WorldWideScience

Sample records for vivo septic lung

  1. Cultured alveolar epithelial cells from septic rats mimic in vivo septic lung.

    Directory of Open Access Journals (Sweden)

    Taylor S Cohen

    2010-06-01

    Full Text Available Sepsis results in the formation of pulmonary edema by increasing in epithelial permeability. Therefore we hypothesized that alveolar epithelial cells isolated from septic animals develop tight junctions with different protein composition and reduced barrier function relative to alveolar epithelial cells from healthy animals. Male rats (200-300 g were sacrificed 24 hours after cecal ligation and double puncture (2CLP or sham surgery. Alveolar epithelial cells were isolated and plated on fibronectin-coated flexible membranes or permeable, non-flexible transwell substrates. After a 5 day culture period, cells were either lysed for western analysis of tight junction protein expressin (claudin 3, 4, 5, 7, 8, and 18, occludin, ZO-1, and JAM-A and MAPk (JNK, ERK, an p38 signaling activation, or barrier function was examined by measuring transepithelial resistance (TER or the flux of two molecular tracers (5 and 20 A. Inhibitors of JNK (SP600125, 20 microM and ERK (U0126, 10 microM were used to determine the role of these pathways in sepsis induced epithelial barrier dysfunction. Expression of claudin 4, claudin 18, and occludin was significantly lower, and activation of JNK and ERK signaling pathways was significantly increased in 2CLP monolayers, relative to sham monolayers. Transepithelial resistance of the 2CLP monolayers was reduced significantly compared to sham (769 and 1234 ohm-cm(2, respectively, however no significant difference in the flux of either tracer was observed. Inhibition of ERK, not JNK, significantly increased TER and expression of claudin 4 in 2CLP monolayers, and prevented significant differences in claudin 18 expression between 2CLP and sham monolayers. We conclude that alveolar epithelial cells isolated from septic animals form confluent monolayers with impaired barrier function compared to healthy monolayers, and inhibition of ERK signaling partially reverses differences between these monolayers. This model provides a unique

  2. Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals

    Science.gov (United States)

    Harrison, Jacqueline M. E.; Quanstrom, Leah M.; Robinson, Alex R.; Wobeser, Bruce; Anderson, Stacy L.

    2017-01-01

    Sepsis causes significant mortality in neonatal foals; however, there is little data describing the cellular and molecular pathways of lung inflammation in septic foals. This study was conducted to characterize lung inflammation in septic foals. Lung tissue sections from control (n = 6) and septic (n = 17) foals were compared using histology and immunohistology. Blinded pathologic scoring of hematoxylin and eosin stained samples revealed increased features of lung inflammation such as thickened alveolar septa and sequestered inflammatory cells in septic foals. Septic foal lungs showed increased expression of von Willebrand factor in blood vessels, demonstrating vascular inflammation. Use of MAC387 antibody to detect calprotectin as a reflection of mononuclear cell infiltration revealed a significant increase in their numbers in alveolar septa of lungs from septic foals compared to those from control foals. The mononuclear cells appeared to be mature macrophages and were located in the septal capillaries, suggesting they were pulmonary intravascular macrophages (PIMs). Finally, lungs from septic foals showed increased expression of Toll-like receptor 4 and 9 in mononuclear cells relative to the control. Taken together, this study is the first to show the expression of inflammatory molecules and an increase in PIMs in lungs from foals that died from sepsis. PMID:27297419

  3. Vascular endothelial growth factor (VEGF) expression in the lung in toxic septic shock.

    Science.gov (United States)

    Manoilescu, Irina; Teleman, S; Cojocaru, Elena; Mihăilă, Doina; Plămădeală, P

    2011-01-01

    The need for reasoning with medical evidence the different types of shock, especially when there are medical and legal implications, has determined the search of biological markers of the shock. In the case of toxic septic shock, the most important markers to be used are: the cytokines, the tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6), procalcitonin, lactoferin and the vascular endothelial growth factor (VEGF). VEGF has an essential role in angiogenesis and vascular permeability. In our study group, we included 30 cases of different types of shock in which we studied the VEGF expression in the lungs. We added also 10 fragments of lung as control group. According to the etiology, the 30 cases of shock were: 15 with a toxic septic shock and 15 with a hemorrhagic shock. In all these cases we used the classical Hematoxylin and Eosin staining method and the immunohistochemical reactions for VEGF-A. Statistical analysis was performed using SPSS 13.0. The VEGF expression was decreased in all the cases of toxic septic shock, in the endothelium and also in the alveolar epithelium, compared to a high level of expression in other cases of shock and in the control lung. These data allow us to appreciate that VEGF has a different expression in different types of shock and in the normal lung. We observed a statistically significant difference between VEGF expression in toxic septic shock and hemorrhagic shock (p=0.000001). There is a similarity of VEGF expression between hemorrhagic shock and the control lungs (p=0.00001). An obviously low VEGF expression in the toxic septic shock represents a useful biological marker in the forensic medical cases.

  4. Lung microbicidal mechanisms and pulmonary hypertension in septic piglets

    Energy Technology Data Exchange (ETDEWEB)

    Bowdy, B.D.

    1989-01-01

    These studies sought to determine whether the pulmonary hemodynamic abnormalities elicited in infant piglets in response to an intravascular bacterial challenge are dependent upon the clearance and killing of the organism by an oxygen radical dependent mechanism residing within the pulmonary circulation of the host. Initial studies were conducted to ascertain the effect of dimethylthiourea (DMTU), a relatively selective scavenger of hydroxyl radical, on Group B Streptococcus (GBS)-induced pulmonary abnormalities in young piglets. Lung samples from piglets infused with GBS and evaluated by transmission electron microscopy revealed that the GBS had been taken up by pulmonary intravascular macrophages. To determine clearance characteristics of intravascularly administered GBS as well as oxygen radical involvement in pulmonary bactericidal mechanisms, studies were performed in which GBS was radiolabelled with {sup 111}Indium-oxine and infused into piglets in the presence or absence of DMTU. In accord with the previous study, animals receiving GBS only exhibited profound increases in Ppa and TPR with concomitant arterial hypoxemia, all of which were attenuated by the co-administration of DMTU. Bacterial accumulated to the greatest extent in the lung, followed by the liver and spleen.

  5. Ozone Therapy and Hyperbaric Oxygen Treatment in Lung Injury in Septic Rats

    Science.gov (United States)

    Yamanel, Levent; Kaldirim, Umit; Oztas, Yesim; Coskun, Omer; Poyrazoglu, Yavuz; Durusu, Murat; Cayci, Tuncer; Ozturk, Ahmet; Demirbas, Seref; Yasar, Mehmet; Cinar, Orhan; Tuncer, Salim Kemal; Eyi, Yusuf Emrah; Uysal, Bulent; Topal, Turgut; Oter, Sukru; Korkmaz, Ahmet

    2011-01-01

    Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome. PMID:21234269

  6. Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Yuqing Wu

    2013-01-01

    and 20 μg/kg significantly decreased mortality and pulmonary inflammation of septic rats, as well as suppressed CLP-induced elevation of TNF-α and IL-6 and inhibited TLR4/MyD88 expression and NF-κB activation. These results suggest that dexmedetomidine may decrease mortality and inhibit inflammatory reaction in lung tissues of septic rats by suppressing TLR4/MyD88/NF-κB pathway.

  7. Esophagopericardial fistula, septic shock and intracranial hemorrhage with hydrocephalus after lung transplantation

    Directory of Open Access Journals (Sweden)

    M.M. Schuurmans

    2017-05-01

    Full Text Available A 57-year old woman underwent lung transplantation for non-specific interstitial pneumonia. Primary graft dysfunction was diagnosed requiring continued use of extracorporeal membrane oxygenation (ECMO. Within three days she developed recurring hemothoraces requiring two surgical evacuations. After ECMO removal a series of complications occurred within four months: femoral thrombosis, persisting tachycardic atrial fibrillation, pneumopericardium with an esophagopericardial fistula and purulent pericarditis, septic shock, multiorgan failure and intracerebral hemorrhage with ventricular involvement requiring external ventricular drainage. Interdisciplinary management coordinated by the intensive care specialist, transplant surgeon and pulmonologist with various interventions by the respective specialists followed by intensive physical rehabilitation allowed for discharge home on day 235 post transplant. Subsequently quality of life was considered good by the patient and family. Keywords: Lung transplantation, Esophagopericardial fistula, Intracranial hemorrhage, Complications, Treatment

  8. Ex vivo lung perfusion review of a revolutionary technology.

    Science.gov (United States)

    Makdisi, George; Makdisi, Tony; Jarmi, Tambi; Caldeira, Christiano C

    2017-09-01

    Donor lung shortage has been the main reason to the increasing number of patients waiting for lung transplant. Ex vivo lung perfusion (EVLP) is widely expanding technology to assess and prepare the lungs who are considered marginal for transplantation. the outcomes are encouraging and comparable to the lungs transplanted according to the standard criteria. in this article, we will discuss the history of development, the techniques and protocols of ex vivo, and the logics and rationales for ex vivo use.

  9. Ursolic acid improves survival and attenuates lung injury in septic rats induced by cecal ligation and puncture.

    Science.gov (United States)

    Hu, Zhansheng; Gu, Zhilong; Sun, Meina; Zhang, Ke; Gao, Penghui; Yang, Qinwu; Yuan, Yuan

    2015-04-01

    Sepsis is characterized as a systemic inflammatory response syndrome during infection, which can result in multiple organ dysfunction and death. Ursolic acid (UA), a pentacyclic triterpene acid, has been reported to have potent anti-inflammatory and antioxidant properties. The aim of this study was to detect the possible protective effects of UA on sepsis-evoked acute lung injury. A rat model of sepsis induced by cecal ligation and puncture (CLP) was used. Rats were injected intraperitoneally with UA (10 mg/kg) after CLP, and then the survival was determined twice a day for 4 d. The protective effects of UA on CLP-induced acute lung injury were assayed at 24 h after CLP. The results revealed that UA treatment markedly improved the survival of septic rats, and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, infiltration of leukocytes and proteins, myeloperoxidase activity, and malondialdehyde content. In addition, UA significantly decreased the serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β, inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lung, which are involved in the productions of nitric oxide and prostaglandin E2. These findings indicate that UA exerts protective effects on CLP-induced septic rats. UA may be a potential therapeutic agent against sepsis. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. In vivo detection of free radicals in mouse septic encephalopathy using molecular MRI and immuno-spin trapping.

    Science.gov (United States)

    Towner, Rheal A; Garteiser, Philippe; Bozza, Fernando; Smith, Nataliya; Saunders, Debra; d' Avila, Joana C P; Magno, Flora; Oliveira, Marcus F; Ehrenshaft, Marilyn; Lupu, Florea; Silasi-Mansat, Robert; Ramirez, Dario C; Gomez-Mejiba, Sandra E; Mason, Ronald P; Castro Faria-Neto, Hugo C

    2013-12-01

    Free radicals are known to play a major role in sepsis. Combined immuno-spin trapping and molecular magnetic resonance imaging (MRI) was used to detect in vivo and in situ levels of free radicals in murine septic encephalopathy after cecal ligation and puncture (CLP). DMPO (5,5-dimethyl pyrroline N-oxide) was injected over 6h after CLP, before administration of an anti-DMPO probe (anti-DMPO antibody bound to albumin-gadolinium-diethylene triamine pentaacetic acid-biotin MRI targeting contrast agent). In vitro assessment of the anti-DMPO probe in oxidatively stressed mouse astrocytes significantly decreased T1 relaxation (p free radicals in murine septic encephalopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Physiologic assessment of the ex vivo donor lung for transplantation.

    Science.gov (United States)

    Yeung, Jonathan C; Cypel, Marcelo; Machuca, Tiago N; Koike, Terumoto; Cook, Douglas J; Bonato, Riccardo; Chen, Manyin; Sato, Masaaki; Waddell, Thomas K; Liu, Mingyao; Slutsky, Arthur S; Keshavjee, Shaf

    2012-10-01

    The evaluation of donor lungs by normothermic ex vivo acellular perfusion has improved the safety of organ utilization. However, this strategy requires a critical re-evaluation of the parameters used to assess lungs during ex vivo perfusion compared with those traditionally used to evaluate the donor lung in vivo. Using a porcine model, we studied the physiology of acellular lung perfusion with the aim of improving the accuracy of clinical ex vivo evaluation. Porcine lungs after 10 hours of brain death and 24 hours of cold ischemia and uninjured control lungs were perfused for 12 hours and then transplanted. PaO2, compliance, airway pressure and pulmonary vascular resistance were measured. Ventilation with 100% nitrogen and addition of red blood cells to the perfusate were used to clarify the physiologic disparities between in vivo blood perfusion and ex vivo acellular perfusion. During 12 hours of ex vivo perfusion, injured lungs developed edema with decreased compliance and increased airway pressure, but ex vivo PO2 remained stable. After transplantation, injured lungs demonstrated high vascular resistance and poor PaO2. A reduced effect of shunt on ex vivo lung perfusion PO2 was found to be attributable to the linearization of the relationship between oxygen content and PO2, which occurs with acellular perfusate. Ex vivo PO2 may not be the first indication of lung injury and, taken alone, may be misleading in assessing the ex vivo lung. Thus, evaluation of other physiologic parameters takes on greater importance. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  12. Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI.

    Directory of Open Access Journals (Sweden)

    Miriam Kalbitz

    Full Text Available Severe blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS. In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury.12 hrs after DH in mice the local and systemic cytokines and chemokines were quantified by multiplex bead array or ELISA, activated caspase-3 by western blot. Data were analyzed using one-way ANOVA followed by post-hoc Sidak's multiple comparison test (significance, p≤ 0.05.In lung tissue interleukin (IL-6, monocyte chemo attractant protein-1 (MCP-1 and granulocyte-colony stimulating factor (G-CSF was elevated in both C5-/- mice and wildtype littermates (wt, whereas caspase-3 was reduced in lungs after DH in C5-/- mice. Systemically, reduced keratinocyte-derived chemokine (KC levels were observed after DH in C5-/- compared to wt mice. Locally, lung myeloperoxidase (MPO, protein, IL-6, MCP-1 and G-CSF in brochoalveolar lavage fluid (BALF were elevated after DH in C5-/- compared to wt.In the complex but clinically relevant DH model the local and systemic inflammatory immune response features both, C5-dependent and C5-independent characteristics. Activation of caspase-3 in lung tissue after DH was C5-dependent whereas local inflammation in lung tissue was C5-independent.

  13. Role of Complement C5 in Experimental Blunt Chest Trauma-Induced Septic Acute Lung Injury (ALI).

    Science.gov (United States)

    Kalbitz, Miriam; Karbach, Michael; Braumueller, Sonja; Kellermann, Philipp; Gebhard, Florian; Huber-Lang, Markus; Perl, Mario

    2016-01-01

    Severe blunt chest trauma is associated with high mortality. Sepsis represents a serious risk factor for mortality in acute respiratory distress syndrome (ARDS). In septic patients with ARDS complement activation products were found to be elevated in the plasma. In single models like LPS or trauma complement has been studied to some degree, however in clinically highly relevant double hit models such as the one used here little data is available. Here, we hypothesized that absence of C5 is correlated with a decreased inflammatory response in trauma induced septic acute lung injury. 12 hrs after DH in mice the local and systemic cytokines and chemokines were quantified by multiplex bead array or ELISA, activated caspase-3 by western blot. Data were analyzed using one-way ANOVA followed by post-hoc Sidak's multiple comparison test (significance, p≤ 0.05). In lung tissue interleukin (IL)-6, monocyte chemo attractant protein-1 (MCP-1) and granulocyte-colony stimulating factor (G-CSF) was elevated in both C5-/- mice and wildtype littermates (wt), whereas caspase-3 was reduced in lungs after DH in C5-/- mice. Systemically, reduced keratinocyte-derived chemokine (KC) levels were observed after DH in C5-/- compared to wt mice. Locally, lung myeloperoxidase (MPO), protein, IL-6, MCP-1 and G-CSF in brochoalveolar lavage fluid (BALF) were elevated after DH in C5-/- compared to wt. In the complex but clinically relevant DH model the local and systemic inflammatory immune response features both, C5-dependent and C5-independent characteristics. Activation of caspase-3 in lung tissue after DH was C5-dependent whereas local inflammation in lung tissue was C5-independent.

  14. Ex Vivo Lung Perfusion: Establishment and Operationalization in Iran.

    Science.gov (United States)

    Shafaghi, Shadi; Abbasi Dezfuli, Azizollah; Ansari Aval, Zahra; Sheikhy, Kambiz; Farzanegan, Behrooz; Mortaz, Esmaeil; Emami, Habib; Aigner, Clemens; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

    2017-02-01

    Although the number of lung transplants is limited because of general shortage of organ donors, ex vivo lung perfusion is a novel method with 2 main benefits, including better evaluation of lung potential and recovery of injured lungs. The main aim of this study was to establish and operationalize ex vivo lung perfusion as the first experience in Iran. This was a prospective operational research study on 5 cases, including 1 pig from Vienna Medical University and 4 patients from Masih Daneshvari Hospital. All organ donations from brain dead donors were evaluated according to lung transplant or ex vivo lung perfusion criteria from May 2013 to July 2015 in Tehran, Iran. If a donor did not have any sign of severe chest trauma or pneumonia but had poor oxygenation due to possible atelectasis or neurogenic pulmonary edema, their lungs were included for ex vivo lung perfusion. A successful trend in the difference between the pulmonary arterial Po2 and the left atrial Po2 was observed, as well as an increasing pattern in other functional parameters, including dynamic lung compliance and a decreasing trend in pulmonary vascular resistance. These initial trials indicate that ex vivo lung perfusion can lead to remarkable progress in lung transplant in Iran. They also provide several important pieces of guidance for successful ex vivo lung perfusion, including the necessity of following standard lung retrieval procedures and monitoring temperature and pressure precisely. The development of novel methods can provide opportunities for further research studies on lungs of deceased donors and lead to undiscovered findings. By keeping this science up to date in Iran and developing such new and creative methods, we can reveal effective strategies to promote the quality of donor lungs to support patients on transplant wait lists.

  15. Predictive value of pulse pressure variation for fluid responsiveness in septic patients using lung-protective ventilation strategies.

    Science.gov (United States)

    Freitas, F G R; Bafi, A T; Nascente, A P M; Assunção, M; Mazza, B; Azevedo, L C P; Machado, F R

    2013-03-01

    The applicability of pulse pressure variation (ΔPP) to predict fluid responsiveness using lung-protective ventilation strategies is uncertain in clinical practice. We designed this study to evaluate the accuracy of this parameter in predicting the fluid responsiveness of septic patients ventilated with low tidal volumes (TV) (6 ml kg(-1)). Forty patients after the resuscitation phase of severe sepsis and septic shock who were mechanically ventilated with 6 ml kg(-1) were included. The ΔPP was obtained automatically at baseline and after a standardized fluid challenge (7 ml kg(-1)). Patients whose cardiac output increased by more than 15% were considered fluid responders. The predictive values of ΔPP and static variables [right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP)] were evaluated through a receiver operating characteristic (ROC) curve analysis. Thirty-four patients had characteristics consistent with acute lung injury or acute respiratory distress syndrome and were ventilated with high levels of PEEP [median (inter-quartile range) 10.0 (10.0-13.5)]. Nineteen patients were considered fluid responders. The RAP and PAOP significantly increased, and ΔPP significantly decreased after volume expansion. The ΔPP performance [ROC curve area: 0.91 (0.82-1.0)] was better than that of the RAP [ROC curve area: 0.73 (0.59-0.90)] and pulmonary artery occlusion pressure [ROC curve area: 0.58 (0.40-0.76)]. The ROC curve analysis revealed that the best cut-off for ΔPP was 6.5%, with a sensitivity of 0.89, specificity of 0.90, positive predictive value of 0.89, and negative predictive value of 0.90. Automatized ΔPP accurately predicted fluid responsiveness in septic patients ventilated with low TV.

  16. Pachymic acid improves survival and attenuates acute lung injury in septic rats induced by cecal ligation and puncture.

    Science.gov (United States)

    Li, J-Y; Wu, H-X; Yang, G

    2017-04-01

    The purpose of this study was to elucidate the possible beneficial effects of pachymic acid (PA) on acute lung injury (ALI) in a rat model of sepsis. A rat model of sepsis induced by cecal ligation and puncture (CLP) was used. Rats were randomly divided into five groups: sham, CLP, CLP + PA 1 mg/kg, CLP + PA 5 mg/kg, CLP + PA 10 mg/kg. CLP + PA groups received PA by intraperitoneal injection daily for consecutive 3 days, respectively, and the rats in sham and CLP groups were given equivalent volume of olive oil. We killed the animals 12 h after CLP and collected blood samples to determine PaO2, PaCO2, tumor necrosis factor-alpha (TNF-a), interleukin-1β (IL-1β) and IL-6. Lung samples were taken for wet/dry weight ratios and histologic assessment. Meanwhile, the levels of lung tissue myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined. The results revealed that PA treatment significantly improved the survival of septic rats and attenuated CLP-induced ALI. In PA-treated rats, the wet/dry weight ratios and the serum levels of TNF-a, IL-1β and IL-6 were down-regulated compared with the CLP group. PA also markedly decreased MDA and MPO contents and increased SOD level. These findings indicate that PA administration ameliorates ALI in a rat model of sepsis induced by CLP.

  17. Role of pulmonary microvascular endothelial cell apoptosis in murine sepsis-induced lung injury in vivo.

    Science.gov (United States)

    Gill, Sean E; Rohan, Marta; Mehta, Sanjay

    2015-09-16

    Sepsis remains a common and serious condition with significant morbidity and mortality due to multiple organ dysfunction, especially acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Sepsis-induced ALI is characterized by injury and dysfunction of the pulmonary microvasculature and pulmonary microvascular endothelial cells (PMVEC), resulting in enhanced pulmonary microvascular sequestration and pulmonary infiltration of polymorphonuclear leukocytes (PMN) as well as disruption of the normal alveolo-capillary permeability barrier with leak of albumin-rich edema fluid into pulmonary interstitium and alveoli. The role of PMVEC death and specifically apoptosis in septic pulmonary microvascular dysfunction in vivo has not been established. In a murine cecal ligation/perforation (CLP) model of sepsis, we quantified and correlated time-dependent changes in pulmonary microvascular Evans blue (EB)-labeled albumin permeability with (1) PMVEC death (propidium iodide [PI]-staining) by both fluorescent intravital videomicroscopy (IVVM) and histology, and (2) PMVEC apoptosis using histologic fluorescent microscopic assessment of a panel of 3 markers: cell surface phosphatidylserine (detected by Annexin V binding), caspase activation (detected by FLIVO labeling), and DNA fragmentation (TUNEL labeling). Compared to sham mice, CLP-sepsis resulted in pulmonary microvascular barrier dysfunction, quantified by increased EB-albumin leak, and PMVEC death (PI+ staining) as early as 2 h and more marked by 4 h after CLP. Septic PMVEC also exhibited increased presence of all 3 markers of apoptosis (Annexin V+, FLIVO+, TUNEL+) as early as 30 mins--1 h after CLP-sepsis, which all similarly increased markedly until 4 h. The time-dependent changes in septic pulmonary microvascular albumin-permeability barrier dysfunction were highly correlated with PMVEC death (PI+; r = 0.976, p pulmonary microvascular dysfunction, including both albumin-permeability barrier dysfunction and

  18. MRI and CT lung biomarkers: Towards an in vivo understanding of lung biomechanics.

    Science.gov (United States)

    Young, Heather M; Eddy, Rachel L; Parraga, Grace

    2017-09-29

    The biomechanical properties of the lung are necessarily dependent on its structure and function, both of which are complex and change over time and space. This makes in vivo evaluation of lung biomechanics and a deep understanding of lung biomarkers, very challenging. In patients and animal models of lung disease, in vivo evaluations of lung structure and function are typically made at the mouth and include spirometry, multiple-breath gas washout tests and the forced oscillation technique. These techniques, and the biomarkers they provide, incorporate the properties of the whole organ system including the parenchyma, large and small airways, mouth, diaphragm and intercostal muscles. Unfortunately, these well-established measurements mask regional differences, limiting their ability to probe the lung's gross and micro-biomechanical properties which vary widely throughout the organ and its subcompartments. Pulmonary imaging has the advantage in providing regional, non-invasive measurements of healthy and diseased lung, in vivo. Here we summarize well-established and emerging lung imaging tools and biomarkers and how they may be used to generate lung biomechanical measurements. We review well-established and emerging lung anatomical, microstructural and functional imaging biomarkers generated using synchrotron x-ray tomographic-microscopy (SRXTM), micro-x-ray computed-tomography (micro-CT), clinical CT as well as magnetic resonance imaging (MRI). Pulmonary imaging provides measurements of lung structure, function and biomechanics with high spatial and temporal resolution. Imaging biomarkers that reflect the biomechanical properties of the lung are now being validated to provide a deeper understanding of the lung that cannot be achieved using measurements made at the mouth. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... introduction. MATERIAL AND METHODS: The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died...

  20. A case of lung volume reduction surgery with decortication for a septic patient in respiratory failure.

    Science.gov (United States)

    Tarazi, M; Mayooran, N; Anwer, M; Anjum, M N; Doddakula, K

    2015-01-01

    Decortication and lung volume reduction surgery are both major operations and each has its independent risk of morbidity and mortality. We present the case of a 41 year old gentleman with left sided empyema and giant bullae of the upper lobe with an active air leak that was transferred to our tertiary referral centre for further management. We performed emergency left thoracotomy, decorticated the left lower lobe with extensive lung volume reduction surgery of the upper lobe. Patient's respiratory status significantly improved along with excellent radiological results. Our case demonstrates that a combination of complex procedures is feasible with excellent outcomes. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs.

    Science.gov (United States)

    Nakajima, D; Cypel, M; Bonato, R; Machuca, T N; Iskender, I; Hashimoto, K; Linacre, V; Chen, M; Coutinho, R; Azad, S; Martinu, T; Waddell, T K; Hwang, D M; Husain, S; Liu, M; Keshavjee, S

    2016-04-01

    Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Methods of in-vivo mouse lung micro-CT

    Science.gov (United States)

    Recheis, Wolfgang A.; Nixon, Earl; Thiesse, Jacqueline; McLennan, Geoffrey; Ross, Alan; Hoffman, Eric

    2005-04-01

    Micro-CT will have a profound influence on the accumulation of anatomical and physiological phenotypic changes in natural and transgenetic mouse models. Longitudinal studies will be greatly facilitated, allowing for a more complete and accurate description of events if in-vivo studies are accomplished. The purpose of the ongoing project is to establish a feasible and reproducible setup for in-vivo mouse lung micro-computed tomography (μCT). We seek to use in-vivo respiratory-gated μCT to follow mouse models of lung disease with subsequent recovery of the mouse. Methodologies for optimizing scanning parameters and gating for the in-vivo mouse lung are presented. A Scireq flexiVent ventilated the gas-anesthetized mice at 60 breaths/minute, 30 cm H20 PEEP, 30 ml/kg tidal volume and provided a respiratory signal to gate a Skyscan 1076 μCT. Physiologic monitoring allowed the control of vital functions and quality of anesthesia, e.g. via ECG monitoring. In contrary to longer exposure times with ex-vivo scans, scan times for in-vivo were reduced using 35μm pixel size, 158ms exposure time and 18μm pixel size, 316ms exposure time to reduce motion artifacts. Gating via spontaneous breathing was also tested. Optimal contrast resolution was achieved at 50kVp, 200μA, applying an aluminum filter (0.5mm). There were minimal non-cardiac related motion artifacts. Both 35μm and 1μm voxel size images were suitable for evaluation of the airway lumen and parenchymal density. Total scan times were 30 and 65 minutes respectively. The mice recovered following scanning protocols. In-vivo lung scanning with recovery of the mouse delivered reasonable image quality for longitudinal studies, e.g. mouse asthma models. After examining 10 mice, we conclude μCT is a feasible tool evaluating mouse models of lung pathology in longitudinal studies with increasing anatomic detail available for evaluation as one moves from in-vivo to ex-vivo studies. Further developments include automated

  3. Dysregulated cytokine expression by CD4+ T cells from post-septic mice modulates both Th1 and Th2-mediated granulomatous lung inflammation.

    Directory of Open Access Journals (Sweden)

    William F Carson

    Full Text Available Previous epidemiological studies in humans and experimental studies in animals indicate that survivors of severe sepsis exhibit deficiencies in the activation and effector function of immune cells. In particular, CD4+ T lymphocytes can exhibit reduced proliferative capacity and improper cytokine responses following sepsis. To further investigate the cell-intrinsic defects of CD4+ T cells following sepsis, splenic CD4+ T cells from sham surgery and post-septic mice were transferred into lymphopenic mice. These recipient mice were then subjected to both TH1-(purified protein derivative and TH2-(Schistosoma mansoni egg antigen driven models of granulomatous lung inflammation. Post-septic CD4+ T cells mediated smaller TH1 and larger TH2 lung granulomas as compared to mice receiving CD4+ T cells from sham surgery donors. However, cytokine production by lymph node cells in antigen restimulation assays indicated increased pan-specific cytokine expression by post-septic CD4+ T cell recipient mice in both TH1 and TH2 granuloma models. These include increased production of T(H2 cytokines in TH1 inflammation, and increased production of T(H1 cytokines in TH2 inflammation. These results suggest that cell-intrinsic defects in CD4+ T cell effector function can have deleterious effects on inflammatory processes post-sepsis, due to a defect in the proper regulation of TH-specific cytokine expression.

  4. Septic Cardiomyopathy.

    Science.gov (United States)

    Beesley, Sarah J; Weber, Gerhard; Sarge, Todd; Nikravan, Sara; Grissom, Colin K; Lanspa, Michael J; Shahul, Sajid; Brown, Samuel M

    2017-12-08

    To describe, with an emphasis on clinical applications, what is known about the pathophysiology, management, and implications of septic cardiomyopathy in the adult ICU. A PubMed literature review was performed for relevant articles. Only articles in English that studied human adults with sepsis were included. Multiple competing definitions for septic cardiomyopathy hinder understanding of this entity. Although many patients with sepsis develop cardiac dysfunction, the impact of septic cardiomyopathy on prognosis and therapy remains to be demonstrated. Treatment of septic cardiomyopathy is aimed at treating the underlying sepsis and providing specific supportive care for cardiogenic shock when present. Septic cardiomyopathy is an important contributor to organ dysfunction in sepsis. Guided treatment of septic cardiomyopathy may affect patients' prognosis, especially when their cardiac index is substantially decreased. The implication of septic cardiomyopathy for both short- and long-term outcomes is an important area for future investigation.

  5. Near-Infrared Emitting PbS Quantum Dots for in Vivo Fluorescence Imaging of the Thrombotic State in Septic Mouse Brain

    Directory of Open Access Journals (Sweden)

    Yukio Imamura

    2016-08-01

    Full Text Available Near-infrared (NIR fluorescent imaging is a powerful tool for the non-invasive visualization of the inner structure of living organisms. Recently, NIR fluorescence imaging at 1000–1400 nm (second optical window has been shown to offer better spatial resolution compared with conventional NIR fluorescence imaging at 700–900 nm (first optical window. Here we report lead sulfide (PbS quantum dots (QDs and their use for in vivo NIR fluorescence imaging of cerebral venous thrombosis in septic mice. Highly fluorescent PbS QDs with a 1100 nm emission peak (QD1100 were prepared from lead acetate and hexamethyldisilathiane, and the surface of QD1100 was coated with mercaptoundecanoic acid so as to be soluble in water. NIR fluorescence imaging of the cerebral vessels of living mice was performed after intravascular injection (200–300 μL of QD1100 (3 μM from a caudal vein. By detecting the NIR fluorescence of QD1100, we achieved non-invasive NIR fluorescence imaging of cerebral blood vessels through the scalp and skull. We also achieved NIR fluorescence imaging of cerebral venous thrombosis in septic mice induced by the administration of lipopolysaccharide (LPS. From the NIR fluorescence imaging, we found that the number of thrombi in septic mice was significantly increased by the administration of LPS. The formation of thrombi in cerebral blood vessels in septic mice was confirmed by enzyme-linked immunosorbent assay (ELISA. We also found that the number of thrombi significantly decreased after the administration of heparin, an inhibitor of blood coagulation. These results show that NIR fluorescence imaging with QD1100 is useful for the evaluation of the pathological state of cerebral blood vessels in septic mice.

  6. RGD peptides protects against acute lung injury in septic mice through Wisp1-integrin β6 pathway inhibition.

    Science.gov (United States)

    Ding, Xibing; Wang, Xin; Zhao, Xiang; Jin, Shuqing; Tong, Yao; Ren, Hao; Chen, Zhixia; Li, Quan

    2015-04-01

    Acute lung injury is a common consequence of sepsis, a life-threatening inflammatory response caused by severe infection. In this study, we elucidate the attenuating effects of synthetic Arg-Gly-Asp-Ser peptides (RGDs) on acute lung injury in a sepsis mouse model. We further reveal that the beneficial effects of RGDs stem from their negative regulation of the Wisp1 (WNT1-inducible signaling pathway)-integrin β6 pathway. After inducing sepsis using cecal ligation and puncture (CLP), mice were randomized into experimental and control groups, and survival rates were recorded over 7 days, whereas only 20% of mice subjected to CLP survived when compared with untreated controls; the addition of RGDs to this treatment regimen dramatically increased the survival rate to 80%. Histological analysis revealed acute lung injury in CLP-treated mice, whereas those subjected to the combined treatment of CLP and RGDs showed a considerable decrease in lung injury severity. The addition of RGDs also dramatically attenuated other common sepsis-associated effects, such as increased white blood cell number in bronchoalveolar lavage fluid and decreased pulmonary capillary barrier function. Furthermore, treatment with RGDs decreased the serum and bronchoalveolar lavage fluid levels of inflammatory cytokines such as tumor necrosis factor α and interleukin 6, contrary to the CLP treatment alone that increased the levels of these proteins. Interestingly, however, RGDs had no detectable effect on bacterial invasion following sepsis induction. In addition, mice treated with RGDs showed decreased levels of wisp1 and integrin β6 when compared with CLP-treated mice. In the present study, a linkage between Wisp1 and integrin β6 was evaluated in vivo. Most strikingly, RGDs resulted in a decreased association of Wisp1 with integrin β6 based on coimmunoprecipitation analyses. These data suggest that RGDs ameliorate acute lung injury in a sepsis mouse model by inhibiting the Wisp1-integrin β6

  7. Fluorometry of ischemia reperfusion injury in rat lungs in vivo

    Science.gov (United States)

    Sepehr, R.; Staniszewski, K.; Jacobs, E. R.; Audi, S.; Ranji, Mahsa

    2013-02-01

    Previously we demonstrated the utility of optical fluorometry to evaluate lung tissue mitochondrial redox state in isolated perfused rats lungs under various chemically-induced respiratory states. The objective of this study was to evaluate the effect of acute ischemia on lung tissue mitochondrial redox state in vivo using optical fluorometry. Under ischemic conditions, insufficient oxygen supply to the mitochondrial chain should reduce the mitochondrial redox state calculated from the ratio of the auto-fluorescent mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavoprotein Adenine Dinucleotide). The chest of anesthetized, and mechanically ventilated Sprague-Dawley rat was opened to induce acute ischemia by clamping the left hilum to block both blood flow and ventilation to one lung for approximately 10 minutes. NADH and FAD fluorescent signals were recorded continuously in a dark room via a fluorometer probe placed on the pleural surface of the left lung. Acute ischemia caused a decrease in FAD and an increase in NADH, which resulted in an increase in the mitochondrial redox ratio (RR=NADH/FAD). Restoration of blood flow and ventilation by unclamping the left hilum returned the RR back to its baseline. These results (increase in RR under ischemia) show promise for the fluorometer to be used in a clinical setting for evaluating the effect of pulmonary ischemia-reperfusion on lung tissue mitochondrial redox state in real time.

  8. Septic arthritis

    Science.gov (United States)

    ... develop symptoms of septic arthritis. Prevention Preventive (prophylactic) antibiotics may be helpful for people at high risk. Alternative Names Bacterial arthritis; Non-gonococcal bacterial arthritis References ...

  9. Avaliação e recondicionamento pulmonar ex vivo Ex vivo lung evaluation and reconditioning

    Directory of Open Access Journals (Sweden)

    Paulo Manuel Pêgo-Fernandes

    2010-12-01

    Full Text Available OBJETIVO: Apenas 15% dos pulmões doados são aproveitados para transplante. Um novo método de Perfusão Pulmonar Ex Vivo (PPEV foi desenvolvido e pode ser usado para avaliação e recondicionamento de pulmões "marginais" e rejeitados para o transplante. Esse trabalho relata nossa experiência com a avaliação funcional da PPEV. MÉTODOS: Foram estudados pulmões de 12 doadores considerados inapropriados para transplante pulmonar. Após a captação, os pulmões são perfundidos ex vivo com Steen Solution, uma solução de composição eletrolítica extracelular com alta pressão coloidosmótica. Um oxigenador de membrana ligado ao circuito recebe uma mistura gasosa (nitrogênio e dióxido de carbono e "desoxigena" o perfusato, mantendo uma concentração de gases semelhante a do sangue venoso. Os pulmões são gradualmente aquecidos, perfundidos e ventilados. A avaliação dos órgãos é feita por gasometrias e medidas como a resistência vascular pulmonar (RVP e complacência pulmonar (CP. RESULTADOS: A PaO2 (FiO2 100% passou de um valor médio de 193,3 mmHg no doador para 495,3 mmHg durante a PPEV. Após uma hora de PPEV, a RVP média era de 737,3 dinas/seg/ cm5 e a CP era de 42,2 ml/cmH2O. CONCLUSÕES: O modelo de avaliação pulmonar ex vivo pode melhorar a capacidade de oxigenação de pulmões "marginais" inicialmente rejeitados para transplante. Isso denota um grande potencial do método para aumentar a disponibilidade de pulmões para transplante e, possivelmente, reduzir o tempo de espera nas filas.OBJECTIVE: Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP has been developed and can be used for evaluation and reconditioning of "marginal" and unacceptable lungs. This is a report of functional evaluation experience with ex vivo perfusion of twelve donor lungs deemed unacceptable in São Paulo, Brazil. METHODS: After harvesting, the

  10. Clinical Outcome of Patients Transplanted with Marginal Donor Lungs via Ex Vivo Lung Perfusion Compared to Standard Lung Transplantation.

    Science.gov (United States)

    Fildes, James E; Archer, Louise D; Blaikley, John; Ball, Alexandra L; Stone, John P; Sjöberg, Trygve; Steen, Stig; Yonan, Nizar

    2015-05-01

    Lung transplantation is limited by a scarcity of suitable donors resulting in high waiting list mortality. Ex vivo lung perfusion (EVLP) allows the evaluation and reconditioning of marginal donor lungs for use in transplantation. This study aimed to compare clinical outcome of patients transplanted with marginal organs by means of EVLP with a standard lung transplant cohort through a multicenter open trial. Group 1 (n = 9) included patients transplanted using EVLP reconditioned marginal lungs. Group 2 (n = 46) consisted of date-matched patients transplanted using standard transplantation of acceptable lungs. The primary composite endpoint included acute rejection and infection at 12 months after transplantation. There was no significant difference in the overall incidence of acute rejection (P = 0.754) and the number of treated infection episodes (proven/probable pneumonia; P = 0.857/0.368 and proven/probable tracheobronchitis; P = 0.226/0.529) up to 12 months after transplantation, between group 1 and group 2. Additionally, there was no significant difference in early clinical outcome, including intensive care unit stay, hospital stay, and 1 year mortality between the two groups (P = 0.338, P = 0.112 and P = 0.372, respectively). This multicenter study demonstrates that EVLP is associated with no adverse effect on clinical outcome, including the incidence of acute rejection and infection after lung transplantation.

