCs) were cultured from human, murine, and rat hearts. Diluted supernatant (conditioned-medium) of the cultures improved the contractile behavior of isolated rat cardiomyocytes (CMCs). This effect is mediated by the paracrine release of cytokines. The present study tested the hypothesis, that the cardiovascular state of the donor's heart influences this effect on CMCs and tries to identify the responsible factors. CDCs were cultured from human tissue samples of cardiac surgery and from murine and rat hearts. The supernatants of cultured CDCs from hypertensive humans and rats showed a higher improvement of the contractile behavior of CMCs compared to CDCs of normotensive origin. Subsequently, the cytokine profile of the supernatants was analyzed. Among the cytokines elevated in supernatants originating from hypertensive humans or rats was Interleukin-6. CDCs were also generated from Interleukin-6(-/-) -mice and their wildtype littermates. The supernatant of the cultured Interleukin-6(-/-) -CDCs had no effect on the contractile behavior, whereas the supernatant of the Interleukin-6(+/+) -CDCs showed a positive effect. To confirm the hypothesis that Interleukin-6 contributes to the paracrine effects, CMCs were incubated with Interleukin-6. It improved the contractile function in a concentration dependent way. Finally, the effect of the supernatant of cultured CDCs derived from a hypertensive human sample could be abolished by simultaneous incubation with a specific Interleukin-6 antibody. CDCs release cytokines that improve the contractile behavior of CMCs. This effect is more intense in CDCs from hypertensive donors. Interleukin-6 is involved in this phenomenon.
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[Nutrition of intensive care patients - how to reach target parameters].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 02-23-2014
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Nutrition of intensive care patients is often complex and challenging due to metabolic changes. For this reason nutritional support adapted to the metabolic state is of key importance to avoid hyper- or hypoalimentation and thus has direct impact on the prognosis. Target parameters might be beneficial to establish an adequate and differentiated nutritional strategy but thus far concerning single nutritional components evidence-based data are only available for adjusting blood glucose levels. Furthermore, an early enteral nutrition is of major prognostic importance. In practice a supplementary parenteral support is often required to provide adequate calorie supply. Monitoring of residual gastric volume as a tool to regulate an effective enteral nutrition might possibly become less important due to recent study data.
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Intrinsic vascular dopamine - a key modulator of hypoxia-induced vasodilatation in splanchnic vessels.
J. Physiol. (Lond.)
PUBLISHED: 02-17-2014
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Dopamine not only is a precursor of the catecholamines noradrenaline and adrenaline but also serves as an independent neurotransmitter and paracrine hormone. It plays an important role in the pathogenesis of hypertension and is a potent vasodilator in many mammalian systemic arteries, strongly suggesting an endogenous source of dopamine in the vascular wall. Here we demonstrated dopamine, noradrenaline and adrenaline in rat aorta and superior mesenteric arteries (SMA) by radioimmunoassay. Chemical sympathectomy with 6-hydroxydopamine showed a significant reduction of noradrenaline and adrenaline, while dopamine levels remained unaffected. Isolated endothelial cells were able to synthesize and release dopamine upon cAMP stimulation. Consistent with these data, mRNAs coding for catecholamine synthesizing enzymes, i.e. tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase, and dopamine-?-hydroxylase were detected by RT-PCR in cultured endothelial cells from SMA. TH protein was detected by immunohistochemisty and Western blot. Exposure of endothelial cells to hypoxia (1% O2) increased TH mRNA. Vascular smooth muscle cells partially expressed catecholaminergic traits. A physiological role of endogenous vascular dopamine was shown in SMA, where D1 dopamine receptor blockade abrogated hypoxic vasodilatation. Experiments on SMA with endothelial denudation revealed a significant contribution of the endothelium, although subendothelial dopamine release dominated. From these results we conclude that endothelial cells and cells of the underlying vascular wall synthesize and release dopamine in an oxygen-regulated manner. In the splanchnic vasculature, this intrinsic non-neuronal dopamine is the dominating vasodilator released upon lowering of oxygen tension.
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Synchronous precessional motion of multiple domain walls in a ferromagnetic nanowire by perpendicular field pulses.
Nat Commun
PUBLISHED: 02-11-2014
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Magnetic storage and logic devices based on magnetic domain wall motion rely on the precise and synchronous displacement of multiple domain walls. The conventional approach using magnetic fields does not allow for the synchronous motion of multiple domains. As an alternative method, synchronous current-induced domain wall motion was studied, but the required high-current densities prevent widespread use in devices. Here we demonstrate a radically different approach: we use out-of-plane magnetic field pulses to move in-plane domains, thus combining field-induced magnetization dynamics with the ability to move neighbouring domain walls in the same direction. Micromagnetic simulations suggest that synchronous permanent displacement of multiple magnetic walls can be achieved by using transverse domain walls with identical chirality combined with regular pinning sites and an asymmetric pulse. By performing scanning transmission X-ray microscopy, we are able to experimentally demonstrate in-plane magnetized domain wall motion due to out-of-plane magnetic field pulses.
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Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.
J. Surg. Res.
PUBLISHED: 01-13-2014
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During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function.
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From human monocytes to genome-wide binding sites--a protocol for small amounts of blood: monocyte isolation/ChIP-protocol/library amplification/genome wide computational data analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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Chromatin immunoprecipitation in combination with a genome-wide analysis via high-throughput sequencing is the state of the art method to gain genome-wide representation of histone modification or transcription factor binding profiles. However, chromatin immunoprecipitation analysis in the context of human experimental samples is limited, especially in the case of blood cells. The typically extremely low yields of precipitated DNA are usually not compatible with library amplification for next generation sequencing. We developed a highly reproducible protocol to present a guideline from the first step of isolating monocytes from a blood sample to analyse the distribution of histone modifications in a genome-wide manner. Conclusion: The protocol describes the whole work flow from isolating monocytes from human blood samples followed by a high-sensitivity and small-scale chromatin immunoprecipitation assay with guidance for generating libraries compatible with next generation sequencing from small amounts of immunoprecipitated DNA.
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Tumor necrosis factor alpha induces a serotonin dependent early increase in ciliary beat frequency and epithelial transport velocity in murine tracheae.
