Plantar Vein Thrombosis due to Busy Night Duty on Intensive Care Unit

A 32-year-old woman with severe foot pain came to our emergency department after a busy night duty in hospital followed by an extended sleep period. Physical examination revealed a discrete swelling of the medial aspect of the right foot and a painful plantar arch during digital examination. Magnetic resonance imaging (MRI) with intravenous gadolinium showed filling efects in the lateral plantar vein. Doppler sonography displayed noncompressible structures in the plantar veins without flow signals, suggesting a plantar vein thrombosis. Therapy was initiated with low-molecular-weight heparin in combination with customized elastic bandages for the lower leg. Follow-up sonography 6 weeks later showed complete patency of the plantar veins. To our knowledge, we present the first case of isolated plantar vein thrombosis independent of trauma, surgery, or malignant disease, most probably caused by a busy night duty on the intensive care unit (ICU) followed by a prolonged sleeping period

Untersuchung der Plasmakonzentration von Diabetikern und Stoffwechselgesunden im Hinblick auf diabetogene Hormone unter besonderer Berücksichtigung von Resistin

Resistin ist ein kürzlich entdecktes Hormon, welches exklusiv im Fettgewebe synthetisiert wird. Die Synthese dieses Hormons ist supprimiert bei genetisch oder diätisch induzierter Adipositas im Tiermodell. Die Gabe von Resistin führt zu einer verschlechterten Glucosetoleranz und zu verminderter Insulinwirkung. Aufgrund dieser Erkenntnisse lag die Vermutung nahe, dass Resistin eine entscheidende Rolle in der Entwicklung eines Diabetes mellitus Typ 2 und Adipositas spielen könnte. Ein weiteres Hormon, Leptin, wird ebenfalls immer wieder in den Zusammenhang mit der Entstehung einer zunehmenden Insulinresistenz und Adipositas gebracht. Die vorliegende Arbeit versucht daher einen Beitrag zur Aufklärung dieser Zusammenhänge zu leisten. Aus diesem Grund wurde das Blutplasma von 76 stoffwechselgesunden Probanden, von 43 Typ 1 Diabetikern und von 75 Typ 2 Diabetikern im Hinblick auf die Konzentration von Resistin, Leptin, Blutzucker, Cholesterin und Triglyceride untersucht. Dabei wurde Resistin erstmals im Blutplasma gemessen. Stoffwechselgesunde Probanden hatten eine durchschnittliche Resistinplasmakonzentration von 38,8+/-7,9 ng/ml. Dabei zeigte sich keine Abhängigkeit zur Höhe des BMI. Die Resistinplasmakonzentration der Probanden mit Diabetes mellitus Typ 1 betrug durchschnittlich 39,4+/-7,2 ng/ml, die der Probanden mit Diabetes mellitus Typ 2 durchschnittlich 38,7ng+/-8,4 ng/ml. Damit ergaben sich weder zwischen den untersuchten Studiengruppen, noch zwischen den männlichen und weiblichen Probanden statistische signifikante Unterschiede bezüglich der Höhe der Resistinplasmakonzentration. Die Leptinplasmakonzentration betrug durchschnittlich 19,8+/-19,5 ng/ml in der Gruppe der stoffwechselgesunden Probanden. Für die Typ 2 Diabetiker konnte eine durchschnittliche Konzentration von 25,1+/-21,7 ng/ml und für die Typ 1 Diabetiker von 12,9+/-18,7 ng/ml ermittelt werden. Dabei war die Höhe der Leptinkonzentration unabhängig vom Vorhandensein eines Diabetes mellitus Typ 2 (p=0,11). Neben der starken Abhängigkeit zwischen Leptinplasmakonzentration und BMI zeigten sich außerdem noch geschlechtsspezifische Unterschiede. So lag die durchschnittliche Leptinplasmakonzentration der weiblichen Probandinnen statistisch signifikant höher als die der männlichen Probanden (p<0,01). Die gemessene Plasmakonzentration für Resistin und Leptin korrelieren nicht miteinander. Im Gegensatz zu den für Resistin gefundenen Ergebnissen zeigte sich für Leptin ein Zusammenhang zwischen der Höhe der Plasmakonzentration und dem Ausmaß der Adipositas. Die neu gewonnen Erkenntnisse über die Plasmakonzentrationen von Resistin und Leptin bei Diabetikern und Stoffwechselgesunden konnten den im Tiermodell gefundenen Zusammenhang zwischen Resistin und Diabetes mellitus, bzw. Insulinresistenz, nicht bestätigen. Weitere Studien sind nötig, um den Pathomechanismus des Diabetes mellitus besser zu verstehen und um somit möglicherweise neue therapeutischer Ansätze und Strategien zur Behandlung zu entwickel