  11. In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell Dissemination

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0184 TITLE: In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell Dissemination PRINCIPAL...Sep 2013 - 14 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER In Vivo Tagging of Lung Epithelial Cells To Define the Early Steps of Tumor Cell...understand the early events that accompany invasive behavior in vivo , we proposed to develop a lineage-labeling system to detect and isolate cells of lung

  12. β2-Adrenoreceptor Agonist Inhalation During Ex Vivo Lung Perfusion Attenuates Lung Injury.

    Science.gov (United States)

    Kondo, Takeshi; Chen, Fengshi; Ohsumi, Akihiro; Hijiya, Kyoko; Motoyama, Hideki; Sowa, Terumasa; Ohata, Keiji; Takahashi, Mamoru; Yamada, Tetsu; Sato, Masaaki; Aoyama, Akihiro; Date, Hiroshi

    2015-08-01

    Attenuation of ischemia reperfusion injury (IRI) is important in lung transplantation. Our group previously reported that β2-adrenoreceptor agonist inhalation during the period before procurement successfully attenuated IRI in donated lungs after cardiac death. We therefore hypothesized that β2-adrenoreceptor agonist inhalation during ex vivo lung perfusion (EVLP) after procurement might also have a protective effect. Cardiac-dead beagles were left at room temperature for 210 minutes, and all lungs were subsequently procured and subjected to EVLP for 240 minutes. The beagles were allocated to 2 groups: the β2 group (receiving an aerosolized β2-adrenoreceptor agonist 20 minutes after initiation of EVLP; n = 7) and the control group (receiving an aerosolized control solvent at the same time point; n = 6). Physiologic data, including lung function, were evaluated during EVLP. The β2 group showed significantly lower peak airway pressure and pulmonary artery pressure than the control group. Dynamic pulmonary compliance was higher, pulmonary vascular resistance (PVR) was lower, and the wet-to-dry lung weight ratio was lower in the β2 group than in the control group. Cyclic adenosine monophosphate (cAMP) and total adenosine nucleotide (TAN) levels in lung tissue after EVLP were higher in the β2 group than in the control group. The β2 group also showed more cystic fibrosis transmembrane conductance regulator (CFTR) gene expression. After procurement, β2-adrenoreceptor agonist inhalation during EVLP attenuates lung injury in a canine model of organ donation after cardiac death. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Septic Arthritis

    Science.gov (United States)

    ... the joint — contributes to the damage. Risk factors Risk factors for septic arthritis include: Existing joint problems. Chronic diseases and conditions that affect your joints — such as osteoarthritis, gout, rheumatoid arthritis or lupus — can increase your ...

  14. Experience with the first 50 ex vivo lung perfusions in clinical transplantation.

    Science.gov (United States)

    Cypel, Marcelo; Yeung, Jonathan C; Machuca, Tiago; Chen, Manyin; Singer, Lianne G; Yasufuku, Kazuhiro; de Perrot, Marc; Pierre, Andrew; Waddell, Thomas K; Keshavjee, Shaf

    2012-11-01

    Normothermic ex vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our experience with 50 consecutive transplants after ex vivo lung perfusion. A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pao(2)/Fio(2) .05). Thirty-day mortality (4% in the ex vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the ex vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Transplantation of high-risk donor lungs after 4 to 6 hours of ex vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  15. Septic Shock

    Science.gov (United States)

    Seymour, Christopher W.; Rosengart, Matthew R.

    2015-01-01

    IMPORTANCE Septic shock is a clinical emergency that occurs in more than 230 000 US patients each year. OBSERVATIONS AND ADVANCES In the setting of suspected or documented infection, septic shock is typically defined in a clinical setting by low systolic (≤90 mm Hg) or mean arterial blood pressure (≤65 mm Hg) accompanied by signs of hypoperfusion (eg, oliguria, hyperlactemia, poor peripheral perfusion, or altered mental status). Focused ultrasonography is recommended for the prompt recognition of complicating physiology (eg, hypovolemia or cardiogenic shock), while invasive hemodynamic monitoring is recommended only for select patients. In septic shock, 3 randomized clinical trials demonstrate that protocolized care offers little advantage compared with management without a protocol. Hydroxyethyl starch is no longer recommended, and debate continues about the role of various crystalloid solutions and albumin. CONCLUSIONS AND RELEVANCE The prompt diagnosis of septic shock begins with obtainment of medical history and performance of a physical examination for signs and symptoms of infection and may require focused ultrasonography to recognize more complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of intravenous fluids and vasoactive medications aimed at restoring adequate circulation, and the limitations of protocol-based therapy, as guided by recent evidence. PMID:26284722

  16. Graft downsizing during ex vivo lung perfusion: case report and technical notes.

    Science.gov (United States)

    Nosotti, M; Rosso, L; Mendogni, P; Tosi, D; Palleschi, A; Righi, I; Froio, S; Valenza, F; Santambrogio, L

    2014-09-01

    Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Normothermic ex vivo lung perfusion of non-heart-beating donor lungs in pigs : from pretransplant function analysis towards a 6-h machine preservation

    NARCIS (Netherlands)

    Erasmus, ME; Fernhout, MH; Elstrodt, JM; Rakhorst, G

    Donor shortage urges optimal use of all lungs available. Ex vivo lung perfusion (EVLP) is a method to evaluate lung function before implantation. EVLP was performed in pigs to evaluate lung function, using two different clinical non-heart-beating (NHS) donor protocols: flush perfusion and topical

  18. Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

    DEFF Research Database (Denmark)

    Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

    1998-01-01

    OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

  19. Comparison of Celsior and Perfadex lung preservation solutions in rat lungs subjected to 6 and 12 hours of ischemia using an ex-vivo lung perfusion system

    Directory of Open Access Journals (Sweden)

    Arteiro Queiroz Menezes

    2012-11-01

    Full Text Available OBJECTIVE: This study evaluated the performance of lungs that were preserved with different solutions (Celsior, Perfadex or saline in an ex vivo rat lung perfusion system. METHODS: Sixty Wistar rats were anesthetized, anticoagulated and randomized into three groups (n = 20. The rats were subjected to antegrade perfusion via the pulmonary artery with Perfadex, Celsior, or saline, followed by 6 or 12 hours of ischemia (4ºC, n = 10 in each group. Respiratory mechanics, gas exchange and hemodynamics were measured at 10-minute intervals during the reperfusion of heart-lung blocks in an ex vivo system (IL2-Isolated Perfused Rat or Guinea Pig Lung System, Harvard Apparatus, Holliston, Massachusetts, USA; Hugo Sachs Elektronik, Germany for 60 minutes. The lungs were prepared for histopathology and evaluated for edema following reperfusion. Group comparisons were performed using ANOVA and the Kruskal-Wallis test with a 5% level of significance. RESULTS: Gas exchange was not significantly different between lungs perfused with either Perfadex or Celsior at the same ischemic times, but it was very low in lungs that were preserved with saline. Airway resistance was greater in the lungs that were preserved for 12 hours. Celsior lungs that were preserved for 6 and 12 hours exhibited lower airway resistance (p = 0.01 compared to Perfadex lungs. Pulmonary artery pressure was not different between the groups, and no significant differences in histopathology and apoptosis were observed between the groups. CONCLUSIONS: Lungs that were preserved with Celsior or Perfadex exhibited similar gas exchange and histopathological findings. Airway resistance was slightly lower in the Celsior-preserved lungs compared with the Perfadex-preserved lungs.

  20. Noninvasive In Vivo Quantification of Neutrophil Elastase Activity in Acute Experimental Mouse Lung Injury

    Directory of Open Access Journals (Sweden)

    Sylvie Kossodo

    2011-01-01

    Full Text Available We developed a neutrophil elastase-specific near-infrared fluorescence imaging agent, which, combined with fluorescence molecular tomographic imaging, allowed us to detect and quantify neutrophil elastase activity in vivo, in real time, and noninvasively in an acute model of lung injury (ALI. Significantly higher fluorescent signal was quantified in mice with LPS/fMLP-induced ALI as compared to healthy controls, correlating with increases in the number of bronchoalveolar lavage cells, neutrophils, and elastase activity. The agent was significantly activated ex vivo in lung sections from ALI but not from control mice, and this activation was ablated by the specific inhibitor sivelestat. Treatment with the specific inhibitor sivelestat significantly reduced lung signal in mice with ALI. These results underscore the unique ability of fluorescence molecular imaging to quantify specific molecular processes in vivo, crucial for understanding the mechanisms underlying disease progression and for assessing and monitoring novel pharmacological interventions.

  1. Effect of lung flooding and high-intensity focused ultrasound on lung tumours: an experimental study in an ex vivo human cancer model and simulated in vivo tumours in pigs.

    Science.gov (United States)

    Wolfram, Frank; Boltze, Carsten; Schubert, Harald; Bischoff, Sabine; Lesser, Thomas Günther

    2014-01-07

    High-intensity focused ultrasound is a valuable tool for minimally invasive tumour ablation. However, due to the air content in ventilated lungs, lung tumours have never been treated with high-intensity focused ultrasound. Lung flooding enables efficient lung sonography and tumour imaging in ex vivo human and in vivo porcine lung cancer models. The current study evaluates the effectiveness of lung flooding and sonography-guided high-intensity focused ultrasound for lung tumour ablation in ex vivo human and in vivo animal models. Lung flooding was performed in four human lung lobes which were resected from non-small cell lung cancers. B-mode imaging and temperature measurements were simultaneously obtained during high-intensity focused ultrasonography of centrally located lung cancers. The tumour was removed immediately following insonation and processed for nicotinamide adenine dinucleotide phosphate-diaphorase and H&E staining. In addition, the left lungs of three pigs were flooded. Purified BSA in glutaraldehyde was injected centrally into the left lower lung lobe to simulate a lung tumour. The ultrasound was focused transthoracically through the flooded lung into the simulated tumour with the guidance of sonography. The temperature of the tumour was simultaneously measured. The vital signs of the animal were monitored during the procedure. A well-demarcated lesion of coagulation necrosis was produced in four of four human lung tumours. There did not appear to be any damage to the surrounding lung parenchyma. After high-intensity focused ultrasound insonation, the mean temperature increase was 7.5-fold higher in the ex vivo human tumour than in the flooded lung tissue (52.1 K ± 8.77 K versus 7.1 K ± 2.5 K). The transthoracic high-intensity focused ultrasound of simulated tumours in the in vivo model resulted in a mean peak temperature increase up to 53.7°C (±4.5). All of the animals survived the procedure without haemodynamic complications. High

  2. In Vivo Imaging of Peripheral Benzodiazepine Receptors in Mouse Lungs: A Biomarker of Inflammation

    Directory of Open Access Journals (Sweden)

    Matthew J. Hardwick

    2005-10-01

    Full Text Available The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-(R-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals (p < .05. These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-(R-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

  3. Feasibility of in vivo measurement of {sup 239}Pu distribution in lungs using an imaging plate

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Masahiro, E-mail: m-hirota@n.t.u-tokyo.ac.j [Department of Nuclear Engineering and Management, University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan); Takada, Chie; Takasaki, Koji; Momose, Takumaro; Kurihara, Osamu [Japan Atomic Energy Agency, Nuclear Fuel Cycle Engineering Laboratories, Tokai, Ibaraki 319-1194 (Japan); Saze, Takuya [Radioisotope Research Center, Tokushima University, Tokushima, Tokushima 770-8503 (Japan); Ito, Shigeki [Faculty of Life Sciences, Kumamoto University, Kumamoto, Kumamoto 862-0976 (Japan); Nishizawa, Kunihide [Radioisotope Research Center, Nagoya University, Chikusa, Nagoya, Aichi 464-8602 (Japan)

    2011-05-15

    An in vivo measurement system using an imaging plate (IP) system was developed, which displayed images reflecting {sup 239}Pu distribution in the lung of a phantom. The detection limits of the IP system for 1-12 h exposures were between 1670 and 245 Bq at a 1.6 cm chest wall thickness. The detection limit of the IP system for a 2.5 h exposure was equal to that of a germanium detector for a 0.5 h measurement. The IP system could be used as a new device for in vivo measurement of {sup 239}Pu in the lung.

  4. Human Lung Cancer Cells Grown in an Ex Vivo 3D Lung Model Produce Matrix Metalloproteinases Not Produced in 2D Culture

    Science.gov (United States)

    Mishra, Dhruva K.; Sakamoto, Jason H.; Thrall, Michael J.; Baird, Brandi N.; Blackmon, Shanda H.; Ferrari, Mauro; Kurie, Jonathan M.; Kim, Min P.

    2012-01-01

    We compared the growth of human lung cancer cells in an ex vivo three-dimensional (3D) lung model and 2D culture to determine which better mimics lung cancer growth in patients. A549 cells were grown in an ex vivo 3D lung model and in 2D culture for 15 days. We measured the size and formation of tumor nodules and counted the cells after 15 days. We also stained the tissue/cells for Ki-67, and Caspase-3. We measured matrix metalloproteinase (MMP) levels in the conditioned media and in blood plasma from patients with adenocarcinoma of the lung. Organized tumor nodules with intact vascular space formed in the ex vivo 3D lung model but not in 2D culture. Proliferation and apoptosis were greater in the ex vivo 3D lung model compared to the 2D culture. After 15 days, there were significantly more cells in the 2D culture than the 3D model. MMP-1, MMP-9, and MMP-10 production were significantly greater in the ex vivo 3D lung model. There was no production of MMP-9 in the 2D culture. The patient samples contained MMP-1, MMP-2, MMP-9, and MMP-10. The human lung cancer cells grown on ex vivo 3D model form perfusable nodules that grow over time. It also produced MMPs that were not produced in 2D culture but seen in human lung cancer patients. The ex vivo 3D lung model may more closely mimic the biology of human lung cancer development than the 2D culture. PMID:23028922

  5. Sustained function of genetically modified porcine lungs in an ex vivo model of pulmonary xenotransplantation.

    Science.gov (United States)

    Westall, Glen P; Levvey, Browyn J; Salvaris, Evelyn; Gooi, Julian; Marasco, Sylvana; Rosenfeldt, Frank; Egan, Chris; McEgan Ccp, Robin; Mennen, Mark; Russell, Prue; Robson, Simon C; Nottle, Mark B; Dwyer, Karen M; Snell, Greg I; Cowan, Peter J

    2013-11-01

    Xenotransplantation could provide a solution to the donor shortage that is currently the major barrier to solid-organ transplantation. The ability to breed pigs with multiple genetic modifications provides a unique opportunity to explore the immunologic challenges of pulmonary xenotransplantation. Explanted lungs from wild-type and 3 groups of genetically modified pigs were studied: (i) α1,3-galactosyltransferase gene knockout (GTKO); (ii) GTKO pigs expressing the human complementary regulatory proteins CD55 and CD59 (GTKO/CD55-59); and (iii) GTKO pigs expressing both CD55-59 and CD39 (GTKO/CD55-59/CD39). The physiologic, immunologic and histologic properties of porcine lungs were evaluated on an ex vivo rig after perfusion with human blood. Lungs from genetically modified pigs demonstrated stable pulmonary vascular resistance and better oxygenation of the perfusate, and survived longer than wild-type lungs. Physiologic function was inversely correlated with the degree of platelet sequestration into the xenograft. Despite superior physiologic profiles, lungs from genetically modified pigs still showed evidence of intravascular thrombosis and coagulopathy after perfusion with human blood. The ability to breed pigs with multiple genetic modifications, and to evaluate lung physiology and histology in real-time on an ex vivo rig, represent significant advances toward better understanding the challenges inherent to pulmonary xenotransplantation. © 2013 International Society for Heart and Lung Transplantation. All rights reserved.

  6. Genetic Variants of Intron Region of Aquaporin AQP5 Gene and Development of Pulmonary Edema in Lung Infection Complicated by Septic Shock

    Directory of Open Access Journals (Sweden)

    A. E. Myazin

    2016-01-01

    Full Text Available Purpose of the study. Determine the value of genetic variants of a single nucleotide polymorphic site rs3736309 of intron 3 of aquaporin5 (AQP5 gene in the course of critical illness in patients with documented pulmonary infection. Materials and methods. Patients with critical illness admitted to the intensive care units were examined during the course of treatment (n=86, age 27 to 82 years, mean age 53.20±14.34 years. Main diagnosis included malignancies (15%, peritonitis (16% and necrotizing pancreatitis (37%. Patients developed nosocomial pneumonia (55%, acute respiratory distress syndrome (ARDS (54%, septic shock (48%, ARDS combined with septic shock (33%. Bacterial species of Pseudomonas aeruginosa , Klebsiella pneumoniae, Acinetobacter baumannii, and/or Proteus mirabilis alone or in association were revealed in lavage fluid. DNA genotyping DNA was carried out using tetraprimer polymerase chain reaction (PCR. Statistical processing was performed using GraphPad InStat program (GraphPad, USA.Results. The distribution of frequencies of genotypes AA, GA and GG (AQP5, rs3736309 in cohort of patients corresponded to HardyWeinberg equilibrium (P=0.923 and was similar to frequencies of same alleles determined in a conditionally healthy Caucasian individuals (literature data (P>0.05. In a subgroup of patients with septic shock and AQP5 AA (rs3736309 genotype the lower EVLWI values were found compared to patients with genotypes GG and GA with septic shock in spite of the same approach to treatment. The differences between genetically different subgroups of patients with septic shock were maintained throughout the life of the survey (P<0.05,days 1, 3, 5 and 7. Genetic variant AQP5 G+ (rs3736309 contributed to the development of pulmonary edema resistant to treatment (odds ratio, OR = 6,75; P=0.032. Only the subgroup of patients with septic shock and genotype G + (but not all patients or the subgroup of patients without septic shock of the

  7. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    Science.gov (United States)

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P transplantation was higher (79 [40-84] vs. 39 [36-46], P transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

  8. Quantification of Lung Metastases from In Vivo Mouse Models

    DEFF Research Database (Denmark)

    Chang, Joan; Erler, Janine T

    2016-01-01

    Cancer research has made significant progress in terms of understanding and targeting primary tumors; however, the challenge remains for the successful treatment of metastatic cancers. This highlights the importance to use in vivo models to study the metastatic process, as well as for preclinical...

  9. Antiproliferative and chemopreventive effects of adlay seed on lung cancer in vitro and in vivo.

    Science.gov (United States)

    Chang, Hui-Chiu; Huang, Yu-Chun; Hung, Wen-Chun

    2003-06-04

    This study examined the effects of different extracts of adlay seed on the growth of human lung cancer cells in vitro and in vivo. The data showed that a methanolic extract, but not a water extract, of adlay seed exerted an antiproliferative effect on A549 lung cancer cells by inducing cell cycle arrest and apoptosis. It was also found that tumor growth in vivo was inhibited by the methanolic extract in a dose-dependent manner. The chemopreventive effect of adlay seed on the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice was also investigated. Groups of mice were pre-fed with different diets, followed by feeding with NNK-containing drinking water for 8 months. The results indicated that feeding with diet containing 30% of powdered adlay seed reduced the number of surface lung tumors by approximately 50%. Taken together, these results indicate that the components of adlay seed exert an anticancer effect in vitro and in vivo and may be useful for the prevention of lung tumorigenesis.

  10. Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo.

    Science.gov (United States)

    Lehmann, Mareike; Korfei, Martina; Mutze, Kathrin; Klee, Stephan; Skronska-Wasek, Wioletta; Alsafadi, Hani N; Ota, Chiharu; Costa, Rita; Schiller, Herbert B; Lindner, Michael; Wagner, Darcy E; Günther, Andreas; Königshoff, Melanie

    2017-08-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown. Here we demonstrate that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells.Primary fibrotic mouse alveolar epithelial type (AT)II cells secreted increased amounts of senescence-associated secretory phenotype (SASP) factors in vitro, as analysed using quantitative PCR, mass spectrometry and ELISA. Importantly, pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced SASP factors and extracellular matrix markers, while increasing alveolar epithelial markers.These data indicate that alveolar epithelial cell senescence contributes to lung fibrosis development and that senolytic drugs may be a viable therapeutic option for IPF. Copyright ©ERS 2017.

  11. Breast cancer cells form primary tumors on ex vivo four-dimensional lung model.

    Science.gov (United States)

    Pence, Kristi A; Mishra, Dhruva K; Thrall, Michael; Dave, Bhuvanesh; Kim, Min P

    2017-04-01

    Breast cancer mortality is most common in cancer in women, and there are no ex vivo models that can capture the primary growth of tumor with fidelity to the in vivo tumor growth. In this study, we grew human breast cancer cell lines in an acellular lung matrix of the ex vivo four-dimensional lung model to determine if they form primary tumor and the extent to which they mimic the histology and characteristics of the human tumors. Rat lungs were harvested, decellularized, and placed in a bioreactor. To study the primary tumor growth, we seeded the lung via the trachea with human breast cancer cells SUM159, MCF7, or MDMB231 and perfused the pulmonary artery with oxygenated media. Lobectomies were performed and processed for hematoxylin and eosin, Ki-67, caspase-3, estrogen receptor, and progesterone receptor antibodies. All three cell lines grew in the ex vivo four-dimensional model and formed perfusable tumor nodules with similar histology and morphology as the primary tumors. SUM159 and MDAMB231 showed higher proliferation and apoptotic indices than MCF7. In addition, MCF7 retained its estrogen receptor and progesterone receptor positivity, whereas SUM159 and MDAMB 231 did not have any staining. Overall, our study showed that human breast cancer cells can be grown on the ex vivo four-dimensional lung model, which then form primary tumor nodules that mimic the morphology and histology of the original tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Contemporary review of the organ care system in lung transplantation: potential advantages of a portable ex-vivo lung perfusion system.

    Science.gov (United States)

    Schmack, Bastian; Weymann, Alexander; Mohite, Prashant; Garcia Saez, Diana; Zych, Bartlomiej; Sabashnikov, Anton; Zeriouh, Mohamed; Schamroth, Joel; Koch, Achim; Soresi, Simona; Ananiadou, Olga; De Robertis, Fabio; Karck, Matthias; Simon, Andre Ruediger; Popov, Aron Frederik

    2016-11-01

    Lung transplantation remains the definite treatment for various end-stage lung diseases. Cold flush perfusion, the standard method for organ procurement has severe limitations. Organ Care System (OCS; TransMedics, Inc., Andover, USA) is an approved method to preserve hearts for transplantation that allows for greatly reduced cold ischemic time. Consequently, the use of an adapted OCS lung as a portable full ex-vivo lung perfusion system in lung transplantation is currently under close evaluation. Areas covered: The aim of this article is to review the advantages and the role of the OCS in the field of lung transplantation by reviewing the latest literature and evaluating this novel procurement technique in the context of conventional methods like cold flush and regular ex-vivo lung perfusion. Expert commentary: The use of OCS in the field of lung transplantation has great potential for improved patients outcomes and is justified in cases with (i) marginal donor lungs, (ii) foreseeable long time of transportation (iii) high-risk recipient or donor /recipient profiles, particularly in the setting of an overall increasing need for suitable donor organs. Results from two major multi-centre prospective studies are pending to objectively assess the possible advantages of this portable ex-vivo lung perfusion system.

  13. In vivo imaging of the spectral line broadening of the human lung in a single breathhold.

    Science.gov (United States)

    Carinci, Flavio; Meyer, Cord; Breuer, Felix A; Jakob, Peter M

    2016-09-01

    To present a technique, which allows for the in vivo quantification of the spectral line broadening of the human lung in a single breathhold. The line broadening is an interesting parameter of the lung because it can provide information about important lung properties, namely: inflation and oxygen uptake. The proposed technique integrates the asymmetric spin-echo (ASE) approach, which is commonly used to quantify the line broadening, with a single shot turbo spin-echo pulse sequence with half-Fourier acquisition (HASTE), to reduce the acquisition times. Imaging experiments were performed at 1.5 Tesla on 14 healthy volunteers, using a ASE-prepared HASTE sequence. The line broadening was quantified using a two-points method. Data were acquired at different breathing states: functional residual capacity (FRC) and total lung capacity (TLC), and with different breathing gases: room-air and pure-oxygen. Image acquisition was accomplished within a single breathhold of approximately 15 s duration. The violation of the Carr-Purcell-Meiboom-Gill conditions, deriving from inhomogeneities of the static magnetic field, was overcome by means of radiofrequency-phase cycling and generalized autocalibrating partially parallel acquisitions (GRAPPA) reconstruction. Significant increase of the line broadening was observed with both lung inflation and oxygen concentration (P lung parenchyma at different breathing states (1.48 ± 0.29 ppm at FRC and 1.95 ± 0.43 ppm at TLC) are in agreement with previous reports and show excellent reproducibility, with a coefficient of variation lung in vivo. Image acquisition can be accomplished in a single breathhold, which could be suitable for clinical applications on patients with lung diseases. J. Magn. Reson. Imaging 2016;44:745-757. © 2016 International Society for Magnetic Resonance in Medicine.

  14. Towards in vivo bacterial detection in human lung(Conference Presentation)

    Science.gov (United States)

    Choudhary, Tushar R.; Bradley, Mark; Duncan, Rory R.; Dhaliwal, Kevin

    2017-04-01

    Antibiotic resistance is a serious global concern. One way to tackle this problem is to develop new and sensitive approaches to diagnose bacterial infections and prevent unnecessary antibiotic use. With recent developments in optical molecular imaging, we are one step closer to in situ rapid detection of bacterial infections. We present here bespoke fluorescent probes for bacterial detection in ex vivo human lung tissue using fluorescence lifetime imaging microscopy (FLIM). Two in-house synthesised bespoke probes were used in this study to detect and differentiate between Gram positive and Gram negative bacterial strain using their fluorescence lifetime in the ex vivo human lung tissue. The average fluorescence lifetime of Gram positive probe (n=12) was 2.40 ± 0.25 ns and Gram negative (n=12) was 6.73 ± 0.49 ns. The human lung tissue (n=12) average fluorescence lifetime value was found to be 3.43 ± 0.19 ns. Furthermore we were also able to distinguish between dead or alive bacteria in ex vivo lung tissue based on difference in their lifetime. We have developped Fibre-FLIM methods to enable clinical translation within the Proteus Project (www.proteus.ac.uk).

  15. Calibration of the Accuscan II IN Vivo System for High Energy Lung Counting

    Energy Technology Data Exchange (ETDEWEB)

    Ovard R. Perry; David L. Georgeson

    2011-07-01

    This report describes the April 2011 calibration of the Accuscan II HpGe In Vivo system for high energy lung counting. The source used for the calibration was a NIST traceable lung set manufactured at the University of Cincinnati UCLL43AMEU & UCSL43AMEU containing Am-241 and Eu-152 with energies from 26 keV to 1408 keV. The lung set was used in conjunction with a Realistic Torso phantom. The phantom was placed on the RMC II counting table (with pins removed) between the v-ridges on the backwall of the Accuscan II counter. The top of the detector housing was positioned perpendicular to the junction of the phantom clavicle with the sternum. This position places the approximate center line of the detector housing with the center of the lungs. The energy and efficiency calibrations were performed using a Realistic Torso phantom (Appendix I) and the University of Cincinnati lung set. This report includes an overview introduction and records for the energy/FWHM and efficiency calibration including performance verification and validation counting. The Accuscan II system was successfully calibrated for high energy lung counting and verified in accordance with ANSI/HPS N13.30-1996 criteria.

  16. Morphology, in vivo distribution and antitumor activity of bexarotene nanocrystals in lung cancer.

    Science.gov (United States)

    Wang, Yongjie; Rong, Jinghong; Zhang, Jiaozhen; Liu, Yu; Meng, Xuelian; Guo, Hejian; Liu, Hongsheng; Chen, Lijiang

    2017-01-01

    The objective of this study was to develop and evaluate the morphology, biodistribution and antitumor activity of bexarotene nanocrystals delivery system. The morphology was investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscope and bexarotene nanocrystals exhibited the advantages of making the efficacy more steady and durable compared with control group in lung with less cardiac accumulation as shown by biodistribution studies in vivo. In addition, MTT assay, flow cytometry analysis, observation of morphological changes and apoptotic body demonstrated that bexarotene nanocrystals could significantly enhance the in vitro cytotoxicity and induced G1 cycle arrest and apoptosis against A549 cells. Also, bexarotene nanocrystals had significant antitumor activity in mice bearing A549 cell line. This finding was correlated with both in vitro and in vivo. Thereby, the overall results suggest that the bexarotene nanocrystals represent a potential source of medicine, which made bexarotene nanocrystals a promising candidate for the treatment of lung cancer.

  17. Using Dual Fluorescence Reporting Genes to Establish an In Vivo Imaging Model of Orthotopic Lung Adenocarcinoma in Mice.

    Science.gov (United States)

    Lai, Cheng-Wei; Chen, Hsiao-Ling; Yen, Chih-Ching; Wang, Jiun-Long; Yang, Shang-Hsun; Chen, Chuan-Mu

    2016-12-01

    Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy. A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system. For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells. We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung.

  18. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died...... of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155......% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted...

  19. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    % improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died...... of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155...

  20. How to Recondition Ex Vivo Initially Rejected Donor Lungs for Clinical Transplantation: Clinical Experience from Lund University Hospital

    Directory of Open Access Journals (Sweden)

    Sandra Lindstedt

    2011-01-01

    Full Text Available A major problem in clinical lung transplantation is the shortage of donor lungs. Only about 20% of donor lungs are accepted for transplantation. We have recently reported the results of the first six double lung transplantations performed with donor lungs reconditioned ex vivo that had been deemed unsuitable for transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant organizations because the arterial oxygen pressure was less than 40 kPa. The three-month survival of patients undergoing transplant with these lungs was 100%. One patient died due to sepsis after 95 days, and one due to rejection after 9 months. Four recipients are still alive and well 24 months after transplantation, with no signs of bronchiolitis obliterans syndrome. The donor lungs were reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue. Functional evaluation was performed with deoxygenated perfusate at different inspired fractions of oxygen. The arterial oxygen pressure was significantly improved in this model. This ex vivo evaluation model is thus a valuable addition to the armamentarium in increasing the number of acceptable lungs in a donor population with inferior arterial oxygen pressure values, thereby, increasing the lung donor pool for transplantation. In the following paper we present our clinical experience from the first six patients in the world. We also present the technique we used in detail with flowchart.

  1. Supernatant of Aged Erythrocytes Causes Lung Inflammation and Coagulopathy in a "Two-Hit" In Vivo Syngeneic Transfusion Model

    NARCIS (Netherlands)

    Vlaar, Alexander P. J.; Hofstra, Jorrit J.; Levi, Marcel; Kulik, Willem; Nieuwland, Rienk; Tool, Anton T. J.; Schultz, Marcus J.; de Korte, Dirk; Juffermans, Nicole P.

    2010-01-01

    Background: Transfusion of erythrocytes is associated with increased morbidity in certain patient groups. Storage time of erythrocytes may contribute to respiratory complications. Using a syngeneic in vivo transfusion model, we investigated whether transfusion of stored rat erythrocytes causes lung

  2. Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

    Directory of Open Access Journals (Sweden)

    Cyril Francioli

    Full Text Available Damaged lung grafts obtained after circulatory death (DCD lungs and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP. Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6 or in presence of PDTC (2.5g/L, PDTC group, N = 6. Static pulmonary compliance (SPC, peak airway pressure (PAWP, pulmonary vascular resistance (PVR, and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema, and the concentration of LDH (cell damage, proteins (permeability edema and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL, and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

  3. In vivo fluorescence imaging of bacteriogenic cyanide in the lungs of live mice infected with cystic fibrosis pathogens.

    Directory of Open Access Journals (Sweden)

    Seong-Won Nam

    Full Text Available BACKGROUND: Pseudomonas aeruginosa (PA and Burkholderia cepacia complex (Bcc, commonly found in the lungs of cystic fibrosis (CF patients, often produce cyanide (CN, which inhibits cellular respiration. CN in sputa is a potential biomarker for lung infection by CF pathogens. However, its actual concentration in the infected lungs is unknown. METHODS AND FINDINGS: This work reports observation of CN in the lungs of mice infected with cyanogenic PA or Bcc strains using a CN fluorescent chemosensor (4',5'-fluorescein dicarboxaldehyde with a whole animal imaging system. When the CN chemosensor was injected into the lungs of mice intratracheally infected with either PA or B. cepacia strains embedded in agar beads, CN was detected in the millimolar range (1.8 to 4 mM in the infected lungs. CN concentration in PA-infected lungs rapidly increased within 24 hours but gradually decreased over the following days, while CN concentration in B. cepacia-infected lungs slowly increased, reaching a maximum at 5 days. CN concentrations correlated with the bacterial loads in the lungs. In vivo efficacy of antimicrobial treatments was tested in live mice by monitoring bacteriogenic CN in the lungs. CONCLUSIONS: The in vivo imaging method was also found suitable for minimally invasive testing the efficacy of antibiotic compounds as well as for aiding the understanding of bacterial cyanogenesis in CF lungs.

  4. IN VIVO EVIDENCE OF FREE RADICAL FORMATION IN THE RAT LUNG AFTER EXPOSURE TO AN EMISSION SOURCE AIR POLLUTION PARTICLE

    Science.gov (United States)

    Exposure to air pollution particles can be associated with increased human morbidity and mortality. The mechanism(s) of lung injury remains unknown. We tested the hypothesis that lung exposure to oil fly ash (an emission source air pollution particle) causes in vivo free radical ...

  5. Inflation Pressures for Ex Vivo Lung Biopsies After Application of Graduated Compression Staples.

    Science.gov (United States)

    Imhoff, Darren J; Monnet, Eric

    2016-01-01

    To compare 2 graduated compression staples (Tri-Staple™, Covidien, Norwalk, CT) and standard staples (Endo GIA™, Covidien) for lung biopsy in dogs. Ex vivo experimental study, randomized, unblocked. Lung lobes (n = 18) from 4 canine cadavers. Eighteen lung lobes were harvested from 4 dogs immediately after euthanasia and randomized to 1 of 3 staples (n = 6 per stapler type). Each lung lobe was intubated and maintained inflated at 10 cmH2O. A biopsy of the periphery of each lung lobe was taken approximately 3 cm from the edge with a stapling device; the Tri-Staple™ medium/thick (TST), Tri-Staple™ vascular/medium (TSV), and Endo GIA™ 45-2.5 (EG). Each lobe was inflated to a maximum of 45 cmH2O of water to determine the pressure at which air leakage occurred (leak pressure). The mean (95% confidence interval) leak pressure was 38.0 cmH2O (33.1-42.9) for EG, 29.2 (24.3-34.0) for TSV, and 26.0 (21.1-30.9) for TST. The mean leak pressure was significantly higher for EG than TSV (P = .016) and for EG than TST (P = .002), but was not different between TSV and TST (P = .344). One TSV leaked at 20 cmH2O and 1 TST leaked at 17 cmH2O. The surface area of the biopsy samples was not significantly different for staple types (P = .183). Both TST and TSV leaked at significantly lower airway pressures than EG and may not be suitable for canine lung biopsy as some specimens leaked at pressures of 20 cmH2O or less. © Copyright 2015 by The American College of Veterinary Surgeons.

  6. Hyaluronan with dextran added to therapeutic lung surfactants improves effectiveness in vitro and in vivo.

    Science.gov (United States)

    Lu, Karen W; Taeusch, H William; Clements, John A

    2013-01-01

    Surfactants in current clinical use are largely ineffective in treating acute lung injury (ALI)/ acute respiratory distress syndrome. In part, this ineffectiveness is due to inactivation of surfactant by serum leakage into the alveoli. Previously, we reported that adding hyaluronan and some nonionic polymers to synthetic lipids combined with native SP-B and SP-C enhanced surface activity. In this study, we first tested two therapeutic lung surfactants and then retested after adding hyaluronan, polyethylene glycol or dextran alone or in two-polymer combinations including hyaluronan in the absence or presence of serum. Surface activities were measured in a modified bubble surfactometer. Results indicate that the inhibition threshold (defined as the amount of serum required to produce a minimum surface tension above 10 mN/m after 5 minutes of cycling) was 35 times higher with hyaluronan plus dextran added to Infasurf than with Infasurf alone, and better than all other mixtures tested. The threshold for Survanta with hyaluronan plus polyethylene glycol was 7 times higher than Survanta alone. We next tested selected surfactant mixtures in an animal model that mimicked ALI. All measurements of lung function showed significant improvement (P ≤ .05) with hyaluronan, or with hyaluronan and dextran added to Infasurf compared to Infasurf alone. Also, for these two groups, lung function was still improving at the end of the experiment. We conclude that certain polymers added to clinical surfactants can greatly increase resistance to inactivation in vitro, while in vivo, both Infasurf mixtures containing hyaluronan tended to normalize measures of lung function unlike other mixtures tested.

  7. Monte Carlo simulation of in-vivo measurement of lung contamination; Simulacion Monte Carlo de medida in-vivo de contaminacion en pulmon

    Energy Technology Data Exchange (ETDEWEB)

    Moraleda, M.; Gomez-Ros, J. M.; Lopez, M. A.; Navarro, J. F.; Broggio, D.

    2011-07-01

    This paper describes the technique used to simulate in-vivo measurement of lung contaminated with enriched uranium using an anthropomorphic phantom of thorax. This work was carried out as part of an international intercomparison between different institutions within collaborative actions EURADOS promoted.

  8. First in vivo magnetic particle imaging of lung perfusion in rats

    Science.gov (United States)

    Zhou, Xinyi Y.; Jeffris, Kenneth E.; Yu, Elaine Y.; Zheng, Bo; Goodwill, Patrick W.; Nahid, Payam; Conolly, Steven M.

    2017-05-01

    Pulmonary embolism (PE), along with the closely related condition of deep vein thrombosis, affect an estimated 600 000 patients in the US per year. Untreated, PE carries a mortality rate of 30%. Because many patients experience mild or non-specific symptoms, imaging studies are necessary for definitive diagnosis of PE. Iodinated CT pulmonary angiography is recommended for most patients, while nuclear medicine-based ventilation/perfusion (V/Q) scans are reserved for patients in whom the use of iodine is contraindicated. Magnetic particle imaging (MPI) is an emerging tracer imaging modality with high image contrast (no tissue background signal) and sensitivity to superparamagnetic iron oxide (SPIO) tracer. Importantly, unlike CT or nuclear medicine, MPI uses no ionizing radiation. Further, MPI is not derived from magnetic resonance imaging (MRI); MPI directly images SPIO tracers via their strong electronic magnetization, enabling deep imaging of anatomy including within the lungs, which is very challenging with MRI. Here, the first high-contrast in vivo MPI lung perfusion images of rats are shown using a novel lung perfusion agent, MAA-SPIOs.

  9. [Proteus mirabilis septic arthritis].