PLoS ONE
PUBLISHED: 01-01-2014
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The tracheal epithelium prevents via its highly effective clearance mechanism the contamination of the lower airways by pathogens. This mechanism is driven by ciliary bearing cells which are not only in contact with the gas phase; in addition they are also influenced by inflammatory mediators. These mediators can alter the protective function of the epithelium. Since the pro-inflammatoric cytokine tumor necrosis factor-? (TNF-?) plays a pivotal role within the inflammatory cascade, we investigated its effect onto the tracheal epithelium measured by its ciliary beat frequency and the particle transport velocity. In organ explant experiments the ciliary beat frequency and the particle transport velocity were measured under the application of TNF-? using tracheae from male C57BL6J mice. We observed a dose dependent TNF-? induced increase of both particle transport velocity and ciliary beat frequency. Knock out mice experiments made evident that the increase was depended on the expression of tumor necrosis factor receptor 1 (TNF-R1). The increases in ciliary beat frequency as well as the accelerated particle transport velocity were either inhibited by the unspecific serotonin antagonist methysergide or by cyproheptadine a specific 5-HT2 receptor antagonist. Thus, acetylcholine antagonists or nitric oxide synthase (NOS) inhibitors failed to inhibit the TNF-? induced activation. In conclusion, TNF-? may play a pivotal role in the protection of lower airways by inducing ciliary activity and increase in particle transport velocity via TNF-R1 and 5-HT2 receptor.
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Rapid Prototyping of Fresnel Zone Plates via Direct Ga(+) Ion Beam Lithography for High-Resolution X-ray Imaging.
ACS Nano
PUBLISHED: 11-07-2013
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A significant challenge to the wide utilization of X-ray microscopy lies in the difficulty in fabricating adequate high-resolution optics. To date, electron beam lithography has been the dominant technique for the fabrication of diffractive focusing optics called Fresnel zone plates (FZP), even though this preparation method is usually very complicated and is composed of many fabrication steps. In this work, we demonstrate an alternative method that allows the direct, simple, and fast fabrication of FZPs using focused Ga(+) beam lithography practically, in a single step. This method enabled us to prepare a high-resolution FZP in less than 13 min. The performance of the FZP was evaluated in a scanning transmission soft X-ray microscope where nanostructures as small as sub-29 nm in width were clearly resolved, with an ultimate cutoff resolution of 24.25 nm, demonstrating the highest first-order resolution for any FZP fabricated by the ion beam lithography technique. This rapid and simple fabrication scheme illustrates the capabilities and the potential of direct ion beam lithography (IBL) and is expected to increase the accessibility of high-resolution optics to a wider community of researchers working on soft X-ray and extreme ultraviolet microscopy using synchrotron radiation and advanced laboratory sources.
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Correlation between spin structure oscillations and domain wall velocities.
Nat Commun
PUBLISHED: 07-19-2013
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Magnetic sensing and logic devices based on the motion of magnetic domain walls rely on the precise and deterministic control of the position and the velocity of individual magnetic domain walls in curved nanowires. Varying domain wall velocities have been predicted to result from intrinsic effects such as oscillating domain wall spin structure transformations and extrinsic pinning due to imperfections. Here we use direct dynamic imaging of the nanoscale spin structure that allows us for the first time to directly check these predictions. We find a new regime of oscillating domain wall motion even below the Walker breakdown correlated with periodic spin structure changes. We show that the extrinsic pinning from imperfections in the nanowire only affects slow domain walls and we identify the magnetostatic energy, which scales with the domain wall velocity, as the energy reservoir for the domain wall to overcome the local pinning potential landscape.
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Ion beam lithography for Fresnel zone plates in X-ray microscopy.
Opt Express
PUBLISHED: 06-06-2013
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Fresnel Zone Plates (FZP) are to date very successful focusing optics for X-rays. Established methods of fabrication are rather complex and based on electron beam lithography (EBL). Here, we show that ion beam lithography (IBL) may advantageously simplify their preparation. A FZP operable from the extreme UV to the limit of the hard X-ray was prepared and tested from 450 eV to 1500 eV. The trapezoidal profile of the FZP favorably activates its 2nd order focus. The FZP with an outermost zone width of 100 nm allows the visualization of features down to 61, 31 and 21 nm in the 1st, 2nd and 3rd order focus respectively. Measured efficiencies in the 1st and 2nd order of diffraction reach the theoretical predictions.
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Peridural analgesia may affect long-term survival in patients with colorectal cancer after surgery (PACO-RAS-Study): an analysis of a cancer registry.
Ann. Surg.
PUBLISHED: 05-01-2013
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To determine the effect of peridural analgesia on long-term survival in patients who underwent surgical treatment of colorectal carcinoma.
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Reactive metabolites and AGE-RAGE-mediated inflammation in patients following liver transplantation.
Mediators Inflamm.
PUBLISHED: 04-29-2013
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Recent investigations have indicated that reactive metabolites and AGE-RAGE-mediated inflammation might play an important role in the pathogenesis of ischemia-reperfusion injury in liver transplantation. In this observational clinical study, 150 patients were enrolled following liver transplantation from deceased donors. The occurrence of short-term complications within 10 days of transplantation was documented. Blood samples were collected prior to transplantation, immediately after transplantation, and at consecutive time points, for a total of seven days after transplantation. Plasma levels of methylglyoxal were determined using HPLC, whereas plasma levels of L-arginine, asymmetric dimethylarginine, advanced glycation endproducts-carboxylmethyllysine, soluble receptor for advanced glycation endproducts, and total antioxidant capacity were measured by ELISA. Patients following liver transplantation were shown to suffer from increased RAGE-associated inflammation with an AGE load mainly dependent upon reactive carbonyl species-derived AGEs. In contrast, carboxylmethyllysine-derived AGEs were of a minor importance. As assessed by the ratio of L-arginine/asymmetric dimethylarginine, the bioavailability of nitric oxide was shown to be reduced in hepatic IRI, especially in those patients suffering from perfusion disorders following liver transplantation. For the early identification of patients at high risk of perfusion disorders, the implementation of asymmetric dimethylarginine measurements in routine diagnostics following liver transplantation from deceased donors should be taken into consideration.
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Patients enrolled in randomised clinical trials are not representative of critically ill patients in clinical practice: observational study focus on tigecycline.
Int. J. Antimicrob. Agents
PUBLISHED: 03-27-2013
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It is being increasingly recognised by clinicians and scientists that participants in randomised clinical trials (RCTs) of antibiotics of last resort do not represent the patients who will later be treated with these drugs. Data on this subject are limited and have not been investigated systematically. This observational study aimed to examine this hypothesis quantitatively, using the example of tigecycline. To evaluate the influence of recruitment, patients eligible for clinical trials were retrospectively compared with ineligible patients regarding baseline and clinical characteristics as well as outcome parameters, e.g. length of hospital stay, intensive care unit (ICU) stay, ventilation and mortality. The clinical characteristics of 187 patients illustrated differences in the nature and severity of disease, co-morbidities and outcome. Eligible and ineligible patients differed in a number of parameters, e.g. median APACHE II score (15.5 vs. 28.0), number of liver transplantations (5% vs. 18%; P=0.048), septic shock (21% vs. 49%; P=0.001), need for mechanical ventilation (30% vs. 79%; P<0.001), mean length of ICU stay (19.3 days vs. 40.7 days) and death (19% vs. 46%; P=0.001). Critically ill patients were under-represented in clinical trials. Moreover, only a minority of patients in clinical practice (13%) were potentially eligible for a pivotal RCT. The disparities likely result from strict exclusion criteria in RCTs and recruitment bias. These data emphasise the importance of including critically ill patients in RCTs of antibiotics against multiresistant bacteria in order to account for those who will later be treated.
