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Search Results: 1 - 10 of 2069 matches for " Henrik Thorlacius "
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Soluble CD40 ligand is not solely related to the presence and severity of sepsis
Michelle S Chew, Henrik Thorlacius
Critical Care , 2011, DOI: 10.1186/cc10316
Abstract: We believe that the functional role of soluble CD40L is complex, however, and not solely related to the presence of sepsis or its severity. This is indicated in the study by Lorente and colleagues, in which no associations were found between soluble levels of CD40L and Acute Physiology and Chronic Health Evaluation scores, Sequential Organ Failure Assessment scores, and TNFα and IL-10 levels [1], which is in agreement with previous findings [3,4]. Further, although the study was conducted in patients with sepsis, we suggest that soluble CD40L is a common denominator for patients with shock, rather than with sepsis per se. Thus, in a study of critically ill patients admitted to the intensive care unit with shock due to different aetiologies, we found no differences in the levels of soluble CD40L between septic and nonseptic shock patients [4]. The relevance of soluble CD40L as a potential therapeutic target for sepsis therefore remains to be explored.We suggest that targeting CD40L in order to ameliorate pathological inflammatory responses is not limited to septic patients but also includes nonseptic shock patients.Leonardo Lorente, María del Mar Martín, Nerea Varo and José Antonio PáramoWe read with interest the letter by Chew and Thorlacius discussing our recent manuscript showing that circulating levels of soluble CD40L were associated with mortality in sepsis [1].Chew and Thorlacius stated that the functional role of soluble CD40L is complex and not solely related to the presence of sepsis; they suggested that soluble CD40L is a common denominator for patients with shock, rather than with sepsis per se. Indeed, in a recent study these authors found higher soluble CD40L levels in patients with nonseptic shock and septic shock than in healthy controls, but the levels were no different between patients with nonseptic shock and patients with septic shock [4].We have reanalysed the data from our study, and we found higher serum soluble CD40L levels in patients with se
Use of Probiotics as Prophylaxis for Postoperative Infections
Bengt Jeppsson,Peter Mangell,Henrik Thorlacius
Nutrients , 2011, DOI: 10.3390/nu3050604
Abstract: Postoperative bacterial infections are common despite prophylactic administration of antibiotics. The wide-spread use of antibiotics in patients has contributed to the emergence of multiresistant bacteria. A restricted use of antibiotics must be followed in most clinical situations. In surgical patients there are several reasons for an altered microbial flora in the gut in combination with an altered barrier function leading to an enhanced inflammatory response to surgery. Several experimental and clinical studies have shown that probiotics (mainly lactobacilli) may reduce the number of potentially pathogenia bacteria (PPM) and restore a deranged barrier function. It is therefore of interest to test if these abilities of probiotics can be utilized in preoperative prophylaxis. These factors may be corrected by perioperative administration of probiotics in addition to antibiotics. Fourteen randomized clinical trials have been presented in which the effect of such regimens has been tested. It seems that in patients undergoing liver transplantation or elective surgery in the upper gastrointestinal tract prophylactic administration of different probiotic strains in combination with different fibers results in a three-fold reduction in postoperative infections. In parallel there seems to be a reduction in postoperative inflammation, although that has not been studied in a systematic way. The use of similar concepts in colorectal surgery has not been successful in reducing postoperative infections. Reasons for this difference are not obvious. It may be that higher doses of probiotics with longer duration are needed to influence microbiota in the lower gastrointestinal tract or that immune function in colorectal patients may not be as important as in transplantation or surgery in the upper gastrointestinal tract. The favorable results for the use of prophylactic probiotics in some settings warrant further controlled studies to elucidate potential mechanisms, impact on gut microbiota and influence on clinical management. The use of probiotics must be better delineated in relation to type of bacteria, dose and length of?administration.