    Science.gov (United States)

    Sbiti, Mohammed; Bouhamidi, Bahia; Louzi, Lhoussaine

    2017-01-01

    Acute septic arthritis is rare. It is associated with poor prognosis in terms of mortality and morbidity. We report the case of a 61-year old patient with spontaneous Proteus mirabilis septic arthritis. He suffered from complicated diabetes associated with positive blood cultures and synovial fluid cultures. Patient's evolution was favorable thanks to early diagnosis and initiation of adequate antibiotic therapy. Proteus mirabilis septic arthritis is rare. On that basis we conducted a literature review of cases of Proteus mirabilis pyogenic arthritis to highlight the risk factors, pathogenesis, treatment and evolution of these diseases. Diagnosis is commonly based on microbiological analysis, early articular puncture biopsy is performed before the initiation of antibiotic treatment, direct examination, culture and antibiogram which are useful as guidance for antibiotic therapy. Septic arthritis is a diagnostic and therapeutic emergency; early management of this disease allows total healing without after-effects.

  10. In vitro and in vivo evaluation of a novel integrated wearable artificial lung.

    Science.gov (United States)

    Madhani, Shalv P; Frankowski, Brian J; Burgreen, Greg W; Antaki, Jim F; Kormos, Robert; D'Cunha, Jonathan; Federspiel, William J

    2017-07-01

    Conventional extracorporeal membrane oxygenation (ECMO) is cumbersome and is associated with high morbidity and mortality. We are currently developing the Pittsburgh Ambulatory Assist Lung (PAAL), which is designed to allow for ambulation of lung failure patients during bridge to transplant or recovery. In this study, we investigated the in vitro and acute in vivo performance of the PAAL. The PAAL features a 1.75-inch-diameter, cylindrical, hollow-fiber membrane (HFM) bundle of stacked sheets, with a surface area of 0.65 m(2) integrated with a centrifugal pump. The PAAL was tested on the bench for hydrodynamic performance, gas exchange and hemolysis. It was then tested in 40- to 60-kg adult sheep (n = 4) for 6 hours. The animals were cannulated with an Avalon Elite 27Fr dual-lumen catheter (DLC) inserted through the right external jugular into the superior vena cava (SVC), right atrium (RA) and inferior vena cava (IVC). The PAAL pumped >250 mm Hg at 3.5 liters/min at a rotation speed of 2,100 rpm. Oxygenation performance met the target of 180 ml/min at 3.5 liters/min of blood flow in vitro, resulting in a gas-exchange efficiency of 278 ml/min/m(2). The normalized index of hemolysis (NIH) for the PAAL and cannula was 0.054 g per 100 liters (n = 2) at 3.5 liters/min, as compared with 0.020 g per 100 liters (n = 2) for controls (DLC cannula and a Centrimag pump). Plasma-free hemoglobin (pfHb) was liters/min. The PAAL met in vitro and acute in vivo performance targets. Five-day chronic sheep studies are planned for the near future. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  11. AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo.

    Science.gov (United States)

    Chen, Xinglu; Chen, Sansan; Pei, Nana; Mao, Yingying; Wang, Shengyao; Yan, Renhe; Bai, Na; Li, Andrew; Zhang, Yanling; Du, Hongyan; Chen, Baihong; Sumners, Colin; Li, Jinlong; Li, Hongwei

    2017-01-03

    Ang-(1-7) inhibits lung cancer cell growth both in vitro and in vivo. However, the molecular mechanism of action is unclear and also the rapid degradation of Ang-(1-7) in vivo limits its clinical application. Here, we have demonstrated that Ang- (1-7) inhibits lung cancer cell growth by interrupting pre-replicative complex assembly and restrains epithelial-mesenchymal transition via Cdc6 inhibition. Furthermore, we constructed a mutant adeno-associated viral vector AAV8 (Y733F) that produced stable and high efficient Ang-(1-7) expression in a xenograft tumor model. The results show that AAV8-mediated Ang-(1-7) over-expression can remarkably suppress tumor growth in vivo by down-regulating Cdc6 and anti-angiogenesis. Ang-(1-7) over-expression via the AAV8 method may be a promising strategy for lung cancer treatment.

  12. Septic arthritis in children

    African Journals Online (AJOL)

    Age in years . \\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\\M. -~ A It. Aki/zy/mla at a! 30 “". Elbow Ankle. 3(32) 2(2.1). %. 74.2. 69.9. 38.7. Shoulder. 14(15.1). Septic (li'I/ll'iti.\\' in children. 2. 69. 36. Hip Knee. No of patients. 14. Age distribution and prevalence of septic arthritis of different joints. Total(%) 45(48.4) 24(25.8). Age (yrs). Table]. 0-1. >10~ 15.

  13. Ex vivo expansion of alveolar macrophages with Mycobacterium tuberculosis from the resected lungs of patients with pulmonary tuberculosis.

    Science.gov (United States)

    Ufimtseva, Elena; Eremeeva, Natalya; Petrunina, Ekaterina; Umpeleva, Tatiana; Karskanova, Svetlana; Bayborodin, Sergey; Vakhrusheva, Diana; Kravchenko, Marionella; Skornyakov, Sergey

    2018-01-01

    Tuberculosis (TB), with the Mycobacterium tuberculosis (Mtb) as the causative agent, remains to be a serious world health problem. Traditional methods used for the study of Mtb in the lungs of TB patients do not provide information about the number and functional status of Mtb, especially if Mtb are located in alveolar macrophages. We have developed a technique to produce ex vivo cultures of cells from different parts of lung tissues surgically removed from patients with pulmonary TB and compared data on the number of cells with Mtb inferred by the proposed technique to the results of bacteriological and histological analyses used for examination of the resected lungs. The ex vivo cultures of cells obtained from the resected lungs of all patients were largely composed of CD14-positive alveolar macrophages, foamy or not, with or without Mtb. Lymphocytes, fibroblasts, neutrophils, and multinucleate Langhans giant cells were also observed. We found alveolar macrophages with Mtb in the ex vivo cultures of cells from the resected lungs of even those TB patients, whose sputum smears and lung tissues did not contain acid-fast Mtb or reveal growing Mtb colonies on dense medium. The detection of alveolar macrophages with Mtb in ex vivo culture as soon as 16-18 h after isolation of cells from the resected lungs of all TB patients suggests that the technique proposed for assessing the level of infection in alveolar macrophages of TB patients has higher sensitivity than do prolonged bacteriological or pathomorphological methods. The proposed technique allowed us to rapidly (in two days after surgery) determine the level of infection with Mtb in the cells of the resected lungs of TB patients and, by the presence or absence of Mtb colonies, including those with cording morphology, the functional status of the TB agent at the time of surgery.

  14. Normothermic Ex Vivo Lung Perfusion in Brain-dead Donors Reduces Inflammatory Cytokines and Toll-like Receptor Expression.

    Science.gov (United States)

    Shafaghi, Shadi; Mortaz, Esmaeil; Abbasi Dezfuli, Azizollah; Godarzi, Hoda; Sheikhy, Kambiz; Ansari Aval, Zahra; Farzanegan, Behrooz; Emami, Habib; Hosseini-Baharanchi, Fatemeh Sadat; Najafizadeh, Katayoun

    2016-10-01

    Inflammatory responses and innate immunologic reactions play an important role in the respiratory system. Ex vivo lung perfusion (EVLP) is considered a novel method in the evaluation and reconditioning of donor lungs prior to transplantation. However, EVLP's effect on inflammatory and metabolic markers of human lung tissue is unknown.  This study investigated how the performance of EVLP on brain-dead (BD) donor lungs affects the production and release of inflammatory cytokines (IL-6, IL-8, and TNF-a), inflammatory cells and toll-like receptors (TLR) -2, 4. This study was conducted with an animal subject for qualification of EVLP team and then EVLP was performed on 4 human cases referred to Masih Daneshvari Hospital (Tehran,Iran), from May 2013 to July 2015. Two of these cases, who had acceptable lung function parameters, were enrolled in this study for immunologic investigations. Bronchoalveolar lavages (BAL) were taken before and after EVLP. Cytokines were quantitatively measured before lung retrieval, at the end of the lung removal, at the start of EVLP, and at the end of the each hour of EVLP. TLR expression was measured on the cells obtained by flow cytometry. TNF-a, IL-6 and IL-8 decreased in each stage of washing perfusate in both cases, and the level of cytokines in serum was in the normal range. Flow cytometry analysis revealed a decreasing expression of CD3, CD4/8, CD19, and CD16+56, as well as TLR-2 and TLR-4 in both cases. Intra-capillary pools of pro-inflammatory cytokines (IL-6, IL-8, and TNF-a) were determined to contribute to the lung injury during prolonged lung perfusion. This raises the possibility that EVLP donor lungs could be less immunogenic than standard lungs. However, to assess EVLP's effects on lung grafts and optimize recipient outcomes, further studies with a sufficient number of lungs are required.

  15. Rho inhibition by lovastatin affects apoptosis and DSB repair of primary human lung cells in vitro and lung tissue in vivo following fractionated irradiation

    Science.gov (United States)

    Ziegler, Verena; Henninger, Christian; Simiantonakis, Ioannis; Buchholzer, Marcel; Ahmadian, Mohammad Reza; Budach, Wilfried; Fritz, Gerhard

    2017-01-01

    Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy). The statin improved the repair of radiation-induced DNA double-strand breaks (DSBs) in all cell types and, moreover, protected lung endothelial cells from IR-induced caspase-dependent apoptosis, likely involving p53-regulated mechanisms. Under the in vivo situation, treatment with lovastatin or the Rac1-specific small molecule inhibitor EHT1864 attenuated the IR-induced increase in breathing frequency and reduced the percentage of γH2AX and 53BP1-positive cells. This indicates that inhibition of Rac1 signaling lowers IR-induced residual DNA damage by promoting DNA repair. Moreover, lovastatin and EHT1864 protected lung tissue from IR-triggered apoptosis and mitigated the IR-stimulated increase in regenerative proliferation. Our data document beneficial anti-apoptotic and genoprotective effects of pharmacological targeting of Rho signaling following hypo-fractionated irradiation of lung cells in vitro and in vivo. Rac1-targeting drugs might be particular useful for supportive care in radiation oncology and, moreover, applicable to improve the anticancer efficacy of radiotherapy by widening the therapeutic window of thoracic radiation exposure. PMID:28796249

  16. Role of complement in in vitro and in vivo lung inflammatory reactions

    DEFF Research Database (Denmark)

    Czermak, B J; Lentsch, A B; Bless, N M

    1998-01-01

    Complement is one of the integral buttresses of the inflammatory response. In addition to host defense activities, proinflammatory properties of several complement components are described. This overview elucidates the role of complement in inflammatory reactions in vitro and in vivo, focusing...... on the complement activation products, C5a, and the membrane attack complex, C5b-9. Using several approaches, the impact of these complement components in mechanisms relevant to neutrophil recruitment is emphasized. In addition, the participation of complement in endothelial superoxide generation and its essential...... requirement for full expression of lung injury is demonstrated, as are the involved intracellular signal transduction pathways. Understanding the mechanisms of complement-induced proinflammatory effects may provide a basis for future therapeutic blockade of complement and/or its activation products....

  17. Biosynthesized Platinum Nanoparticles Inhibit the Proliferation of Human Lung-Cancer Cells in vitro and Delay the Growth of a Human Lung-Tumor Xenograft in vivo -In vitro and in vivo Anticancer Activity of bio-Pt NPs-

    Directory of Open Access Journals (Sweden)

    Bendale Yogesh

    2016-06-01

    Full Text Available Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached 70 ─ 75 mm3, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

  18. Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung.

    Science.gov (United States)

    Skoog, David J; Pohlmann, Joshua R; Demos, David S; Scipione, Christopher N; Iyengar, Amit; Schewe, Rebecca E; Suhaib, Ahmed B; Koch, Kelly L; Cook, Keith E

    The compliant thoracic artificial lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL's long-term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic artificial lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL's resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.

  19. Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

    Directory of Open Access Journals (Sweden)

    Anastasia Velalopoulou

    2017-11-01

    Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS, pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

  20. Gastrointestinal perfusion in septic shock.

    NARCIS (Netherlands)

    Haren, E.M. van; Sleight, J.W.; Pickkers, P.; Hoeven, J.G. van der

    2007-01-01

    Septic shock is characterised by vasodilation, myocardial depression and impaired microcirculatory blood flow, resulting in redistribution of regional blood flow. Animal and human studies have shown that gastrointestinal mucosal blood flow is impaired in septic shock. This is consistent with

  1. An interesting septic embolism

    Directory of Open Access Journals (Sweden)

    Funda Uluorman

    2014-01-01

    Full Text Available Septic pulmonary embolism is a rare disease but mortality and morbidity of it is high. Septic pulmonary emboli comes from infected heart valves, thrombophlebitis, and pulmonary artery catheter or infected pacemaker wires as many sources [1,2]. In recent years, pacemaker is a common treatment of the bradiarrhythmia that is persisted in the etiology of septic embolism, its applications has started to pick up [3]. There is the growing number of patients with pacemaker, according to this the frequency of pacemaker lead infection and the number of patients at risk for right-sided endocarditis increase [4]. The patients don't have specific clinical and radiological features because of this it is very difficult to define, so the diagnosis is often delayed [5]. A detailed medical history, a detailed physical examination in diagnosis and evaluation of good additional imaging methods is very important. Early diagnosis and proper treatment, the implementation of the management, can provide good results.

  2. Chronic alcohol ingestion increases mortality and organ injury in a murine model of septic peritonitis.

    Directory of Open Access Journals (Sweden)

    Benyam P Yoseph

    Full Text Available BACKGROUND: Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was to determine how chronic alcohol ingestion alters the host response to sepsis in mice. METHODS: Mice were randomized to receive either alcohol or water for 12 weeks and then subjected to cecal ligation and puncture. Mice were sacrificed 24 hours post-operatively or followed seven days for survival. RESULTS: Septic alcohol-fed mice had a significantly higher mortality than septic water-fed mice (74% vs. 41%, p = 0.01. This was associated with worsened gut integrity in alcohol-fed mice with elevated intestinal epithelial apoptosis, decreased crypt proliferation and shortened villus length. Further, alcohol-fed mice had higher intestinal permeability with decreased ZO-1 and occludin protein expression in the intestinal tight junction. The frequency of splenic and bone marrow CD4+ T cells was similar between groups; however, splenic CD4+ T cells in septic alcohol-fed mice had a marked increase in both TNF and IFN-γ production following ex vivo stimulation. Neither the frequency nor function of CD8+ T cells differed between alcohol-fed and water-fed septic mice. NK cells were decreased in both the spleen and bone marrow of alcohol-fed septic mice. Pulmonary myeloperoxidase levels and BAL levels of G-CSF and TFG-β were higher in alcohol-fed mice. Pancreatic metabolomics demonstrated increased acetate, adenosine, xanthine, acetoacetate, 3-hydroxybutyrate and betaine in alcohol-fed mice and decreased cytidine, uracil, fumarate, creatine phosphate, creatine, and choline. Serum and peritoneal cytokines were generally similar between alcohol-fed and water-fed mice, and there were no differences in bacteremia, lung wet to dry weight, or pulmonary, liver or splenic histology. CONCLUSIONS: When subjected to the same septic insult, mice with chronic alcohol ingestion have increased mortality

  3. Imaging of thrombosis and microcirculation in mouse lungs of initial melanoma metastasis with in vivo cryotechnique.

    Science.gov (United States)

    Saitoh, Yurika; Terada, Nobuo; Ohno, Nobuhiko; Hamano, Akiei; Okumura, Nobuo; Jin, Takashi; Saiki, Ikuo; Ohno, Shinichi

    2014-01-01

    Microscopic bioimaging of blood flow and distribution of cancer cells in lungs is essential to analyze mechanism of lung metastasis. Such cancer metastasis has been well known to induce hypercoagulable states and thrombosis. In histopathological tissue sections, however, it has been difficult to capture rapid phenomenon of thrombus formation due to technical problems associated with much less retention of soluble serum components as well as dynamic histological features reflecting their living states. In this study, to achieve bioimaging of both hypercoagulable states and thrombosis induced by early metastasis of mouse B16-BL6 melanoma, "in vivo cryotechnique" (IVCT) was used, which retained soluble components at their original sites. Glutathione-coated quantum dots (QDs) were subsequently injected after melanoma cells via right ventricles to examine plasma flow with fluorescence emission. At 5s after the melanoma injection, melanoma cells were mostly stacked and intruded in alveolar capillaries with changing their shapes. Assembly of platelets initially appeared at 1min, and they aggregated around the stacked melanoma cells at 5min. Such aggregated platelets were immunopositive for both phospho-tyrosine 418 and 527 of Src, indicating their partial signal activation. Fibrin monomers were also immunolocalized around both melanoma cells and platelet aggregates, and massive immunoreaction deposits of fibrinogen were also detected near the same areas, but more strongly detected around the melanoma cells, indicating initial thrombus formation. In those areas, QDs were rarely detected, probably because of the lack of blood supply. Thus, IVCT revealed histopathological features of initial thrombosis under their circulatory conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. An optimized two-photon method for in vivo lung imaging reveals intimate cell collaborations during infection

    Science.gov (United States)

    Fiole, Daniel; Deman, Pierre; Trescos, Yannick; Douady, Julien; Tournier, Jean-Nicolas

    2013-02-01

    Lung tissue motion arising from breathing and heart beating has been described as the largest annoyance of in vivo imaging. Consequently, infected lung tissue has never been imaged in vivo thus far, and little is known concerning the kinetics of the mucosal immune system at the cellular level. We have developed an optimized post-processing strategy to overcome tissue motion, based upon two-photon and second harmonic generation (SHG) microscopy. In contrast to previously published data, we have freed the lung parenchyma from any strain and depression in order to maintain the lungs under optimal physiological parameters. Excitation beams swept the sample throughout normal breathing and heart movements, allowing the collection of many images. Given that tissue motion is unpredictably, it was essential to sort images of interest. This step was enhanced by using SHG signal from collagen as a reference for sampling and realignment phases. A normalized cross-correlation criterion was used between a manually chosen reference image and rigid transformations of all others. Using CX3CR1+/gfp mice this process allowed the collection of high resolution images of pulmonary dendritic cells (DCs) interacting with Bacillus anthracis spores, a Gram-positive bacteria responsible for anthrax disease. We imaged lung tissue for up to one hour, without interrupting normal lung physiology. Interestingly, our data revealed unexpected interactions between DCs and macrophages, two specialized phagocytes. These contacts may participate in a better coordinate immune response. Our results not only demonstrate the phagocytizing task of lung DCs but also infer a cooperative role of alveolar macrophages and DCs.

  5. In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mylonaki, Effie; Manika, Katerina [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Zarogoulidis, Paul, E-mail: pzarog@hotmail.com [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas [Pulmonary Department, “G.Papanikolaou” General Hospital, Aristotle University of Thessaloniki (Greece); Mourelatos, Dionysios [Biology and Genetics, Medical School, Aristotle University of Thessaloniki (Greece)

    2012-12-15

    Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p < 0.001). The in vivo administration of AM after chemotherapy increased SCEs in both cancer types (SCLC: p < 0.001, NSCLC: p = 0.003) and this increase was synergistic, the rates of SCEs in the presence of AM were higher than the expected SCE values if the increases above background for chemotherapy and AM were independent and additive (SCLC: p < 0.001, NSCLC: p = 0.008). Although in both groups of patients cell division delays were observed after the combined chemotherapy plus in vivo AM treatment, the correlation between the magnitude of the SCE response and the PRI depression was not statistically significant (p > 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer.

  6. A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Lang Dagmar S

    2007-06-01

    Full Text Available Abstract Background Non-small cell lung cancer (NSCLC causes most of cancer related deaths in humans and is characterized by poor prognosis regarding efficiency of chemotherapeutical treatment and long-term survival of the patients. The purpose of the present study was the development of a human ex vivo tissue culture model and the analysis of the effects of conventional chemotherapy, which then can serve as a tool to test new chemotherapeutical regimens in NSCLC. Methods In a short-term tissue culture model designated STST (Short-Term Stimulation of Tissues in combination with the novel *HOPE-fixation and paraffin embedding method we examined the responsiveness of 41 human NSCLC tissue specimens to the individual cytotoxic drugs carboplatin, vinorelbine or gemcitabine. Viability was analyzed by LIFE/DEAD assay, TUNEL-staining and colorimetric MTT assay. Expression of Ki-67 protein and of BrdU (bromodeoxyuridine uptake as markers for proliferation and of cleaved (activated effector caspase-3 as indicator of late phase apoptosis were assessed by immunohistochemistry. Transcription of caspase-3 was analyzed by RT-PCR. Flow cytometry was utilized to determine caspase-3 in human cancer cell lines. Results Viability, proliferation and apoptosis of the tissues were moderately affected by cultivation. In human breast cancer, small-cell lung cancer (SCLC and human cell lines (CPC-N, HEK proliferative capacity was clearly reduced by all 3 chemotherapeutic agents in a very similar manner. Cleavage of caspase-3 was induced in the chemo-sensitive types of cancer (breast cancer, SCLC. Drug-induced effects in human NSCLC tissues were less evident than in the chemo-sensitive tumors with more pronounced effects in adenocarcinomas as compared to squamous cell carcinomas. Conclusion Although there was high heterogeneity among the individual tumor tissue responses as expected, we clearly demonstrate specific multiple drug-induced effects simultaneously. Thus, STST

  7. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo.

    Science.gov (United States)

    Chan, Michael C W; Kuok, Denise I T; Leung, Connie Y H; Hui, Kenrie P Y; Valkenburg, Sophie A; Lau, Eric H Y; Nicholls, John M; Fang, Xiaohui; Guan, Yi; Lee, Jae W; Chan, Renee W Y; Webster, Robert G; Matthay, Michael A; Peiris, J S Malik

    2016-03-29

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstrated that the effects are prevented or reduced by bone marrow-derived multipotent mesenchymal stromal cells. We verified the in vivo relevance of these findings in mice experimentally infected with influenza A/H5N1. We found that, in vitro, the alveolar epithelium's protein permeability and fluid clearance were dysregulated by soluble immune mediators released upon infection with avian (A/Hong Kong/483/97, H5N1) but not seasonal (A/Hong Kong/54/98, H1N1) influenza virus. The reduced alveolar fluid transport associated with down-regulation of sodium and chloride transporters was prevented or reduced by coculture with mesenchymal stromal cells. In vivo, treatment of aged H5N1-infected mice with mesenchymal stromal cells increased their likelihood of survival. We conclude that mesenchymal stromal cells significantly reduce the impairment of alveolar fluid clearance induced by A/H5N1 infection in vitro and prevent or reduce A/H5N1-associated acute lung injury in vivo. This potential adjunctive therapy for severe influenza-induced lung disease warrants rapid clinical investigation.

  8. Evaluation of combination therapy for Burkholderia cenocepacia lung infection in different in vitro and in vivo models.

    Directory of Open Access Journals (Sweden)

    Freija Van den Driessche

    Full Text Available Burkholderia cenocepacia is an opportunistic pathogen responsible for life-threatening infections in cystic fibrosis patients. B. cenocepacia is extremely resistant towards antibiotics and therapy is complicated by its ability to form biofilms. We investigated the efficacy of an alternative antimicrobial strategy for B. cenocepacia lung infections using in vitro and in vivo models. A screening of the NIH Clinical Collection 1&2 was performed against B. cenocepacia biofilms formed in 96-well microtiter plates in the presence of tobramycin to identify repurposing candidates with potentiator activity. The efficacy of selected hits was evaluated in a three-dimensional (3D organotypic human lung epithelial cell culture model. The in vivo effect was evaluated in the invertebrate Galleria mellonella and in a murine B. cenocepacia lung infection model. The screening resulted in 60 hits that potentiated the activity of tobramycin against B. cenocepacia biofilms, including four imidazoles of which econazole and miconazole were selected for further investigation. However, a potentiator effect was not observed in the 3D organotypic human lung epithelial cell culture model. Combination treatment was also not able to increase survival of infected G. mellonella. Also in mice, there was no added value for the combination treatment. Although potentiators of tobramycin with activity against biofilms of B. cenocepacia were identified in a repurposing screen, the in vitro activity could not be confirmed nor in a more sophisticated in vitro model, neither in vivo. This stresses the importance of validating hits resulting from in vitro studies in physiologically relevant model systems.

  9. First Evaluation of the New Thin Convex Probe Endobronchial Ultrasound Scope: A Human Ex Vivo Lung Study.

    Science.gov (United States)

    Patel, Priya; Wada, Hironobu; Hu, Hsin-Pei; Hirohashi, Kentaro; Kato, Tatsuya; Ujiie, Hideki; Ahn, Jin Young; Lee, Daiyoon; Geddie, William; Yasufuku, Kazuhiro

    2017-04-01

    Endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration allows for sampling of mediastinal lymph nodes. The external diameter, rigidity, and angulation of the convex probe EBUS renders limited accessibility. This study compares the accessibility and transbronchial needle aspiration capability of the prototype thin convex probe EBUS against the convex probe EBUS in human ex vivo lungs rejected for transplant. The prototype thin convex probe EBUS (BF-Y0055; Olympus, Tokyo, Japan) with a thinner tip (5.9 mm), greater upward angle (170 degrees), and decreased forward oblique direction of view (20 degrees) was compared with the current convex probe EBUS (6.9-mm tip, 120 degrees, and 35 degrees, respectively). Accessibility and transbronchial needle aspiration capability was assessed in ex vivo human lungs declined for lung transplant. The distance of maximum reach and sustainable endoscopic limit were measured. Transbronchial needle aspiration capability was assessed using the prototype 25G aspiration needle in segmental lymph nodes. In all evaluated lungs (n = 5), the thin convex probe EBUS demonstrated greater reach and a higher success rate, averaging 22.1 mm greater maximum reach and 10.3 mm further endoscopic visibility range than convex probe EBUS, and could assess selectively almost all segmental bronchi (98% right, 91% left), demonstrating nearly twice the accessibility as the convex probe EBUS (48% right, 47% left). The prototype successfully enabled cytologic assessment of subsegmental lymph nodes with adequate quality using the dedicated 25G aspiration needle. Thin convex probe EBUS has greater accessibility to peripheral airways in human lungs and is capable of sampling segmental lymph nodes using the aspiration needle. That will allow for more precise assessment of N1 nodes and, possibly, intrapulmonary lesions normally inaccessible to the conventional convex probe EBUS. Copyright © 2017 The Society of Thoracic Surgeons. Published

  10. IL-7 restores lymphocyte functions in septic patients.

    Science.gov (United States)

    Venet, Fabienne; Foray, Anne-Perrine; Villars-Méchin, Astrid; Malcus, Christophe; Poitevin-Later, Françoise; Lepape, Alain; Monneret, Guillaume

    2012-11-15

    Septic syndrome is the leading cause of mortality for critically ill patients worldwide. Patients develop lymphocyte dysfunctions associated with increased risk of death and nosocomial infections. In this study, we performed preclinical experiments testing the potential of recombinant human IL-7 (rhIL-7) as a lymphostimulating therapy in sepsis. Circulating IL-7 and soluble IL-7 receptor α-chain (soluble CD127) concentrations were measured in plasma, whereas cellular CD127 expression was evaluated on circulating CD4(+) and CD8(+) lymphocytes from septic shock patients and healthy volunteers. Lymphocyte proliferation, IFN-γ production, STAT5 phosphorylation, and B cell lymphoma 2 induction were measured ex vivo in response to T cell stimulation in the presence or not of rhIL-7. We show that IL-7 pathway (plasmatic IL-7 concentration and cellular and soluble CD127 expressions) is not overtly altered and remains activable in septic patients. Most importantly ex vivo treatment of patients' cells with rhIL-7 significantly improves lymphocyte functionality (CD4(+) and CD8(+) lymphocyte proliferations, IFN-γ production, STAT5 phosphorylation, and B cell lymphoma 2 induction after stimulation). To our knowledge, this constitutes the first report of rhIL-7 ability to restore normal lymphocyte functions in septic patients. These results support the rational for initiating a clinical trial testing rhIL-7 in septic shock.

  11. Mechanisms of Enhanced Lung Injury during Sepsis

    Science.gov (United States)

    Czermak, Boris J.; Breckwoldt, Maren; Ravage, Zachary B.; Huber-Lang, Markus; Schmal, Hagen; Bless, Nicolas M.; Friedl, Hans P.; Ward, Peter A.

    1999-01-01

    A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility to injury after a direct pulmonary insult (deposition of IgG immune complexes or airway instillation of lipopolysaccharide). By itself, cecal ligation/puncture did not produce evidence of lung injury. However, after a direct pulmonary insult, lung injury in septic animals was significantly enhanced. Enhanced lung injury was associated with increased accumulation of neutrophils in lung, enhanced production of CXC chemokines (but not tumor necrosis factor-α) in bronchoalveolar lavage fluids, and increased expression of lung vascular intercellular adhesion molecule-1 (ICAM-1). Complement depletion or treatment with anti-C5a abolished all evidence of enhanced lung injury in septic animals. When stimulated in vitro, bronchoalveolar lavage macrophages from septic animals had greatly enhanced CXC chemokine responses as compared with macrophages from sham-operated animals or from septic animals that had been complement depleted. These data indicate that the septic state causes priming of lung macrophages and suggest that enhanced lung injury in the septic state is complement dependent and related to increased production of CXC chemokines. PMID:10233844

  12. Senolytic drugs target?alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo

    OpenAIRE

    Lehmann, Mareike; Korfei, Martina; Mutze, Kathrin; Klee, Stephan; Skronska-Wasek, Wioletta; Alsafadi, Hani N.; Ota, Chiharu; Costa, Rita; Schiller, Herbert B.; Lindner, Michael; Wagner, Darcy E; G?nther, Andreas; K?nigshoff, Melanie

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and...

  13. Higher vs. lower haemoglobin threshold for transfusion in septic shock

    DEFF Research Database (Denmark)

    Rygård, S L; Holst, L B; Wetterslev, J

    2017-01-01

    BACKGROUND: Using a restrictive transfusion strategy appears to be safe in sepsis, but there may be subgroups of patients who benefit from transfusion at a higher haemoglobin level. We explored if subgroups of patients with septic shock and anaemia had better outcome when transfused at a higher vs....... a lower haemoglobin threshold. METHODS: In post-hoc analyses of the full trial population of 998 patients from the Transfusion Requirements in Septic Shock (TRISS) trial, we investigated the intervention effect on 90-day mortality in patients with severe comorbidity (chronic lung disease, haematological...... malignancy or metastatic cancer), in patients who had undergone surgery (elective or acute) and in patients with septic shock as defined by the new consensus definition: lactate above 2 mmol/l and the need for vasopressors to maintain a mean arterial pressure above 65 mmHg. RESULTS: The baseline...

  14. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

    Directory of Open Access Journals (Sweden)

    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  15. Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

    Science.gov (United States)

    Kawamura, Tomohiro; Wakabayashi, Nobunao; Shigemura, Norihisa; Huang, Chien-Sheng; Masutani, Kosuke; Tanaka, Yugo; Noda, Kentaro; Peng, Ximei; Takahashi, Toru; Billiar, Timothy R.; Okumura, Meinoshin; Toyoda, Yoshiya; Kensler, Thomas W.

    2013-01-01

    Hyperoxic lung injury is a major concern in critically ill patients who receive high concentrations of oxygen to treat lung diseases. Successful abrogation of hyperoxic lung injury would have a huge impact on respiratory and critical care medicine. Hydrogen can be administered as a therapeutic medical gas. We recently demonstrated that inhaled hydrogen reduced transplant-induced lung injury and induced heme oxygenase (HO)-1. To determine whether hydrogen could reduce hyperoxic lung injury and investigate the underlying mechanisms, we randomly assigned rats to four experimental groups and administered the following gas mixtures for 60 h: 98% oxygen (hyperoxia), 2% nitrogen; 98% oxygen (hyperoxia), 2% hydrogen; 98% balanced air (normoxia), 2% nitrogen; and 98% balanced air (normoxia), 2% hydrogen. We examined lung function by blood gas analysis, extent of lung injury, and expression of HO-1. We also investigated the role of NF-E2-related factor (Nrf) 2, which regulates HO-1 expression, by examining the expression of Nrf2-dependent genes and the ability of hydrogen to reduce hyperoxic lung injury in Nrf2-deficient mice. Hydrogen treatment during exposure to hyperoxia significantly improved blood oxygenation, reduced inflammatory events, and induced HO-1 expression. Hydrogen did not mitigate hyperoxic lung injury or induce HO-1 in Nrf2-deficient mice. These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen. PMID:23475767

  16. A porcine ex vivo lung perfusion model with maximal argon exposure to attenuate ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    An Martens

    2017-01-01

    Full Text Available Argon (Ar is a noble gas with known organoprotective effects in rodents and in vitro models. In a previous study we failed to find a postconditioning effect of Ar during ex vivo lung perfusion (EVLP on warm-ischemic injury in a porcine model. In this study, we further investigated a prolonged exposure to Ar to decrease cold ischemia-reperfusion injury after lung transplantation in a porcine model with EVLP assessment. Domestic pigs (n = 6/group were pre-conditioned for 6 hours with 21% O 2 and 79% N 2 (CONTR or 79% Ar (ARG. Subsequently, lungs were cold flushed and stored inflated on ice for 18 hours inflated with the same gas mixtures. Next, lungs were perfused for 4 hours on EVLP (acellular while ventilated with 12% O 2 and 88% N 2 (CONTR group or 88% Ar (ARG group. The perfusate was saturated with the same gas mixture but with the addition of CO 2 to an end-tidal CO 2 of 35-45 mmHg. The saturated perfusate was drained and lungs were perfused with whole blood for an additional 2 hours on EVLP. Evaluation at the end of EVLP did not show significant effects on physiologic parameters by prolonged exposure to Ar. Also wet-to-dry weight ratio did not improve in the ARG group. Although in other organ systems protective effects of Ar have been shown, we did not detect beneficial effects of a high concentration of Ar on cold pulmonary ischemia-reperfusion injury in a porcine lung model after prolonged exposure to Ar in this porcine model with EVLP assessment.

  17. Protein secretion is required for pregnancy-associated plasma protein-A to promote lung cancer growth in vivo.

    Directory of Open Access Journals (Sweden)

    Hong Pan

    Full Text Available Pregnancy-associated plasma protein-A (PAPPA has been reported to regulate the activity of insulin-like growth factor (IGF signal pathway through proteolytic degradation of IGF binding proteins (IGFBPs thereby increasing the local concentration of free IGFs available to receptors. In this study we found that PAPPA is secreted from two out of seven lung cancer cell lines examined. None of immortalized normal bronchial epithelial cells (HBE tested secrets PAPPA. There is no correlation between expression level and secretion of PAPPA in these cells. A cell line over-expressing PAPPA accompanied with secretion shows no notable changes in proliferation under cell culture conditions in vitro, but displays significantly augmentation of tumor growth in vivo in a xenograft model. In contrast, a cell line over-expressing PAPPA without secretion exhibits reduction of tumor growth both in vitro and in vivo. Down-regulation of PAPPA expression and secretion by RNAi knockdown decreases tumor growth after implanted in vivo. The tumor promoting activity of PAPPA appears to be mediated mainly through augmentation of the IGF signaling pathway as indicated by notable increases in downstream Akt kinase phosphorylation in tumor samples. Our results indicate that PAPPA secretion may play an important role in lung cancer growth and progression.

  18. Differential in vivo expression of mycobacterial antigens in Mycobacterium tuberculosis infected lungs and lymph node tissues.

    Science.gov (United States)

    Mustafa, Tehmina; Leversen, Nils Anders; Sviland, Lisbet; Wiker, Harald Gotten

    2014-10-03

    The clinical course of tuberculosis (TB) infection, bacterial load and the morphology of lesions vary between pulmonary and extrapulmonary TB. Antigens expressed in abundance during infection could represent relevant antigens in the development of diagnostic tools, but little is known about the in vivo expression of various M. tuberculosis antigens in different clinical manifestations. The aim of this study was to study the differences in the presence of major secreted as well as somatic mycobacterial antigens in host tissues during advanced rapidly progressing and fatal pulmonary disease with mainly pneumonic infiltrates and high bacterial load, and to compare this to the presence of the same antigens in TB lymphadenitis cases, which is mainly chronic and self-limiting disease with organised granulomas and lower bacterial load. Human pulmonary (n = 3) and lymph node (n = 17) TB biopsies, and non-TB controls (n = 12) were studied. Ziehl-Neelsen stain, nested PCR 1S6110 and immunohistochemistry were performed. Major secreted (MPT32, MPT44, MPT46, MPT51, MPT53, MPT59, MPT63, and MPT64) and somatic mycobacterial antigens (Mce1A, Hsp65, and MPT57) were detected by using rabbit polyclonal antibodies. Plenty of bacilli were detectable with Ziehl-Neelsen stain in the lung biopsies while no bacilli were detected in the lymph node biopsies. All the cases were shown to be positive by PCR. Both secretory and somatic antigens were expressed in abundance in pulmonary infiltrates, while primarily somatic antigens were detected in the lymphadenitis cases. Of the secreted antigens, only MPT64 was consistently detected in both cases, indicating a preferential accumulation of this antigen within the inflammatory cells, even if the cells of the granuloma can efficiently restrict bacterial growth and clear away the secreted antigens. This study shows that major secreted mycobacterial antigens were found in high amounts in advanced pulmonary lesions without proper granuloma

  19. Alveolar macrophages from allergic lungs are not committed to a pro-allergic response and can reduce airway hyperresponsiveness following ex vivo culture

    Science.gov (United States)

    Pouliot, P.; Spahr, A.; Careau, É.; Turmel, V.; Bissonnette, E. Y.

    2016-01-01

    Summary Background We already demonstrated that adoptive transfer of alveolar macrophages (AMs) from non-allergic rats into AM-depleted allergic rats prevents airway hyperresponsiveness (AHR). We also showed that AMs from non-sensitized, but not from sensitized, allergy-prone rats can prevent AHR following allergen challenge in sensitized allergic animals, establishing the importance of rat immunological status on the modulation of AM functions and suggesting that an allergic lung environment alters AM functions. Objective We investigated how the activation of allergic AMs can be modulated to reinstitute them with their capacity to reduce AHR. Methods AMs from sensitized Brown Norway rats were cultured ex vivo for up to 18 h in culture media to deprogram them from the influence of the allergic lung before being reintroduced into the lung of AM-depleted sensitized recipient. AHR and cytokines in bronchoalveolar lavage (BAL) were measured following allergen challenge. AMs stimulated ex vivo with Bacillus Calmette-Guerin(BCG) were used as positive controls as BCG induces a T-helper type 1 activation in AMs. Results AMs ex vivo cultured for 4–18 h reduced AHR to normal level. Interestingly, pro-allergic functions of AMs were dampened by 18 h culture and they reduced AHR even after spending 48 h in an allergic lung microenvironment. Furthermore, transfer of cultured AMs caused an increase in the levels of IFN-γ and IL-12 in BAL when compared with their ovalbumin control. After 18 h of ex vivo culture, AMs expressed reduced levels of TNF, IL-1α, IL-6, and Arginase-2 mRNAs compared with freshly isolated AMs, suggesting that ex vivo culture exempted AMs from lung stimuli that affected their functions. Conclusions There is a significant crosstalk between lung microenvironment and AMs, affecting their functions. It is also the first report showing that sensitized AMs can be modulated ex vivo to reduce lung pro-allergic environment, opening the way to therapies targetting

  20. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    Science.gov (United States)

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  1. Swarm Rat Chondrosarcoma Cells as an in vivo model: Lung Colonization and Effects of Tissue Environment on Tumor Growth

    Science.gov (United States)

    Morcuende, Jose A.; Stevens, Jeff W.; Scheetz, Todd E.; de Fatima Bonaldoc, Maria; Casavant, Thomas L.; Otero, Jesse E.; Soares, Marcelo B.