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Wave modes of collective vortex gyration in dipolar-coupled-dot-array magnonic crystals.
Sci Rep
PUBLISHED: 03-18-2013
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Lattice vibration modes are collective excitations in periodic arrays of atoms or molecules. These modes determine novel transport properties in solid crystals. Analogously, in periodical arrangements of magnetic vortex-state disks, collective vortex motions have been predicted. Here, we experimentally observe wave modes of collective vortex gyration in one-dimensional (1D) periodic arrays of magnetic disks using time-resolved scanning transmission x-ray microscopy. The observed modes are interpreted based on micromagnetic simulation and numerical calculation of coupled Thiele equations. Dispersion of the modes is found to be strongly affected by both vortex polarization and chirality ordering, as revealed by the explicit analytical form of 1D infinite arrays. A thorough understanding thereof is fundamental both for lattice vibrations and vortex dynamics, which we demonstrate for 1D magnonic crystals. Such magnetic disk arrays with vortex-state ordering, referred to as magnetic metastructure, offer potential implementation into information processing devices.
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Efficient focusing of 8 keV X-rays with multilayer Fresnel zone plates fabricated by atomic layer deposition and focused ion beam milling.
J Synchrotron Radiat
PUBLISHED: 03-07-2013
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Fresnel zone plates (FZPs) recently showed significant improvement by focusing soft X-rays down to ~10 nm. In contrast to soft X-rays, generally a very high aspect ratio FZP is needed for efficient focusing of hard X-rays. Therefore, FZPs had limited success in the hard X-ray range owing to difficulties of manufacturing high-aspect-ratio zone plates using conventional techniques. Here, employing a method of fabrication based on atomic layer deposition (ALD) and focused ion beam (FIB) milling, FZPs with very high aspect ratios were prepared. Such multilayer FZPs with outermost zone widths of 10 and 35 nm and aspect ratios of up to 243 were tested for their focusing properties at 8 keV and shown to focus hard X-rays efficiently. This success was enabled by the outstanding layer quality thanks to ALD. Via the use of FIB for slicing the multilayer structures, desired aspect ratios could be obtained by precisely controlling the thickness. Experimental diffraction efficiencies of multilayer FZPs fabricated via this combination reached up to 15.58% at 8 keV. In addition, scanning transmission X-ray microscopy experiments at 1.5 keV were carried out using one of the multilayer FZPs and resolved a 60 nm feature size. Finally, the prospective of different material combinations with various outermost zone widths at 8 and 17 keV is discussed in the light of the coupled wave theory and the thin-grating approximation. Al2O3/Ir is outlined as a promising future material candidate for extremely high resolution with a theoretical efficiency of more than 20% for as small an outermost zone width as 10 nm at 17 keV.
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Diagnosis and management for urosepsis.
Int. J. Urol.
PUBLISHED: 03-02-2013
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Urosepsis is defined as sepsis caused by a urogenital tract infection. Urosepsis in adults comprises approximately 25% of all sepsis cases, and is in most cases due to complicated urinary tract infections. The urinary tract is the infection site of severe sepsis or septic shock in approximately 10-30% of cases. Severe sepsis and septic shock is a critical situation, with a reported mortality rate nowadays still ranging from 30% to 40%. Urosepsis is mainly a result of obstructed uropathy of the upper urinary tract, with ureterolithiasis being the most common cause. The complex pathogenesis of sepsis is initiated when pathogen or damage-associated molecular patterns recognized by pattern recognition receptors of the host innate immune system generate pro-inflammatory cytokines. A transition from the innate to the adaptive immune system follows until a T(H2) anti-inflammatory response takes over, leading to immunosuppression. Treatment of urosepsis comprises four major aspects: (i) early diagnosis; (ii) early goal-directed therapy including optimal pharmacodynamic exposure to antimicrobials both in the plasma and in the urinary tract; (iii) identification and control of the complicating factor in the urinary tract; and (iv) specific sepsis therapy. Early adequate tissue oxygenation, adequate initial antibiotic therapy, and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with urosepsis, which includes early imaging, and an optimal interdisciplinary approach encompassing emergency unit, urological and intensive-care medicine specialists.
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Pretransplant model for end stage liver disease score predicts posttransplant incidence of fungal infections after liver transplantation.
Mycoses
PUBLISHED: 01-24-2013
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Liver transplant recipients are at a significant risk for invasive fungal infections (IFI). This retrospective study evaluated the impact of the pretransplant model for end stage liver disease (MELD) on the incidence of posttransplant IFI in a single centre. From 2004 to 2008, 385 liver transplantations were included, from which 210 transplantations were conducted allocated by Child Turcotte Pugh and 175 were allocated by MELD score. Both groups differed regarding the age of transplant recipients (50.1?±?10.7 vs. 52.5?±?9.9, P?=?0.036), pretransplant MELD score (16.43?±?8.33 vs. 18.29?±?9.05), rate of re-transplantations, duration of surgery, demand in blood transfusions and rates of renal impairments. In the MELD era, higher incidences of IFI (pre-MELD 11.9%, MELD 24.0%, P?
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Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages.
FASEB J.
PUBLISHED: 10-31-2011
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Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization-deficient GR (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-? is normally regulated in these mice, but down-regulation of IL-6 and IL-1? is diminished. LPS-treated macrophages derived from GR(dim) mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL-1 receptor antagonist improved survival of GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1? in macrophages by GCs is pivotal to control sepsis.
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High contrast magnetic and nonmagnetic sample current microscopy for bulk and transparent samples using soft X-rays.
Microsc. Microanal.