Implementation of Endoscopic Submucosal Dissection for Early Colorectal Neoplasms in Sweden
Henrik Thorlacius,Noryia Uedo,Ervin Toth
Gastroenterology Research and Practice , 2013, DOI: 10.1155/2013/758202
Abstract: Objectives. Endoscopic submucosal dissection (ESD) is an effective method for en bloc removal of large colorectal tumors in Japan, but this technique is not yet widely established in western countries. The purpose here was to report the experience of implementing colorectal ESD in Sweden. Methods. Twenty-nine patients with primarily nonmalignant and early colorectal neoplasms considered to be too difficult to remove en bloc with EMR underwent ESD. Five cases of invasive cancer underwent ESD due to high comorbidity excluding surgical intervention or as an unexpected finding. Results. The median age of the patients was 74 years. The median tumor size was 26?mm (range 11–89?mm). The median procedure time was 142?min (range 57–291?min). En bloc resection rate was 72% and the R0 resection rate was 69%. Two perforations occurred amounting to a perforation rate of 6.9%. Both patients with perforation could be managed conservatively. One bleeding occurred during ESD but no postoperative bleeding was observed. Conclusion. Our data confirms that ESD is an effective method for en bloc resection of large colorectal adenomas and early cancers. This study demonstrates that implementation of colorectal ESD is feasible in Sweden after proper training, careful patient selection, and standardization of the ESD procedure. 1. Introduction Colorectal cancer is one of the most frequent malignancies in the world and is the third leading cause of cancer-related death in Sweden. Neoplastic polyps (adenoma) are considered to be precursors of cancers in the colon and rectum. Stalked polyps can easily be removed by use of snare polypectomy. Sessile and flat adenomas can be eliminated efficiently using endoscopic mucosal resection (EMR) [1]. EMR is a relatively widespread and standardized method in western countries, but one problem is that large (>2?cm) sessile and flat adenomas are difficult to remove in one piece (“en bloc”) with EMR, and the endoscopist is usually forced to eliminate such tumors in multiple pieces (“piecemeal resection”). One disadvantage with fragmented polyps is that piecemeal resection makes it difficult for the pathologist to determine depth of invasion, lymphovascular infiltration, and lateral spread of the tumors in order to ensure radical removal. Uncertain radicality after EMR is a common reason for recommending surgical resection. Another disadvantage with piecemeal resection is that the rate of tumor recurrence is higher than that after en bloc resection [2, 3]. In order to avoid these problems associated with EMR, a new method referred to as
High recovery of cell-free methylated DNA based on a rapid bisulfite-treatment protocol
Inge Pedersen, Henrik Krarup, Ole Thorlacius-Ussing, Poul Madsen
BMC Molecular Biology , 2012, DOI: 10.1186/1471-2199-13-12
Abstract: Here we introduce an alternative method for the crucial steps of bisulfite treatment with high recovery. The method is based on an accelerated deamination step and alkaline desulfonation in combination with magnetic silica purification of DNA, allowing preparation of deaminated DNA from patient samples in less than 2 hours.The method presented here allows low levels of DNA to be easily and reliably analysed, a prerequisite for the clinical usefulness of cell-free methylated DNA detection in plasma.Bisulfite induced modification of nucleic acids was originally described in the 1970s [1-3] and since the emergence of PCR and sequencing based detection methods [4,5] bisulfite treatment has played a pivotal role in the analysis of DNA methylation. In its original form it is a time consuming and labour intensive procedure involving numerous experimental steps: DNA denaturation, treatment with bisulfite for 12-16 hr, desalting and desulfonation with NaOH, and finally neutralisation and desalting. Recently published improvements include an accelerated deamination step, cutting down incubation time from 12-16 hr to 40 min, achieved by the use of a more concentrated bisulfite solution at higher temperatures [6,7]. The accelerated and the conventional methods have been explicitly compared by Genereux et al. [8]. The accelerated method leads to a more homogenous conversion of cytosine both across sites and molecules, conceivably due to facilitation of DNA denaturation in concentrated bisulfite solution at 70°C. Hence, inappropriate conversion of 5-methylcytosine, a result of prolonged bisulfite exposure of molecules with complete conversion of cytosine, is more controllable.In addition to deamination of cytosine, bisulfite also induces chain breakage of DNA [9]. The DNA degradation caused by bisulfite treatment results in DNA fragments of an average length of approximately 600 nucleotides [10]. Real-time PCR based methods rely on amplification of short DNA fragments of 60-150 n
Self-expanding metal stents in malignant colonic obstruction: experiences from Sweden
Mattias Lepsenyi, Stefan Santen, Ingvar Syk, J?rgen Nielsen, Artur Nemeth, Ervin Toth, Henrik Thorlacius
BMC Research Notes , 2011, DOI: 10.1186/1756-0500-4-274