    2012-01-01

    Swarm rat chondrosarcoma cells have been used extensively for biochemical studies of extra-cellular matrix metabolism in cartilage. However, these cells also possess tumor-like behavior in vivo and are useful in investigation of chondrosarcoma biology. the current study was designed to develop a metastatic model using swarm rat chondrosarcoma cells, and to assess the effect of tissue-environment on tumor behavior in vivo. Tumors were implanted subcutaneously or into bone, and animals were assessed radiographically and microscopically for tumor growth and metastasis. The subcutaneous tumor grew to an average mass of 35 g, while tumor implanted into bone grew 75 mg. Transplantation of the cells into the bone led to extensive bone remodeling with invasion of the medullary cavity and destruction of the bone cortex. Light microscopy demonstrated no significant differences in the number of mitoses, cellular atypia or extracellular matrix staining between the two sites of tumor implantation. Interestingly, lung colonization was observed in none of the animals in the subcutaneous tumor injection group, while tumors colonized the lungs in 95% of the rats with tumor injected into bone. Analysis of cDNA libraries from subcutaneous and bone-transplanted tumors demonstrated a complex and diverse array of expressed transcripts, and there were significant differences in gene expression between tumors at different sites. The results of this study suggest swarm rat chondrosarcoma is a model that resembles human chondrosarcoma mimicking its ability to infiltrate and remodel local bone and to colonize the lungs. Furthermore, the interaction between host-tissue and tumor cells plays a major role in the tumor behavior in this model. Identifying these interactions will lead to further understanding of chondrosarcoma and contribute to therapeutic targets in the future. PMID:23576921

  2. Coadministration of Trametinib and Palbociclib Radiosensitizes KRAS-Mutant Non-Small Cell Lung Cancers In Vitro and In Vivo.

    Science.gov (United States)

    Tao, Zhen; Le Blanc, Justin M; Wang, Chenguang; Zhan, Tingting; Zhuang, Hongqing; Wang, Ping; Yuan, Zhiyong; Lu, Bo

    2016-01-01

    To investigate the potential roles that p16 (CDKN2A) and RB activation have in sensitization to MEK inhibitor in resistant KRAS-mutant non-small cell lung cancer cells (NSCLC) in vitro and in vivo. Cell viability was measured with MTS assays. Effects of administration of radiation and combination drug treatments were evaluated by clonogenic assay, flow cytometry, and Western blots. DNA repair was assessed using immunofluorescent analysis. Finally, lung cancer xenografts were used to examine in vivo effects of drug treatment and radiation therapy. In this study, we showed that sensitivity to MEK inhibitor correlated to the RB/p16/CDK4 pathway and knockdown of RB induced resistance in cell lines sensitive to MEK inhibitor. Also, overexpression of p16 and inhibition of CDK4 had the ability to sensitize normally resistant cell lines. Our data indicated that the MEK inhibitor (trametinib, GSK112012) cooperated with the CDK4/6 inhibitor (palbociclib, PD0332991) to strongly reduce cell viability of KRAS-mutant NSCLCs that were resistant to the MEK inhibitor in vitro and in vivo. In addition, we report for the first time that resistance of KRAS-mutant NSCLCs to MEK inhibitor is, at least partly, due to p16 mutation status, and we described a drug combination that efficiently reactivates the RB tumor suppressor pathway to trigger radiosensitizing effects, apoptosis, and cell-cycle arrest. Our findings suggest that MEK inhibitor in combination with CDK4/6 inhibitor has significant anti-KRAS-mutant NSCLC activity and radiosensitizing effect in preclinical models, potentially providing a novel therapeutic strategy for patients with advanced KRAS-mutant NSCLCs. ©2016 American Association for Cancer Research.

  3. First experiences with in-vivo x-ray dark-field imaging of lung cancer in mice

    Science.gov (United States)

    Gromann, Lukas B.; Scherer, Kai; Yaroshenko, Andre; Bölükbas, Deniz A.; Hellbach, Katharina; Meinel, Felix G.; Braunagel, Margarita; Eickelberg, Oliver; Reiser, Maximilian F.; Pfeiffer, Franz; Meiners, Silke; Herzen, Julia

    2017-03-01

    Purpose: The purpose of the present study was to evaluate if x-ray dark-field imaging can help to visualize lung cancer in mice. Materials and Methods: The experiments were performed using mutant mice with high-grade adenocarcinomas. Eight animals with pulmonary carcinoma and eight control animals were imaged in radiography mode using a prototype small-animal x-ray dark-field scanner and three of the cancerous ones additionally in CT mode. After imaging, the lungs were harvested for histological analysis. To determine their diagnostic value, x-ray dark-field and conventional attenuation images were analyzed by three experienced readers in a blind assessment. Results radiographic imaging: The lung nodules were much clearer visualized on the dark-field radiographs compared to conventional radiographs. The loss of air-tissue interfaces in the tumor leads to a significant loss of x-ray scattering, reflected in a strong dark-field signal change. The difference between tumor and healthy tissue in terms of x-ray attenuation is significantly less pronounced. Furthermore, the signal from the overlaying structures on conventional radiographs complicates the detection of pulmonary carcinoma. Results CT imaging: The very first in-vivo CT-imaging results are quite promising as smaller tumors are often better visible in the dark-field images. However the imaging quality is still quite low, especially in the attenuation images due to un-optimized scanning parameters. Conclusion: We found a superior diagnostic performance of dark-field imaging compared to conventional attenuation based imaging, especially when it comes to the detection of small lung nodules. These results support the motivation to further develop this technique and translate it towards a clinical environment.

  4. Inhibition of Murine Pulmonary Microvascular Endothelial Cell Apoptosis Promotes Recovery of Barrier Function under Septic Conditions

    Directory of Open Access Journals (Sweden)

    Lefeng Wang

    2017-01-01

    Full Text Available Sepsis is characterized by injury of the pulmonary microvasculature and the pulmonary microvascular endothelial cells (PMVEC, leading to barrier dysfunction and acute respiratory distress syndrome (ARDS. Our recent work identified a strong correlation between PMVEC apoptosis and microvascular leak in septic mice in vivo, but the specific role of apoptosis in septic PMVEC barrier dysfunction remains unclear. Thus, we hypothesize that PMVEC apoptosis is likely required for PMVEC barrier dysfunction under septic conditions in vitro. Septic stimulation (mixture of tumour necrosis factor α, interleukin 1β, and interferon γ [cytomix] of isolated murine PMVEC resulted in a significant loss of barrier function as early as 4 h after stimulation, which persisted until 24 h. PMVEC apoptosis, as reflected by caspase activation, DNA fragmentation, and loss of membrane polarity, was first apparent at 8 h after cytomix. Pretreatment of PMVEC with the pan-caspase inhibitor Q-VD significantly decreased septic PMVEC apoptosis and was associated with reestablishment of PMVEC barrier function at 16 and 24 h after stimulation but had no effect on septic PMVEC barrier dysfunction over the first 8 h. Collectively, our data suggest that early septic murine PMVEC barrier dysfunction driven by proinflammatory cytokines is not mediated through apoptosis, but PMVEC apoptosis contributes to late septic PMVEC barrier dysfunction.

  5. Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

    DEFF Research Database (Denmark)

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R.

    2016-01-01

    a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging.Administration of a [64Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus...

  6. In vivo lung morphometry with accelerated hyperpolarized (3) He diffusion MRI: a preliminary study.

    Science.gov (United States)

    Chang, Yulin V; Quirk, James D; Yablonskiy, Dmitriy A

    2015-04-01

    Parallel imaging can be used to reduce imaging time and to increase the spatial coverage in hyperpolarized gas magnetic resonance imaging of the lung. In this proof-of-concept study, we investigate the effects of parallel imaging on the morphometric measurement of lung microstructure using diffusion magnetic resonance imaging with hyperpolarized (3) He. Fully sampled and under-sampled multi-b diffusion data were acquired from human subjects using an 8-channel (3) He receive coil. A parallel imaging reconstruction technique (generalized autocalibrating partially parallel acquisitions [GRAPPA]) was used to reconstruct under-sampled k-space data. The morphometric results of the generalized autocalibrating partially parallel acquisitions-reconstructed data were compared with the results of fully sampled data for three types of subjects: healthy volunteers, mild, and moderate chronic obstructive pulmonary disease patients. Morphometric measurements varied only slightly at mild acceleration factors. The results were largely well preserved compared to fully sampled data for different lung conditions. Parallel imaging, given sufficient signal-to-noise ratio, provides a reliable means to accelerate hyperpolarized-gas magnetic resonance imaging with no significant difference in the measurement of lung morphometry from the fully sampled images. GRAPPA is a promising technique to significantly reduce imaging time and/or to improve the spatial coverage for the morphometric measurement with hyperpolarized gases. © 2014 Wiley Periodicals, Inc.

  7. SR 11302, an AP-1 Inhibitor, Reduces Metastatic Lesion Formation in Ex Vivo 4D Lung Cancer Model.

    Science.gov (United States)

    Mishra, Dhruva Kumar; Kim, Min P

    2017-12-01

    Activator protein (AP) -1 is a transcription factor, plays important role in cell differentiation, proliferation and apoptosis. Analysis of tumor cells grown on ex vivo 4D lung cancer model shows increase in components of AP-1, c-Fos and c-Jun in circulating tumor cells (CTC) compared to primary tumor. Our aim was to determine whether the AP-1 inhibitor SR11302 reduces metastatic lesion formation in the 4D model. Human lung cancer cell lines A549, H1299, and H460 were grown in the 4D model and treated with SR11302 (1 μM). We compared the number of cells in the metastatic site upon SR11302 treatment and number of viable CTCs isolated from the 4D model with parental cells treated/untreated with SR11302 on a petri dish. There were significantly fewer tumor cells per high-power field on metastatic site in 4D model seeded with H460 (p = 0.009), A549 (p = 0.01), or H1299 (p = 0.02) cells treated with SR11302. Furthermore, the CTCs from SR11302 treated 4D models, seeded with H460 (p = 0.04), A549 (p = 0.008), or H1299 (p = 0.01) cells had significantly fewer viable tumor cells after 4 days in culture than the respective untreated control. However, the SR11302 had no impact on the viability of parental H460 (p = 0.87), A549 (p = 0.93), or H1299 (p = 0.25) cells grown on a petri dish (2D). SR11302 reduces metastatic lesion formation in the ex vivo 4D lung cancer model due to the presence of an independent yet common pathway among three cell lines. The ex vivo 4D model may provide a tool to better understand the complex process of metastasis.

  8. Fipronil induces lung inflammation in vivo and cell death in vitro.

    Science.gov (United States)

    Merkowsky, Kaitlin; Sethi, Ram S; Gill, Jatinder P S; Singh, Baljit

    2016-01-01

    Fipronil is an insecticide that acts at the gamma-aminobutyric acid receptor and glutamate-gated chloride channels in the central nervous systems of target organisms. The use of fipronil is increasing across the globe. Presently, very little data exist on the potential impact of exposure to fipronil on the lungs. We studied effects of intranasal (N = 8) and oral (N = 8) treatment with fipronil (10 mg/kg) on lungs of mice. Control mice were given groundnut oil orally (N = 7) or ethanol intranasally (N = 7) as these were the vehicles for respective treatments. Hematoxylin-eosin stained lung sections showed normal histology in the control lungs compared to the thickened alveolar septa, disruption of the airways epithelium and damage to vascular endothelium in the intranasal and the oral groups. Mice exposed to fipronil either orally or intranasally showed increased von Willebrand factor staining in the endothelium and septal capillaries. Compared to the control mice, TLR4 expression in airway epithelium was increased in mice treated intranasally but not orally with fipronil. Oral fipronil reduced TLR9 staining in the airway epithelium but intranasal exposure caused intense staining in the alveolar septa and airway epithelium. There were higher numbers of TLR4 positive cells in alveolar septa in lungs of mice treated intranasally (P = 0.010) compared to the respective control and orally treated mice but no significant differences between treatments for TLR9 positive stained cells (P = 0.226). The U937 macrophage cells exposed to fipronil at concentrations of 0.29 μm to 5.72 μm/ml over 3- or 24-hour showed significant increase in cell death at higher concentrations of fipronil (P fipronil on TLR4 (P = 0.49) or TLR9 (P = 0.94) expression on macrophage cell line. While both oral or intranasal fipronil treatments induced signs of lung inflammation, the number TLR4-positive septal cells was increased only following intranasal treatment

  9. Biosynthesis of collagen crosslinks. III. In vivo labeling and stability of lung collagen in rats with bleomycin-induced pulmonary fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Last, J.A.; Reiser, K.M. (Univ. of California, Davis (USA))

    1989-08-01

    Rats were injected intraperitoneally with 1 mCi (each) of (3H)lysine at Day 11 of neonatal life to label their lung collagen. Five weeks later, half of the animals were given an intratracheal injection of 1.5 U of bleomycin sulfate via a tracheostomy; control animals received saline intratracheally by the same technique. Age-matched groups of control and bleomycin-treated rats were killed, and their lung collagen was analyzed at zero (control animals only), 1, 2, 4, 6, and 10 wk after bleomycin administration, a time course appropriate for development of pulmonary fibrosis in this animal model. We measured radioactivity in hydroxylysine and in the difunctional collagen crosslinks hydroxylysinonorleucine and dihydroxylysinonorleucine at each time point. No evidence of breakdown of this pool of mature, preformed collagen was observed in lungs of either the control or the bleomycin-treated rats. We also measured the total lung content of hydroxypyridinium, a trifunctional collagen crosslink, by its intrinsic fluorescence. There was no evidence of collagen degradation in lungs of either group of rats by this criterion either. We conclude that there is no biochemically detectable turnover of mature lung collagen, defined as that pool of lung collagen that is obligatorily extracellular (i.e., crosslinked and containing labeled hydroxylysine from an injection of precursor 5 to 15 wk earlier), in either normal rat lungs or lungs of rats made fibrotic with bleomycin. Statistical analysis of the data suggests that our methodology was sensitive and precise enough to have detected turnover of less than 0.5% of lung collagen per day, some 20-fold less than estimates of lung collagen turnover that have been suggested to be occurring in vivo by others using different techniques and presumably studying different pools of lung collagen.

  10. SU-E-T-92: Achieving Desirable Lung Doses in Total Body Irradiation Based On in Vivo Dosimetry and Custom Tissue Compensation

    Energy Technology Data Exchange (ETDEWEB)

    Cui, G; Shiu, A; Zhou, S; Cui, J; Ballas, L [Univ Southern California, Los Angeles, CA (United States)

    2015-06-15

    Purpose: To achieve desirable lung doses in total body irradiation (TBI) based on in vivo dosimetry and custom tissue compensation. Methods: The 15 MV photon beam of a Varian TrueBeam STx linac was used for TBI. Patients were positioned in the lateral decubitus position for AP/PA treatment delivery. Dose was calculated using the midpoint of the separation distance across the patient’s umbilicus. Patients received 200 cGy twice daily for 3 days. The dose rate at the patient’s midplane was approximately 10 cGy/min. Cerrobend blocks with a 5-HVL thickness were used for the primary lung shielding. A custom styrofoam holder for rice-flour filled bags was created based on the lung block cutouts. This was used to provide further lung shielding based on in vivo dose measurements. Lucite plates and rice-flour bags were placed in the head, neck, chest, and lower extremity regions during the treatment to compensate for the beam off-axis output variations. Two patients were included in the study. Patients 1 and 2 received a craniospinal treatment (1080 cGy) and a mediastinum treatment (2520 cGy), respectively, before the TBI. During the TBI nanoDot dosimeters were placed on the patient skin in the forehead, neck, umbilicus, and lung regions for dose monitoring. The doses were readout immediately after the treatment. Based on the readings, fine tuning of the thickness of the rice-flour filled bags was exploited to achieve the desirable lung doses. Results: For both patients the mean lung doses, which took into consideration all treatments, were controlled within 900 +/−10% cGy, as desired. Doses to the forehead, neck, and umbilicus were achieved within +/−10% of the prescribed dose (1200 cGy). Conclusion: A reliable and robust method was developed to achieve desirable lung doses and uniform body dose in TBI based on in vivo dosimetry and custom tissue compensator.

  11. In Vivo Evaluation of TNF-Alpha in the Lungs of Patients Affected by Sarcoidosis

    Science.gov (United States)

    Pietrangeli, Vittorio; Ricci, Alberto; Bruno, Pierdonato; Ragni, Paola; Scopinaro, Francesco; Mariotta, Salvatore; Signore, Alberto

    2015-01-01

    Introduction. Sarcoidosis is a multisystemic granulomatous disorder characterized by multiple noncaseating granulomas involving intrathoracic lymph nodes and lung parenchyma. Recently, the use of anti-tumor necrosis factor alpha (anti-TNFα) agents has been introduced for therapy of chronic and refractory sarcoidosis with controversial results. Infliximab (Remicade) is a chimeric monoclonal antibody (mAb) that recognizes and binds TNFα, neutralizing its biological effects. In the present study,   99mTc labelled infliximab was used to study the expression of TNFα in sarcoid lesions and to evaluate its role as a predictive marker in response to therapy with Remicade. Material and Methods. A total of 10 patients with newly diagnosed sarcoidosis were enrolled together with 10 control patients affected by rheumatoid arthritis. All patients were studied by planar imaging of the chest with   99mTc-infliximab at 6 h and 24 h and total body [18F]-FDG PET/CT. Regions of interest were drawn over the lungs and the right arm and target-to-background ratios were analysed for   99mTc-infliximab. SUVmean and SUVmax were calculated over lungs for FDG. Results and Discussion. Image analysis showed low correlation between T/B ratios and BAL results in patients despite positivity at [18F]-FDG PET. Conclusion. In conclusion, patients with newly diagnosed pulmonary sarcoidosis, with FDG-PET and BAL positivity, showed a negative   99mTc-infliximab scintigraphy. PMID:25866780

  12. In Vivo Evaluation of TNF-Alpha in the Lungs of Patients Affected by Sarcoidosis

    Directory of Open Access Journals (Sweden)

    Filippo Galli

    2015-01-01

    Full Text Available Introduction. Sarcoidosis is a multisystemic granulomatous disorder characterized by multiple noncaseating granulomas involving intrathoracic lymph nodes and lung parenchyma. Recently, the use of anti-tumor necrosis factor alpha (anti-TNFα agents has been introduced for therapy of chronic and refractory sarcoidosis with controversial results. Infliximab (Remicade is a chimeric monoclonal antibody (mAb that recognizes and binds TNFα, neutralizing its biological effects. In the present study, Tc 99m labelled infliximab was used to study the expression of TNFα in sarcoid lesions and to evaluate its role as a predictive marker in response to therapy with Remicade. Material and Methods. A total of 10 patients with newly diagnosed sarcoidosis were enrolled together with 10 control patients affected by rheumatoid arthritis. All patients were studied by planar imaging of the chest with Tc 99m-infliximab at 6 h and 24 h and total body [18F]-FDG PET/CT. Regions of interest were drawn over the lungs and the right arm and target-to-background ratios were analysed for Tc 99m-infliximab. SUVmean and SUVmax were calculated over lungs for FDG. Results and Discussion. Image analysis showed low correlation between T/B ratios and BAL results in patients despite positivity at [18F]-FDG PET. Conclusion. In conclusion, patients with newly diagnosed pulmonary sarcoidosis, with FDG-PET and BAL positivity, showed a negative Tc 99m-infliximab scintigraphy.

  13. In vivo imaging of the airway wall in asthma: fibered confocal fluorescence microscopy in relation to histology and lung function

    Directory of Open Access Journals (Sweden)

    Bel Elisabeth H

    2011-06-01

    Full Text Available Abstract Background Airway remodelling is a feature of asthma including fragmentation of elastic fibres observed in the superficial elastin network of the airway wall. Fibered confocal fluorescence microscopy (FCFM is a new and non-invasive imaging technique performed during bronchoscopy that may visualize elastic fibres, as shown by in vitro spectral analysis of elastin powder. We hypothesized that FCFM images capture in vivo elastic fibre patterns within the airway wall and that such patterns correspond with airway histology. We aimed to establish the concordance between the bronchial elastic fibre pattern in histology and FCFM. Second, we examined whether elastic fibre patterns in histology and FCFM were different between asthmatic subjects and healthy controls. Finally, the association between these patterns and lung function parameters was investigated. Methods In a cross-sectional study comprising 16 subjects (8 atopic asthmatic patients with controlled disease and 8 healthy controls spirometry and bronchoscopy were performed, with recording of FCFM images followed by endobronchial biopsy at the airway main carina. Elastic fibre patterns in histological sections and FCFM images were scored semi-quantitatively. Agreement between histology and FCFM was analysed using linearly weighted kappa κw. Results The patterns observed in histological sections and FCFM images could be divided into 3 distinct groups. There was good agreement between elastic fibre patterns in histology and FCFM patterns (κw 0.744. The semi-quantitative pattern scores were not different between asthmatic patients and controls. Notably, there was a significant difference in post-bronchodilator FEV1 %predicted between the different patterns by histology (p = 0.001 and FCFM (p = 0.048, regardless of asthma or atopy. Conclusion FCFM captures the elastic fibre pattern within the airway wall in humans in vivo. The association between post-bronchodilator FEV1 %predicted and

  14. Novel automatic detection of pleura and B-lines (comet-tail artifacts) on in vivo lung ultrasound scans

    Science.gov (United States)

    Moshavegh, Ramin; Hansen, Kristoffer Lindskov; Møller Sørensen, Hasse; Hemmsen, Martin Christian; Ewertsen, Caroline; Nielsen, Michael Bachmann; Jensen, Jørgen Arendt

    2016-04-01

    This paper presents a novel automatic method for detection of B-lines (comet-tail artifacts) in lung ultrasound scans. B-lines are the most commonly used artifacts for analyzing the pulmonary edema. They appear as laser-like vertical beams, which arise from the pleural line and spread down without fading to the edge of the screen. An increase in their number is associated with presence of edema. All the scans used in this study were acquired using a BK3000 ultrasound scanner (BK Ultrasound, Denmark) driving a 192-element 5:5 MHz wide linear transducer (10L2W, BK Ultrasound). The dynamic received focus technique was employed to generate the sequences. Six subjects, among those three patients after major surgery and three normal subjects, were scanned once and Six ultrasound sequences each containing 50 frames were acquired. The proposed algorithm was applied to all 300 in-vivo lung ultrasound images. The pleural line is first segmented on each image and then the B-line artifacts spreading down from the pleural line are detected and overlayed on the image. The resulting 300 images showed that the mean lateral distance between B-lines detected on images acquired from patients decreased by 20% in compare with that of normal subjects. Therefore, the method can be used as the basis of a method of automatically and qualitatively characterizing the distribution of B-lines.

  15. Granzyme A Is Expressed in Mouse Lungs during Mycobacterium tuberculosis Infection but Does Not Contribute to Protection In Vivo

    Science.gov (United States)

    Uranga, Santiago; Marinova, Dessislava; Martin, Carlos; Pardo, Julián; Aguilo, Nacho

    2016-01-01

    Granzyme A, a serine protease expressed in the granules of cytotoxic T and Natural Killer cells, is involved in the generation of pro-inflammatory cytokines by macrophages. Granzyme A has been described to induce in macrophages in vitro the activation of pro-inflammatory pathways that impair intracellular mycobacterial replication. In the present study, we explored the physiological relevance of Granzyme A in the control of pulmonary Mycobacterium tuberculosis infection in vivo. Our results show that, even though Granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of M. tuberculosis infection. In addition our findings indicate that absence of Granzyme A does not affect the protection conferred by the live-attenuated M. tuberculosis vaccine MTBVAC. Altogether, our findings are in apparent contradiction with previously published in vitro results and suggest that Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis. PMID:27055232

  16. Granzyme A Is Expressed in Mouse Lungs during Mycobacterium tuberculosis Infection but Does Not Contribute to Protection In Vivo.

    Science.gov (United States)

    Uranga, Santiago; Marinova, Dessislava; Martin, Carlos; Pardo, Julián; Aguilo, Nacho

    2016-01-01

    Granzyme A, a serine protease expressed in the granules of cytotoxic T and Natural Killer cells, is involved in the generation of pro-inflammatory cytokines by macrophages. Granzyme A has been described to induce in macrophages in vitro the activation of pro-inflammatory pathways that impair intracellular mycobacterial replication. In the present study, we explored the physiological relevance of Granzyme A in the control of pulmonary Mycobacterium tuberculosis infection in vivo. Our results show that, even though Granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of M. tuberculosis infection. In addition our findings indicate that absence of Granzyme A does not affect the protection conferred by the live-attenuated M. tuberculosis vaccine MTBVAC. Altogether, our findings are in apparent contradiction with previously published in vitro results and suggest that Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis.

  17. Sepsis and Septic Shock Strategies.

    Science.gov (United States)

    Armstrong, Bracken A; Betzold, Richard D; May, Addison K

    2017-12-01

    Three therapeutic principles most substantially improve organ dysfunction and survival in sepsis: early, appropriate antimicrobial therapy; restoration of adequate cellular perfusion; timely source control. The new definitions of sepsis and septic shock reflect the inadequate sensitivity, specify, and lack of prognostication of systemic inflammatory response syndrome criteria. Sequential (sepsis-related) organ failure assessment more effectively prognosticates in sepsis and critical illness. Inadequate cellular perfusion accelerates injury and reestablishing perfusion limits injury. Multiple organ systems are affected by sepsis and septic shock and an evidence-based multipronged approach to systems-based therapy in critical illness results in improve outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Dispersion of single-walled carbon nanotubes by a natural lung surfactant for pulmonary in vitro and in vivo toxicity studies

    Directory of Open Access Journals (Sweden)

    Mercer Robert R

    2010-10-01

    Full Text Available Abstract Background Accumulating evidence indicate that the degree of dispersion of nanoparticles has a strong influence on their biological activities. The aims of this study were to develop a simple and rapid method of nanoparticle dispersion using a natural lung surfactant and to evaluate the effect of dispersion status of SWCNT on cytotoxicity and fibrogenicity in vitro and in vivo. Results The natural lung surfactant Survanta® was used to disperse single-walled carbon nanotubes (SWCNT in a biological medium. At physiologically relevant concentrations, Survanta® produced well dispersed SWCNT without causing a cytotoxic or fibrogenic effect. In vitro studies show that Survanta®-dispersed SWCNT (SD-SWCNT stimulated proliferation of lung epithelial cells at low doses (0.04-0.12 μg/ml or 0.02-0.06 μg/cm2 exposed surface area but had a suppressive effect at high doses. Non-dispersed SWCNT (ND-SWCNT did not exhibit these effects, suggesting the importance of dispersion status of SWCNT on bioactivities. Studies using cultured human lung fibroblasts show that SD-SWCNT stimulated collagen production of the cells. This result is supported by a similar observation using Acetone/sonication dispersed SWCNT (AD-SWCNT, suggesting that Survanta® did not mask the bioactivity of SWCNT. Likewise, in vivo studies show that both SD-SWCNT and AD-SWCNT induced lung fibrosis in mice, whereas the dispersing agent Survanta® alone or Survanta®-dispersed control ultrafine carbon black had no effect. Conclusions The results indicate that Survanta® was effective in dispersing SWCNT in biological media without causing cytotoxic effects at the test concentrations used in this study. SD-SWCNT stimulated collagen production of lung fibroblasts in vitro and induced lung fibrosis in vivo. Similar results were observed with AD-SWCNT, supporting the conclusion that Survanta® did not mask the bioactivities of SWCNT and thus can be used as an effective dispersing agent

  19. 10 Kinyanjui-Septic.indd

    African Journals Online (AJOL)

    It can be difficult to differentiate septic from aseptic loosening of prosthesis and especially those due to delayed and late prosthetic-joint infection. In delayed and late prosthetic-joint infection, the acute signs and symptoms of infection such as fever, swelling, erythema and warmth are usually absent and the only.

  20. Pediatric acute lung injury

    NARCIS (Netherlands)

    Dahlem, P.; van Aalderen, W. M. C.; Bos, A. P.

    2007-01-01

    Among ventilated children, the incidence of acute lung injury (ALI) was 9%; of that latter group 80% developed the acute respiratory distress syndrome (ARDS). The population-based prevalence of pediatric ARDS was 5.5 cases/100.000 inhabitants. Underlying diseases in children were septic shock (34%),

  1. Terpinen-4-ol Induces Apoptosis in Human Nonsmall Cell Lung Cancer In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Chieh-Shan Wu

    2012-01-01

    Full Text Available Terpinen-4-ol, a monoterpene component of the essential oils of several aromatic plants, exhibits antitumor effects. In this study, the antitumor effects of terpinen-4-ol and the cellular and molecular mechanisms responsible for it were evaluated and studied, respectively on human nonsmall cell lung cancer (NSCLC cells. Our results indicated that terpinen-4-ol elicited a dose-dependent cytotoxic effect, as determined by MTT assay. Increased sub-G1 population and annexin-V binding, activation of caspases 9 and 3, cleavage of poly(ADPribose polymerase (PARP, and a decrease of mitochondrial membrane potential (MMP indicated involvement of the mitochondrial apoptotic pathway in terpinen-4-ol-treated A549 and CL1-0 cells. Elevation of the Bax/Bcl-2 ratio and a decrease in IAP family proteins XIAP and survivin were also observed following terpinen-4-ol treatment. Notably, terpinen-4-ol was able to increase p53 levels in A549 and CL1-0 cells. Diminution of p53 by RNA interference induced necrosis instead of apoptosis in A549 cells following terpinen-4-ol treatment, indicating that terpinen-4-ol-elicited apoptosis is p53-dependent. Moreover, intratumoral administration of terpinen-4-ol significantly suppressed the growth of s.c. A549 xenografts by inducing apoptosis, as confirmed by TUNEL assay. Collectively, these data provide insight into the molecular mechanisms underlying terpinen-4-ol-induced apoptosis in NSCLC cells, rendering this compound a potential anticancer drug for NSCLC.

  2. Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo

    DEFF Research Database (Denmark)

    Davies, Genna; Rolle, Anna-Maria; Maurer, Andreas

    2017-01-01

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture...... of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography...... infection using a [64Cu] NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu] NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds...

  3. Application of Voxel Phantoms to Study the Influence of Heterogeneous Distribution of Actinides in Lungs on In Vivo Counting Calibration Factors Using Animal Experimentations

    Energy Technology Data Exchange (ETDEWEB)

    Lamart, S.; Pierrat, N.; De Carlan, L.; Franck, D. [IRSN/DRPH/SDI/LEDI, BP 17, F-92 262 Fontenay-aux-Roses (France); Dudoignon, N. [IRSN/DRPH/SRBE/LRPAT, BP 17, F-92 262 Fontenay-aux-Roses (France); Rateau, S.; Van der Meeren, A.; Rouit, E. [CEA/DSV/DRR/SRCA/LRT BP no 12, F-91680 Bruyeres-le-Chatel (France); Bottlaender, M. [CEA/SHFJ, 4, place du General Leclerc F-91400 Orsay (France)

    2006-07-01

    Calibration of lung counting system dedicated to retention assessment of actinides in the lungs remains critical due to large uncertainties in calibration factors. Among them, the detector positioning, the chest wall thickness and composition (muscle/fat) assessment, and the distribution of the contamination are the main parameters influencing the detector response. In order to reduce these uncertainties, a numerical approach based on the application of voxel phantoms (numerical phantoms based on tomographic images, CT or MRI) associated to a Monte-Carlo code (namely M.C.N.P.) was developed. It led to the development of a dedicated tool, called O.E.D.I.P.E., that allows to easily handle realistic voxel phantoms for the simulation of in vivo measurement (or dose calculation, application that will not be presented in this paper). The goal of this paper is to present our study of the influence of the lung distribution on calibration factors using both animal experimentations and our numerical method. Indeed, physical anthropomorphic phantoms used for calibration always consider a uniform distribution of the source in the lungs, which is not true in many contamination conditions. The purpose of the study is to compare the response of the measurement detectors using a real distribution of actinide particles in the lungs, obtained from animal experimentations, with the homogeneous one considered as the reference. This comparison was performed using O.E.D.I.P.E. that can almost simulate any source distribution. A non human primate was contaminated heterogeneously by intra-tracheal administration of actinide oxide. After euthanasia, gamma spectrometry measurements were performed on the pulmonary lobes to obtain the distribution of the contamination in the lungs. This realistic distribution was used to simulate an heterogeneous contamination in the numerical phantom of the non human primate, which was compared with a simulation of an homogeneous contamination presenting the

  4. Caffeine inhibits TGFβ activation in epithelial cells, interrupts fibroblast responses to TGFβ, and reduces established fibrosis in ex vivo precision-cut lung slices.

    Science.gov (United States)

    Tatler, Amanda L; Barnes, Josephine; Habgood, Anthony; Goodwin, Amanda; McAnulty, Robin J; Jenkins, Gisli

    2016-06-01

    Caffeine is a commonly used food additive found naturally in many products. In addition to potently stimulating the central nervous system caffeine is able to affect various systems within the body including the cardiovascular and respiratory systems. Importantly, caffeine is used clinically to treat apnoea and bronchopulmonary dysplasia in premature babies. Recently, caffeine has been shown to exhibit antifibrotic effects in the liver in part through reducing collagen expression and deposition, and reducing expression of the profibrotic cytokine TGFβ. The potential antifibrotic effects of caffeine in the lung have not previously been investigated. Using a combined in vitro and ex vivo approach we have demonstrated that caffeine can act as an antifibrotic agent in the lung by acting on two distinct cell types, namely epithelial cells and fibroblasts. Caffeine inhibited TGFβ activation by lung epithelial cells in a concentration-dependent manner but had no effect on TGFβ activation in fibroblasts. Importantly, however, caffeine abrogated profibrotic responses to TGFβ in lung fibroblasts. It inhibited basal expression of the α-smooth muscle actin gene and reduced TGFβ-induced increases in profibrotic genes. Finally, caffeine reduced established bleomycin-induced fibrosis after 5 days treatment in an ex vivo precision-cut lung slice model. Together, these findings suggest that there is merit in further investigating the potential use of caffeine, or its analogues, as antifibrotic agents in the lung. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Improved antitumor activity and reduced toxicity of doxorubicin encapsulated in poly(ε-caprolactone) nanoparticles in lung and breast cancer treatment: An in vitro and in vivo study.

    Science.gov (United States)

    Cabeza, Laura; Ortiz, Raul; Prados, Jose; Delgado, Ángel V; Martín-Villena, Maria J; Clares, Beatriz; Perazzoli, Gloria; Entrena, Jose M; Melguizo, Consolación; Arias, Jose L

    2017-05-01

    Poly(ε-caprolactone) (PCL) nanoparticles (NPs) offer many possibilities for drug transport because of their good physicochemical properties and biocompatibility. Doxorubicin-loaded PCL NPs have been synthesized to try to reduce the toxicity of doxorubicin (DOX) for healthy tissues and enhance its antitumor effect in two tumor models, breast and lung cancer, which have a high incidence in the global population. PCL NPs were synthesized using a modified nanoprecipitation solvent evaporation method. The in vitro toxicity of PCL NPs was evaluated in breast and lung cancer cell lines from both humans and mice, as was the inhibition of cell proliferation and cell uptake of DOX-loaded PCL NPs compared to free DOX. Breast and lung cancer xenografts were used to study the in vivo antitumor effect of DOX-loaded NPs. Moreover, healthy mice were used for in vivo toxicity studies including weight loss, blood toxicity and tissue damage. The results showed good biocompatibility of PCL NPs in vitro, as well as a significant increase in the cytotoxicity and cell uptake of the drug-loaded in PCL NPs, which induced almost a 98% decrease of the IC50 (E0771 breast cancer cells). Likewise, DOX-loaded PCL NPs led to a greater reduction in tumor volume (≈36%) in studies with C57BL/6 mice compared to free DOX in both lung and breast tumor xenograft models. Nevertheless, no differences were found in terms of mouse weight. Only in the lung cancer model were significant differences in mice survival observed. In addition, DOX-loaded PCL NPs were able to reduce myocardial and blood toxicity in mice compared to free DOX. Our results showed that DOX-loaded PCL NPs were biocompatible, enhanced the antitumor effect of DOX and reduced its toxicity, suggesting that they may have an important potential application in lung and breast cancer treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Mortality rates in pediatric septic shock

    OpenAIRE

    Desy Rusmawatiningtyas; Nurnaningsih Nurnaningsih

    2017-01-01

    Background Septic shock remains a major cause of morbidity and mortality in children admitted to the intensive care unit. Recent investigations from developed countries have reported mortality rates of 20-30%. Few studies have reported mortality rates from pediatric septic shock in intensive care settings in developing countries with limited resources.  Objective  To determine the current mortality rates for pediatric patients with septic shock in a developing country. Methods A retr...

  7. SU-E-J-64: Evaluation of a Commercial EPID-Based in Vivo Dosimetric System in the Presence of Lung Tissue Heterogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Gimeno-Olmos, J; Palomo-Llinares, R; Candela-Juan, C; Carmona Meseguer, V; Lliso-Valverde, F [Hospital Universitari i Politecnic La Fe, Valencia, Valencia (Spain); Garcia-Martinez, T [Hospital de la Ribera, Alzira, Valencia (Spain); Richart-Sancho, J [Clinica Benidorm, Benidorm, Alicante (Spain); Ballester, F [University of Valencia, Burjassot (Spain); Perez-Calatayud, J [Hospital Universitari i Politecnic La Fe, Valencia, Valencia (Spain); Clinica Benidorm, Benidorm, Alicante (Spain)

    2014-06-01

    Purpose: To study the performance of Dosimetry Check (DC), an EPID-based dosimetry software, which allows performing transit dosimetry, in low density medium, by comparing calculations in-phantom, and analysing results for 15 lung patients. Methods: DC software (v.3.8, pencil beam-based algorithm) has been tested, for plans (Eclipse v.10.0 TPS) delivered in two Varian Clinac iX equipped with aS1000 EPIDs.In the CIRS lung phantom, comparisons between DC and Eclipse (Acuros) were performed for several plans: (1) four field box; (2) square field delivered in arc mode; (3) RapidArc lung patient plan medially centred; (4) RapidArc lung patient plan centred in one lung. Reference points analysed: P1 (medial point, plans 1–3) and P2 (located inside one lung, plan 4).For fifteen lung patients treated with RapidArc, the isocentre and 9 additional points inside the PTV as well as the gamma passing rate (3%/3mm) for the PTV and at the main planes were studied. Results: In-phantom:P1: Per-field differences in plan 1: good agreement for AP-PA fields; discrepancy of 7% for the lateral fields. Global differences (plans 1–3): about 4%, showing a compensating effect of the individual differences.P2: Global difference (plan 4): 15 %. This represents the worst case situation as it is a point surrounded by lung tissue, where the DC pencil beam algorithm is expected to give the greater difference against Acuros.Lung patients: Mean point difference inside the PTV:(5.4±4.2) %. Gamma passing rate inside the PTV:(45±12) %. Conclusion: The performance of DC in heterogeneous lung medium was studied with a special phantom and the results for 15 patients were analysed. The found deviations show that even though DC is a highly promising in vivo dosimetry tool, there is a need of incorporating a more accurate algorithm mainly for plans with low density regions involved.