PUBLISHED: 08-25-2011
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The soft X-ray energy range provides important detection capabilities for a wide range of material systems, e.g., the K-edge behavior of biological materials or magnetic contrast imaging at the L2,3- and M4,5-edges, respectively, using the X-ray magnetic circular dichroism effect. The need for thinned samples due to the short penetration depth of soft X-rays is a limiting factor for microscopic imaging in transmission microscopy. In contrast, the more surface sensitive photoelectron emission microscopy allows the X-ray microscopic investigation of nontransparent bulk samples, but only small magnetic fields and very smooth surfaces are possible. As both high magnetic fields as well as bulk samples are important for magnetic imaging, we present total electron yield (TEY) microscopy results using the total sample current detection performed at the new ultra high vacuum scanning microscope "MAXYMUS" at HZB/BESSY II. We compare synchronous measurements in TEY and transmission mode to demonstrate the capabilities of TEY microscopy. Pictures and spectra with high absorption contrast and three-dimensional-like edge enhancement are observed as known for scanning electron microscopy. This unveils details on smallest length scales of the surface morphology. Furthermore, surface sensitive in- and out-of-plane magnetic TEY measurements at nontransparent samples are shown.
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Noninvasive indocyanine green plasma disappearance rate predicts early complications, graft failure or death after liver transplantation.
HBPD INT
PUBLISHED: 08-05-2011
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Early detection of graft malfunction or postoperative complications is essential to save patients and organs after orthotopic liver transplantation (OLT). Predictive tests for graft dysfunction are needed to enable earlier implementation of organ-saving interventions following transplantation. This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications, graft dysfunction, and patient survival following OLT.
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Viral infections in septic shock (VISS-trial)-crosslinks between inflammation and immunosuppression.
J. Surg. Res.
PUBLISHED: 08-03-2011
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Recent investigations provided evidence that herpes simplex virus (HSV-1) and cytomegalovirus (CMV) are reactivated in critically ill individuals. However, at this time, it remains unclear whether these viral infections are of real pathogenetic relevance or represent innocent bystanders.
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Hemodynamic actions of corticotropin-releasing hormone and proopiomelanocortin derivatives in septic patients.
J. Cardiovasc. Pharmacol.
PUBLISHED: 06-02-2011
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Proopiomelanocortin (POMC) derivatives and mRNA of POMC have been detected in cardiomyocytes and vascular smooth muscle cells. Increased plasma levels of POMC derivatives have been found in septic patients during cardiovascular deregulation; therefore, we evaluated whether corticotroph-type (ACTH, ?-endorphin, ?-lipotropin) or melanotroph-type (?-melanocyte-stimulating hormone and N-acetyl-?-END) POMC derivatives have influences on patients hemodynamics during sepsis. Seventeen septic patients were monitored by pulmonary artery catheter and corticotropin-releasing hormone (CRH) tests were performed by intravenous administration of 100 ?g CRH. Before, 15, 30, 45, and 60 minutes after CRH administration, hemodynamic variables were measured, and plasma concentrations of POMC derivatives were determined. After CRH administration, heart rate, cardiac index, and stroke index increased, and the systemic vascular resistance index decreased; moreover, a correlation between ACTH concentration and stroke index as well as an inverse correlation between (?-melanocyte-stimulating hormone concentration and systemic vascular resistance index was observed. CRH and ACTH may have opposite effects on the blood pressure (mean arterial pressure). Immediately after CRH injection mean arterial pressure decreased. ACTH (in contrast to ?-endorphin or ?-lipotropin), released into the cardiovascular compartment 15 minutes after CRH injection, might have raised mean arterial pressure as compatible with the correlation between ACTH levels and stroke index. (?-melanocyte-stimulating hormone appears to have a vasodilative effect during sepsis.
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[How much insulin does the critical ill need?].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 04-11-2011
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Metabolism and nutrition of the critical ill are dynamic parameters of the severe disease influencing the blood glucose concentration. After the finding of increased survival in an initial study in tight glucose control, further large multicenter trials could not show such a benefit and even an increased mortality has been found. Hyperglycemia may be a feature of the stress metabolism and is possibly an adaptive process. Next to the endogenous response, therapy with catecholamines and glucosteroids impacts the response to insulin and the glucose metabolism. Hypo- and hypercaloric nutrition also interact with the insulin therapy. Nutritional therapy should be adapted to the actual state of the patient avoiding hypercaloric feeding and an energy deficit. Using this framework, therapy with insulin may be used to achieve a targeted range of glucose avoiding an increased risk of hypoglycaemia.
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The use of high-dose melatonin in liver resection is safe: first clinical experience.
J. Pineal Res.
PUBLISHED: 03-29-2011
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Experimental data suggest that melatonin decreases inflammatory changes after major liver resection, thus positively influencing the postoperative course. To assess the safety of a preoperative single dose of melatonin in patients undergoing major liver resection, a randomized controlled double-blind pilot clinical trial with two parallel study arms was designed at the Department of General and Transplantation Surgery, Ruprecht-Karls-University, Heidelberg. A total of 307 patients, who were referred for liver surgery, were screened. One hundred and thirteen patients, for whom a major liver resection (?3 segments) was scheduled, were eligible. Sixty-three eligible patients refused to participate, and therefore, 50 patients were randomized. A preoperative single dose of melatonin (50?mg/kg BW) dissolved in 250?mL of milk was administered through the gastric tube after the intubation for general anesthesia. Controls were given the same amount of microcrystalline cellulose. Primary endpoint was safety. Secondary endpoints were postoperative complications. Melatonin was effectively absorbed with serum concentrations of 1142.8?±?7.2?ng/mL (mean?±?S.E.M.) versus 0.3?±?7.8?ng/mL in controls (P?
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Infrahepatic inferior vena cava clamping for reduction of central venous pressure and blood loss during hepatic resection: a randomized controlled trial.
Ann. Surg.
PUBLISHED: 03-18-2011
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To evaluate the effectiveness and safety of infrahepatic inferior vena cava (IVC) clamping for reduction of central venous pressure (CVP) and blood loss during hepatic resection.
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Magnetic vortex core reversal by excitation of spin waves.
Nat Commun
PUBLISHED: 03-16-2011
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Micron-sized magnetic platelets in the flux-closed vortex state are characterized by an in-plane curling magnetization and a nanometer-sized perpendicularly magnetized vortex core. Having the simplest non-trivial configuration, these objects are of general interest to micromagnetics and may offer new routes for spintronics applications. Essential progress in the understanding of nonlinear vortex dynamics was achieved when low-field core toggling by excitation of the gyrotropic eigenmode at sub-GHz frequencies was established. At frequencies more than an order of magnitude higher vortex state structures possess spin wave eigenmodes arising from the magneto-static interaction. Here we demonstrate experimentally that the unidirectional vortex core reversal process also occurs when such azimuthal modes are excited. These results are confirmed by micromagnetic simulations, which clearly show the selection rules for this novel reversal mechanism. Our analysis reveals that for spin-wave excitation the concept of a critical velocity as the switching condition has to be modified.
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Posaconazole as part of the antifungal armamentarium in the intensive care unit--case reports from a surgical ICU.
Mycoses
PUBLISHED: 03-02-2011
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The authors describe two cases of successful and safe posaconazole use in patients of a surgical intensive care unit of a university hospital.