Selection of reliable reference genes for quantitative real-time PCR in human T cells and neutrophils

<p>Abstract</p> <p>Background</p> <p>The choice of reliable reference genes is a prerequisite for valid results when analyzing gene expression with real-time quantitative PCR (qPCR). This method is frequently applied to study gene expression patterns in immune cells, yet a thorough validation of potential reference genes is still lacking for most leukocyte subtypes and most models of their in vitro stimulation. In the current study, we evaluated the expression stability of common reference genes in two widely used cell culture models-anti-CD3/CD28 activated T cells and lipopolysaccharide stimulated neutrophils-as well as in unselected untreated leukocytes.</p> <p>Results</p> <p>The mRNA expression of 17 (T cells), 7 (neutrophils) or 8 (unselected leukocytes) potential reference genes was quantified by reverse transcription qPCR, and a ranking of the preselected candidate genes according to their expression stability was calculated using the programs NormFinder, geNorm and BestKeeper. <it>IPO8</it>, <it>RPL13A</it>, <it>TBP </it>and <it>SDHA </it>were identified as suitable reference genes in T cells. <it>TBP</it>, <it>ACTB </it>and <it>SDHA </it>were stably expressed in neutrophils. <it>TBP </it>and <it>SDHA </it>were also the most stable genes in untreated total blood leukocytes. The critical impact of reference gene selection on the estimated target gene expression is demonstrated for <it>IL-2 </it>and <it>FIH </it>expression in T cells.</p> <p>Conclusions</p> <p>The study provides a shortlist of suitable reference genes for normalization of gene expression data in unstimulated and stimulated T cells, unstimulated and stimulated neutrophils and in unselected leukocytes.</p

Visceral embolus protection by catheters with balloon-inflatable tips during hybrid repair of thoracoabdominal aortic aneurysm

Thoracoabdominal aortic aneurysms (TAAA) are associated with high rupture rates and poor outcome in patients who do not have surgical repair. Endovascular and hybrid techniques have gained increasing acceptance for the treatment of TAAA in patients with multiple comorbidities and an increased anesthetic risk. One of the complications of endovascular repair in TAAA is procedurally related embolism to visceral vessels. Visceral embolism causes bowel ischemia and is a potentially lethal complication. This report illustrates the intermittent use of catheters with balloon-inflatable tips as visceral embolus protection systems. These catheters are easy to apply and demonstrated perfect prevention of visceral embolization. To date, 10 patients have undergone operations at our clinic using this protection system, and no embolic complications were observed at the visceral vessels. Therefore, catheters with balloon-inflatable tips for visceral embolous protection should be considered in patients undergoing a two-stage hybrid TAAA repair to avoid embolus-associated morbidity and mortality

Enhanced Transmission in Rolled-up Hyperlenses utilizing Fabry-Pe\'rot Resonances

We experimentally demonstrate that the transmission though rolled-up metal/semiconductor hyperlenses can be enhanced at desired frequencies utilizing Fabry-P\'erot resonances. By means of finite difference time domain simulations we prove that hyperlensing occurs at frequencies of high transmission.Comment: 3 pages, 3 figure

EuroScore and IL-6 predict the course in ICU after cardiac surgery.

BACKGROUND Despite modern advances in intensive care medicine and surgical techniques, mortality rates in cardiac surgical patients are still about 3%. Considerable efforts were made to predict morbidity and mortality after cardiac surgery. In this study, we analysed the predictive properties of EuroScore and IL-6 for mortality in ICU, prolonged postoperative mechanical ventilation, and prolonged stay in ICU. METHODS We enrolled 2972 patients undergoing cardiac surgery. The patients either underwent aortic valve surgery (AV), mitral valve surgery (MV), coronary artery bypass grafting (CABG), and combined operations of aortic valve and coronary artery bypass grafting (AV + CABG) or of mitral and tricuspid valve (MV + TV). Different laboratory and clinical parameters were analysed. RESULTS EuroScore as well as IL-6 were associated with increased mortality after cardiac surgery. Furthermore, a higher EuroScore and elevated levels of IL-6 were predictors for prolonged mechanical ventilation and a longer stay in ICU. Especially, highly significant elevated IL-6 levels and an increased EuroScore showed a strong association. Statistics suggested superiority when both parameters were combined in a single model. CONCLUSION Our results suggest that EuroScore and IL-6 are helpful in predicting the course in ICU after cardiac surgery, and therefore, the use of intensive care resources. Especially, the combination of highly elevated levels of IL-6 and EuroScore may prove to be excellent predictors for an unfortunate postoperative course in ICU