Abstract: SEMS was used for palliation in 64 (85%) cases and as a bridge to surgery in 11 (15%) cases. The majority of obstructions, 53 (71%) cases, were located in the recto-sigmoid. Technical success was achieved in 65 (87%) cases and clinical decompression was achieved in 60 (80%) cases. Reasons for technical failure were inability to cannulate the stricture in 5 (7%) cases and suboptimal SEMS placement in 3 (4%) cases. Complications included 4 (5%) procedure-related bowel perforations of which 2 (3%) patients died in junction to post operative complications. Three cases of bleeding after SEMS occurred, none of which needed invasive treatment. Five of the SEMS occluded. Two cases of stent erosion were diagnosed at the time of surgery. Average survival after palliative SEMS treatment was 6 months.Our results correspond well to previously published data and we conclude that SEMS is a relatively safe and effective method of treating malignant colonic obstruction although the risk of SEMS-related perforations has to be taken into account.Acute or pending colonic obstruction, on the basis of colorectal malignancy, is a condition traditionally treated with surgery with a single or a multi-stage operative procedure. Acute surgery with colonic resection and primary anastomosis with or without a diverting stoma is the most common surgical approach in relatively healthy patients. The multi-stage approach includes initial decompression of the obstruction with a temporary colostomy and a later colonic resection with reversal of the stoma if possible. This method is mainly considered in patients with deteriorated general condition, serious co-morbidity or in cases with advanced tumors. Regardless of the technique used, surgical procedures are associated with a high morbidity and mortality rate [1]. The use of self-expanding metal stents (SEMS) for decompression of colonic obstructions was first described by Spinelli et al [2] in 1992 as a palliative treatment. In 1994, Tejero et al [3]
Proteomic Analysis of Tissue from α1,3-galactosyltransferase Knockout Mice Reveals That a Wide Variety of Proteins and Protein Fragments Change Expression Level
Louise Thorlacius-Ussing, Maja Ludvigsen, Svend Kirkeby, Henrik Vorum, Bent Honoré
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080600
Abstract: A barrier in a pig-to-man xenotransplantation is that the Galα1-3Galβ1-4GlcNAc-R carbohydrate (α-Gal epitope) expressed on pig endothelial cells reacts with naturally occurring antibodies in the recipient’s blood leading to rejection. Deletion of the α1,3-galactosyltransferase gene prevents the synthesis of the α-Gal epitope. Therefore, knockout models of the α1,3-galactosyltransferase gene are widely used to study xenotransplantation. We have performed proteomic studies on liver and pancreas tissues from wild type and α1,3-galactosyltransferase gene knockout mice. The tissues were analyzed by two-dimensional polyacrylamide gel electrophoresis and liquid chromatography - tandem mass spectrometry. The analyses revealed that a wide variety of proteins and protein fragments are differentially expressed suggesting that knockout of the α1,3-galactosyltransferase gene affects the expression of several other genes.
Targeting Rac1 Signaling Inhibits Streptococcal M1 Protein-Induced CXC Chemokine Formation, Neutrophil Infiltration and Lung Injury
Songen Zhang, Milladur Rahman, Su Zhang, Lei Song, Heiko Herwald, Henrik Thorlacius
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0071080
Abstract: Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS). The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766) on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage.
Black Hole Evolution
Larus Thorlacius
Physics , 1994, DOI: 10.1016/0920-5632(95)00435-C
Abstract: Black hole formation and evaporation is studied in the semiclassical approximation in simple 1+1-dimensional models, with emphasis on issues related to Hawking's information paradox. Exact semiclassical solutions are described and questions of boundary conditions and vacuum stability are discussed. The validity of the semiclassical approximation has been called into question in the context of the information puzzle. A different approach, where black hole evolution is assumed to be unitary, is described. It requires unusual causal properties and kinematic behavior of matter that may be realized in string theory. Based on lectures given at the 1994 Trieste Spring School
Introduction to D-branes
Larus Thorlacius
Physics , 1997, DOI: 10.1016/S0920-5632(97)00521-5
Abstract: D-branes are string theory solitons defined by boundary conditions on open strings that end on them. They play an important role in the non-perturbative dynamics of string theory and have found a wide range of applications. These lectures give a basic introduction to D-branes and their dynamics.
Born-Infeld String as a Boundary Conformal Field Theory
Larus Thorlacius
Physics , 1997, DOI: 10.1103/PhysRevLett.80.1588
Abstract: Solutions of Born-Infeld theory, representing strings extending from a Dirichlet p-brane, are also solutions of the higher derivative generalization of the Born-Infeld equations defining an exact open string vacuum configuration.
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