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[The neuroendocrine axis and the pathophysiology of sepsis].
Anasthesiol Intensivmed Notfallmed Schmerzther
PUBLISHED: 09-13-2010
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The immune system and the central nervous system are able to affect each other. Proinflammatory cytokines induce the expression of CRH or AVP in the hypothalamus and ACTH in the pituitary gland. Thus, enhanced adrenal release of cortisol suppresses the activation of NF-?B and activates antiinflammatory cytokines. The cholinergic antiinflammatory pathway, the efferent arm of the inflammatory reflex, is another mechanism of the CNS to control inflammation. It consists of the efferent vagus nerve, the neurotransmitter actylcholine and the ?7 subunit of the nicotinic acteylcholine receptor. Probably, the transmission of information takes place to postsynaptic sympathetic fibres in the celiac plexus which terminate in the spleen and act on splenic immune cells. Cholinesterase inhibitors have antiinflammatory effects in experimental sepsis when administered early.
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Mitochondrial complex II participates in normoxic and hypoxic regulation of ?-keto acids in the murine heart.
J. Mol. Cell. Cardiol.
PUBLISHED: 09-09-2010
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?-Keto acids (?-KAs) are not just metabolic intermediates but are also powerful modulators of different cellular pathways. Here, we tested the hypothesis that ?-KA concentrations are regulated by complex II (succinate dehydrogenase=SDH), which represents an intersection between the mitochondrial respiratory chain for which an important function in cardiopulmonary oxygen sensing has been demonstrated, and the Krebs cycle, a central element of ?-KA metabolism. SDH subunit D heterozygous (SDHD(+/-)) and wild-type (WT) mice were housed at normoxia or hypoxia (10% O(2)) for 4 days or 3 weeks, and right ventricular pressure, right ventricle/(left ventricle+septum) ratio, cardiomyocyte ultrastructure, pulmonary vascular remodelling, ventricular complex II subunit expression, SDH activity and ?-KA concentrations were analysed. In both strains, hypoxia induced increases in right ventricular pressure and enhanced muscularization of distal pulmonary arteries. Right ventricular hypertrophy was less severe in SDHD(+/-) mice although the cardiomyocyte ultrastructure and mitochondrial morphometric parameters were unchanged. Protein amounts of SDHA, SDHB and SDHC, and SDH activity were distinctly reduced in SDHD(+/-) mice. In normoxic SDHD(+/-) mice, ?-ketoisocaproate concentration was lowered to 50% as compared to WT animals. Right/left ventricular concentration differences and the hypoxia-induced decline in individual ?-KAs were less pronounced in SDHD(+/-) animals indicating that mitochondrial complex II participates in the adjustment of cardiac ?-KA concentrations both under normoxic and hypoxic conditions. These characteristics are not related to the hemodynamic consequences of hypoxia-induced pulmonary vascular remodelling, since its extent and right ventricular pressure were not affected in SDHD(+/-) mice albeit right ventricular hypertrophy was attenuated.
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Patients suffering due to complicated peritonitis may not benefit from splenectomy: clinical data from a retrospective study.
J. Surg. Res.
PUBLISHED: 07-03-2010
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In this retrospective observational study, we investigated the impact of prior splenectomy on the outcome of patients with complicated peritonitis.
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Sepsis-induced degradation of endothelial glycocalix.
ScientificWorldJournal
PUBLISHED: 05-25-2010
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Sepsis, a general inflammatory response to microbiological infection, is still a major cause of high mortality rates in intensive care units. This mortality rate strongly correlates with sepsis-induced impairment of organ blood supply as a consequence of disturbed capillary circulation and vascular leakage. Within this pathophysiological process, endothelial cell function plays a key role. Recent studies provide evidence that degradation of the glycocalix on the luminal cell membrane is an early step in septic vascular endothelial cell disorder and its shed compounds, such syndecan-1, heparan sulfate, intercellular-adhesion-molecule-1 (ICAM-1), and vascular-cell-adhesion-molecule-1 (VCAM-1), can be quantified in the plasma. The plasma concentrations of heparan sulfate and syndecan-1 strongly correlate with severity of sepsis and with inflammatory markers such as interleukin-6 (IL-6). Furthermore, a nonspecific deterioration of the glycocalix occurs during major abdominal surgery and during ischemia/reperfusion after vascular surgery. Both surgical treatments cause vascular leakage and, consequently, tissue edema, similar to that triggered by inflammatory impairment of the endothelial cell barrier. So far, no specific therapeutic strategies exist to maintain glycocalix integrity; hence, conserving endothelial function. Detection of glycocalix compounds in the plasma can be utilized as diagnostic markers to evaluate sepsis-induced endothelial damage and to estimate severity of sepsis. In the future, efforts will be made to prevent glycocalix damage during sepsis or major surgery. As a result, this will possibly preserve organ function and improve patient outcome.
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Effects of physostigmine on microcirculatory alterations during experimental endotoxemia.
Shock
PUBLISHED: 04-22-2010
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Microcirculatory dysfunction plays a pivotal role in the clinical development and manifestation of severe sepsis and as a marker for mortality. During this process, endothelial damage is characterized by structural and functional alterations that contribute to a great extent to tissue edema. Recent findings revealed the vagus nerve as an important transmitter of the cholinergic anti-inflammatory pathway. By inhibition of the cholinesterase, physostigmine increases acetylcholine and induces the cholinergic anti-inflammatory pathway. The aim of this study was to determine the effects of physostigmine on microcirculatory alterations during experimental endotoxemia. In male Wistar rats, venular wall shear rate, macromolecular efflux, and leukocyte-endothelial interaction were determined in mesenteric postcapillary venules using intravital microscopy at time 0, 60, and 120 min after beginning the experiment. The trials were divided into 2 parts. In part 1, we investigated the effects of physostigmine in a pretreatment setting where the animals in the treatment group obtained physostigmine (70 microg/kg) 15 min before starting endotoxemia (LPS, 2 mg/kg per hour). Part 2 of the experiment was a posttreatment setting, in which the effects of the application of physostigmine (70 microg/kg) 30 min after inducing endotoxemia were explored. In our study, we showed that macromolecular efflux and leukocyte-endothelial interaction were significantly reduced during endotoxinemia in the pretreatment and posttreatment settings with physostigmine. On the other hand, venular wall shear rate showed no differences. In summary, by inducing the cholinergic anti-inflammatory pathway, physostigmine reduced the capillary leakage and the leukocyte-endothelial interaction. The treatment with physostigmine in endotoxemia may be of interest for clinical use, and further studies should be performed.
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New insights into paracrine mechanisms of human cardiac progenitor cells.