  8. Septic and non-septic olecranon bursitis in the accident and emergency department--an approach to management.

    OpenAIRE

    Stell, I M

    1996-01-01

    Olecranon bursitis is relatively common. One third of episodes are septic. Most of the remainder are non-septic, with occasional rheumatological causes. Trauma can cause both septic and non-septic olecranon bursitis. Clinical features are helpful in separating septic from non-septic olecranon bursitis, but there may be local erythema in both. Aspiration should be carried out in all cases, and if the presence of infection is still in doubt, microscopy, Gram staining, and culture of the aspirat...

  9. A RATIONAL APPROACH TO SEPTIC TANK DESIGN

    African Journals Online (AJOL)

    2012-03-01

    Mar 1, 2012 ... A Rational Approach to Septic Tank Design. 69. Table 1: Schedule of Septic Tank Sizing and Dimensions (PWD, 1943). ... ficiency, hence three classes of plan specifications will be included in the evolving design .... 15 people in a typical Nigerian middle class city, say Enugu. It is required to construct a ...

  10. In vitro and in vivo anti-tumor effects of selected platinum(IV) and dinuclear platinum(II) complexes against lung cancer cells.

    Science.gov (United States)

    Arsenijevic, Milos; Milovanovic, Marija; Jovanovic, Snezana; Arsenijevic, Natalija; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Vladislav

    2017-08-01

    In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer. Results obtained by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], Lactate dehydrogenase and Annexin V/Propidium Iodide assays showed that, among all tested complexes, [PtCl4(en)] had the highest cytotoxicity against human and murine lung carcinoma cells in vitro. [PtCl4(en)] showed significantly higher cytotoxicity then cisplatin in all tested concentrations, mainly by inducing apoptosis in lung cancer cells. [PtCl4(en)] was well tolerated in vivo. Clinical signs of [PtCl4(en)]-induced toxicity, such as changes in food, water consumption or body weight, nephrotoxicity or hepatotoxicity was not observed in [PtCl4(en)]-treated mice. [PtCl4(en)] managed to increase presence of CD45+ leukocytes, including F4/80+ macrophages, CD11c+ dendritic cells, CD4+ helper and CD8+ cytotoxic T cells (CTLs) in the lungs, cytotoxic NK, NKT and CTLs in the spleens of tumor bearing mice, resulting with reduction of metastatic lesions in the lungs, indicating its potential to stimulate anti-tumor immune response in vivo. Due to its anti-tumor cytotoxicity, biocompatibility, and potential for stimulation of anti-tumor immune response, [PtCl4(en)] may be a good candidate for further testing in the field of medicinal chemistry.

  11. CCN5 overexpression inhibits profibrotic phenotypes via the PI3K/Akt signaling pathway in lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis and in an in vivo model of lung fibrosis.

    Science.gov (United States)

    Zhang, Lin; Li, Yingna; Liang, Chunlian; Yang, Weilin

    2014-02-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease with unknown etiology and undefined treatment modality. Fibroblasts are regarded as the major cell type that mediates the onset and progression of lung fibrosis by secreting large amounts of extracellular matrix (ECM) proteins, such as connective tissue growth factor (CTGF/CCN2). Current knowledge confers a crucial role of CCN2 in lung fibrosis. CCN5, another member of the CCN family, has been suggested to play an inhibitory role in some fibrotic diseases, such as cardiac fibrosis. However, the role of CCN5 in the process of IPF remains unknown. In the present study, using western blot analysis, we demonstrate that CCN2 is highly expressed in fibroblasts derived from IPF tissue, but is only slightly expressed in normal human lung fibroblasts. However, CCN5 was weakly expressed in all the above cells. qRT-PCR revealed that transforming growth factor (TGF)-β1 stimulation increased CCN2 expression in the IPF-derived cultures of primary human lung fibroblasts (PIFs) in a time- and concentration-dependent manner, but only slightly affected the expression of CCN5. The overexpression of CCN5 induced by the transfection of PIFs with recombinant plasmid did not affect cell viability, proliferation and apoptosis; however, it significantly suppressed the expression of CCN2, α-smooth muscle actin (α-SMA) and collagen type I. The TGF-β1-induced upregulation of the phosphorylation of Akt was reversed by CCN5 overexpression. Our results also demonstrated that adenovirus-mediated CCN5 overexpression in a mouse model of bleomycin-induced IPF significantly decreased the hydroxyproline content in the lungs, as well as TGF-β1 expression in bronchoalveolar lavage fluid. Taken together, our data demonstrate that CCN5 exerts an inhibitory effect on the fibrotic phenotypes of pulmonary fibroblasts in vitro and in vivo, and as such may be a promising target for the treatment of IPF.

  12. Simultaneous in vivo synchrotron radiation computed tomography of regional ventilation and blood volume in rabbit lung using combined K-edge and temporal subtraction

    Energy Technology Data Exchange (ETDEWEB)

    Suhonen, H [Department of Physical Sciences, University of Helsinki (Finland); Porra, L [Department of Physical Sciences, University of Helsinki (Finland); Bayat, S [Universite de Picardie Jules Verne, Faculte de Medecine, PERITOX (EA-INI RIS) and Cardiologie et Pneumo-Allerglogie Pediatriques, CHU Amiens (France); Sovijaervi, A R A [Department of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki (Finland); Suortti, P [Department of Physical Sciences, University of Helsinki (Finland)

    2008-02-07

    In K-edge subtraction (KES) imaging with synchrotron radiation computed tomography (SRCT), two images are taken simultaneously using energies above and below the K-absorption edge of a contrast agent. A logarithmic difference image reveals the contrast agent concentration with good accuracy. Similarly, in temporal subtraction imaging (TSI) the reference image is taken before the introduction of the contrast agent. Quantitative comparisons of in vivo images of rabbit lung indicated that similar results for concentrations of iodine in blood vessels and xenon in airways are obtained by KES and TSI, but the level of noise and artifacts was higher in the latter. A linear fit showed that in the lung parenchyma {rho}{sub TSI} = (0.97 {+-} 0.03){rho}{sub KES} + (0.00 {+-} 0.05) for xenon and {rho}{sub TSI} = (1.21 {+-} 0.15){rho}{sub KES} + (0.0 {+-} 0.1) for iodine. For xenon the calculation of time constant of ventilation gave compatible values for both of the methods. The two methods are combined for the simultaneous determination of the xenon concentration (by KES) and the iodine concentration (by TSI) in lung imaging, which will allow simultaneous in vivo determination of ventilation and perfusion.

  13. A case of Lemierre's syndrome with septic shock and complicated parapneumonic effusions requiring intrapleural fibrinolysis

    Directory of Open Access Journals (Sweden)

    Daniel P. Croft

    2015-01-01

    Full Text Available Lemierre's syndrome is a septic thrombophlebitis of the internal jugular vein, which can lead to severe systemic illness. We report a case of an otherwise healthy 26-year-old man who suffered from pharyngitis followed by septic shock requiring intubation and vasopressor support from Fusobacterium necrophorum bacteremia. The septic emboli to his lungs caused complicated bilateral parapneumonic effusions, which recurred after initial drainage. He required bilateral chest tubes and intrapleural tPA to successfully drain his effusions. His fever curve and overall condition improved with the resolution of his effusions and after a 33-day hospitalization, he recovered without significant disability. The severity of his illness and difficult to manage complicated parapneumonic effusions were the unique facets of this case. Using an evidence-based approach of tPA and DNase for complicated parapneumonic effusions in Lemierre's syndrome can be safe and effective.

  14. Control groups in recent septic shock trials

    DEFF Research Database (Denmark)

    Pettilä, Ville; Hjortrup, Peter B; Jakob, Stephan M

    2016-01-01

    PURPOSE: The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. METHODS: We searched for original articles presenting...... randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics...... % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2...

  15. The anti-lung cancer activity of SEP is mediated by the activation and cytotoxicity of NK cells via TLR2/4 in vivo.

    Science.gov (United States)

    Ke, Mengyun; Wang, Hui; Zhang, Min; Tian, Yuwei; Wang, Yizhou; Li, Bing; Yu, Jie; Dou, Jie; Xi, Tao; Zhou, Changlin

    2014-05-01

    Strongylocentrotus nudus egg polysaccharide (SEP) has been reported to display antitumor activity. However, the effects of SEP and its underlying mechanism in the treatment of lung cancer remain unclear, particularly with an immunodeficient mouse model of human non-small cell lung cancer (NSCLC). In the present study, we investigated the anti-lung cancer effects of SEP and its underlying mechanism of action in both Lewis lung cancer (LLC)-bearing C57/BL6J mice and human NSCLC H460-bearing nude mice. Although SEP showed no inhibitory effects on tumor cells in vitro, it markedly stimulated the percentage of CD3-NK1.1(+) cells and natural killer (NK) cell cytotoxicity in the spleens of nude mice and C57/BL6J mice. In LLC-bearing mice, SEP not only inhibited tumor growth but also promoted NK-mediated cytotoxicity, the NK1.1(+) cell population, and IL-2 and IFN-γ secretion. SEP significantly suppressed H460 growth in nude mice, which was abrogated by the selective depletion of NK cells via the intraperitoneal injection of anti-asialo GM-1 antibodies. Furthermore, anti-TLR2/4 antibodies blocked both SEP and NK cell binding and SEP-induced perforin secretion. SEP-induced proliferation and IFN-γ secretion by NK cells in wild type mice were partially impaired in TLR2 or TLR4 knockout mice. These results suggest that SEP-promoted NK cytotoxicity, which was partially mediated via TLR2 and TLR4, was the main contributing factor to lung cancer inhibition in vivo and that SEP may be a potential immunotherapy candidate for the treatment of lung cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Lung density

    DEFF Research Database (Denmark)

    Garnett, E S; Webber, C E; Coates, G

    1977-01-01

    The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...... breathing in the sitting position ranged from 0.25 to 0.37 g.cm-3. Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 g.cm-3. The lung density measurement correlated well with the findings in chest radiographs...... but the lung density values were more sensitive indices. This was particularly evident in serial observations of individual patients....

  17. Down-regulation of human complement factor H sensitizes non-small cell lung cancer cells to complement attack and reduces in vivo tumor growth.

    Science.gov (United States)

    Ajona, Daniel; Hsu, Yi-Fan; Corrales, Leticia; Montuenga, Luis M; Pio, Ruben

    2007-05-01

    Malignant cells are often resistant to complement activation through the enhanced expression of complement inhibitors. In this work, we examined the protective role of factor H, CD46, CD55, and CD59 in two non-small cell lung cancer cell lines, H1264 and A549, upon activation of the classical pathway of complement. Complement was activated with polyclonal Abs raised against each cell line. After blocking factor H activity with a neutralizing Ab, C3 deposition and C5a release were more efficient. Besides, a combined inhibition of factor H and CD59 significantly increased complement-mediated lysis. CD46 and CD55 did not show any effect in the control of complement activation. Factor H expression was knockdown on A549 cells using small interfering RNA. In vivo growth of factor H-deficient cells in athymic mice was significantly reduced. C3 immunocytochemistry on explanted xenografts showed an enhanced activation of complement in these cells. Besides, when mice were depleted of complement with cobra venom factor, growth was recovered, providing further evidence that complement was important in the reduction of in vivo growth. In conclusion, we show that expression of the complement inhibitor factor H by lung cancer cells can prevent complement activation and improve tumor development in vivo. This may have important consequences in the efficiency of complement-mediated immunotherapies.

  18. Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

    Directory of Open Access Journals (Sweden)

    Patsouris Efstratios

    2011-04-01

    Full Text Available Abstract Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory versus normocapnic (metabolic acidosis in an ex vivo model of ventilator-induced lung injury (VILI. Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA, metabolic acidosis (MA and normocapnic-normoxic (Control - C groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain, changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024, while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276 and 40 min (P = 0.0012 compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

  19. Use of high-dose nandrolone aggravates septic shock in a mouse model

    Directory of Open Access Journals (Sweden)

    Che Lin

    2011-06-01

    Full Text Available Nandrolone, an anabolic-androgenic steroid, is widely misused by athletes who wish to rapidly increase muscle mass and performance. An increasing number of reports have indicated that nandrolone may affect and modulate the immune system. This study aimed to investigate the effects of nandrolone on septic shock-caused immune responses and the cellular mechanism of action using a sepsis murine model. Before septic shock induction, BALB/c mice were given a high dose of nandrolone or peanut oil only. After septic shock induction, mice were sacrificed at different time points. Their blood and tissue specimens were analyzed. It was found that the high-dose nandrolone group had significantly increased mortality compared with the control group (p<0.001. The serum malondialdehyde level was significantly increased in the high-dose group compared with the control group. Animals administered a high dose of nandrolone had significantly increased hepatic tumor necrosis factor-α or splenic interferon-γ at 0 and 6 hours. In lung tissue, insulin-like growth factor-1, insulin-like growth factor binding proteins (IGFBPs and insulin-like growth factor-1 receptor, and IGFBP1 and IGFBP2 mRNA expression were increased in the high-dose nandrolone group at 6 hours. Nandrolone abuse may hasten the death of patients with septic shock and may aggravate septic shock in mice.

  20. An integrated array of microfluidic oxygenators as a neonatal lung assist device: in vitro characterization and in vivo demonstration.

    Science.gov (United States)

    Rochow, Niels; Manan, Asmaa; Wu, Wen-I; Fusch, Gerhard; Monkman, Shelley; Leung, Jennifer; Chan, Emily; Nagpal, Dipen; Predescu, Dragos; Brash, John; Selvaganapathy, Ponnambalam Ravi; Fusch, Christoph

    2014-10-01

    A miniaturized oxygenator device that is perfused like an artificial placenta via the umbilical vessels may have significant potential to save the lives of newborns with respiratory insufficiency. Recently we presented the concept of an integrated modular lung assist device (LAD) that consists of stacked microfluidic single oxygenator units (SOUs) and demonstrated the technical details and operation of SOU prototypes. In this article, we present a LAD prototype that is designed to accommodate the different needs of term and preterm infants by permitting changing of the number of parallel-stacked microfluidic SOUs according to the actual body weight. The SOUs are made of polydimethylsiloxane, arranged in parallel, and connected though 3D-printed polymeric interconnects to form the LAD. The flow characteristics and the gas exchange properties were tested in vitro using human blood. We found that the pressure drop of the LAD increased linearly with flow rate. Gas exchange rates of 2.4-3.8 μL/min/cm(2) (0.3-0.5 mL/kg/min) and 6.4-10.1 μL/min/cm(2) (0.8-1.3 mL/kg/min) for O2 and CO2 , respectively, were achieved. We also investigated protein adsorption to provide preliminary information on the need for application of anticoagulant coating of LAD materials. Albumin adsorption, as measured by gold staining, showed that surface uptake was evenly distributed and occurred at the monolayer level (>0.2 μg/cm(2) ). Finally, we also tested the LAD under in vivo conditions using a newborn piglet model (body weight 1.65-2.0 kg). First, the effect of an arteriovenous bypass via a carotid artery-to-jugular vein shortcut on heart rate and blood pressure was investigated. Heart rate and mean arterial blood pressure remained stable for extracorporeal flow rates of up to 61 mL/kg/min (101 mL/min). Next, the LAD was connected to umbilical vessels (maximum flow rate of 24 mL/min [10.4 mL/kg/min]), and O2 gas exchange was measured under hypoxic conditions (Fi O2

  1. Intratumoral pharmacokinetic analysis by 19F-magnetic resonance spectroscopy and cytostatic in vivo activity of gemcitabine (dFdC) in two small cell lung cancer xenografts

    DEFF Research Database (Denmark)

    Kristjansen, P E; Quistorff, B; Spang-Thomsen, M

    1993-01-01

    BACKGROUND: Gemcitabine, 2'2'difluoro-deoxycytidine (dFdC), has shown activity in several preclinical models, and presently the compound is being clinically evaluated in patients with lung cancer and other solid tumors. DESIGN: The cytostatic in vivo activity of dFdC was tested in the two human.......p. every third day, four times were applied. RESULTS AND CONCLUSION: Significant activity of gemcitabine was demonstrated in both SCLC tumor lines. The tumor line 54A is the most sensitive to radiotherapy, doxorubicin, and nitrosoureas; but in this case the 54B tumors were more sensitive to gemcitabine...

  2. Electroporation-mediated in vivo gene delivery of the Na+/K+-ATPase pump reduced lung injury in a mouse model of lung contusion.

    Science.gov (United States)

    Machado-Aranda, David A; Suresh, M V; Yu, Bi; Raghavendran, Krishnan

    2012-01-01

    Lung contusion (LC) is an independent risk factor for acute respiratory distress syndrome. The final common pathway in ARDS involves accumulation of fluid in the alveoli. In this study, we demonstrate the application of a potential gene therapy approach by delivering the Na+/K+-ATPase pump subunits in a murine model of LC. We hypothesized that restoring the activity of the pump will result in removal of excess alveolar fluid and additionally reduce inflammation. Under anesthesia, C57/BL6 mice were struck along the right posterior axillary line 1 cm above the costal margin with a cortical contusion impactor. Immediately afterward, 100 μg of plasmid DNA coding for the α,β of the Na+/K+-ATPase pump were instilled into the lungs (LC-electroporation-pump group). Contusion only (LC-only) and a sham saline instillation group after contusion were used as controls (LC-electroporation-sham). By using a BTX 830 electroporator, eight electrical pulses of 200 V/cm field strength were applied transthoracically. Mice were killed at 24 hours, 48 hours, and 72 hours after delivery. Bronchial alveolar lavage was recollected to measure albumin and cytokines by enzyme-linked immunosorbent assay. Pulmonary compliance was measured, and lungs were subject to histopathologic analysis. After the electroporation and delivery of genes coding for the α,β subunits of the Na+/K+-ATPase pump, there was a significant mitigation of acute lung injury as evidenced by reduction in bronchial alveolar lavage levels of albumin, improved pressure volume curves, and reduced inflammation seen on histology. Electroporation-mediated gene transfer of the subunits of the Na+/K+-ATPase pump enhanced recovery from acute inflammatory lung injury after LC.

  3. Genetics and genomics in pediatric septic shock.

    Science.gov (United States)

    Wong, Hector R

    2012-05-01

    Pediatric septic shock continues to be an important public health problem. Several investigative groups have applied genetic and genomic approaches as a means of identifying novel pathways and therapeutic targets, discovery of sepsis-related biomarkers, and identification of septic shock subclasses. This review will highlight studies in pediatric sepsis with a focus on gene association studies and genome-wide expression profiling. A summary of published literature involving gene association and expression profiling studies specifically involving pediatric sepsis and septic shock. Several polymorphisms of genes broadly involved in inflammation, immunity, and coagulation have been linked with susceptibility to sepsis, or outcome of sepsis in children. Many of these studies involve meningococcemia, and the strongest association involves a functional polymorphism of the plasminogen activator inhibitor-1 promoter region and meningococcal sepsis. Expression profiling studies in pediatric septic shock have identified zinc supplementation and inhibition of matrix metalloproteinase-8 activity as potential, novel therapeutic approaches in sepsis. Studies focused on discovery of sepsis-related biomarkers have identified interleukin-8 as a robust outcome biomarker in pediatric septic shock. Additional studies have demonstrated the feasibility and clinical relevance of gene expression-based subclassification of pediatric septic shock. Pediatric sepsis and septic shock are increasingly being studied by genetic and genomic approaches and the accumulating data hold the promise of enhancing our future approach to this ongoing clinical problem.

  4. Long-term physical outcome in patients with septic shock

    DEFF Research Database (Denmark)

    Poulsen, J. B.; Møller, Kirsten; Kehlet, H

    2009-01-01

    Limited information is available on physical function after septic shock. The aim of the present study was to assess the physical outcome in survivors 1 year after septic shock.......Limited information is available on physical function after septic shock. The aim of the present study was to assess the physical outcome in survivors 1 year after septic shock....

  5. Different early effect of irradiation in brain and small cell lung cancer examined by in vivo 31P-magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Kristjansen, P E; Pedersen, A G; Quistorff, B

    1992-01-01

    Early effects of irradiation were evaluated by non-invasive in vivo 31P-magnetic resonance spectroscopy (31P-MRS) of two small cell lung cancer (SCLC) tumor lines CPH SCCL 54A and 54B, in nude mice. The tumors were originally derived from the same patient and have similar morphology and growth......-MRS. No effect was observed in brain at any dose level. In contrast, 40 Gy induced a statistically significant reduction in ATP/Pi ratio during the 12-h post-irradiation period. This effect was more pronounced in 54A than in 54B. Some reduction was observed following 10 Gy, whereas 2.5 Gy induced no changes...... in ATP/Pi. The differential effect on tumors and brain might be relevant for monitoring irradiation effects by in vivo 31P-MRS in patients with brain metastases....

  6. Mechanisms of enhanced lung injury during sepsis

    DEFF Research Database (Denmark)

    Czermak, B J; Breckwoldt, M; Ravage, Z B

    1999-01-01

    A major complication in sepsis is progressively impaired lung function and susceptibility to intrapulmonary infection. Why sepsis predisposes the lung to injury is not clear. In the current studies, rats were rendered septic by cecal ligation/puncture and evaluated for increased susceptibility...

  7. Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo

    Science.gov (United States)

    Davies, Genna; Rolle, Anna-Maria; Maurer, Andreas; Spycher, Philipp R.; Schillinger, Claudia; Solouk-Saran, Djamschid; Hasenberg, Mike; Weski, Juliane; Fonslet, Jesper; Dubois, Adrien; Boschetti, Frederic; Denat, Franck; Gunzer, Matthias; Eichner, Martin; Ryder, Lauren S; Jensen, Mikael; Schibli, Roger; Pichler, Bernd J.; Wiehr, Stefan; Thornton, Christopher R.

    2017-01-01

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy or bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [64Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung infection using a [64Cu]NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu]NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant β1,5-galactofuranose (Galf) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Galf in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [64Cu]NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting. PMID:28912884

  8. Lung-cancer chemoprevention by induction of synthetic lethality in mutant KRAS premalignant cells in vitro and in vivo

    National Research Council Canada - National Science Library

    Huang, Shaoyi; Ren, Xiaoyang; Wang, Lai; Zhang, Ling; Wu, Xiangwei

    2011-01-01

    .... These data underscore the great need for effective chemoprevention of this cancer. Mutations and activation of KRAS occur frequently in, and are thought to be a primary driver of the development of, non-small cell lung cancers (NSCLC...

  9. Ex vivo analysis of the contribution of FGF10(+) cells to airway smooth muscle cell formation during early lung development.

    Science.gov (United States)

    El Agha, Elie; Kheirollahi, Vahid; Moiseenko, Alena; Seeger, Werner; Bellusci, Saverio

    2017-07-01

    Airway smooth muscle cells (ASMCs) have been widely studied during embryonic lung development. These cells have been shown to control epithelial bifurcation during branching morphogenesis. Fibroblast growth factor 10-positive (FGF10(+) ) cells, originally residing in the submesothelial mesenchyme, contribute to ASMC formation in the distal lung. The reported work aims at monitoring the response of FGF10(+) progenitors and differentiated ASMCs to growth factor treatment in real time using lineage tracing in the background of an air-liquid interface (ALI) culture system. FGF ligands impose divergent effects on iterative lung branching in vitro. Moreover, time-lapse imaging and endpoint analysis show that FGF9 treatment leads to amplification of the FGF10(+) lineage and represses its differentiation to ASMCs. Sonic hedgehog (SHH) treatment reduces the amplification of this lineage and leads to decreased lung branching. Finally, differentiated ASMCs in proximal regions fail to expand upon FGF9 treatment. Our data demonstrate, in real time, that FGF9 is an important regulator of amplification, migration, and subsequent differentiation of ASMC progenitors during early lung development. The attained results agree with previous findings regarding ASMC formation and highlight the complexity of growth factor signaling networks in controlling mesenchymal cell-fate decisions in the developing mouse lung. Developmental Dynamics 246:531-538, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  10. Mortality rates in pediatric septic shock

    National Research Council Canada - National Science Library

    Rusmawatiningtyas, Desy; Nurnaningsih, Nurnaningsih

    2017-01-01

    .... Recent investigations from developed countries have reported mortality rates of 20-30%. Few studies have reported mortality rates from pediatric septic shock in intensive care settings in developing countries with limited resources.  Objective...

  11. [Concomitant septic and gouty olecranon bursitis].

    Science.gov (United States)

    Abrazhda, D; Andras, L; Van Linthoudt, D

    2007-09-26

    A case of coexistent acute gout and septic olecranon bursitis is presented. Our hypothesis is that asymptomatic monosodium urate crystals, possibly present in the bursa could secondarily been triggered by the infection.

  12. Effect of subchronic in vivo exposure to nitrogen dioxide on lung tissue inflammation, airway microvascular leakage, and in vitro bronchial muscle responsiveness in rats.

    Science.gov (United States)

    Chitano, P; Rado, V; Di Stefano, A; Papi, A; Boniotti, A; Zancuoghi, G; Boschetto, P; Romano, M; Salmona, M; Ciaccia, A; Fabbri, L M; Mapp, C E

    1996-06-01

    In a previous study on bronchoalveolar lavage fluid from rats exposed in vivo for seven days to 10 ppm nitrogen dioxide (NO2), it has been shown that there is an influx of macrophages into the airways. The present study investigated the effect of seven day exposure to 10 ppm NO2, on: (a) lung tissue inflammation and morphology; (b) airway microvascular leakage; (c) in vitro contractile response of main bronchi. Lung tissue was studied by light microscopy, after fixing the lungs by inflation with 4% formalin at a pressure of 20 cm H2O. Microvascular leakage was measured by extravasation of Evans blue dye in the larynx, trachea, main bronchi, and intrapulmonary airways. Smooth muscle responsiveness was evaluated by concentration-responses curves to acetylcholine (10(-9)-10(-3) M), serotonin (10(-9)-10(-4) M), and voltage-response curves (12-28 V) to electrical field stimulation. Histology showed an increased total inflammation at the level of respiratory bronchioles and alveoli. No influx of inflammatory cells was found in the main bronchi. A loss of cilia in the epithelium of small airways and ectasia of alveolar capillaries was also found. By contrast, no alterations to microvascular permeability or modification of bronchial smooth muscle responsiveness was found. Subchronic exposure to 10 ppm NO2 causes airway inflammation and structural damage, but does not cause any persistent alteration to microvascular permeability or bronchial smooth muscle responsiveness in rats.

  13. Tumor-targeting magnetic lipoplex delivery of short hairpin RNA suppresses IGF-1R overexpression of lung adenocarcinoma A549 cells in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chunmao; Ding, Chao; Kong, Minjian [Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009 (China); Dong, Aiqiang, E-mail: dr_dongaiqiang@sina.com [Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009 (China); Qian, Jianfang; Jiang, Daming; Shen, Zhonghua [Department of Cardiothoracic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009 (China)

    2011-07-08

    Highlights: {yields} We compared lipofection with magnetofection about difference of transfection efficiency on delivery a therapeutic gene in vitro and in vivo. {yields} We investigated the difference of shRNA induced by magnetofection and lipofection into A549 cell and subcutaneous tumor to knockdown IGF-1R overexpressed in A549 cell and A549 tumor. {yields} We investigated in vivo shRNA silenced IGF-1R overexpression 24, 48, and 72 h after shRNA intravenous injection into tumor-bearing mice by way of magnetofection and lipofection. {yields} Our results showed that magnetofection could achieve therapeutic gene targeted delivery into special site, which contributed to targeted gene therapy of lung cancers. -- Abstract: Liposomal magnetofection potentiates gene transfection by applying a magnetic field to concentrate magnetic lipoplexes onto target cells. Magnetic lipoplexes are self-assembling ternary complexes of cationic lipids with plasmid DNA associated with superparamagnetic iron oxide nanoparticles (SPIONs). Type1insulin-like growth factor receptor (IGF-1R), an important oncogene, is frequently overexpressed in lung cancer and mediates cancer cell proliferation and tumor growth. In this study, we evaluated the transfection efficiency (percentage of transfected cells) and therapeutic potential (potency of IGF-1R knockdown) of liposomal magnetofection of plasmids expressing GFP and shRNAs targeting IGF-1R (pGFPshIGF-1Rs) in A549 cells and in tumor-bearing mice as compared to lipofection using Lipofectamine 2000. Liposomal magnetofection provided a threefold improvement in transgene expression over lipofection and transfected up to 64.1% of A549 cells in vitro. In vitro, IGF-1R specific-shRNA transfected by lipofection inhibited IGF-1R protein by 56.1 {+-} 6% and by liposomal magnetofection by 85.1 {+-} 3%. In vivo delivery efficiency of the pGFPshIGF-1R plasmid into the tumor was significantly higher in the liposomal magnetofection group than in the

  14. Clinical characteristics and outcomes of septic bursitis.

    Science.gov (United States)

    Lieber, Sarah B; Fowler, Mary Louise; Zhu, Clara; Moore, Andrew; Shmerling, Robert H; Paz, Ziv

    2017-12-01

    Limited data guide practice in evaluation and treatment of septic bursitis. We aimed to characterize clinical characteristics, microbiology, and outcomes of patients with septic bursitis stratified by bursal involvement, presence of trauma, and management type. We conducted a retrospective cohort study of adult patients admitted to a single center from 1998 to 2015 with culture-proven olecranon and patellar septic bursitis. Baseline characteristics, clinical features, microbial profiles, operative interventions, hospitalization lengths, and 60-day readmission rates were determined. Patients were stratified by bursitis site, presence or absence of trauma, and operative or non-operative management. Of 44 cases of septic bursitis, patients with olecranon and patellar bursitis were similar with respect to age, male predominance, and frequency of bursal trauma; patients managed operatively were younger (p = 0.05). Clinical features at presentation and comorbidities were similar despite bursitis site, history of trauma, or management. The most common organism isolated from bursal fluid was Staphylococcus aureus. Patients managed operatively were discharged to rehabilitation less frequently (p = 0.04). This study of septic bursitis is among the largest reported. We were unable to identify presenting clinical features that differentiated patients treated surgically from those treated conservatively. There was no clear relationship between preceding trauma or bursitis site and clinical course, management, or outcomes. Patients with bursitis treated surgically were younger. Additional study is needed to identify patients who would benefit from early surgical intervention for septic bursitis.

  15. Septic pericarditis in a cat with pyometra.

    Science.gov (United States)

    Majoy, Sean B; Sharp, Claire R; Dickinson, Amy E; Cunningham, Suzanne M

    2013-01-01

    To describe a unique cause of septic pericarditis in a cat and detail the successful case management strategy. A 6-year-old sexually intact female Ragdoll cat was evaluated for a 7-day history of progressive lethargy, anorexia, and vaginal discharge. Thoracic radiographs revealed a markedly globoid cardiac silhouette and pleural effusion while the initial echocardiogram showed moderate volume pericardial effusion. Following pericardiocentesis, cytologic evaluation of the pericardial effusion revealed septic suppurative inflammation with intra- and extracellular Gram-negative rod-shaped bacteria. Abdominal ultrasound demonstrated a moderate amount of echogenic uterine fluid accumulation with a right-sided uterine horn mass. After stabilization with pericardiocentesis, IV fluid therapy and IV antimicrobials, the cat underwent ovariohysterectomy and partial pericardiectomy. Histopathology confirmed a diagnosis of pyometra and septic pericarditis. Uterine and pericardial fluid bacterial culture yielded Escherichia coli with identical antimicrobial sensitivity spectrums. Septic pericarditis is a rare cause of pericardial effusion in the cat. Previous reported cases have either suggested the cause to be secondary to transient bacteremia resulting from a local infection seeding the pericardium or for the cause to remain unknown. To the authors' knowledge, this is the first veterinary report of septic pericarditis resulting from hematogeneously spread bacteria originating from a urogenital infection. It is also the first report of successful surgical management of septic pericarditis in the cat. © Veterinary Emergency and Critical Care Society 2012.

  16. Monoclonal Antibodies Inhibit the Adhesion of Mouse B 16 Melanoma Cells in vitro and Block Lung Metastasis in vivo

    Science.gov (United States)

    Vollmers, H. Peter; Birchmeier, Walter

    1983-06-01

    Seven monoclonal antibodies against mouse B 16 melanoma cells (produced in syngeneic C57BL/6 mice) were selected that blocked the adhesion of melanoma cells to tissue culture dishes. These antibodies were found to be directed against antigens on the surface of mouse B 16 melanoma cells but not on normal mouse cells such as 3T3 fibroblasts. Similarly, the antigens could not be detected in normal mouse tissues (e.g., lung, kidney, liver) but were found in lungs colonized by B 16 melanoma cells. Significantly, three of these antibodies virtually abolished lung colonization of highly invasive B 16 sublines injected into the animals' bloodstream. They exerted their effect both when preabsorbed by the melanoma cell in vitro and when delivered to the animals prior to the tumor cells. It is suggested that monoclonal antibodies might be a promising tool for preventing metastasis.

  17. Human mesenchymal stromal cells reduce influenza A H5N1-associated acute lung injury in vitro and in vivo

    OpenAIRE

    Chan, Michael C. W.; Kuok, Denise I. T.; Leung, Connie Y. H.; Hui, Kenrie P. Y.; Valkenburg, Sophie A.; Lau, Eric H. Y.; Nicholls, John M.; Fang, Xiaohui; Guan, Yi; Lee, Jae W.; Chan, Renee W. Y.; Webster, Robert G.; Matthay, Michael A.; Peiris, J. S. Malik

    2016-01-01

    Influenza can cause acute lung injury. Because immune responses often play a role, antivirals may not ensure a successful outcome. To identify pathogenic mechanisms and potential adjunctive therapeutic options, we compared the extent to which avian influenza A/H5N1 virus and seasonal influenza A/H1N1 virus impair alveolar fluid clearance and protein permeability in an in vitro model of acute lung injury, defined the role of virus-induced soluble mediators in these injury effects, and demonstr...

  18. Rapid 3D in vivo 1H human lung respiratory imaging at 1.5 T using ultra-fast balanced steady-state free precession.

    Science.gov (United States)

    Pusterla, Orso; Bauman, Grzegorz; Wielpütz, Mark O; Nyilas, Sylvia; Latzin, Philipp; Heussel, Claus P; Bieri, Oliver

    2017-09-01

    To introduce a reproducible, nonenhanced 1H MRI method for rapid in vivo functional assessment of the whole lung at 1.5 Tesla (T). At different respiratory volumes, the pulmonary signal of ultra-fast steady-state free precession (ufSSFP) follows an adapted sponge model, characterized by a respiratory index α. From the model, α reflects local ventilation-related information, is virtually independent from the lung density and thus from the inspiratory phase and breathing amplitude. Respiratory α-mapping is evaluated for healthy volunteers and patients with obstructive lung disease from a set of five consecutive 3D ultra-fast steady-state free precession (ufSSFP) scans performed in breath-hold and at different inspiratory volumes. For the patients, α-maps were compared with CT, dynamic contrast-enhanced MRI (DCE-MRI), and Fourier decomposition (FD). In healthy volunteers, respiratory α-maps showed good reproducibility and were homogeneous on iso-gravitational planes, but showed a gravity-dependent respiratory gradient. In patients with obstructive pulmonary disease, the functional impairment observed in respiratory α-maps was associated with emphysematous regions present on CT images, perfusion defects observable on DCE-MRI, and impairments visualized on FD ventilation and perfusion maps. Respiratory α-mapping derived from multivolumetric ufSSFP provides insights into functional lung impairment and may serve as a reproducible and normative measure for clinical studies. Magn Reson Med 78:1059-1069, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  19. Synergistic Activity of Berberine with Azithromycin against Pseudomonas Aeruginosa Isolated from Patients with Cystic Fibrosis of Lung In Vitro and In Vivo.

    Science.gov (United States)

    Li, YongTao; Huang, JianRong; Li, LanJuan; Liu, LinSheng

    2017-01-01

    Pseudomonas aeruginosa (PA) is one of the major opportunistic pathogens which can cause chronic lung infection of cystic fibrosis (CF). The formation of PA biofilm promotes CF development and restricts the antimicrobial efficacies of current antibiotics. The antimicrobial effects of azithromycin (AZM) and berberine (BER) alone and in combination were evaluated using microdilution method, checkerboard assay, time-kill test, qRT-PCR analysis and absorption method. The treatments of AZM and/or BER were further evaluated in an animal lung infection model via observing survival rate, bacterial burden and histopathology of lung, the levels of pro-/anti-inflammatory cytokines. AZM-BER were demonstrated to be synergistic against ten clinical PA isolates as well as the standard reference PA ATCC27853, in which PA03 was the most susceptible isolate to AZM-BER with FICI of 0.13 and chosen for subsequent experiments. The synergism of AZM-BER was further confirmed against PA03 in time-kill test and scanning electron microscope (SEM) at their concentrations showing synergism. In PA03, we found that AZM-BER could significantly attenuate productions of a series of virulence factors including alginate, LasA protease, LasB protease, pyoverdin, pyocyanin, chitinase as well as extracellular DNA, and remarkably inhibit the levels of quorum sensing (QS) molecules and the expressions of lasI, lasR, rhlI, rhlR at 1/2×MIC, 1×MIC and 2×MIC. In the infection model, the mice survival were increased markedly, the inflammations of infected lungs were improved greatly along with reduced IL-6, IL-8 and ascended IL-10 at 0.8 mg/kg of AZM combined with 3.2 mg/kg of BER. BER might be a promising synergist to enhance the antimicrobial activity of AZM in vitro and in vivo. © 2017 The Author(s). Published by S. Karger AG, Basel.

  20. Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN.

    Science.gov (United States)

    Coya, Juan Manuel; Akinbi, Henry T; Sáenz, Alejandra; Yang, Li; Weaver, Timothy E; Casals, Cristina

    2015-08-15

    The anionic antimicrobial peptide SP-B(N), derived from the N-terminal saposin-like domain of the surfactant protein (SP)-B proprotein, and SP-A are lung anti-infective proteins. SP-A-deficient mice are more susceptible than wild-type mice to lung infections, and bacterial killing is enhanced in transgenic mice overexpressing SP-B(N). Despite their potential anti-infective action, in vitro studies indicate that several microorganisms are resistant to SP-A and SP-B(N). In this study, we test the hypothesis that these proteins act synergistically or cooperatively to strengthen each other's microbicidal activity. The results indicate that the proteins acted synergistically in vitro against SP-A- and SP-B(N)-resistant capsulated Klebsiella pneumoniae (serotype K2) at neutral pH. SP-A and SP-B(N) were able to interact in solution (Kd = 0.4 μM), which enabled their binding to bacteria with which SP-A or SP-B(N) alone could not interact. In vivo, we found that treatment of K. pneumoniae-infected mice with SP-A and SP-B(N) conferred more protection against K. pneumoniae infection than each protein individually. SP-A/SP-B(N)-treated infected mice showed significant reduction of bacterial burden, enhanced neutrophil recruitment, and ameliorated lung histopathology with respect to untreated infected mice. In addition, the concentrations of inflammatory mediators in lung homogenates increased early in infection in contrast with the weak inflammatory response of untreated K. pneumoniae-infected mice. Finally, we found that therapeutic treatment with SP-A and SP-B(N) 6 or 24 h after bacterial challenge conferred significant protection against K. pneumoniae infection. These studies show novel anti-infective pathways that could drive development of new strategies against pulmonary infections. Copyright © 2015 by The American Association of Immunologists, Inc.