miR-124a and miR-155 enhance differentiation of regulatory T cells in patients with neuropathic pain

Background: Accumulating evidence indicates that neuropathic pain is a neuro-immune disorder with enhanced activation of the immune system. Recent data provided proof that neuropathic pain patients exhibit increased numbers of immunosuppressive regulatory T cells (Tregs), which may represent an endogenous attempt to limit inflammation and to reduce pain levels. We here investigate the molecular mechanisms underlying these alterations. Methods: Our experimental approach includes functional analyses of primary human T cells, 3'-UTR reporter assays, and expression analyses of neuropathic pain patients' samples. Results: We demonstrate that microRNAs (miRNAs) are involved in the differentiation of Tregs in neuropathic pain. We identify miR-124a and miR-155 as direct repressors of the histone deacetylase sirtuin1 (SIRT1) in primary human CD4+ cells. Targeting of SIRT1 by either specific siRNA or by these two miRNAs results in an increase of Foxp3 expression and, consecutively, of anti-inflammatory Tregs (siRNA: 1.7 +/- 0.4;miR-124a: 1.5 +/- 0.4;miR-155: 1.6 +/- 0.4;p < 0.01). As compared to healthy volunteers, neuropathic pain patients exhibited an increased expression of miR124a (2.5 +/- 0.7, p < 0.05) and miR-155 (1.3 +/- 0.3;p < 0.05) as well as a reduced expression of SIRT1 (0.5 +/- 0.2;p < 0.01). Moreover, the expression of these two miRNAs was inversely correlated with SIRT1 transcript levels. Conclusions: Our findings suggest that in neuropathic pain, enhanced targeting of SIRT1 by miR-124a and miR-155 induces a bias of CD4(+) T cell differentiation towards Tregs, thereby limiting pain-evoking inflammation. Deciphering miRNA-target interactions that influence inflammatory pathways in neuropathic pain may contribute to the discovery of new roads towards pain amelioration

miRIAD-integrating microRNA inter- and intragenic data

MicroRNAs (miRNAs) are a class of small (similar to 22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter-and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations

miRIAD-integrating microRNA inter- and intragenic data

MicroRNAs (miRNAs) are a class of small (similar to 22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter-and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations

Allele-Level KIR Genotyping of More Than a Million Samples: Workflow, Algorithm, and Observations

The killer-cell immunoglobulin-like receptor (KIR) genes regulate natural killer cell activity, influencing predisposition to immune mediated disease, and affecting hematopoietic stem cell transplantation (HSCT) outcome. Owing to the complexity of the KIR locus, with extensive gene copy number variation (CNV) and allelic diversity, high-resolution characterization of KIR has so far been applied only to relatively small cohorts. Here, we present a comprehensive high-throughput KIR genotyping approach based on next generation sequencing. Through PCR amplification of specific exons, our approach delivers both copy numbers of the individual genes and allelic information for every KIR gene. Ten-fold replicate analysis of a set of 190 samples revealed a precision of 99.9%. Genotyping of an independent set of 360 samples resulted in an accuracy of more than 99% taking into account consistent copy number prediction. We applied the workflow to genotype 1.8 million stem cell donor registry samples. We report on the observed KIR allele diversity and relative abundance of alleles based on a subset of more than 300,000 samples. Furthermore, we identified more than 2,000 previously unreported KIR variants repeatedly in independent samples, underscoring the large diversity of the KIR region that awaits discovery. This cost-efficient high-resolution KIR genotyping approach is now applied to samples of volunteers registering as potential donors for HSCT. This will facilitate the utilization of KIR as additional selection criterion to improve unrelated donor stem cell transplantation outcome. In addition, the approach may serve studies requiring high-resolution KIR genotyping, like population genetics and disease association studies