Eur. J. Heart Fail.
PUBLISHED: 04-20-2010
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Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration in vivo. Understanding the function of CPCs is essential for further implementation of these cells in the treatment of cardiac diseases. The present study tested the hypothesis that adult CPC exert paracrine effects that lead to an improvement in the functional characteristics of cardiomyocytes. This study also investigated whether aging (we included patients aged between 4 months and 81 years) has any effect on the paracrine mechanisms of CPC.
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Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: a prospective trial.
Resuscitation
PUBLISHED: 04-11-2010
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Focused ultrasound is increasingly used in the emergency setting, with an ALS-compliant focused echocardiography algorithm proposed as an adjunct in peri-resuscitation care (FEEL). The purpose of this study was to evaluate the feasibility of FEEL in pre-hospital resuscitation, the incidence of potentially treatable conditions detected, and the influence on patient management.
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Macrophage migration inhibitory factor (MIF) and manganese superoxide dismutase (MnSOD) as early predictors for survival in patients with severe sepsis or septic shock.
J. Surg. Res.
PUBLISHED: 03-22-2010
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Severe sepsis, septic shock, and resulting organ failure appear as the most common cause of death in intensive care medicine. Inflammatory mediators (interleukin-6/IL-6), cell adhesion molecules (intercellular adhesion molecule-1/ICAM-1, vascular cell adhesion molecule-1/VCAM-1), and redox active substances (manganese superoxide dismutase/MnSOD, macrophage migration inhibitory factor/MIF) must be considered to be central hubs in the inflammatory process. However, their exact pathophysiologic function and prognostic value are still poorly understood.
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Redox responses in patients with sepsis: high correlation of thioredoxin-1 and macrophage migration inhibitory factor plasma levels.
Mediators Inflamm.
PUBLISHED: 02-22-2010
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Background. Redox active substances (e.g., Thioredoxin-1, Macrophage Migration Inhibitory Factor) seem to be central hubs in the septic inflammatory process. Materials and Methods. Blood samples from patients with severe sepsis or septic shock (n = 15) were collected at the time of sepsis diagnosis (t0), and 24 (t24) and 48 (t48) hours later; samples from healthy volunteers (n = 18) were collected once; samples from postoperative patients (n = 28) were taken one time immediately after surgery. In all patients, we measured plasma levels of IL-6, TRX1 and MIF. Results. The plasma levels of MIF and TRX1 were significantly elevated in patients with severe sepsis or septic shock. Furthermore, TRX1 and MIF plasma levels showed a strong correlation (t0: r(sp) = 0.720, ? = 0.698/t24: r(sp) = 0.771, ? = 0.949). Conclusions. Proinflammatory/~oxidative and anti-inflammatory/~oxidative agents show a high correlation in order to maintain a redox homeostasis and to avoid the harmful effects of an excessive inflammatory/oxidative response.
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Analgesia and sedation for painful interventions in children and adolescents.
Dtsch Arztebl Int
PUBLISHED: 01-12-2010
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Painful procedures on children and adolescents often have to be performed with the aid of analgesia and sedation in order to prevent pain and emotional distress. Moreover, many procedures can be performed more rapidly and more effectively in a relaxed patient. Because the combination of analgesia and sedation can cause serious or even life-threatening complications, it must be accompanied by the same safety precautions as a general anesthetic.
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IVC CLAMP: infrahepatic inferior vena cava clamping during hepatectomy--a randomised controlled trial in an interdisciplinary setting.
Trials
PUBLISHED: 10-13-2009
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Intraoperative haemorrhage is a known predictor for perioperative outcome of patients undergoing hepatic resection. While anaesthesiological lowering of central venous pressure (CVP) by fluid restriction is known to reduce bleeding during transection of the hepatic parenchyma its potential side effects remain poorly investigated. In theory it may have negative effects on kidney function and tissue perfusion and bears the risk to result in severe haemodynamic instability in case of profound intraoperative blood loss. The present randomised controlled trial evaluates efficacy and safety of infrahepatic inferior vena cava (IVC) clamping as an alternative surgical technique to reduce CVP during hepatic resection.
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A new pediatric liver transplantation program in Southern Germany. The Heidelberg experience.
Pediatr Transplant
PUBLISHED: 09-28-2009
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pLTx is a highly complex procedure. It can only be performed safely by experienced teams. Starting a new pLTx program in a country with established centers must therefore avoid a learning curve. We have initiated a liver transplantation program for children in 2003. Medical standards were defined by a team of surgeons, pediatricians, radiologists, anesthesiologists, and pathologists before the first transplantation. An external expert in the field of pLTx supervised the whole process. In a pilot phase, six children weighing more than 20 kg were successfully transplanted. Following this series, the clinical pathways were re-evaluated, and the program was opened for children of all age groups. Between 2003 and 2008, 32 children received 34 organs. Sixty-eight percent of patients received a split-liver, 26% a full size organ, and 6% a reduced size graft. Four LRLTx were performed. Patient survival rate was 91%. We conclude that a new pLTx program can be established without a significant learning curve regarding mortality if a strict strategy of team-building is followed. In the pilot phase, small children and infants have to be referred and transplanted in an established center. An interdisciplinary team of specialists closely working together is the key for sustained success.
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Tissue penetration of moxifloxacin into human gallbladder wall in patients with biliary tract infections.
J. Antimicrob. Chemother.
PUBLISHED: 09-04-2009
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Moxifloxacin, the newest fourth-generation fluoroquinolone, has a broad spectrum of antibacterial activity covering both Gram-positive and Gram-negative aerobic and anaerobic bacteria and is therefore very well suited for the treatment of biliary tract infections. The present study aimed to determine the penetration of moxifloxacin into gallbladder tissue to evaluate its antibiotic potential in this indication.
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Pharmacokinetics of linezolid in septic patients with and without extended dialysis.
Eur. J. Clin. Pharmacol.
PUBLISHED: 08-18-2009
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Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively.
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Thioredoxin in human and experimental sepsis.
Crit. Care Med.
PUBLISHED: 06-03-2009
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Thioredoxin (TRX) is assumed to be beneficial in acute inflammatory diseases because of its potent antioxidant properties and an inhibitory effect on neutrophil evasion into sites of inflammation.
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Midline versus transverse incision in major abdominal surgery: a randomized, double-blind equivalence trial (POVATI: ISRCTN60734227).
Ann. Surg.
PUBLISHED: 05-29-2009
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There are 2 main types of access for patients requiring major open, elective abdominal surgery: the midline or the transverse approach. The aim of this study is to compare both approaches by focusing on postoperative pain, complications, and frequency of incisional hernias.
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Lipid peroxidation in acute respiratory distress syndrome and liver failure.