  1. Synergistic Activity of Berberine with Azithromycin against Pseudomonas Aeruginosa Isolated from Patients with Cystic Fibrosis of Lung In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    YongTao Li

    2017-07-01

    Full Text Available Background/Aims: Pseudomonas aeruginosa (PA is one of the major opportunistic pathogens which can cause chronic lung infection of cystic fibrosis (CF. The formation of PA biofilm promotes CF development and restricts the antimicrobial efficacies of current antibiotics. Methods: The antimicrobial effects of azithromycin (AZM and berberine (BER alone and in combination were evaluated using microdilution method, checkerboard assay, time-kill test, qRT-PCR analysis and absorption method. The treatments of AZM and/or BER were further evaluated in an animal lung infection model via observing survival rate, bacterial burden and histopathology of lung, the levels of pro-/anti-inflammatory cytokines. Results: AZM-BER were demonstrated to be synergistic against ten clinical PA isolates as well as the standard reference PA ATCC27853, in which PA03 was the most susceptible isolate to AZM-BER with FICI of 0.13 and chosen for subsequent experiments. The synergism of AZM-BER was further confirmed against PA03 in time-kill test and scanning electron microscope (SEM at their concentrations showing synergism. In PA03, we found that AZM-BER could significantly attenuate productions of a series of virulence factors including alginate, LasA protease, LasB protease, pyoverdin, pyocyanin, chitinase as well as extracellular DNA, and remarkably inhibit the levels of quorum sensing (QS molecules and the expressions of lasI, lasR, rhlI, rhlR at 1/2×MIC, 1×MIC and 2×MIC. In the infection model, the mice survival were increased markedly, the inflammations of infected lungs were improved greatly along with reduced IL-6, IL-8 and ascended IL-10 at 0.8 mg/kg of AZM combined with 3.2 mg/kg of BER. Conclusion: BER might be a promising synergist to enhance the antimicrobial activity of AZM in vitro and in vivo.

  2. Exploring polyvinylpyrrolidone in the engineering of large porous PLGA microparticles via single emulsion method with tunable sustained release in the lung: In vitro and in vivo characterization.

    Science.gov (United States)

    Ni, Rui; Muenster, Uwe; Zhao, Jing; Zhang, Lan; Becker-Pelster, Eva-Maria; Rosenbruch, Martin; Mao, Shirui

    2017-03-10

    Sustained pulmonary drug delivery is regarded as an effective strategy for local treatment of chronic lung diseases. Despite of the progress made so far, there remains a need for respirable drug loaded porous microparticles, where porosity of the microparticles can be readily engineered during the preparation process, with tunable sustained drug release upon lung deposition. In this work, polyvinyl pyrrolidone (PVP) was used as a novel porogen to engineer PLGA-based large porous particles (LPPs) using single emulsion method, with fine tuning of the porosity, sustained drug release both in vitro and in vivo. Using cinaciguat as the model drug, influence of PVP content and PLGA type on the properties of the LPPs was characterized, including geometric particle size, drug encapsulation efficiency, tap density, theoretical and experimental aerodynamic particle size, specific surface area, morphology, and in vitro drug release. Solid state of cinaciguat in the LPPs was studied based on DSC and X-ray analysis. LPPs retention in the rat lung was carried out using bronchoalveolar lavage fluid method. Raw 264.7 macrophage cells were used for LPPs uptake study. Pharmacodynamic study was performed in mini-pigs in a well-established model of pulmonary arterial hypertension (thromboxane challenge). It was demonstrated that porosity of the LPPs is tunable via porogen content variation. Cinaciguat can be released from the LPP in a controlled manner for over 168h. Significant reduction of macrophage phagocytosis was presented for LPPs. Furthermore, LPPs was found to have extended retention time (~36h) in the rat lung and accordingly, sustained pharmacodynamics effect was achieved in mini-pig model. Taken together, our results demonstrated that this simple PLGA based LPPs engineering using single emulsion method with PVP as porogen may find extensive application for the pulmonary delivery of hydrophobic drugs to realize tunable sustained effect with good safety profile. Copyright

  3. Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 Cells In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Rea Bingula

    2016-01-01

    Full Text Available We investigated the effects of betaine, C-phycocyanin (C-PC, and their combined use on the growth of A549 lung cancer both in vitro and in vivo. When cells were coincubated with betaine and C-PC, an up to 60% decrease in viability was observed which is significant compared to betaine (50% or C-PC treatment alone (no decrease. Combined treatment reduced the stimulation of NF-κB expression by TNF-α and increased the amount of the proapoptotic p38 MAPK. Interestingly, combined treatment induced a cell cycle arrest in G2/M phase for ~60% of cells. In vivo studies were performed in pathogen-free male nude rats injected with A549 cells in their right flank. Their daily food was supplemented with either betaine, C-PC, both, or neither. Compared to the control group, tumour weights and volumes were significantly reduced in either betaine- or C-PC-treated groups and no additional decrease was obtained with the combined treatment. This data indicates that C-PC and betaine alone may efficiently inhibit tumour growth in rats. The synergistic activity of betaine and C-PC on A549 cells growth observed in vitro remains to be further confirmed in vivo. The reason behind the nature of their interaction is yet to be sought.

  4. In Vivo Pharmacodynamic Target Assessment of Delafloxacin against Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae in a Murine Lung Infection Model.

    Science.gov (United States)

    Lepak, Alexander J; Andes, David R

    2016-08-01

    Delafloxacin is a broad-spectrum anionic fluoroquinolone under development for the treatment of bacterial pneumonia. The goal of the study was to determine the pharmacokinetic/pharmacodynamic (PK/PD) targets in the murine lung infection model for Staphylococcus aureus, Streptococcus pneumoniae, and Klebsiella pneumoniae Four isolates of each species were utilized for in vivo studies: for S. aureus, one methicillin-susceptible and three methicillin-resistant isolates; S. pneumoniae, two penicillin-susceptible and two penicillin-resistant isolates; K. pneumoniae, one wild-type and three extended-spectrum beta-lactamase-producing isolates. MICs were determined using CLSI methods. A neutropenic murine lung infection model was utilized for all treatment studies, and drug dosing was by the subcutaneous route. Single-dose plasma pharmacokinetics was determined in the mouse model after administration of 2.5, 10, 40, and 160 mg/kg. For in vivo studies, 4-fold-increasing doses of delafloxacin (range, 0.03 to 160 mg/kg) were administered every 6 h (q6h) to infected mice. Treatment outcome was measured by determining organism burden in the lung (CFU counts) at the end of each experiment (24 h). The Hill equation for maximum effect (Emax) was used to model the dose-response data. The magnitude of the PK/PD index, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC), associated with net stasis and 1-log kill endpoints was determined in the lung model for all isolates. MICs ranged from 0.004 to 1 mg/liter. Single-dose PK parameter ranges include the following: for maximum concentration of drug in serum (Cmax), 2 to 70.7 mg/liter; AUC from 0 h to infinity (AUC0-∞), 2.8 to 152 mg · h/liter; half-life (t1/2), 0.7 to 1 h. At the start of therapy mice had 6.3 ± 0.09 log10 CFU/lung. In control mice the organism burden increased 2.1 ± 0.44 log10 CFU/lung over the study period. There was a relatively steep dose-response relationship

  5. An In Vivo and In Vitro Evaluation of the Mutual Interactions between the Lung and the Large Intestine

    Directory of Open Access Journals (Sweden)

    Lei-Miao Yin

    2013-01-01

    Full Text Available One of the most important theories of the traditional Chinese medicine is the exterior-interior relationship between the lung and the large intestine; so far, little direct experimental evidence has been reported to support such relationship. Here we for the first time investigated the mutual interactions between the lung and the large intestine by examining the relevancies between the pulmonary functions and the rectal resting pressure in the rat models of asthma and constipation. We also evaluated the effects of the lung homogenate and the large intestine homogenate on the isolated large intestine muscle strip and the isolated tracheal spiral, respectively. Our results showed that the pulmonary resistance and pulmonary compliance were closely related to the rectal resting pressure in the asthmatic rat model, while the rectal resting pressure was much correlated with the pulmonary resistance in the rat model of constipation. Moreover, it was shown that the lung homogenate could specifically contract the isolated large intestine muscle strip. Overall, this study provided new lines of evidence for the theory and highlighted the potential application in the treatment of the corresponding diseases.

  6. Ameliorative potential of linagliptin and/or calcipotriol on bleomycin-induced lung fibrosis: In vivo and in vitro study.

    Science.gov (United States)

    Kabel, Ahmed M; Abd Elmaaboud, Maaly A; Atef, Aliaa; Baali, Mohammed H

    2017-03-01

    Pulmonary fibrosis is a serious medical problem that may significantly compromise respiratory functions. The aim of this work was to study the effect of linagliptin and/or calcipotriol on bleomycin-induced pulmonary fibrosis and to explore the possible mechanisms underlying this effect. One hundred and twenty male C57BL/6 mice were divided into 6 equal groups as follows: control group; bleomycin group; bleomycin+carboxymethylcellulose group; bleomycin+linagliptin group; bleomycin+calcipotriol group and bleomycin+linagliptin+calcipotriol group. Lung weight/body weight index, lung tissue hydroxyproline, collagen, toll-like receptor 4 (TLR4), nuclear factor-like 2 (Nrf2), heme oxygenase-1 (HO-1), malondialdehyde (MDA), glutathione peroxidase (GPx) and catalase (CAT) were measured. Also, bronchoalveolar lavage fluid (BALF) was analyzed for total and differential leucocytic count, lactate dehydrogenase, tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10) and transforming growth factor-beta 1 (TGF-β1). Vascular response to potassium chloride, phenylephrine and carbachol as well as tracheal response to carbachol were measured. Also, lung tissue was subjected to histopathological and immunohistochemical examination. Administration of linagliptin and/or calcipotriol induced significant decrease in the lung weight/body weight index, total leucocytic count, BALF lactate dehydrogenase activity, IL-10, TNF-α and TGF-β1 associated with significant decrease in lung tissue MDA, Nrf2, HO-1, TLR4, hydroxyproline and collagen content with significant increase in tissue GPx and CAT and improvement of the pulmonary architecture, vascular and tracheal response compared to bleomycin group. These effects were significant in linagliptin/calcipotriol combination group compared to the use of each of these drugs alone. In conclusion, linagliptin/calcipotriol combination may represent an effective therapeutic modality for amelioration of bleomycin-induced pulmonary fibrosis

  7. Septic and non-septic olecranon bursitis in the accident and emergency department--an approach to management.

    Science.gov (United States)

    Stell, I M

    1996-09-01

    Olecranon bursitis is relatively common. One third of episodes are septic. Most of the remainder are non-septic, with occasional rheumatological causes. Trauma can cause both septic and non-septic olecranon bursitis. Clinical features are helpful in separating septic from non-septic olecranon bursitis, but there may be local erythema in both. Aspiration should be carried out in all cases, and if the presence of infection is still in doubt, microscopy, Gram staining, and culture of the aspirate will resolve the issue. Septic olecranon bursitis should be treated by aspiration, which may need to be repeated, and a long course of antibiotics. Some cases will need admission, and a few will need surgical treatment. Non-septic olecranon bursitis can be managed with aspiration alone. Non-steroidal anti-inflammatory drugs probably hasten symptomatic improvement. Intrabursal corticosteroids produce a rapid resolution but concern remains over their long term local effects. Recovery from septic olecranon bursitis can take months.

  8. In vitro and in vivo evaluation of tubulin inhibitors with non-small cell lung cancer pre-clinical models

    Directory of Open Access Journals (Sweden)

    Lama R

    2015-05-01

    Full Text Available Synthetic small molecule tubulin inhibitors have many advantages as novel anti-cancer agents compared to the current tubulin inhibitors generated from natural products. Our previous studies led to the design and synthesis of a series of novel tubulin inhibitors. Some of these compounds also inhibited heat shock protein 27 (Hsp27, and showed promising in vitro anti-cancer activities in several breast cancer cell lines at sub nano-molar concentrations. However, whether these compounds could suppress tumor growth in animals was not investigated yet. In the current study, to identify the best drug candidates, therapeutic efficacy of the representative compounds from previous analyses was evaluated using non-small cell lung cancer preclinical models. These agents dose-dependently inhibited the growth of lung cancer cells in both monolayer cultures and three-dimensional multicellular spheroids. Several compounds also showed promising tumor growth suppressive activity in nude mice xenograft model

  9. Computer-aided detection of artificial pulmonary nodules using an ex vivo lung phantom: Influence of exposure parameters and iterative reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Wielpütz, Mark O., E-mail: Mark.Wielpuetz@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Amalienstr. 5, 69126 Heidelberg (Germany); Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Wroblewski, Jacek [Department of Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg (Germany); Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Amalienstr. 5, 69126 Heidelberg (Germany); Department of Radiology, German Cancer Research Center (dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Lederlin, Mathieu [Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Im Neuenheimer Feld 350, 69120 Heidelberg (Germany); Department of Radiology, University Hospital of Rennes, F-35033 Rennes (France); University of Rennes 1, UEB, F-35043 Rennes (France); and others

    2015-05-15

    Highlights: • CAD on chest MDCT is robust over a wide range of exposure settings, and may be applied on low-dose MDCT. • Iterative reconstruction (IR) is not detrimental for CAD sensitivity. • IR may not be used for further dose reduction with CAD on low-dose MDCT. • IR may be applicable with CAD for management of low-dose MDCT for lung cancer screening. - Abstract: Objectives: To evaluate the influence of exposure parameters and raw-data based iterative reconstruction (IR) on the performance of computer-aided detection (CAD) of pulmonary nodules on chest multidetector computed tomography (MDCT). Material and methods: Seven porcine lung explants were inflated in a dedicated ex vivo phantom shell and prepared with n = 162 artificial nodules of a clinically relevant volume and maximum diameter (46–1063 μl, and 6.2–21.5 mm). n = 118 nodules were solid and n = 44 part-solid. MDCT was performed with different combinations of 120 and 80 kV with 120, 60, 30 and 12 mA*s, and reconstructed with both filtered back projection (FBP) and IR. Subsequently, 16 datasets per lung were subjected to dedicated CAD software. The rate of true positive, false negative and false positive CAD marks was measured for each reconstruction. Results: The rate of true positive findings ranged between 88.9–91.4% for FBP and 88.3–90.1% for IR (n.s.) with most exposure settings, but was significantly lower with the combination of 80 kV and 12 mA*s (80.9% and 81.5%, respectively, p < 0.05). False positive findings ranged between 2.3 - 8.1 annotations per lung. For nodule volumes <200 μl the rate of true positives was significantly lower than for >300 μl (p < 0.05). Similarly, it was significantly lower for diameters <12 mm compared to ≥12 mm (p < 0.05). The rate of true positives for solid and part-solid nodules was similar. Conclusions: Nodule CAD on chest MDCT is robust over a wide range of exposure settings. Noise reduction by IR is not detrimental for CAD, and may be used to

  10. Different energy metabolism in two human small cell lung cancer subpopulations examined by 31P magnetic resonance spectroscopy and biochemical analysis in vivo and in vitro

    DEFF Research Database (Denmark)

    Kristjansen, P E; Spang-Thomsen, M; Quistorff, B

    1991-01-01

    Two human small cell lung cancer tumor lines, maintained as solid tumor xenografts on nude mice and as in vitro cell cultures, were studied by in vivo 31P magnetic resonance spectroscopy and by biochemical analysis of extracts of solid tumors and cell cultures. The tumor lines CPH SCCL 54A and CPH...... SCCL 54B are subpopulations from the same tumor. In solid tumors (n = 125), the ATP/Pi ratio was greater in 54A than in 54B. This was due to a higher ATP level in 54A, whereas there was no difference in Pi, ADP, and AMP. A decrease in ATP/Pi during growth was caused by a decline in ATP, whereas Pi...... originated from the stroma. A difference in ATP content between 54A and 54B was also found in cell cultures; hence, the metabolic difference is an intrinsic quality of the malignant cells and is not caused by the host system....

  11. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo.

    Science.gov (United States)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu; Mikkelsen, Jørn D; Meyer, Anne S

    2011-10-01

    Fucoidan is known to exhibit crucial biological activities, including anti-tumor activity. In this study, we examined the influence of crude fucoidan extracted from Sargassum sp. (MTA) and Fucus vesiculosus (SIG) on Lewis lung carcinoma cells (LCC) and melanoma B16 cells (MC). In vitro studies were performed using cell viability analysis and showed that SIG and MTA fucoidans significantly decreased the viable number of LCC and MC cells in a dose-response fashion. Histochemical staining showed morphological changes of melanoma B16 cells after exposure to fucoidan. The observed changes were indicative of crude fucoidan induced apoptosis. Male C57BL/6JJCL mice were subjected to daily i.p. injections over 4 days with either SIG or MTA fucoidan (50mg/kg body wt.). The cytolytic activity of natural killer (NK) cells was enhanced by crude fucoidan in a dose-dependent manner as indicated by (51)Cr labeled YAC-1 target cell release. This study provides substantial indications that crude fucoidan exerts bioactive effects on lung and skin cancer model cells in vitro and induces enhanced natural killer cell activity in mice in vivo. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo.

    Science.gov (United States)

    Wu, Yuan-Yuan; Zhang, Jing-Hua; Gao, Jing-Hua; Li, Yong-Sheng

    2017-08-26

    Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells. However, the translational and clinical use of AE has been limited owing to its rapid degradation and poor bioavailability. To improve its efficacy, a poly (lactic-co-glycolic acid) based AE nanoparticle formulation (NanoAE) was prepared. Our study indicated that compared to the free AE, nanoAE significantly suppressed cancer cell proliferation, induced cell cycle arrest and apoptosis, evidenced by high cleavage of Caspase-3, poly (ADP-ribose) polymerase (PARP), Caspase-8 and Caspase-9. NanoAE enhanced reactive oxygen species (ROS) production, along with Mitogen-activated protein kinases (MAPKs) activation and PI3K/AKT inactivation. Cell proliferation, apoptosis and MAPKs and PI3K/AKT were dependent on ROS production in nanoAE-treated groups. In vivo, nanoAE exhibited inhibitory effects on the tumor growth with little toxicity. Together, our results indicated that nanoAE might be an effective treatment for human lung squamous cell carcinoma. Copyright © 2017. Published by Elsevier Inc.

  13. Cinnamomum cassia extracts reverses TGF-β1-induced epithelial-mesenchymal transition in human lung adenocarcinoma cells and suppresses tumor growth in vivo.

    Science.gov (United States)

    Lin, Chin-Yin; Hsieh, Yi-Hsien; Yang, Shun-Fa; Chu, Shu-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou

    2017-07-01

    Metastasis is the most common cause of cancer-related mortality in patients, and epithelial-mesenchymal transition (EMT) is essential for cancer metastasis and antidrug resistance. Cinnamomum cassia has several antioxidative, anti-inflammatory, and anticancer biological effects. However, the anti-EMT effect of C. cassia in human lung carcinoma is rarely reported. In this study, we determined whether C. cassia extracts (CCE) reduces the EMT and tumor growth of human lung adenocarcinoma cells. CCE inhibited the transforming growth factor (TGF)-β1-induced cell motility and invasiveness of A549 and H1299 cells by repressing matrix metalloproteinase-2 and urokinase-type plasminogen activator as well as impaired cell adhesion to collagen. CCE also affected the TGF-β1-induced EMT by downregulating the expression of vimentin and fibronectin and upregulating E-cadherin. The nude mice xenograft model showed that CCE reduced A549 tumor growth. Thus, CCE possesses antimetastatic activity of A549 and H1299 cells by affecting EMT and suppressing A549 tumor growth in vivo. This result suggested that CCE could be used as an antimetastatic agent or as an adjuvant for anticancer therapy. © 2017 Wiley Periodicals, Inc.

  14. Chlorella sorokiniana induces mitochondrial-mediated apoptosis in human non-small cell lung cancer cells and inhibits xenograft tumor growth in vivo.

    Science.gov (United States)

    Lin, Ping-Yi; Tsai, Ching-Tsan; Chuang, Wan-Ling; Chao, Ya-Hsuan; Pan, I-Horng; Chen, Yu-Kuo; Lin, Chi-Chen; Wang, Bing-Yen

    2017-02-01

    Lung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC). In this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS. Our results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP. We demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

  15. Modeling Serum Creatinine in Septic ICU Patients

    DEFF Research Database (Denmark)

    De Gaetano, Andrea; Cortese, Giuliana; Pedersen, Morten Gram

    2004-01-01

    Serum creatinine is a metabolite assumed to be constantly produced by the normally functioning muscle mass and is a good measure for monitoring daily renal function in the intensive care unit (ICU). High serum creatinine levels or an abnormal departure from normal pre-disease basal levels...... are indices of acute renal failure (ARF). Septic ICU patients develop multi-organ failure and ARF is often an important complication. In order to attempt to substitute artificially for the failing renal function, septic ARF patients often undergo hemodialytic procedures until kidney damage resolves....... The present work details the structure of a model describing observed creatinine serum concentration (CSC) variations, depending on the time-varying septic insult to renal function in ICU patients, as well as the estimation of its parameters. CSC determinations were routinely obtained from 12 patients...

  16. Red blood cell transfusion in septic shock

    DEFF Research Database (Denmark)

    Rosland, Ragnhild G; Hagen, Marte U; Haase, Nicolai

    2014-01-01

    BACKGROUND: Treating anaemia with red blood cell (RBC) transfusion is frequent, but controversial, in patients with septic shock. Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients. METHODS: We did a prospective cohort study at 7...... general intensive care units (ICUs) including all adult patients with septic shock in a 5-month period. RESULTS: Ninety-five of the 213 included patients (45%) received median 3 (interquartile range 2-5) RBC units during shock. The median pre-transfusion haemoglobin level was 8.1 (7.4-8.9) g...... and SAPS II and SOFA-score on day 1. CONCLUSIONS: The decision to transfuse patients with septic shock was likely affected by disease severity and bleeding, but haemoglobin level was the only measure that consistently differed between transfused and non-transfused patients....

  17. Improving adherence to PALS septic shock guidelines.

    Science.gov (United States)

    Paul, Raina; Melendez, Elliot; Stack, Anne; Capraro, Andrew; Monuteaux, Michael; Neuman, Mark I

    2014-05-01

    Few studies have demonstrated improvement in adherence to Pediatric Advanced Life Support guidelines for severe sepsis and septic shock. We sought to improve adherence to national guidelines for children with septic shock in a pediatric emergency department with poor guideline adherence. Prospective cohort study of children presenting to a tertiary care pediatric emergency department with septic shock. Quality improvement (QI) interventions, including repeated plan-do-study-act cycles, were used to improve adherence to a 5-component sepsis bundle, including timely (1) recognition of septic shock, (2) vascular access, (3) administration of intravenous (IV) fluid, (4) antibiotics, and (5) vasoactive agents. The intervention focused on IV fluid delivery as a key driver impacting bundle adherence, and adherence was measured using statistical process control methodology. Two-hundred forty-two patients were included: 126 subjects before the intervention (November 2009 to March 2011), and 116 patients during the QI intervention (October 2011 to May 2013). We achieved 100% adherence for all metrics, including (1) administration of 60 mL/kg IV fluid within 60 minutes (increased from baseline adherence rate of 37%), (2) administration of vasoactive agents within 60 minutes (baseline rate of 35%), and (3) 5-component bundle adherence (baseline rate of 19%). Improvement was sustained over 9 months. The number of septic shock cases between each death from this condition increased after implementation of the QI intervention. Using QI methodology, we have demonstrated improved adherence to national guidelines for severe sepsis and septic shock. Copyright © 2014 by the American Academy of Pediatrics.

  18. Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação de desempenho de pulmões submetidos à administração de prostaciclina inalada versus parenteral An experimental rat model of ex vivo lung perfusion for the assessment of lungs after prostacyclin administration: inhaled versus parenteral routes

    Directory of Open Access Journals (Sweden)

    Paulo Francisco Guerreiro Cardoso

    2011-10-01

    Full Text Available OBJETIVO: Apresentar um modelo experimental de administração de prostaglandina I2 (PGI2 por via inalatória vs. parenteral e avaliar o desempenho funcional dos pulmões em um sistema de perfusão pulmonar ex vivo. MÉTODOS: Quarenta ratos Wistar foram anestesiados, ventilados, submetidos a laparotomia com ressecção do esterno e anticoagulados. O tronco da artéria pulmonar foi canulado. Todos os animais foram submetidos a ventilação mecânica. Os animais foram randomizados em quatro grupos (10 ratos/grupo: salina nebulizada (SN; salina parenteral (SP; PGI2 nebulizada (PGI2N; e PGI2 parenteral (PGI2P. A dose de PGI2 nos grupos PGI2N e PGI2P foi de 20 e 10 µg/kg, respectivamente. Os blocos cardiopulmonares foram submetidos in situ a perfusão anterógrada com solução de baixo potássio e dextrana a 4ºC via artéria pulmonar, extraídos em bloco e armazenados a 4ºC por 6 h. Os blocos foram ventilados e perfundidos em um sistema ex vivo por 50 min, sendo obtidas medidas de mecânica ventilatória, hemodinâmica e trocas gasosas. RESULTADOS: Houve redução da pressão arterial pulmonar média após a nebulização em todos os grupos (p OBJECTIVE:To present a model of prostaglandin I2 (PGI2 administration (inhaled vs. parenteral and to assess the functional performance of the lungs in an ex vivo lung perfusion system. METHODS: Forty Wistar rats were anesthetized and placed on mechanical ventilation followed by median sterno-laparotomy and anticoagulation. The main pulmonary artery was cannulated. All animals were maintained on mechanical ventilation and were randomized into four groups (10 rats/group: inhaled saline (IS; parenteral saline (PS; inhaled PGI2 (IPGI2; and parenteral PGI2 (PPGI2. The dose of PGI2 used in the IPGI2 and PPGI2 groups was 20 and 10 µg/kg, respectively. The heart-lung blocks were submitted to antegrade perfusion with a low potassium and dextran solution via the pulmonary artery, followed by en bloc extraction and

  19. Chronic ethanol ingestion impairs alveolar type II cell glutathione homeostasis and function and predisposes to endotoxin-mediated acute edematous lung injury in rats.

    Science.gov (United States)

    Holguin, F; Moss, I; Brown, L A; Guidot, D M

    1998-01-01

    Chronic alcohol abuse increases the incidence and mortality of the acute respiratory distress syndrome (ARDS) in septic patients. To examine a potential mechanism, we hypothesized that ethanol ingestion predisposes to sepsis-mediated acute lung injury by decreasing alveolar type II cell glutathione homeostasis and function. Lungs isolated from rats fed ethanol (20% in water for >/= 3 wk), compared with lungs from control-fed rats, had greater (P Ethanol ingestion decreased (P glutathione levels in the plasma, lung tissue, and lung lavage fluid, and increased (P glutathione levels in the lung lavage fluid. Furthermore, ethanol ingestion decreased type II cell glutathione content by 95% (P glutathione precursors S-adenosyl-L-methionine and N-acetylcysteine in the final week of ethanol ingestion significantly reduced lung edema during perfusion ex vivo. We conclude that ethanol ingestion in rats alters alveolar type II cell glutathione levels and function, thereby predisposing the lung to acute edematous injury after endotoxemia. We speculate that chronic alcohol abuse in humans predisposes to ARDS through similar mechanisms. PMID:9466970

  20. Septic arthritis caused by Peptostreptococcus asaccharolyticus

    Directory of Open Access Journals (Sweden)

    Carlos Costa

    2016-07-01

    Full Text Available Peptostreptococcus spp are commensal organisms, usually involved in periodontal disease. Peptostreptococcus asaccharolyticus is an anaerobic gram-negative cocci, difficult to isolate due to its slow growth. Septic arthritis by this microorganism is a rare entity, but it can occur by hematogenous dissemination from a distant focus. Colonization and growth are more likely to occur in an already damaged articulation. We report the case of a 57 year-old woman with peripheral spondyloarthritis who developed knee septic arthritis by Peptostreptococcus asaccharolyticus.

  1. Novel Automatic Detection of Pleura and B-lines (Comet-Tail Artifacts) on In-Vivo Lung Ultrasound Scans

    DEFF Research Database (Denmark)

    Moshavegh, Ramin; Hansen, Kristoffer Lindskov; Møller-Sørensen, Hasse

    2016-01-01

    images. The pleural line is first segmented on each image and then the B-line artifacts spreading down from the pleural line are detected and overlayed on the image. The resulting 300 images showed that the mean lateral distance between B-lines detected on images acquired from patients decreased by 20......This paper presents a novel automatic method for detection of B-lines (comet-tail artifacts) in lung ultrasound scans. B-lines are the most commonly used artifacts for analyzing the pulmonary edema. They appear as laser-like vertical beams, which arise from the pleural line and spread down without...

  2. A simple method to assess in vivo proliferation in lung vasculature with EdU: the case of MMC-induced PVOD in rat.

    Science.gov (United States)

    Fabrice, Antigny; Benoît, Ranchoux; Valérie, Nadeau; Lau, Edmund; Sébastien, Bonnet; Frédéric, Perros

    2015-01-01

    5-Ethynyl-2'-deoxyuridine (EdU) incorporation is becoming the gold standard method for in vitro and in vivo visualization of proliferating cells. The small size of the fluorescent azides used for detection results in a high degree of specimen penetration. It can be used to easily detect DNA replication in large tissue samples or organ explants with low proliferation and turnover of cells formerly believed to be in a "terminal" state of differentiation. Here we describe a protocol for the localization and identification of proliferating cells in quiescent or injured pulmonary vasculature, in a model of pulmonary veno-occlusive disease (PVOD). PVOD is an uncommon form of pulmonary hypertension characterized by progressive obstruction of small pulmonary veins. We previously reported that mitomycin-C (MMC) therapy is associated with PVOD in human. We demonstrated that MMC can induce PVOD in rats, which currently represents the sole animal model that recapitulates human PVOD lesions. Using the EdU assay, we demonstrated that MMC-exposed lungs displayed areas of exuberant microvascular endothelial cell proliferation which mimics pulmonary capillary hemangiomatosis, one of the pathologic hallmarks of human PVOD. In vivo pulmonary cell proliferation measurement represents an interesting methodology to investigate the potential efficacy of therapies aimed at normalizing pathologic angioproliferation.

  3. Toxicity of copper oxide nanoparticles in lung epithelial cells exposed at the air-liquid interface compared with in vivo assessment.

    Science.gov (United States)

    Jing, Xuefang; Park, Jae Hong; Peters, Thomas M; Thorne, Peter S

    2015-04-01

    The toxicity of spark-generated copper oxide nanoparticles (CuONPs) was evaluated in human bronchial epithelial cells (HBEC) and lung adenocarcinoma cells (A549 cells) using an in vitro air-liquid interface (ALI) exposure system. Dose-response results were compared to in vivo inhalation and instillation studies of CuONPs. Cells were exposed to filtered, particle-free clean air (controls) or spark-generated CuONPs. The number median diameter, geometric standard deviation and total number concentration of CuONPs were 9.2 nm, 1.48 and 2.27×10(7)particles/cm(3), respectively. Outcome measures included cell viability, cytotoxicity, oxidative stress and proinflammatory chemokine production. Exposure to clean air (2 or 4h) did not induce toxicity in HBEC or A549 cells. Compared with controls, CuONP exposures significantly reduced cell viability, increased lactate dehydrogenase (LDH) release and elevated levels of reactive oxygen species (ROS) and IL-8 in a dose-dependent manner. A549 cells were significantly more susceptible to CuONP effects than HBEC. Antioxidant treatment reduced CuONP-induced cytotoxicity. When dose was expressed per area of exposed epithelium there was good agreement of toxicity measures with murine in vivo studies. This demonstrates that in vitro ALI studies can provide meaningful data on nanotoxicity of metal oxides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. High-mobility group nucleosome-binding domain 2 protein inhibits the invasion of Klebsiella pneumoniae into mouse lungs in vivo.

    Science.gov (United States)

    Zheng, Shuang; Ren, Laibin; Li, Heng; Shen, Xiaofei; Yang, Xiaolong; Li, Na; Wang, Xinyuan; Guo, Xiaojuan; Wang, Xiaoying; Huang, Ning

    2015-07-01

    Since bacterial invasion into host cells is a critical step in the infection process and the predominance of multiple-antibiotic-resistant Klebsiella (K.) pneumoniae strains, using molecular agents to interfere with K. pneumoniae invasion is an attractive approach for the prevention of infection and suppress the immune inflammatory response. In previous studies by our group, high-mobility group nucleosome-binding domain 2 (HMGN2) protein was shown to exhibit anti-bacterial activity in vitro. The objective of the present study was to investigate the effects of HMGN2 protein on the invasion of K. pneumoniae 03183 in vivo. The results showed that pre-treatment with 128 µg/ml HMGN2 significantly reduced K. pneumoniae 03183 invasion into mouse lungs and increased the mRNA expression of CXCL1 and LCN2 within 2 h. Immunohistochemical staining showed that F-actin expression was significantly decreased, and fluorescence microscopy and western blot analysis further demonstrated that HMGN2 significantly blocked K. pneumoniae 03183-induced actin polymerization. These changes implied that HMGN2 may provide protection against K. pneumoniae 03183 infection in vivo.

  5. Septic Systems - What to Do after the Flood

    Science.gov (United States)

    Where can I find information on my septic system? Do I pump my tank during flooded or saturated drainfield conditions? What if my septic system has been used to dispose wastewater from my business? What do I do with my septic system after the flood?

  6. Quantification of Shallow Groundwater Nutrient Dynamics in Septic Areas

    Science.gov (United States)

    Ying Ouyang; Jia-En Zhang

    2012-01-01

    Of all groundwater pollution sources, septic systems are the second largest source of groundwater nitrate contamination in USA. This study investigated shallow groundwater (SGW) nutrient dynamics in septic areas at the northern part of the Lower St. Johns River Basin, Florida, USA. Thirty-five SGW-monitoring wells, located at nine different urban areas served by septic...

  7. Mirasol Pathogen Reduction Technology® treatment does not affect acute lung injury in a two-event in vivo model caused by stored blood components

    Science.gov (United States)

    Silliman, C. C.; Khan, S. Y.; Ball, J. Bradley; Kelher, M. R.; Marschner, S.

    2011-01-01

    Introduction Mirasol Pathogen Reduction Technology® (PRT) treatment uses riboflavin and UV light to inactivate pathogens in blood components. Neutrophil [polymorphonuclear cells (PMN)] priming activity accumulates during routine storage of cellular blood components, and this activity has been implicated in transfusion-related acute lung injury (TRALI). We hypothesize that PRT-treatment of blood components affects the priming activity generated during storage of packed RBCs (PRBCs) or platelet concentrates (PCs), which can elicit ALI in vivo. Methods Plasma, PRBCs and PCs were isolated from healthy donor’s whole blood or by apheresis. Half of a collected unit was treated with PRT treatment and the remainder was left as an unmodified control. Supernatant was collected during storage of PCs and PRBCs and assayed for PMN priming activity and used as the second event in a two-event in vivo model of TRALI. Results PRT treatment did not induce priming activity in plasma or affect the priming activity generated during storage of PCs or PRBCs as compared with the unmodified controls. The supernatants from stored, but not fresh, PCs and PRBCs did cause ALI as the second event in a two-event animal model of TRALI, which was unaffected by PRT treatment. We conclude that the PRT® treatment does not induce priming activity in plasma nor does it affect the priming activity generated during storage of PCs or PRBCs or their ability to cause ALI as the second event in a two-event in vivo model of TRALI. Moreover, the amount of priming activity in TRIMA®-isolated PCs was significantly less than SPECTRA®-isolated PCs. PMID:19951305

  8. In Vivo Delivery of miR-34a Sensitizes Lung Tumors to Radiation Through RAD51 Regulation

    Directory of Open Access Journals (Sweden)

    Maria Angelica Cortez

    2015-01-01

    Full Text Available MiR-34a, an important tumor-suppressing microRNA, is downregulated in several types of cancer; loss of its expression has been linked with unfavorable clinical outcomes in non-small-cell lung cancer (NSCLC, among others. MiR-34a represses several key oncogenic proteins, and a synthetic mimic of miR-34a is currently being tested in a cancer trial. However, little is known about the potential role of miR-34a in regulating DNA damage response and repair. Here, we demonstrate that miR-34a directly binds to the 3’ untranslated region of RAD51 and regulates homologous recombination, inhibiting double-strand-break repair in NSCLC cells. We further demonstrate the therapeutic potential of miR-34a delivery in combination with radiotherapy in mouse models of lung cancer. Collectively, our results suggest that administration of miR-34a in combination with radiotherapy may represent a novel strategy for treating NSCLC.

  9. A Monte Carlo Simulation of the In-Vivo Measurement of Lung Activity in the Lawrence Livermore National Laboratory Torso Phantom

    Science.gov (United States)

    Acha, Robert

    A series of torso phantoms have been developed by the Lawrence Livermore National Laboratory (LLNL) to serve as standards for in-vivo counting, and to allow for intercomparison and intercalibration of detector systems used to measure low-energy photons from radionuclides such as plutonium deposited in the lungs. High accuracy quantification of low energy photons sources distributed within the lungs is difficult because of the variable attenuation of these photons in the tissues and bones of the thoracic cavity. Digital Image and Communication in Medicine (DICOM) images of the 2 nd generation Human Monitoring Laboratory - Lawrence Livermore National Laboratory (HML-LLNL) torso phantom were segmented and converted into 3D voxel phantoms. The voxel phantoms were modelled for the precision response of HPGe detector systems, as found in the HML new lung counter using a Monte Carlo technique; and for evaluating the use of reference tissue material in specifying LLNL phantom geometries in Monte Carlo simulations. The photon energies of interest in this study were 17.5, 26.4, 45.4, 59.5, 122, 244, and 344 keV, representing possible photon energies emitted by radionuclides that can be inhaled in the lungs, and a few other energies to fill the calibration curve. The external detection efficiencies at these photon energies were modelled for different chest wall thicknesses (1.49 cm to 6.35cm) and compared with experimental values. It was observed that there was no statistical difference at the 0.05 significant level between the simulated detection efficiencies using either the Lawrence Livermore Laboratories (LLL) Tissue or the Reference Tissue, and the measured detection efficiencies at the energies of interest for a phantom with a chest wall thicknesses (CWT) of 3.99 cm. Comparisons between the simulated and measured detection efficiencies for the 3.99-cm CWT reveal a maximum variation of 20% at 17.5 keV, and a minimum variation of 1% at 59.5 keV. Detection efficiencies

  10. Septic pulmonary embolism caused by a Klebsiella pneumoniae liver abscess: clinical characteristics, imaging findings, and clinical courses

    Directory of Open Access Journals (Sweden)

    Deng-Wei Chou

    2015-06-01

    Full Text Available OBJECTIVES: Septic pulmonary embolism caused by a Klebsiella (K. pneumoniae liver abscess is rare but can cause considerable morbidity and mortality. However, clinical information regarding this condition is limited. This study was conducted to elucidate the full disease spectrum to improve its diagnosis and treatment. METHOD: We reviewed the clinical characteristics, imaging findings, and clinical courses of 14 patients diagnosed with septic pulmonary embolism caused by a K. pneumoniae liver abscess over a period of 9 years. RESULTS: The two most prevalent symptoms were fever and shortness of breath. Computed tomography findings included a feeding vessel sign (79%, nodules with or without cavities (79%, pleural effusions (71%, peripheral wedge-shaped opacities (64%, patchy ground-glass opacities (50%, air bronchograms within a nodule (36%, consolidations (21%, halo signs (14%, and lung abscesses (14%. Nine (64% of the patients developed severe complications and required intensive care. According to follow-up chest radiography, the infiltrates and consolidations were resolved within two weeks, and the nodular opacities were resolved within one month. Two (14% patients died of septic shock; one patient had metastatic meningitis, and the other had metastatic pericarditis. CONCLUSION: The clinical presentations ranged from insidious illness with fever and respiratory symptoms to respiratory failure and septic shock. A broad spectrum of imaging findings, ranging from nodules to multiple consolidations, was detected. Septic pulmonary embolism caused by a K. pneumoniae liver abscess combined with the metastatic infection of other vital organs confers a poor prognosis.