J. Surg. Res.
PUBLISHED: 05-22-2009
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Lipid peroxidation processes (LPO) are evident in many organ failures. Due to their toxic properties, they are causative for cellular dysfunction at the site of their origin and far beyond. This study was conducted to investigate differences in LPO pattern of patients with established acute respiratory distress syndrome (ARDS) and patients with end-stage liver failure undergoing liver transplantation (LTX) as two mayor prototypes of organ failure.
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Is a 4 days transoesophageal training course sufficient to diagnose shock related pathologies?
Resuscitation
PUBLISHED: 04-30-2009
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Echocardiography is a useful tool in patients suffering from shock of unknown origin to evaluate cardiac function and volume status in order to decide on further treatment. The aim of the study was to evaluate how well participants could identify function, preload and regional wall motion abnormalities after attending a 4-day transoesophageal echocardiography (TOE) seminar.
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AGE-modified albumin containing infusion solutions boosts septicaemia and inflammation in experimental peritonitis.
J. Leukoc. Biol.
PUBLISHED: 04-28-2009
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HSA preparations for i.v. use are administered in critically ill patients. Although increasing intravascular osmotic pressure seems to be a pathophysiologically orientated treatment, clinical trials do not indicate a benefit for mortality in HSA-treated patients. Instead, there is evidence for inflammatory reactions upon infusion of different HSA batches. A neglected issue concerning the safety and quality of these therapeutics is processing-related post-transcriptional protein modifications, such as AGEs. We therefore tested the hypothesis that commercially available infusion solutions contain AGEs and studied whether these protein modifications influence outcome and inflammation in a murine model of sepsis induced by CLP. Screening of different HSA and Ig preparations in this study revealed an up to approximate tenfold difference in the amount of AGE modifications. Application of clinically relevant concentrations of CML-modified HSA in CLP led to increased inflammation and enhanced mortality in wild-type mice but not in mice lacking the RAGE. Lethality was paralleled by increased activation of the proinflammatory transcription factor NF-kappaB, NF-kappaB-dependent gene expression, and infiltration of inflammatory cells in the peritoneal cavity. This study implies that infusion solutions containing a high load of the AGE-modified protein have the potential to activate RAGE/NF-kappaB-mediated inflammatory reactions, causing increased mortality in experimental peritonitis.
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Left ventricular end-diastolic area is a measure of cardiac preload in patients with early septic shock.
Eur J Anaesthesiol
PUBLISHED: 04-25-2009
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Central venous pressure, intrathoracic blood volume, and left ventricular end-diastolic area are reliable measures of cardiac preload under stable clinical conditions. The purpose of this study was to compare different preload parameters over 24 h under conditions of multiple, frequently changing treatments in early septic shock.
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Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction.
Crit Care
PUBLISHED: 03-26-2009
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Severe sepsis, septic shock, and resulting organ failure represent the most common cause of death in intensive care medicine, with mortality ranging from 40% to 70%. It is still unclear whether necrosis or apoptosis plays the predominant role in severe sepsis. Determining the prevalent mode of cell death would be valuable, as new therapeutic agents (eg, antiapoptotic drugs such as caspase inhibitors) may improve unsatisfactory outcomes in patients with severe sepsis. Furthermore, the prognostic value of newly developed cell death serum biomarkers is of great interest.
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Soluble TREM-1 is not suitable for distinguishing between systemic inflammatory response syndrome and sepsis survivors and nonsurvivors in the early stage of acute inflammation.
Eur J Anaesthesiol
PUBLISHED: 03-25-2009
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To evaluate plasma levels of soluble TREM-1 (sTREM-1) in patients with systemic inflammatory response syndrome (SIRS), severe sepsis, and septic shock and to determine whether plasma sTREM-1 could be used as a diagnostic and prognostic marker in sepsis in the surgical ICU.
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Vortex core switching by coherent excitation with single in-plane magnetic field pulses.
Phys. Rev. Lett.
PUBLISHED: 02-17-2009
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The response of magnetic vortex cores to subnanosecond in-plane magnetic field pulses was studied by time-resolved x-ray microscopy. Vortex core reversal was observed and the switching events were located in space and time. This revealed a mechanism of coherent excitation by the leading and trailing edges of the pulse, lowering the field amplitude required for switching. The mechanism was confirmed by micromagnetic simulations and can be understood in terms of gyration around the vortex equilibrium positions, displaced by the applied field.
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Is veno-venous bypass still needed during liver transplantation? A review of the literature.
Clin Transplant
PUBLISHED: 02-10-2009
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Orthotopic liver transplantation has been made feasible with intra-operative femoral-to-jugular veno-venous bypass (VVB) to redirect the blood from the lower extremities and the kidneys to the heart. This reduces hemodynamic instability and metabolic disturbances. However, complications such as thromboses with pulmonary thrombembolism or post-reperfusion syndrome were observed in up to 30% of the cases. The latter, recent developments of cava-sparing surgical techniques, shorter anhepatic times plus optimized anesthetic management have made the necessity for a routine use of VVB questionable.
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Lipopolysaccharide-induced activation of coagulation in neonatal cord and adult blood monitored by thrombelastography.
Thromb. Res.
PUBLISHED: 02-09-2009
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Although precisely balanced hemostasis in newborns is rapidly changing during early development. During gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and hemostasis. In the present study we compared LPS-induced activation of coagulation in cord blood (CB) samples of healthy newborns to whole blood (WB) samples from healthy adult volunteers.
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Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalix.
J. Surg. Res.
PUBLISHED: 02-08-2009
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Recent evidence suggests that the endothelial glycocalix plays an important role in lethal outcomes following sepsis. We therefore tested if the endothelial glycocalix is shed in patients with sepsis compared with patients after major abdominal surgery and healthy volunteers.
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Implementation of practice guidelines for antifungal therapy in a surgical intensive care unit and its impact on use and costs.
Chemotherapy
PUBLISHED: 02-05-2009
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Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital.
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Central sympatholytics prolong survival in experimental sepsis.
Crit Care
PUBLISHED: 01-15-2009
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One of the main causes of death in European and US intensive care units is sepsis. It involves a network of pro-inflammatory cytokines such as TNF-alpha, IL-1beta and IL-6. Furthermore, there is an up regulation of transcription factors such as nuclear factor (NF) kappaB. It has previously been shown that clonidine is able to significantly reduce pro-inflammatory cytokines in surgical patients. We therefore hypothesise that the clinically used central alpha-2 agonist clonidine has the ability to improve survival in experimental sepsis by inhibiting the sympathetic tone and consequently inhibiting the pro-inflammatory cytokine release.
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Accurate dosimetry in scanning transmission X-ray microscopes via the cross-linking threshold dose of poly(methyl methacrylate).
J Synchrotron Radiat
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The sensitivity of various polymers to radiation damage by soft X-rays has been measured previously with scanning transmission X-ray microscopes. However, the critical dose values reported by different groups for the same material differ by more than 100%. Possible sources of this variability are investigated here for poly(methyl methacrylate) (PMMA) using controlled exposure to monochromatic soft X-rays at 300 eV. Radiation sensitivity, judged by several different criteria, was evaluated as a function of dose rate, pre-exposure thermal treatments and X-ray polarization. Both the measured critical dose and the dose required to initiate negative mode (cross-linking) were observed to depend only on dose, not the other factors explored. A method of determining detector efficiency from the dose required to initiate negative mode in PMMA is outlined. This method was applied to many of the soft X-ray STXMs presently operating to derive the efficiencies of their transmitted X-ray detectors in the C 1s absorption-edge region.
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Biogenic potassium salt particles as seeds for secondary organic aerosol in the Amazon.
Science
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The fine particles serving as cloud condensation nuclei in pristine Amazonian rainforest air consist mostly of secondary organic aerosol. Their origin is enigmatic, however, because new particle formation in the atmosphere is not observed. Here, we show that the growth of organic aerosol particles can be initiated by potassium-salt-rich particles emitted by biota in the rainforest. These particles act as seeds for the condensation of low- or semi-volatile organic compounds from the atmospheric gas phase or multiphase oxidation of isoprene and terpenes. Our findings suggest that the primary emission of biogenic salt particles directly influences the number concentration of cloud condensation nuclei and affects the microphysics of cloud formation and precipitation over the rainforest.
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Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study.
Eur. Heart J.
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Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study".
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Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury - a randomized interventional trial: the REnal Replacement Therapy Study in Intensive Care Unit PatiEnts.
Crit Care
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ABSTRACT: INTRODUCTION: Acute kidney injury (AKI) is associated with a high mortality of up to 60%. The mode of renal replacement therapy (intermittent versus continuous) has no impact on patient survival. Sustained low efficiency dialysis using a single-pass batch dialysis system (SLED-BD) has recently been introduced for the treatment of dialysis-dependent AKI. To date, however, only limited evidence is available in the comparison of SLED-BD versus continuous veno-venous hemofiltration (CVVH) in intensive care unit (ICU) patients with AKI. METHODS: Prospective, randomized, interventional, clinical study at a surgical intensive care unit of a university hospital. Between 1 April 2006 and 31 January 2009, 232 AKI patients who underwent renal replacement therapy (RRT) were randomized in the study. Follow-up was assessed until 30 August 2009. Patients were either assigned to 12-h SLED-BD or to 24-h predilutional CVVH. Both therapies were performed at a blood flow of 100 to 120 ml/min. RESULTS: 115 patients were treated with SLED-BD (total number of treatments n = 817) and 117 patients with CVVH (total number of treatments n = 877).The primary outcome measure, 90-day mortality, was similar between groups (SLED: 49.6% vs. CVVH: 55.6%, P = 0.43). Hemodynamic stability did not differ between SLED-BD and CVVH, whereas patients in the SLED-BD group had significantly fewer days of mechanical ventilation (17.7 ± 19.4 vs. 20.9 ± 19.8, P = 0.047) and fewer days in the ICU (19.6 ± 20.1 vs. 23.7 ± 21.9, P = 0.04). Patients treated with SLED needed fewer blood transfusions (1,375 ± 2,573 ml vs. 1,976 ± 3,316 ml, P = 0.02) and had a substantial reduction in nursing time spent for renal replacement therapy (P < 0.001) resulting in lower costs. CONCLUSIONS: SLED-BD was associated with reduced nursing time and lower costs compared to CVVH at similar outcomes. In the light of limited health care resources, SLED-BD offers an attractive alternative for the treatment of AKI in ICU patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00322530.
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Cell death biomarkers as early predictors for hepatic dysfunction in patients after orthotopic liver transplantation.
Transplantation
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Valid prognostic factors for early identification of a complicated course after orthotopic liver transplantation from deceased donors are rare. The aim of this study was to investigate the prognostic value of different cell death biomarkers and inflammatory markers in patients after orthotopic liver transplantation from deceased donors.
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L-arginine and asymmetric dimethylarginine are early predictors for survival in septic patients with acute liver failure.
Mediators Inflamm.
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Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24?h, 4?d, 7?d, 14?d and 28?d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24?h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.
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Plasma concentrations of posaconazole administered via nasogastric tube in patients in a surgical intensive care unit.
Antimicrob. Agents Chemother.
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Abdominal surgery may affect intestinal absorption and the resulting levels of posaconazole in the blood. We measured plasma posaconazole levels in surgical intensive care unit (SICU) patients and tried to develop a predictive population pharmacokinetics model. A total of 270 samples from 15 patients receiving posaconazole via nasogastric tube were measured by high-performance liquid chromatography (HPLC). SICU patients showed lower plasma drug concentrations, a higher apparent clearance, and a higher volume of distribution than those in hematology patients, possibly due to poor absorption.
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Inhibition of LPS-Induced Activation of Coagulation by p38 MAPK Inhibitor.
ISRN Hematol
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During Gram-negative sepsis, lipopolysaccharide (LPS) activates toll-like receptor (TLR) 4 and induces complex responses of immune system and coagulation. However, the underlying LPS signalling mechanism on coagulation activation remains complex. To determine the role of the intracellular signalling factors p38 mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-?B), and c-Jun N-terminal kinase (JNK) in the procoagulant response to LPS, coagulation process of human whole blood exposed to specific inhibitors was measured by thrombelastography. Samples were stimulated with LPS (100??g/mL) after preincubation with BAY117082 (specific NF-?B inhibitor), SP600125 (specific JNK inhibitor), SB203580 (specific p38 MAPK inhibitor), or vehicle. SB203580 strongly inhibited LPS-induced coagulation activation, whereas BAY117082 and SP600125 showed no significant effect. Activation of p38 MAPK, NF-?B, and JNK and respective inhibitory effects were confirmed by Multi-Target Sandwich ELISA. In conclusion, activation of p38 MAPK is crucial for early LPS-induced activation of coagulation.
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Predictors of survival in sepsis: what is the best inflammatory marker to measure?
Curr. Opin. Infect. Dis.
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Sepsis is relevant due to its high morbidity and mortality. For both sepsis diagnosis and outcome prediction many biomarkers have been described in the literature. Most of these markers are objects of scientific interest rather than being introduced into daily clinical practice. However, due to their unspecific character and their insufficient predictive value for the individual person, research focus is still on new aspects in sepsis-related biomarkers.
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