  11. Septic Shock: Advances in Diagnosis and Treatment.

    Science.gov (United States)

    Seymour, Christopher W; Rosengart, Matthew R

    2015-08-18

    Septic shock is a clinical emergency that occurs in more than 230,000 US patients each year. OBSERVATIONS AND ADVANCES: In the setting of suspected or documented infection, septic shock is typically defined in a clinical setting by low systolic (≤90 mm Hg) or mean arterial blood pressure (≤65 mm Hg) accompanied by signs of hypoperfusion (eg, oliguria, hyperlactemia, poor peripheral perfusion, or altered mental status). Focused ultrasonography is recommended for the prompt recognition of complicating physiology (eg, hypovolemia or cardiogenic shock), while invasive hemodynamic monitoring is recommended only for select patients. In septic shock, 3 randomized clinical trials demonstrate that protocolized care offers little advantage compared with management without a protocol. Hydroxyethyl starch is no longer recommended, and debate continues about the role of various crystalloid solutions and albumin. The prompt diagnosis of septic shock begins with obtainment of medical history and performance of a physical examination for signs and symptoms of infection and may require focused ultrasonography to recognize more complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of intravenous fluids and vasoactive medications aimed at restoring adequate circulation, and the limitations of protocol-based therapy, as guided by recent evidence.

  12. Severe sepsis and septic shock [author's reply

    NARCIS (Netherlands)

    Angus, Derek C.; van der Poll, Tom

    2013-01-01

    To the Editor: We would like to address two potentially confusing issues concerning venous oxygen saturation (Svo(2)) as presented in Table 1 of the review by Angus and van der Poll (Aug. 29 issue).(1) First, Table 1 suggests that Svo(2) is raised in sepsis, severe sepsis, and septic shock.

  13. Septic arthritis of the pubic symphysis.

    Science.gov (United States)

    Nitsche, A; Mogni, G O; Gorostiaga, P E

    1989-01-01

    Septic arthritis of the pubic symphysis developed in a previously healthy 13-year-old boy. Blood cultures and the culture of material taken by joint aspiration of the pubic symphysis under radioscopic control yielded Staphilococcus aureus. Early treatment with parenteral antibiotics prevented the development of osteomyelitis of the pubic rami in our patient. Open debridement was not necessary.

  14. Deficit of interleukin 7 in septic patients.

    Science.gov (United States)

    Andreu-Ballester, Juan C; Cuellar, Carmen; Garcia-Ballesteros, Carlos; Pérez-Griera, Jaime; Amigó, Victoria; Peiró-Gómez, Ana; Peñarroja-Otero, Carlos; Ballester, Ferran; Mayans, José; Tormo-Calandín, Constantino

    2014-11-01

    We recently demonstrated an overall decrease of all αβ and specially γδ T cell subsets in patients with sepsis compared with healthy subjects. IL-7 is a crucial factor for development of γδ T cells and survival in sepsis but its association with sepsis severity, evolution of organ failure and death still has not been investigated. Sera from 78 patients who met criteria for sepsis were analyzed vs control group. Septic patients showed the lowest levels of IL-7. Patients with severe sepsis reached levels of IL-7 higher than those observed in the groups of uncomplicated sepsis and septic shock. The frequency of γδ T cells at admission was lower in septic patients vs control group. At the time of admission, the frequency of γδ T cells in septic patients who subsequently died was lower than the observed in the group of patients that instead survived. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Development and evaluation of a technique for in vivo monitoring of {sup 60}Co in the lungs

    Energy Technology Data Exchange (ETDEWEB)

    Mello, J.Q. de; Lucena, E.A.; Dantas, A.L.A.; Dantas, B.M., E-mail: bmdantas@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2015-07-01

    {sup 60}Co is a fission product of {sup 235}U and represents a risk of internal exposure of workers in nuclear power plants, especially those involved in the maintenance of potentially contaminated parts and equipment. The control of {sup 60}Co intake by inhalation can be performed through in vivo monitoring. This work describes the evaluation of a technique through the minimum detectable activity and the corresponding minimum detectable effective doses, based on biokinetic and dosimetric models of {sup 60}Co in the human body. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intakes. (author)

  16. Domestic wells have high probability of pumping septic tank leachate

    Directory of Open Access Journals (Sweden)

    J. E. Bremer

    2012-08-01

    Full Text Available Onsite wastewater treatment systems are common in rural and semi-rural areas around the world; in the US, about 25–30% of households are served by a septic (onsite wastewater treatment system, and many property owners also operate their own domestic well nearby. Site-specific conditions and local groundwater flow are often ignored when installing septic systems and wells. In areas with small lots (thus high spatial septic system densities, shallow domestic wells are prone to contamination by septic system leachate. Mass balance approaches have been used to determine a maximum septic system density that would prevent contamination of groundwater resources. In this study, a source area model based on detailed groundwater flow and transport modeling is applied for a stochastic analysis of domestic well contamination by septic leachate. Specifically, we determine the probability that a source area overlaps with a septic system drainfield as a function of aquifer properties, septic system density and drainfield size. We show that high spatial septic system density poses a high probability of pumping septic system leachate. The hydraulic conductivity of the aquifer has a strong influence on the intersection probability. We find that mass balance calculations applied on a regional scale underestimate the contamination risk of individual drinking water wells by septic systems. This is particularly relevant for contaminants released at high concentrations, for substances that experience limited attenuation, and those that are harmful even at low concentrations (e.g., pathogens.

  17. The in vivo study on the radiobiologic effect of prolonged delivery time to tumor control in C57BL mice implanted with Lewis lung cancer

    Directory of Open Access Journals (Sweden)

    Zhu Guo-Pei

    2011-01-01

    Full Text Available Abstract Background High-precision radiation therapy techniques such as IMRT or sterotactic radiosurgery, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The purpose of this work is to explore the radiobiologic effect of prolonged fraction delivery time on tumor response and survival in vivo. Methods 1-cm-diameter Lewis lung cancer tumors growing in the legs of C57BL mice were used. To evaluate effect of dose delivery prolongation, 18 Gy was divided into different subfractions. 48 mice were randomized into 6 groups: the normal control group, the single fraction with 18 Gy group, the two subfractions with 30 min interval group, the seven subfractions with 5 min interval group, the two subfractions with 60 min interval group and the seven subfractions with 10 min interval group. The tumor growth tendency, the tumor growth delay and the mice survival time were analyzed. Results The tumor growth delay of groups with prolonged delivery time was shorter than the group with single fraction of 18 Gy (P 0.05. Compared to the group with single fraction of 18 Gy, the groups with prolonged delivery time shorten the mice survival time while there was no significant difference between the groups with prolonged delivery time 30 min and the groups with prolonged delivery time 60 min. Conclusions The prolonged delivery time with same radiation dose shorten the tumor growth delay and survival time in the mice implanted with Lewis lung cancer. The anti-tumor effect decreased with elongation of the total interfractional time.

  18. Celecoxib enhances radiation response of secondary bone tumors of a human non-small cell lung cancer via antiangiogenesis in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Klenke, Frank Michael [Bern Univ. (Switzerland). Dept. of Orthopedic Surgery; Abdollahi, Amir [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Tufts Univ. School of Medicine, Boston, MA (United States). Center of Cancer Systems Biology; Bischof, Marc; Huber, Peter E. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Dept. of Radiation Oncology; Gebhard, Martha-Maria [Heidelberg Univ. (Germany). Dept. of Experimental Surgery; Ewerbeck, Volker [Heidelberg Univ. (Germany). Dept. of Orthopedic Surgery; Sckell, Axel [Charite Univ. Medical Center, Berlin (Germany). Dept. of Orthopedic, Trauma and Reconstructive Surgery

    2011-01-15

    Purpose: Cyclooxygenase-2 (COX-2) inhibitors mediate a systemic antitumor activity via antiangiogenesis and seem to enhance the response of primary tumors to radiation. Radiosensitizing effects of COX-2 inhibition have not been reported for bone metastases. Therefore, the aim of this study was the investigation of the radiosensitizing effects of the selective COX-2 inhibitor celecoxib in secondary bone tumors of a non-small cell lung carcinoma in vivo. Materials and Methods: Human A549 lung carcinomas were implanted into a cranial window preparation in male SCID mice (n = 24). Animals were treated with either celecoxib or radiation (7 Gy single photon dose) alone or a combination of celecoxib and radiation, respectively. Untreated animals served as controls. The impact of radiation and COX-2 inhibition on angiogenesis, microcirculation, and tumor growth was analyzed over 28 days by means of intravital microscopy and histological methods. Results: Monotherapies with radiation as well as celecoxib had significant antitumor effects compared to untreated controls. Both therapies reduced tumor growth and vascularization to a similar extent. The simultaneous administration of celecoxib and radiation further enhanced the antitumor and antiangiogenic effects of single-beam radiation. With the combined treatment approach, tumor vascularization and tumor size were decreased by 57% and 51%, respectively, as compared to monotherapy with radiation. Conclusion: The combined application of radiation therapy and COX-2 inhibition showed synergistic effects concerning the inhibition of tumor growth and tumor angiogenesis. Therefore, the combination of radiation with COX-2 inhibitor therapy represents a promising approach to improve the therapeutic efficacy of radiotherapy of bone metastases. (orig.)

  19. STAT5 phosphorylation in T cell subsets from septic patients in response to recombinant human interleukin-7: a pilot study.

    Science.gov (United States)

    Demaret, Julie; Dupont, Guillaume; Venet, Fabienne; Friggeri, Arnaud; Lepape, Alain; Rimmelé, Thomas; Morel, Jérôme; Monneret, Guillaume

    2015-04-01

    Septic shock is characterized by lymphocyte alterations associated with increased risk of nosocomial infections and mortality. IL-7, a cytokine required for T cell survival, is thought as a novel therapy for septic patients with severe lymphopenia. We assessed CD4(+) lymphocyte responsiveness to rhIL-7 in septic shock patients ex vivo. Thirteen septic shock patients and 10 controls were included. The MFI of pSTAT5, a key signaling molecule for IL-7, was measured by flow cytometry in CD4(+)FOXP3- (Teffs) and CD4(+)FOXP3(+) (Tregs) lymphocytes after whole-blood incubation with increasing doses of rhIL-7. The basal level of pSTAT5 in nonstimulated T cells was higher in patients. However, the maximal activation level in response to the highest doses of rhIL-7 was similar in both groups. Importantly, low doses of rhIL-7 preferentially activated Teff versus Treg in patients and nonsurvivors tended to present with decreased pSTAT5 expression. This pilot study is the first to highlight, in septic patients, the interest of pSTAT5 measurement in whole blood for the monitoring of rhIL-7 therapy. Such a method could represent an innovative, biologic tool for monitoring leukocyte pharmacological responses to biotherapies in daily clinical practice in other clinical contexts. © Society for Leukocyte Biology.

  20. Hinokitiol Exerts Anticancer Activity through Downregulation of MMPs 9/2 and Enhancement of Catalase and SOD Enzymes: In Vivo Augmentation of Lung Histoarchitecture

    Directory of Open Access Journals (Sweden)

    Chien-Hsun Huang

    2015-09-01

    Full Text Available Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1–5 μM increased the activities of antioxidant enzymes catalase (CAT and superoxide dismutase (SOD from the reduction in melanoma cells. Also, hinokitiol (2–10 µM concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH· formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF, collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

  1. Diallyl Trisulfide Inhibits Growth of NCI-H460in Vitroandin Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice.

    Science.gov (United States)

    Jiang, Xiaoyan; Zhu, Xiaosong; Liu, Na; Xu, Hongya; Zhao, Zhongxi; Li, Siying; Li, Shanzhong; Cai, Jianhua; Cao, Jimin

    2017-01-01

    Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo , and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabilities, cell cycle G 1 arrest, and apoptosis induction were observed in DATS treated NCI-H460 cells ( p <0.05). And injection of DATS (30 or 40 mg/kg) to female Balb/c mice significantly inhibited the growth of human NCI-H460 cell tumor xenograft ( p <0.001). Moreover, DATS in combination with DDP exhibited enhanced anti-tumor activity via induction of apoptosis. Apoptosis pathways were confirmed by modulation of p53, Bcl-2 family members; induction of active caspase-3/8/9 and activation of JNK- and p38-MAPK pathways. Interestedly, DATS+DDP administration exerted fewer side effects, such as suppressing the weight loss and ameliorating DDP-induced oxidative injury, especially in renal parenchyma. In addition, increased E-cadherin and decreased MMP-9 expression levels were observed in DATS-treated tumor tissues. These studies provide supports that DATS might be a potential candidate for combination with DDP in cancer treatment.

  2. EARLY GOAL DIRECTED THERAPY AT SEPTIC SYOK

    Directory of Open Access Journals (Sweden)

    Ayu Widyanti

    2013-04-01

    Full Text Available Sepsis is the most commom cause of death in children with critically ill. Using WHO criteria (severe sepsis defined as sepsis with acidosis, hypotension or both, it was determined that in 1995 there were more than 42.000 cases of severe sepsis in children in the United States with mortality rate was 10.3%. To answer that finding, evicende based protocol was made, it called early goal directed therapy (EGDT. EGDT is a comprehensive strategy to evaluate patient with septic shock include, challenge of fluid, antibiotic, vasopressor, measurement of central vein oxygen saturation, PRC transfusion, administering inotropic dan mechanic ventilation. All of these must be done in the first 6 hours since sepsis or septic shock was found, because if there is a delay of resuscitation, anything we do to increase oxygenation level of the cell will be useless.

  3. Acute septic arthritis due to Streptococcus sanguis.

    Science.gov (United States)

    Papaioannides, Demetrios; Boniatsi, Loukia; Korantzopoulos, Panagiotis; Sinapidis, Demetrios; Giotis, Christos

    2006-01-01

    To present a case of acute septic arthritis due to Streptococcussanguis, a member of the viridans group streptococci. A 73-year-old woman presented with fever and increasing swelling and pain of the right knee several weeks after she had been treated for severe periodontal disease. Arthrocentesis yielded purulent synovial fluid. S. sanguis was isolated in synovial fluid cultures, and the patient was treated with intravenous cefotaxime for 3 weeks and repeated aspiration of the knee joint with gradual resolution of fever, joint swelling and effusion. Although S. sanguis is believed to be a rare cause of septic arthritis in native joints, it should be considered in the differential diagnosis of this disorder, especially in patients with recent treatment of severe dental caries and periodontal disease.

  4. Automated continuous quantitative measurement of proximal airways on dynamic ventilation CT: initial experience using an ex vivo porcine lung phantom

    Directory of Open Access Journals (Sweden)

    Yamashiro T

    2015-09-01

    Full Text Available Tsuneo Yamashiro,1 Maho Tsubakimoto,1 Yukihiro Nagatani,2 Hiroshi Moriya,3 Kotaro Sakuma,3 Shinsuke Tsukagoshi,4 Hiroyasu Inokawa,5 Tatsuya Kimoto,5 Ryuichi Teramoto,6 Sadayuki Murayama1 1Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nishihara, Okinawa; 2Department of Radiology, Shiga University of Medical Science, Otsu; 3Department of Radiology, Ohara General Hospital, Fukushima; 4CT Systems Division, 5Center for Medical Research and Development, Toshiba Medical Systems Corporation, Otawara; 6Corporate Manufacturing Engineering Center, Toshiba Corporation, Yokohama, Japan Background: The purpose of this study was to evaluate the feasibility of continuous quantitative measurement of the proximal airways, using dynamic ventilation computed tomography (CT and our research software. Methods: A porcine lung that was removed during meat processing was ventilated inside a chest phantom by a negative pressure cylinder (eight times per minute. This chest phantom with imitated respiratory movement was scanned by a 320-row area-detector CT scanner for approximately 9 seconds as dynamic ventilatory scanning. Obtained volume data were reconstructed every 0.35 seconds (total 8.4 seconds with 24 frames as three-dimensional images and stored in our research software. The software automatically traced a designated airway point in all frames and measured the cross-sectional luminal area and wall area percent (WA%. The cross-sectional luminal area and WA% of the trachea and right main bronchus (RMB were measured for this study. Two radiologists evaluated the traceability of all measurable airway points of the trachea and RMB using a three-point scale. Results: It was judged that the software satisfactorily traced airway points throughout the dynamic ventilation CT (mean score, 2.64 at the trachea and 2.84 at the RMB. From the maximum inspiratory frame to the maximum expiratory frame, the cross-sectional luminal area of

  5. Clinical management guidelines of pediatric septic shock

    OpenAIRE

    Khilnani Praveen

    2005-01-01

    Septic shock in children is the prototype combination of hypovolemia,cardiogenic and distributive shock. Recently published American college of critical care medinie(ACCM )recommendations for hemodynamic support of neonatal and pediatric patients with sepsis,Surviving sepsis campaign and its pediatric considerations and subsequent revision of definitions for pediatric sepsis has led to compilation of this review article. Practical application of this information in Indian set up in a child wi...

  6. Diallyl Trisulfide Inhibits Growth of NCI-H460 in Vitro and in Vivo, and Ameliorates Cisplatin-Induced Oxidative Injury in the Treatment of Lung Carcinoma in Xenograft Mice

    OpenAIRE

    Jiang, Xiaoyan; Zhu, Xiaosong; Liu, Na; Xu, Hongya; Zhao, Zhongxi; Li, Siying; Li, Shanzhong; Cai, Jianhua; Cao, Jimin

    2017-01-01

    Diallyl trisulfide (DATS), an organosulfuric component of garlic oil, exhibits potential anticancer and chemopreventive effects. Cisplatin (DDP), a common chemotherapeutic agent, has provided great therapeutic contributions to treating solid tumors, but with serious side effects. Here, we verified the anti-tumor properties of DATS on lung cancer in vitro and in vivo, and evaluated synergistic effects of DATS combined with DDP on the NCI-H460 xenograft model. Significantly decreased cell viabi...

  7. Transfer of in vivo primed transgenic T cells supports allergic lung inflammation and FIZZ1 and Ym1 production in an IL-4Rα and STAT6 dependent manner

    Directory of Open Access Journals (Sweden)

    Keegan Achsah D

    2011-10-01

    Full Text Available Abstract Background CD4+ T helper type 2 (TH2 cells, their cytokines IL-4, IL-5 and IL-13 and the transcription factor STAT6 are known to regulate various features of asthma including lung inflammation, mucus production and airway hyperreactivity and also drive alternative activation of macrophages (AAM. However, the precise roles played by the IL-4/IL-13 receptors and STAT6 in inducing AAM protein expression and modulating specific features of airway inflammation are still unclear. Since TH2 differentiation and activation plays a pivotal role in this disease, we explored the possibility of developing an asthma model in mice using T cells that were differentiated in vivo. Results In this study, we monitored the activation and proliferation status of adoptively transferred allergen-specific naïve or in vivo primed CD4+ T cells. We found that both the naïve and in vivo primed T cells expressed similar levels of CD44 and IL-4. However, in vivo primed T cells underwent reduced proliferation in a lymphopenic environment when compared to naïve T cells. We then used these in vivo generated effector T cells in an asthma model. Although there was reduced inflammation in mice lacking IL-4Rα or STAT6, significant amounts of eosinophils were still present in the BAL and lung tissue. Moreover, specific AAM proteins YM1 and FIZZ1 were expressed by epithelial cells, while macrophages expressed only YM1 in RAG2-/- mice. We further show that FIZZ1 and YM1 protein expression in the lung was completely dependent on signaling through the IL-4Rα and STAT6. Consistent with the enhanced inflammation and AAM protein expression, there was a significant increase in collagen deposition and smooth muscle thickening in RAG2-/- mice compared to mice deficient in IL-4Rα or STAT6. Conclusions These results establish that transfer of in vivo primed CD4+ T cells can induce allergic lung inflammation. Furthermore, while IL-4/IL-13 signaling through IL-4Rα and STAT6 is

  8. Myocardial dysfunction in pediatric septic shock.

    Science.gov (United States)

    Raj, Shashi; Killinger, James S; Gonzalez, Jennifer A; Lopez, Leo

    2014-01-01

    To evaluate the prevalence and significance of myocardial dysfunction in children with septic shock. Thirty patients with septic shock were evaluated by transthoracic echocardiography within 24 hours of admission to a pediatric critical care unit. Transthoracic echocardiography evaluation included left ventricular (LV) size and function, mitral valve inflow velocities in early and late diastole, mitral valve annular velocities in systole and early and late diastole, and LV myocardial performance index. LV systolic dysfunction was defined as an ejection fraction or shortening fraction z-score 2. Secondary outcomes included troponin I concentration, acute kidney injury, and 28-day mechanical ventilation-free duration. Mortality for the 30 patients (mean age, 9.5 ± 7 years) was 7%. The prevalence of LV systolic and/or diastolic dysfunction was 53% (16 of 30). Eleven patients (37%) had systolic dysfunction, 10 (33%) had diastolic dysfunction, and 5 (17%) had both. Systolic and/or diastolic dysfunction was significantly associated with troponin I level (P = .007) and acute kidney injury (P = .02), but not with ventilation-free duration (P = .12). Kaplan-Meier analyses for pediatric critical care unit and hospital length of stay identified no differences between patients with and those without myocardial dysfunction. Myocardial dysfunction occurs frequently in children with septic shock but might not affect hospital length of stay. Copyright © 2014 Mosby, Inc. All rights reserved.

  9. MR findings of septic cavernous sinus thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyeong Lae; Lee, Nam Joon; Lee, Jung Hee; Pyo, Hyeon Soon; Eo, Geun; Kim, Kyo Nam; Kim, Young Soon; Kim, Jang Min [Kwang Myung Sung Ae Hospital, Kwang Myung (Korea, Republic of); Lee, Don Young [Korea University Anam Hospital, Seoul (Korea, Republic of)

    2000-08-01

    To evaluate the MR findings of septic thrombosis of the cavernous sinus. Eleven MR images of six patients with septic cavernous sinus thrombosis obtained over a five-year period and proven clinically or radiologically were retrospectively reviewed. The contour and enhancement pattern of the cavernous sinus, changes in the internal carotid artery, orbit, pituitary gland and sphenoid sinus, and intracranial abnormalities were analyzed and compared with the findings of follow-up studies. In all six patients, contrast study revealed asymmetrical enlargement of the ipsilateral cavernous sinus and multiple irregular filling defects within it. Narrowing of the cavernous portion of the ipsilateral internal carotid artery was noted in five patients, upward displacement of the ipsilateral internal carotid artery in four, ipsilateral proptosis with engorgement of the superior ophthalmic vein in two, pituitary enlargement in five, and inflammatory change in the sphenoid sinus in six. Associated intracranial abnormalities included edema and enhancement in the meninx, temporal lobe, or pons adjacent to the cavernous sinus in four patients, hydrocephalus in one, and cerebral infarction in one. Follow-up MR imaging indicated that the extent of asymmetrical enlargement of the cavernous sinus, filling defects within it, as seen on contrast study, and enlarged pituitary glands had all decreased, without significant interval change. MR imaging is useful in the diagnosis of septic cavernous sinus thrombosis. Asymmetrical enlargement of the cavernous sinus, multiple irregular filling defect within it, as seen on contrast study, and changes in the internal carotid artery are characteristic findings. (author)

  10. Angiotensin II in Refractory Septic Shock.

    Science.gov (United States)

    Antonucci, Elio; Gleeson, Patrick J; Annoni, Filippo; Agosta, Sara; Orlando, Sergio; Taccone, Fabio Silvio; Velissaris, Dimitrios; Scolletta, Sabino

    2017-05-01

    Refractory septic shock is defined as persistently low mean arterial blood pressure despite volume resuscitation and titrated vasopressors/inotropes in patients with a proven or suspected infection and concomitant organ dysfunction. Its management typically requires high doses of catecholamines, which can induce significant adverse effects such as ischemia and arrhythmias. Angiotensin II (Ang II), a key product of the renin-angiotensin-aldosterone system, is a vasopressor agent that could be used in conjunction with other vasopressors to stabilize critically ill patients during refractory septic shock, and reduce catecholamine requirements. However, very few clinical data are available to support Ang II administration in this setting. Here, we review the current literature on this topic to better understand the role of Ang II administration during refractory septic shock, differentiating experimental from clinical studies. We also consider the potential role of exogenous Ang II administration in specific organ dysfunction and possible pitfalls with Ang II in sepsis. Various issues remain unresolved and future studies should investigate important topics such as: the optimal dose and timing of Ang II administration, a comparison between Ang II and the other vasopressors (epinephrine; vasopressin), and Ang II effects on microcirculation.

  11. Dopamine versus noradrenaline in septic shock

    Directory of Open Access Journals (Sweden)

    Bo Xu

    2011-10-01

    Full Text Available BackgroundThe ‘Surviving Sepsis’ Campaign guidelines recommend theuse of dopamine or noradrenaline as the first vasopressor inseptic shock. However, information that guides clinicians inchoosing between dopamine and noradrenaline as the firstvasopressor in patients with septic shock is limited.ObjectiveThis article presents a review of the literature regarding theuse of dopamine versus noradrenaline in patients with septicshock.ResultsTwo randomised controlled trials (RCT and two largeprospective cohort studies were analysed. RCT data showeddopamine was associated with increased arrhythmic events.One cohort study found dopamine was associated with higher30-day mortality. The other cohort study found noradrenalinewas associated with higher 28-day mortality.DiscussionData on the use of dopamine versus noradrenaline in patientswith septic shock is limited. Following the recent SOAP IIstudy, there is now strong evidence that the use of dopaminein septic shock is associated with significantly morecardiovascular adverse events, compared tonoradrenaline.ConclusionNoradrenaline should be used as the initial vasopressor inseptic shock to avoid the arrhythmic events associatedwith dopamine.

  12. [Current epidemiologic features of septic abortion].

    Science.gov (United States)

    Spina, V; Bertelli, S; Bartucca, B; Bonessio, L; Aleandri, V

    2001-04-01

    This article deals with the current epidemiological features of septic abortion. Forty-two of 431 abortions (9,74%) were diagnosed as septic abortions during 1998 at the I and II Institute of Obstetrics and Gynecology, University of Rome La Sapienza , and are retrospectively analyzed. Thirty-four women (81%) came from an EEC country, whereas 8 (19%) from a developing country. Their mean age was 31,4 years (range: 18-43 years). Eighteen patients (43%) were nulliparous; 24 (57%) multiparous; 14 (33%) had previous abortions, none had previous septic abortions. Among risk factors, premature rupture of membranes was found in 5 cases (12%); whereas amniocentesis, HIV positivity, diabetes, positive urine culture and illegal pregnancy termination procedures were found in 5 further cases. No risk factors were found in 76% of patients. It is observed that, due to medical-scientific advances, previously unknown risk factors have emerged during the last three decades in Western Countries, such as invasive procedures of prenatal diagnosis, IUD contraception and AIDS immunodepression. However, other previously frequent risk factors, such as sepsis from illegal abortion, may emerge again in Countries where abortion is legal (such as Italy), due to massive immigration of clandestine women from developing Countries.

  13. Septic arthritis due to Streptococcus sanguis.

    Science.gov (United States)

    Mandac, Inga; Prkacin, Ingrid; Matovinović, Mirjana Sabljar; Sustercić, Dunja

    2010-06-01

    Septic arthritis may represent a direct invasion of joint space by various microorganisms, including bacteria, viruses and fungi. Although any infectious agent may cause bacterial arthritis, bacterial pathogens are the most significant because of their rapidly destructive nature. We present a case of septic arthritis in a 56-year old male patient due to Streptococcus viridans which is member of the viridans group streptococci. Patient was admitted to Our Hospital presented as fever of unknown origin, losing more than 30 kg of body weight during couple of months, and anemia of chronic disease as paraneoplastic process. He had long history of arterial hypertension and stroke. There was swelling and pain of the right sternoclavicular joint and precordial systolic murmur in physical status. A large diagnostic panel has been made, computerized tomography (CT) of right sternoclavicular joint showed widening of periarticular soft tissue and loss of clavicular corticalis. Cytologic analysis of synovial fluid showed more than 90% of polymorphonuclear leukocytes. There were no crystals on microscopic examination and Gram stain of fluid was negative. Blood cultures were positive for S. sanguis and there was a consideration about possible periodontal disease. Stomatologic examination verified periapical ostitis and extraction of potential cause of infection has been done. Therapy with benzilpenicilline was followed by the gradual improvement of clinical and laboratory parameters. Although viridans group streptococci and Streptococcus sanguis in particular are rare causes of septic arthritis in native joints, they should be considered in the differential diagnosis of periodontal disease.

  14. Infective Endocarditis Complicated by Septic Pulmonary Emboli in a Case of a Ventricular Septal Defect

    Directory of Open Access Journals (Sweden)

    Roodpeyma

    2015-11-01

    Full Text Available Introduction Infective endocarditis (IE causes serious complications in patients. Congenital heart disease (CHD is an important underlying condition in children. Septic pulmonary embolism is an uncommon syndrome, and pulmonary valve IE is rare. The current study presented a case of right-sided IE with pulmonary valve involvement and its complications as pulmonary septic emboli in a child with CHD. Case Presentation A 6-year-old girl with a ventricular septal defect (VSD was presented. Echocardiography revealed large vegetation in the right ventricular outflow tract near the pulmonary valve. The patient showed clinical symptoms of lung involvement, and radiologic investigation was compatible with a diagnosis of septic pulmonary emboli. She had good response to antibacterial therapy and underwent a successful surgical closure of the heart defect. Conclusions Children with CHD are at risk of severe complications with the involvement of other organs. long-term febrile illness should be taken seriously in these children. They need hospitalization and careful evaluation.

  15. Tussilagone Inhibits the Inflammatory Response and Improves Survival in CLP-Induced Septic Mice.

    Science.gov (United States)

    Kim, Yun Kyu; Yeo, Myeong Gu; Oh, Bo Kang; Kim, Ha Yeong; Yang, Hun Ji; Cho, Seung-Sik; Gil, Minchan; Lee, Kyung Jin

    2017-12-18

    Tussilagone, extracted from Tussilago farfara is an oriental medicine used for asthma and bronchitis. We investigated its mechanism of action, its inhibitory effects on lipopolysaccharide-induced inflammation in macrophages, and its impact on viability in a cecal ligation and puncture (CLP)-induced mouse model of sepsis. Tussilagone suppressed the expression of the inflammatory mediators, nitric oxide and prostaglandin E2, and the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and high-mobility group box 1 (HMGB1), in lipopolysaccharide-stimulated RAW 264.7 cells and peritoneal macrophages. Tussilagone also reduced the activation of the mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) involved in the activation of various inflammatory mediators in activated macrophages. Moreover, tussilagone administration (1 mg/kg and 10 mg/kg) produced decreased mortality and lung injury in CLP-activated septic mice. Augmented expression of cyclooxygenase (COX)-2 and TNF-α in pulmonary alveolar macrophages of septic mice were attenuated by tussilagone administration. Tussilagone also suppressed the induction of nitric oxide, prostaglandin E2, TNF-α and HMGB1 in the serum of the septic mice. Overall, tussilagone exhibited protective effects against inflammation and polymicrobial sepsis by suppressing inflammatory mediators possibly via the inhibition of NF-κB activation and the MAP kinase pathway. These results suggest the possible use of tussilagone for developing novel therapeutic modalities for sepsis and other inflammatory diseases.

  16. Effects and safety of different anisodamine doses on EVLW at early stage of septic shock patients

    Directory of Open Access Journals (Sweden)

    Ri-Xing Wang

    2017-04-01

    Full Text Available Objective: To investigate the effects and safety of different anisodamine doses on EVLW at early stage of septic shock patients. Method: A total of 63 patients with septic shock were enrolled in ICU, and they were randomly divided into control group (C group, 20 cases, normal anisodamine doses group (N group, 25 cases, anisodamine 20–40 mg/d, high anisodamine doses group (H group, 18 cases,anisodamine 80 mg/d. To observe the dynamic changes of temperature (T, heart rate (HR, oxygenation index (OI, cardiac index (CI, intrathoracic blood volume index (ITBVI, and extravascular lung water index (EVLWI. Results: 12 h after treatment, compared with C and N group, CI and ITBVI significantly increased in H group, EVLWI significantly decreased in H group. Meanwhile, T and HR significantly increased in H group, oxygenation index significantly decreased in H group. Some patients are unable to tolerate anisodamine treatment which leads to cessation of experiment. Compared with C group, EVLWI, CI, ITBVI, oxygenation index significantly improved in N group (P<0.05, mortality rates significantly decreased (P<0.05. Conclusions: Normal anisodamine doses would significantly decreased EVLWI and significantly improved outcomes, high anisodamine dose is not recommended on EVLWI in patients with septic shock.

  17. Beware Cold Agglutinins in Organ Donors! Ex Vivo Lung Perfusion From an Uncontrolled Donation After Circulatory-Determination-of-Death Donor With a Cold Agglutinin: A Case Report.

    Science.gov (United States)

    Venkataraman, A; Blackwell, J W; Funkhouser, W K; Birchard, K R; Beamer, S E; Simmons, W T; Randell, S H; Egan, T M

    2017-09-01

    We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported. Lungs were flushed with cold Perfadex, removed, and stored cold. The lungs did not flush well. Medical history revealed a recent hemolytic anemia and a known cold agglutinin. Warm nonventilated ischemia time was 51 minutes. O2-ventilated ischemia time was 141 minutes. Total cold ischemia time was 6.5 hours. At cannulation for EVLP, established clots were retrieved from both pulmonary arteries. At initiation of EVLP with Steen solution, tiny red aggregates were observed initially. With warming, the aggregates disappeared and the perfusate became red. After 1 hour, EVLP was stopped because of florid pulmonary edema. The lungs were cooled to 20°C; tiny red aggregates formed again in the perfusate. Ex vivo CT scan showed areas of pulmonary edema and a pyramidal right middle lobe opacity. Dissection showed multiple pulmonary emboli-the likely cause of death. However, histology showed agglutinated red blood cells in the microvasculature in pre- and post-EVLP biopsies, which may have contributed to inadequate parenchymal preservation. Organ donors with cold agglutinins may not be suitable owing to the impact of hypothermic preservation. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effect of temperature increments in septic tank efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Chi-Tec, M.; Caballero-Arzapalo, N.; Giacoman Vallejo, G.; Mendez-Novelo, R.; Quintal-Franco, C.

    2009-07-01

    Septic tanks are the main sewage disposal system used in Yucatan, Mexico. Septic tank content is stabilized under anaerobic conditions and is considered the temperature has a significant effect on the efficiency. This work was developed in order asses the feasibility to improve communal septic tanks efficiency by increasing content temperature. Temperatures inside the tank were increased using a hybrid heater system (solar and electricity). (Author)

  19. Nonseptic and Septic Lateral Sinus Thrombosis: A Review

    OpenAIRE

    Viswanatha, B.; Thriveni, C. N.; Naseeruddin, Khaja

    2011-01-01

    Thrombosis of the lateral sinus can be classified into nonseptic lateral sinus thrombosis and septic lateral sinus thrombosis. Nonseptic lateral sinus thrombosis differs from septic lateral sinus thrombosis in that it is not associated with ear or sinus infection. Etiologies of these conditions are different and hence the management of these conditions is different. Nonseptic lateral sinus thrombosis requires medical line of management and anticoagulant therapy, where as septic lateral sinus ...

  20. Septic arthritis and subsequent fatal septic shock caused by Vibrio vulnificus infection

    DEFF Research Database (Denmark)

    Emamifar, Amir; Asmussen Andreasen, Rikke; Andersen, Nanna Skaarup

    2015-01-01

    Vibrio vulnificus is a rare but potential fatal bacterium that can cause severe infections. Wound infections, primary sepsis and gastroenteritis are the most common clinical features. Septic arthritis caused by V. vulnificus is an atypical presentation that has been reported in only two case...... reports; however, it has not been previously noted in Denmark. The authors report a case of septic arthritis caused by V. vulnificus in an immunocompromised patient. The disease progressed to severe sepsis and subsequent death within 10 h of admission....

  1. Coenzyme Q10 deficiency in septic shock patients

    OpenAIRE

    Dupic, Laurent; Huet, Olivier; Duranteau, Jacques

    2011-01-01

    Donnino and colleagues provide new insights into the field of oxidative stress and mitochondrial dysfunction during septic shock. These authors suggest a coenzyme Q10 (CoQ10) deficiency in patients with septic shock. Larger prospective observational trials measuring CoQ10 in patients with septic shock are required to confirm the possibility of CoQ10 depletion. This study is a new step toward a study testing CoQ10 as a potential therapeutic agent for patients with septic shock.

  2. The Role of Complement System in Septic Shock

    Directory of Open Access Journals (Sweden)

    Jean Charchaflieh

    2012-01-01

    Full Text Available Septic shock is a critical clinical condition with a high mortality rate. A better understanding of the underlying mechanisms is important to develop effective therapies. Basic and clinical studies suggest that activation of complements in the common cascade, for example, complement component 3 (C3 and C5, is involved in the development of septic shock. The involvement of three upstream complement pathways in septic shock is more complicated. Both the classical and alternative pathways appear to be activated in septic shock, but the alternative pathway may be activated earlier than the classical pathway. Activation of these two pathways is essential to clear endotoxin. Recent investigations have shed light on the role of lectin complement pathway in septic shock. Published reports suggest a protective role of mannose-binding lectin (MBL against sepsis. Our preliminary study of MBL-associated serine protease-2 (MASP-2 in septic shock patients indicated that acute decrease of MASP-2 in the early phase of septic shock might correlate with in-hospital mortality. It is unknown whether excessive activation of these three upstream complement pathways may contribute to the detrimental effects in septic shock. This paper also discusses additional complement-related pathogenic mechanisms and intervention strategies for septic shock.

  3. N-terminal-pro-brain natriuretic peptide elevations in the course of septic and non-septic shock reflect systolic left ventricular dysfunction assessed by transpulmonary thermodilution

    NARCIS (Netherlands)

    A.J. Groeneveld; R.J. Trof (R.)

    2016-01-01

    textabstractBackground: The cardiac correlates, if any, of N-terminal probrain natriuretic peptide (NT-proBNP) levels in septic and non-septic shock patients remain controversial. Methods: In the 38 septic and 22 non-septic shock patients in the transpulmonary thermodilution arm of a previous

  4. Septic and non-septic olecranon bursitis in the accident and emergency department--an approach to management.

    Science.gov (United States)

    Stell, I M

    1996-01-01

    Olecranon bursitis is relatively common. One third of episodes are septic. Most of the remainder are non-septic, with occasional rheumatological causes. Trauma can cause both septic and non-septic olecranon bursitis. Clinical features are helpful in separating septic from non-septic olecranon bursitis, but there may be local erythema in both. Aspiration should be carried out in all cases, and if the presence of infection is still in doubt, microscopy, Gram staining, and culture of the aspirate will resolve the issue. Septic olecranon bursitis should be treated by aspiration, which may need to be repeated, and a long course of antibiotics. Some cases will need admission, and a few will need surgical treatment. Non-septic olecranon bursitis can be managed with aspiration alone. Non-steroidal anti-inflammatory drugs probably hasten symptomatic improvement. Intrabursal corticosteroids produce a rapid resolution but concern remains over their long term local effects. Recovery from septic olecranon bursitis can take months. PMID:8894865

  5. Advances in lung preservation.

    Science.gov (United States)

    Machuca, Tiago N; Cypel, Marcelo; Keshavjee, Shaf

    2013-12-01

    After a brief review of conventional lung preservation, this article discusses the rationale behind ex vivo lung perfusion and how it has shifted the paradigm of organ preservation from conventional static cold ischemia to the utilization of functional normothermia, restoring the lung's own metabolism and its reparative processes. Technical aspects and previous clinical experience as well as opportunities to address specific donor organ injuries in a personalized medicine approach are also reviewed. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Role of fibrinogen-binding adhesin expression in septic arthritis and septicemia caused by Streptococcus agalactiae.

    Science.gov (United States)

    Jonsson, Ing-Marie; Pietrocola, Giampiero; Speziale, Pietro; Verdrengh, Margareta; Tarkowski, Andrzej

    2005-10-15

    Streptococcus agalactiae (group B streptococcus) is an important human pathogen that causes neonatal pneumonia, sepsis, septic arthritis, and meningitis, as well as severe infections in immunocompromised adult patients. The streptococci produce several molecules important for virulence. We used a murine model of sepsis and septic arthritis to assess the role of FbsA, a fibrinogen-binding adhesin of S. agalactiae as a virulence determinant. NMRI mice were inoculated intravenously with S. agalactiae strains isogenic for the expression of FbsA. Inoculation with wild-type (wt) streptococci resulted in significantly higher mortality, more-pronounced weight decrease, and more-severe arthritis, compared with inoculation with the FbsA mutant isogenic strain. Neither active nor passive immunization with FbsA or FbsA-specific antibodies, respectively, resulted in any protection against subsequent infection with the S. agalactiae wt strain. Our results clearly indicate that the expression of FbsA by Streptococcus agalactiae is a significant virulence determinant in septic arthritis and septicemia. However, because blocking of the fibrinogen binding properties did not protect the host against the action of FbsA-expressing streptococci, we believe that the FbsA molecule has some other presently unknown biological in vivo properties.

  7. The race against the "septic shark".

    Science.gov (United States)

    Westphal, Martin; Kampmeier, Tim

    2015-01-01

    Great white sharks are responsible for about 10 cases of death annually worldwide, as compared with millions of deaths caused by sepsis. However, the basic principles of avoiding shark attacks and fighting sepsis seem to be similar: avoidance, attention, and speed, if necessary. The present review discusses the current status of the systemic inflammatory response syndrome (SIRS) criteria, which are actually content for discussion because of their low specificity. Current data suggest that one in eight patients with severe sepsis does not fulfill the SIRS criteria and is consequently missed, and therefore the calls for new definitions of sepsis are getting louder. Furthermore, the need for early treatment of sepsis and fast admission to an intensive care unit (ICU) with experienced stuff is reviewed as well as the early and appropriate initiation of therapy, namely antibiotic and volume therapy. A key feature is the analysis of the studies from the so-called "Sepsis Trilogy" (ProCESS, ARISE, and ProMiSe studies), with a focus on the status of early goal-directed therapy (EGDT). The authors of the "Sepsis Trilogy" concluded that there is no benefit regarding survival in septic patients by using EGDT as compared with standard therapy. However, the low mortality of the control groups within the "Sepsis Trilogy" studies as compared with the Rivers et al. study from 2001 leads to the conclusion that there has been an improvement in the therapy of septic patients, most probably due to the early initiation of therapy as a kind of "standard" in sepsis therapy. Finally, the phenomenon of a "large trial disease" is discussed, exemplary in a trial which investigated the maintenance of the "right" mean arterial pressure in sepsis patients. Even if the result of a large randomized trial might be that there is no difference between two study groups, the real exercise is to identify the patient collectives who might benefit or experience harm due to an intervention. In summary, as

  8. Septic lens implantation syndrome in a cat.

    Science.gov (United States)

    Dalesandro, Nicole; Stiles, Jean; Miller, Margaret

    2011-09-01

    A 13-year-old female spayed domestic shorthair cat was presented initially for a change in the appearance of the left eye. On initial examination, a small penetrating wound was suspected as the cause for a corneal scar, an anterior cortical incipient cataract and mild iritis. The cat was not re-presented until 1 year later at which time ocular pain was marked. Severe anterior uveitis and glaucoma were diagnosed and the eye enucleated. Histopathology documented intralenticular coccoid bacteria and septic lens implantation syndrome. © 2011 American College of Veterinary Ophthalmologists.

  9. The Impact of the Sepsis-3 Septic Shock Definition on Previously Defined Septic Shock Patients.

    Science.gov (United States)

    Sterling, Sarah A; Puskarich, Michael A; Glass, Andrew F; Guirgis, Faheem; Jones, Alan E

    2017-09-01

    The Third International Consensus Definitions Task Force (Sepsis-3) recently recommended changes to the definitions of sepsis. The impact of these changes remains unclear. Our objective was to determine the outcomes of patients meeting Sepsis-3 septic shock criteria versus patients meeting the "old" (1991) criteria of septic shock only. Secondary analysis of two clinical trials of early septic shock resuscitation. Large academic emergency departments in the United States. Patients with suspected infection, more than or equal to two systemic inflammatory response syndrome criteria, and systolic blood pressure less than 90 mm Hg after fluid resuscitation. Patients were further categorized as Sepsis-3 septic shock if they demonstrated hypotension, received vasopressors, and exhibited a lactate greater than 2 mmol/L. We compared in-hospital mortality in patients who met the old definition only with those who met the Sepsis-3 criteria. Four hundred seventy patients were included in the present analysis. Two hundred (42.5%) met Sepsis-3 criteria, whereas 270 (57.4%) met only the old definition. Patients meeting Sepsis-3 criteria demonstrated higher severity of illness by Sequential Organ Failure Assessment score (9 vs 5; p definition demonstrated significant mortality benefit following implementation of a quantitative resuscitation protocol (35% vs 10%; p = 0.006). In this analysis, 57% of patients meeting old definition for septic shock did not meet Sepsis-3 criteria. Although Sepsis-3 criteria identified a group of patients with increased organ failure and higher mortality, those patients who met the old criteria and not Sepsis-3 criteria still demonstrated significant organ failure and 14% mortality rate.

  10. Geophysical Assessment of Two Collapsed and Concealed Septic ...

    African Journals Online (AJOL)

    A geophysical study was carried out in the vicinity of two collapsed and concealed septic tanks to delineate the structures responsible for their failure. Two-dimensional resistivity and seismic refraction tomography data were collected along a profile laid across the septic tanks. The data were collected using ABEM ...

  11. Septic Abortion Managed in a Tertiary Hospital in West Bengal ...

    African Journals Online (AJOL)

    Background: Septic abortion is still a challenging problem and a major cause of maternal mortality and morbidity in developing countries. Aim: The present study was conducted to estimate incidence, causes, risk factors, associated microorganisms, and treatment modalities of cases of septic abortion managed in a tertiary ...

  12. Enteral nutrition intolerance in critically ill septic burn patients.

    Science.gov (United States)

    Lavrentieva, Athina; Kontakiotis, Theodore; Bitzani, Militsa

    2014-01-01

    The purpose of this study was to investigate the frequency of enteral feeding intolerance in critically ill septic burn patients, the effect of enteral feeding intolerance on the efficacy of feeding, the correlation between the infection marker (procalcitonin [PCT]) and the nutrition status marker (prealbumin) and the impact of feeding intolerance on the outcome of septic burn patients. From January 2009 to December 2012 the data of all burn patients with the diagnosis of sepsis who were placed on enteral nutrition were analyzed. Septic patients were divided into two groups: group A, septic patients who developed feeding intolerance; group B, septic patients who did not develop feeding intolerance. Demographic and clinical characteristics of patients were analyzed and compared. The diagnosis of sepsis was applied to 29% of all patients. Of these patients 35% developed intolerance to enteral feeding throughout the septic period. A statistically significant increase in mean PCT level and a decrease in prealbumin level was observed during the sepsis period. Group A patients had statistically significant lower mean caloric intake, higher PCT:prealbumin ratio, higher pneumonia incidence, higher Sequential Organ Failure Assessment Maximum Score, a longer duration of mechanical ventilation, and a higher mortality rate in comparison with the septic patients without gastric feeding intolerance. The authors concluded that a high percentage of septic burn patients developed enteral feeding intolerance. Enteral feeding intolerance seems to have a negative impact on the patients' nutritional status, morbidity, and mortality.

  13. Arthroscopy of septic carpitis in donkeys ( Equus asinus ) | Elkasapy ...

    African Journals Online (AJOL)

    Experimental septic arthritis was induced in the radiocarpal joint of 18 donkeys by intra-articular injection of Staphylococcus aureus (3-4X106 CFU). The inoculated animals were divided into three groups (6 donkeys in each group). The arthroscopic examination was carried out before induction of septic carpitis and 3 days ...

  14. Outcome of management of non-gonococcal septic arthritis at ...

    African Journals Online (AJOL)

    Septic arthritis is an acute bacterial infection of a synovial joint. It is an orthopaedic emergency that can lead to morbidity or mortality if not properly treated. The fundamental issues in the management of septic arthritis include the duration of antibiotic therapy, the mode of joint drainage and the role of physiotherapy. There is ...

  15. Red blood cell transfusion during septic shock in the ICU

    DEFF Research Database (Denmark)

    Perner, A; Smith, S H; Carlsen, S

    2012-01-01

    Transfusion of red blood cells (RBCs) remains controversial in patients with septic shock, but current practice is unknown. Our aim was to evaluate RBC transfusion practice in septic shock in the intensive care unit (ICU), and patient characteristics and outcome associated with RBC transfusion....

  16. Streptococcus gordonii septic arthritis : two cases and review of literature

    Directory of Open Access Journals (Sweden)

    Yombi Jean cyr

    2012-09-01

    Full Text Available Abstract Background Despite advances in antimicrobial and surgical therapy, septic arthritis remains a rheumatologic emergency that can lead to rapid joint destruction and irreversible loss of function. In adults, Staphylococcus aureus is the most common microorganism isolated from native joints. Streptococcus gordonii is a prominent member of the viridans group of oral bacteria and is among the bacteria most frequently identified as being primary agent of subacute bacterial endocarditis. To the best of our knowledge, Streptococcus gordonii has not yet been described as agent of septic arthritis. Case Presentation We describe here two cases of septic arthritis due to Streptococcus gordonii. It gives us an opportunity to review epidemiology, diagnosis criteria and management of septic arthritis. Conclusion Although implication of S. gordonii as aetiologic agent of subacute endocarditis is well known, this organism is a rare cause of septic arthritis. In this case, the exclusion of associated endocarditis is warranted.

  17. [Pneumococcal septic arthritis in a Spanish university hospital (1993- 2003)].

    Science.gov (United States)

    Barahona, Lucía; Soriano, Francisco; Fernández-Robles, Ricardo; Granizo, Juan José; López-Durán, Juan Carlos

    2005-01-01

    Cases of pneumococcal septic arthritis treated in the Fundación Jiménez Díaz (Madrid, Spain) were reviewed. A retrospective record review was conducted for all patients presenting with pneumococcal septic arthritis between January 1993 and August 2003. Four patients out of a total of 267 reviewed had a clinical and microbiological diagnosis of septic arthritis caused by Streptococcus pneumoniae. The most frequent locations were the knee, ankle and tarsus. Three of the four patients had underlying diseases and one patient died. Pneumococcal septic arthritis, a very rare clinical entity diagnosed by clinical and microbiological findings, should be suspected in patients with underlying disease. Early antibiotic therapy focussed on the most common microorganisms causing septic arthritis is necessary for optimal outcome.

  18. Leucocyte esterase in the rapid diagnosis of paediatric septic arthritis.

    LENUS (Irish Health Repository)

    Kelly, E G

    2013-02-01

    Septic arthritis may affect any age group but is more common in the paediatric population. Infection is generally bacterial in nature. Prompt diagnosis is crucial, as delayed treatment is associated with lifelong joint dysfunction. A clinical history and application of Kocher\\'s criteria may indicate that there is a septic arthritis. However, definitive diagnosis is made on culture of septic synovial fluid. The culture process can take over 24h for the initial culture to yield bacterial colonies. Leucocyte esterase is released by leucocytes at the site of an infection. We hypothesise that leucocyte esterase can be utilized in the rapid diagnosis of septic arthritis and shorten the time to decisive treatment whilst simultaneously decreasing unnecessary treatment of non-septic joints.

  19. Current Opinions in Pediatric Septic Shock

    Directory of Open Access Journals (Sweden)

    José Irazuzta

    2009-11-01

    Full Text Available Objectives: Our aim is to describe the current clinical practice related to the management of septic shock (SS. Methods: Review of medical literature using the MEDLINE database. Articles were selected according to their relevancy to the objective and according to the author’s opinion. Summary of the findings: The outcome from SS is dependent on an early recognition and a sequential implementation of time-sensitive goal-directed therapies. The goals of the resuscitation are rapid restoration of micro circulation and improved organ tissue perfusion. Clinical and laboratory markers are needed to assess the adequacy of the treatments. Initial resuscitation involves the use of isotonic solutions (>60ml/kg either crystalloid (normal saline or colloid infusion often followed by vasoactive medications. Altered pharmacokinetics and pharmacodynamics responses dictate that vasoactive agents should be adjusted to achieve predetermined goals. An assessment of central venous pressure complements clinical and serological findings to tailor therapies. Elective airway instrumentation and mechanical ventilation as well as adjunctive therapy with stress dose of corticosteroid are indicated in selected populations. In neonates, a special attention to the presence of electrolyte imbalance and increase pulmonary vascular resistance needs to be considered early. Conclusions: Septic shock hemodynamic is a changing process that requires frequent assessment and therapeutic adjustments.

  20. In vitro/in vivo correlation and modeling of emitted dose and lung deposition of inhaled salbutamol from metered dose inhalers with different types of spacers in noninvasively ventilated patients.

    Science.gov (United States)

    Hussein, Raghda R S; M A Ali, Ahmed; Salem, Heba F; Abdelrahman, Maha M; Said, Amira S A; Abdelrahim, Mohamed E A

    2017-11-01

    Substituting spacer by another in noninvasive ventilation (NIV) involves many variables, e.g. total emitted dose (TED), mass median aerodynamic diameter (MMAD), type of spacer, total lung deposition and total systemic absorption, which must be adjusted to ensure patient optimum therapy. Data mining based on artificial neural networks and genetic algorithms were used to model in vitro inhalation process, predict and optimize bioavailability from inhaled doses delivered by metered dose inhaler (MDI) using different spacers in NIV. Modeling of data indicated that in vitro performance of MDI-spacer systems was dependent mainly on fine particle dose (FPD), fine particle fraction (FPF), MMAD and to lesser extent on spacer type. Ex vivo model indicated that amount of salbutamol collected on facemask filter was directly affected by FPF. In vivo model (24hQ) depended directly on spacer type, FPF and TED. Female patients showed higher 0.5hQ and 24hQ values than males. AeroChamber VC spacer demonstrated higher TED and 24hQ in vivo values. Results indicated suitability of MDI-spacer systems in achieving appropriate in vitro inhalation performance. The possibility of modeling and predicting both ex vivo and in vivo capabilities of MDI-spacer systems from knowledge of in vitro attributes enabled detailed focus on important variables required to deliver safe and accurate doses of salbutamol to ventilated patients.

  1. [Role of procalcitonin in monitoring the antibiotic therapy in septic surgical patients].

    Science.gov (United States)

    Pundiche, M; Sârbu, V; Unc, O D; Grasa, C; Martinescu, A; Bădărău, V; Durbală, I; Sapte, E; Pasăre, R; Voineagu, L; Iordache, I; Vâncă, A; Adam, A

    2012-01-01

    Based on the need for rigorous monitoring of antibiotic and a proper assessment of patients with sepsis, procalcitonina as biological marker appears to have significant value, being proposed for both detection and for evaluation of bacterial infection and antibiotic management. We conducted a prospective study on a group of 73 patients admitted in Surgical Clinic II you SCJU Constanta between 2010-2011, which is included in the study criteria ACCP/SCCM Consensus Conference in 1992. We have made determinations of the PCT, in dynamic, since the admission of patients, with imunocromatographic method, monitoring the antibiotics on the studied group depending on cut-off fluctuations and PCT. The level of procalcitonin reflect the degree of systemic inflammatory response. PCT dosages were performed in 17 patients without inflammation/infection in 21 patients with local infections, 20 with systemic infection (sepsis), 7 with severe sepsis and septic shock 3/MSOF. In the studied group we excluded 5 patients with associated pathology (on the first day after a major trauma, major surgery, burns, treatment with drugs that stimulate the release of pro-inflammatory cytokines, small cell lung cancer, medullary thyroid carcinoma) in that the PCT was in the absence of an inflammatory process cresct/infectious manifesto. Starting, monitoring and stopping the antibiotic was carried out based on PCT levels. The dosage of procalcitonin (PCT) revealed significantly elevated values in patients with severe sepsis and septic shock/MSOF. PCT was significantly lower in patients with sepsis compared with those with septic shock, and the difference between PCT values in patients with sepsis and severe sepsis was the limit of statistical significance. PCT values were not predictive of death, however. In conclusion, dynamic measurement of PCT may be a predictor for life-threatening infections with antibiotics that can monitor and direct the time and efficiency. The value of PCT as a guide of

  2. An alternate pathophysiologic paradigm of sepsis and septic shock

    Science.gov (United States)

    Kumar, Anand

    2014-01-01

    The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role. PMID:24184742

  3. Salmonella enteridis Septic Arthritis: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Esat Uygur

    2013-01-01

    Full Text Available Introduction. Nontyphoidal salmonellosis causes significant morbidity, is transmitted via fecal-oral route, and is a worldwide cause of gastroenteritis, bacteremia, and local infections. Salmonella is a less common etiologic factor for septic arthritis compared with other gram-negative bacteria. Cases. We present two septic arthritis cases with Salmonella enteridis as a confirmed pathogen and also discuss the predisposing factors and treatment. Discussion. Septic arthritis is an orthopedic emergency. The gold standard treatment of septic arthritis is joint debridement, antibiotic therapy according to the culture results, and physiotherapy, which should start in the early postoperative period to prevent limitation of motion. Salmonella is an atypical agent for septic arthritis. It must be particularly kept in mind as an etiologic factor for the acute arthritis of a patient with sickle cell anemia and systemic lupus erythematosus. Clinicians should be cautious that the white blood cell count in synovial fluid can be under 50.000/mm3 in immune compromised individuals with septic arthritis. The inflammatory response can be deficient, or the microorganism may be atypical. Conclusion. Atypical bacteria such as Salmonella species in immune compromised patients can cause joint infections. Therefore, Salmonella species must always be kept in mind for the differential diagnosis of septic arthritis in a clinically relevant setting.

  4. The Protective Effect of Lidocaine on Septic Rats via the Inhibition of High Mobility Group Box 1 Expression and NF-κB Activation

    Science.gov (United States)

    Wang, Huan-Liang; Xing, Yan-Qiu; Xu, Ying-Xue; Rong, Fei; Lei, Wei-Fu; Zhang, Wen-Hua

    2013-01-01

    Lidocaine, a common local anesthetic drug, has anti-inflammatory effects. It has demonstrated a protective effect in mice from septic peritonitis. However, it is unknown whether lidocaine has effects on high mobility group box 1 (HMGB1), a key mediator of inflammation. In this study, we investigated the effect of lidocaine treatment on serum HMGB1 level and HMGB1 expression in liver, lungs, kidneys, and ileum in septic rats induced by cecal ligation and puncture (CLP). We found that acute organ injury induced by CLP was mitigated by lidocaine treatment and organ function was significantly improved. The data also demonstrated that lidocaine treatment raised the survival of septic rats. Furthermore, lidocaine suppressed the level of serum HMGB1, the expression of HMGB1, and the activation of NF-κB p65 in liver, kidneys, lungs, and ileum. Taken together, these results suggest that lidocaine treatment exerts its protective effection on CLP-induced septic rats. The mechanism was relative to the inhibitory effect of lidocaine on the mRNA expression level of HMGB1 in multiple organs, release of HMGB1 to plasma, and activation of NF-κB. PMID:24371375

  5. Septic Arthritis of the Shoulder Complicating Pregnancy

    Directory of Open Access Journals (Sweden)

    Sara Raiser

    2014-01-01

    Full Text Available Septic arthropathy leads to rapid joint destruction, impairment, and disability. Staphylococcus can be particularly virulent to bone and joints leading to adverse obstetric events. At 28 of weeks gestation, a patient presented with pyelonephritis and progressive left shoulder pain. Magnetic resonance imaging indicated early clavicular destruction and acromial involvement. Glenohumeral joint aspiration produced Staphylococcus aureus. The patient then had premature rupture of membranes and progressed rapidly to preterm delivery. Placental pathology revealed chorioamnionitis and microabscesses. Treatment of the infected joint required further surgical drainage and bone resection as well as extended antibiotics. It is important to remember that joint pain in pregnancy may indicate infective arthritis, and pyelonephritis can be a source of such an infection. Evaluation includes magnetic resonance imaging and consultation for joint aspiration. Prompt recognition and treatment are necessary to prevent joint destruction.

  6. Blood coagulation disorders in septic patients.

    Science.gov (United States)

    Knoebl, Paul

    2010-03-01

    Host defense and blood coagulation are tightly connected and interacting systems, necessary for the integrity of an organism. Complex mechanisms regulate the intensity of a host response to invading pathogens or other potentially dangerous situations. Under regular conditions, this response is limited in time and located to the site of injury. Sometimes, however, systemic host response is overwhelming and disproportional and causes damage, not cure. Dependent on the genetical predisposition of the host, its current immunocompetence, or the type of injury, the reaction leads to the clinical picture of the different degrees of sepsis. Septic organ dysfunction is caused by intravascular fibrin deposition as a result of coagulation activation, anticoagulant breakdown, and shut down of fibrinolysis. This article describes the major pathophysiologic reactions in these situations and presents www.SepDIC.eu, an online tool on sepsis and associated coagulopathy.

  7. Co-introduced functional CCR2 potentiates in vivo anti-lung cancer functionality mediated by T cells double gene-modified to express WT1-specific T-cell receptor.

    Directory of Open Access Journals (Sweden)

    Hiroaki Asai

    Full Text Available BACKGROUND AND PURPOSE: Although gene-modification of T cells to express tumor-related antigen-specific T-cell receptor (TCR or chimeric antigen receptor (CAR has clinically proved promise, there still remains room to improve the clinical efficacy of re-directed T-cell based antitumor adoptive therapy. In order to achieve more objective clinical responses using ex vivo-expanded tumor-responsive T cells, the infused T cells need to show adequate localized infiltration into the tumor. METHODOLOGY/PRINCIPAL FINDINGS: Human lung cancer cells variously express a tumor antigen, Wilms' Tumor gene product 1 (WT1, and an inflammatory chemokine, CCL2. However, CCR2, the relevant receptor for CCL2, is rarely expressed on activated T-lymphocytes. A HLA-A2402(+ human lung cancer cell line, LK79, which expresses high amounts of both CCL2 and WT1 mRNA, was employed as a target. Normal CD8(+ T cells were retrovirally gene-modified to express both CCR2 and HLA-A*2402-restricted and WT1(235-243 nonapeptide-specific TCR as an effector. Anti-tumor functionality mediated by these effector cells against LK79 cells was assessed both in vitro and in vivo. Finally the impact of CCL2 on WT1 epitope-responsive TCR signaling mediated by the effector cells was studied. Introduced CCR2 was functionally validated using gene-modified Jurkat cells and human CD3(+ T cells both in vitro and in vivo. Double gene-modified CD3(+ T cells successfully demonstrated both CCL2-tropic tumor trafficking and cytocidal reactivity against LK79 cells in vitro and in vivo. CCL2 augmented the WT1 epitope-responsive TCR signaling shown by relevant luciferase production in double gene-modified Jurkat/MA cells to express luciferase and WT1-specific TCR, and CCL2 also dose-dependently augmented WT1 epitope-responsive IFN-γ production and CD107a expression mediated by these double gene-modified CD3(+ T cells. CONCLUSION/SIGNIFICANCE: Introduction of the CCL2/CCR2 axis successfully potentiated in

  8. Adjunctive Steroid Therapy for Treatment of Pediatric Septic Shock.

    Science.gov (United States)

    Zimmerman, Jerry J

    2017-10-01

    Septic shock remains the major cause of childhood morbidity and mortality worldwide. Although early sepsis recognition, fluid resuscitation, timely administration of antimicrobials, and vasoactive-inotropic drug infusions are all key to achieving good sepsis outcomes, therapy using various steroid drug classes remains an attractive adjunctive intervention to minimize the duration of septic shock and transition to multiple organ dysfunction syndrome. All steroid drug classes possess biological plausibility to affect a beneficial clinical effect among children with septic shock, but none has undergone rigorous, prospective assessment in a large, high-quality pediatric interventional trial. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Thiamine in septic shock patients with alcohol use disorders

    DEFF Research Database (Denmark)

    Holmberg, Mathias Johan; Moskowitz, Ari; Patel, Parth Vijay

    2018-01-01

    PURPOSE: Alcohol-use disorders (AUDs) have been associated with increased sepsis-related mortality. As patients with AUDs are often thiamine deficient, we investigated practice patterns relating to thiamine administration in patients with AUDs presenting with septic shock and explored...... the association between receipt of thiamine and mortality. MATERIALS: We performed a retrospective cohort study of patients presenting with septic shock between 2008 and 2014 at a single tertiary care center. We identified patients with an AUD diagnosis, orders for microbial cultures and use of antibiotics...... with AUDs admitted for septic shock do not receive thiamine. Thiamine administration in this patient population was associated with decreased mortality....

  10. Septic/unsafe abortion: a preventable tragedy.

    Science.gov (United States)

    Sultana, Ruqqia; Noor, Shehla; Fawwad, Ali; Abbasi, Nasreen; Bashir, Rubina

    2012-01-01

    Unsafe abortion is one of the greatest neglected problems of health care in developing countries like Pakistan. In countries where abortions are restricted women have to resort to clandestine interventions to have an unwanted pregnancy terminated. The study was conducted to find out the prevalence of septic induced abortion and the associated morbidity and mortality and to highlight the measures to reduce it. This cross-sectional descriptive study was carried out in Obs/Gyn B Unit, Ayub Teaching Hospital, Abbottabad from January 2007 to December 2011. During this period all the patients presenting with pyrexia lower abdominal pain, vaginal bleeding, acute abdomen, septic or hypovolaemic shock after undergoing some sort of intervention for abortion outside the hospital were included. After thorough history, examination and detailed investigations including high vaginal and endocervical swabs for culture and sensitivity and pelvic ultrasound supportive management was given followed by antibiotics, surgical evacuation of uterus/ major laparotomy in collaboration with surgeon as required. Patients with DIC or multiple system involvement were managed in High Dependency Unit (HDU) by multidisciplinary team. During the study period out of a total 6,906 admissions 968 presented with spontaneous abortion. There were 110 cases (11.36%) of unsafe abortion, 56.4% presented with vaginal discharge, 34.5% with vaginal bleeding, 21.8% with acute abdomen, while 18.9% in shock and 6.8% with DIC. Forty-nine percent patients used termination as a method of contraception. Mortality rate was 16.36%, leading cause being septicaemia. Death and severe morbidity from unsafe abortions and its complications is avoidable through health education, effective contraception, early informed recognition and management of the problem once it occurs.

  11. Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Wang; Chunhua, Ma, E-mail: machunhuabest@126.com; Shumin, Wang, E-mail: wangshuminch@126.com

    2015-06-01

    The purpose of the present study was to investigate the protective role of acteoside (AC) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). BalB/c mice intraperitoneally received AC (30, and 60 mg/kg) or dexamethasone (2 mg/kg) 2 h prior to or after intratracheal instillation of LPS. Treatment with AC significantly decreased lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity and ameliorated LPS-induced lung histopathological changes. In addition, AC increased super oxide dismutase (SOD) level and inhibited malondialdehyde (MDA) content, total cell and neutrophil infiltrations, and levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) in LPS-stimulated mice. Furthermore, we demonstrated that AC inhibited the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, inhibitor of nuclear factor kappa-B kinase-α (IKK-α) and inhibitor of nuclear factor kappa-B kinase-β (IKKβ) in LPS-induced inflammation in A549 cells. Our data suggested that LPS evoked the inflammatory response in lung epithelial cells A549. The experimental results indicated that the protective mechanism of AC might be attributed partly to the inhibition of proinflammatory cytokine production and NF-κB activation. - Highlights: • Acteoside inhibited inflammation in LPS-induced lung injury in mice. • Acteoside inhibited inflammation in lung epithelial cells A549. • Acteoside inhibited NF-kB activation in LPS-induced mice and lung epithelial cells A549.

  12. Septic arthritis of the acromioclavicular joint: an uncommon location.

    Science.gov (United States)

    Martínez-Morillo, Melania; Mateo Soria, Lourdes; Riveros Frutos, Anne; Tejera Segura, Beatriz; Holgado Pérez, Susana; Olivé Marqués, Alejandro

    2014-01-01

    Septic pyogenic arthritis of the acromioclavicular joint is a rare entity that occurs in immunosuppressed patients or those with discontinuity of defense barriers. There are only 15 cases described in the literature. The diagnosis is based on clinical features and the isolation of a microorganism in synovial fluid or blood cultures. The evidence of arthritis by imaging (MRI, ultrasound or scintigraphy) may be useful. Antibiotic treatment is the same as in septic arthritis in other locations. Staphylococcus aureus is the microorganism most frequently isolated. Our objective was to describe the clinical features, treatment and outcome of patients diagnosed with septic arthritis of the acromioclavicular joint at a Rheumatology Department. We developed a study with a retrospective design (1989-2012). The medical records of patients with septic arthritis were reviewed (101 patients). Those involving the acromioclavicular joint were selected (6 patients; 6%). Copyright © 2013 Elsevier España, S.L. All rights reserved.

  13. Preliminary characterization of abandoned septic tank systems. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    This report documents the activities and findings of the Phase I Preliminary Characterization of Abandoned Septic Tank Systems. The purpose of the preliminary characterization activity was to investigate the Tiger Team abandoned septic systems (tanks and associated leachfields) for the purpose of identifying waste streams for closure at a later date. The work performed was not to fully characterize or remediate the sites. The abandoned systems potentially received wastes or effluent from buildings which could have discharged non-domestic, petroleum hydrocarbons, hazardous, radioactive and/or mixed wastes. A total of 20 sites were investigated for the preliminary characterization of identified abandoned septic systems. Of the 20 sites, 19 were located and characterized through samples collected from each tank(s) and, where applicable, associated leachfields. The abandoned septic tank systems are located in Areas 5, 12, 15, 25, and 26 on the Nevada Test Site.

  14. Location of Septic Sewer Systems in the Pacific Northwest

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Septic systems are useful for removing and processing human waste. However, they have the potential of leaking or discharging waste into the nearby system and...

  15. Bordetella holmesii, an emerging cause of septic arthritis.

    Science.gov (United States)

    Abouanaser, Salaheddin F; Srigley, Jocelyn A; Nguyen, Tram; Dale, Suzanne E; Johnstone, Jennie; Wilcox, Lindsay; Jamieson, Frances; Rawte, Prasad; Pernica, Jeffrey M

    2013-04-01

    Bordetella holmesii is a well-described pathogen in asplenic and immunocompromised patients. Here we report the first two published cases of septic arthritis caused by B. holmesii documented in apparently immunocompetent patients and unaccompanied by bacteremia.

  16. Current concepts on hemodynamic support and therapy in septic shock.

    Science.gov (United States)

    Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Corrêa, Thiago Domingos; Pereira, Adriano José; de Assunção, Murillo Santucci Cesar; Silva, Eliézer

    2015-01-01

    Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  17. Current concepts on hemodynamic support and therapy in septic shock

    Directory of Open Access Journals (Sweden)

    Leonardo Lima Rocha

    2015-10-01

    Full Text Available ABSTRACTSevere sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration.

  18. [Current concepts on hemodynamic support and therapy in septic shock].

    Science.gov (United States)

    Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Corrêa, Thiago Domingos; Pereira, Adriano José; de Assunção, Murillo Santucci Cesar; Silva, Eliézer

    2015-01-01

    Severe sepsis and septic shock represent a major healthcare challenge. Much of the improvement in mortality associated with septic shock is related to early recognition combined with timely fluid resuscitation and adequate antibiotics administration. The main goals of septic shock resuscitation include intravascular replenishment, maintenance of adequate perfusion pressure and oxygen delivery to tissues. To achieve those goals, fluid responsiveness evaluation and complementary interventions - i.e. vasopressors, inotropes and blood transfusion - may be necessary. This article is a literature review of the available evidence on the initial hemodynamic support of the septic shock patients presenting to the emergency room or to the intensive care unit and the main interventions available to reach those targets, focusing on fluid and vasopressor therapy, blood transfusion and inotrope administration. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  19. Safety and vasopressor effect of rosuvastatin in septic patients

    Directory of Open Access Journals (Sweden)

    Hanaa A. El Gendy

    2014-07-01

    Conclusions: Rosuvastatin 20 mg/day in septic patients increased number ABPSPD, decreased time to initial ABPSPD, norepinephrine dose and duration, with no significant elevation in transaminases or CPK.

  20. Cardiac Arrhythmias in a Septic ICU Population: A Review

    Directory of Open Access Journals (Sweden)

    Schwartz Andrei

    2015-10-01

    Full Text Available Progressive cardiovascular deterioration plays a central role in the pathogenesis of multiple organ failure (MOF caused by sepsis. Evidence of various cardiac arrhythmias in septic patients has been reported in many published studies. In the critically ill septic patients, compared to non-septic patients, new onset atrial fibrillation episodes are associated with high mortality rates and poor outcomes, amongst others being new episodes of stroke, heart failure and long vasopressor usage. The potential mechanisms of the development of new cardiac arrhythmias in sepsis are complex and poorly understood. Cardiac arrhythmias in critically ill septic patients are most likely to be an indicator of the severity of pre-existing critical illness.

  1. Higher vs. lower fluid volume for septic shock

    DEFF Research Database (Denmark)

    Smith, Søren H; Perner, Anders

    2012-01-01

    ABSTRACT: INTRODUCTION: Patients with septic shock require fluid, but the optimum amount is unknown. Therefore we assessed patient characteristics and outcome associated with fluid volume in unselected patients with septic shock including those with three days of shock. METHODS: We conducted...... a prospective, multicenter, observational study of all adult patients with septic shock during a 3-month study period at six general ICUs: three in university hospitals and three in regional hospitals. After day 1 and 3 of shock, patients were divided into two groups according to the overall median fluid...... volumes. Characteristics between these groups were compared using non-parametric and Chi-square statistics. RESULTS: The 164 included patients received median 4.0 l (IQR 2.3-6.3) of fluid during the first day of septic shock. Patients receiving higher volumes (> 4.0 l) on day 1 had higher p-lactate (3...

  2. Early recognition and management of septic shock in children

    Directory of Open Access Journals (Sweden)

    Paolo Biban

    2012-03-01

    Full Text Available Septic shock remains a major cause of morbidity and mortality among children, mainly due to acute haemodynamic compromise and multiple organ failures. In the last decade, international guidelines for the management of septic shock, as well as clinical practice parameters for hemodynamic support of pediatric patients, have been published. Early recognition and aggressive therapy of septic shock, by means of abundant fluid resuscitation, use of catecholamines and other adjuvant drugs, are widely considered of pivotal importance to improve the short and long-term outcome of these patients. The aim of this paper is to summarize the modern approach to septic shock in children, particularly in its very initial phase, when pediatric healthcare providers may be required to intervene in the pre-intensive care unit setting or just on admission in the pediatric intensive care unit.

  3. Clinical effect of alprostadil in patients with septic shock associated with acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Li-ping LIU

    2017-10-01

    Full Text Available Objective To evaluate the clinical efficacy of alprostadil in patients with septic shock associated with acute respiratory distress syndrome (ARDS, and to explore its possible mechanism. Methods From January 2015 to June 2016, patients with septic shock associated with ARDS and meeting the inclusion criteria were involved in the study in department of critical care medicine in First Hospital of Lanzhou University and randomly divided into the control group and alprostadil group. The standard treatment was given in control group, alprostadil 10μg 2/d was given in alprostadil group on base of standard treatment. Monitoring indexes were recorded in 1, 3 and 6 days after enrollment. General condition of patients, APACHE Ⅱ score, ventilator conditions (PO2, PCO2, RR, PEEP, FiO2, oxygenation index, airway resistance, lung compliance, mechanical ventilation time, ICU stay time, hospital follow-up, 28-day follow-up, immune index (CD4+/CD8+, inflammatory markers (CRP, PCT, IL-6 were monitored. Results Sixty-five patients were included in this study, 32 in control group and 33 in alprostadil group. At 3 and 6 days after the treatment, APACHE Ⅱ score, respiratory rate (RR, the inspired oxygen concentration (FiO2, airway resistance, and C reactive protein (CRP, procalcitonin (PCT -6 and interleukin (IL-6 levels significantly decreased, compared with pretreatment and 1 day posttreatment, in the two groups and lower in alprostadil group than in the control group on the 6th day (P<0.05; at the same time, these indexes such as arterial partial pressure of oxygen (PaO2, lung compliance, oxygenation index, CD4+/CD8+ significantly increased 3 and 6 days after the treatment compared with pretreatment and 1 day posttreatment in the two groups, and on the 6th day, significantly higher in the alprostadil group than in the control group (P<0.05. Time of mechanical ventilation, ICU stay and hospital stay in the alprostadil group was respectively lower than that in

  4. Prognostic value of nitric oxide in pediatric septic shock

    OpenAIRE

    Ari L. Runtunuwu; Jeanette I. Ch. Manoppo; Dasril Daud; Irawan Yusuf; Idham Jaya Ganda

    2016-01-01

    Background Nitric oxide (NO) play a key role in the pathogenesis of septic shock. Nitrit oxide metabolite is reported as a good predictor for shock although its role as mortality predictor in sepsis still controversial. Objective To assess the serum nitric oxide (NO) levels and outcomes in pediatric patients with septic shock. Methods We conducted a prospective cohort study from January 2013 to April 2014 in Pediatric Intensive Care Unit (PICU) Prof. Dr. R. D. Kandou Hospital, Manad...

  5. Septic Acromioclavicular Arthritis in a Patient with Diabetes Mellitus

    OpenAIRE

    Laktašić-Žerjavić, Nadica; Babić-Naglić, Đurđica; Ćurković, Božidar; Potočki, Kristina; Soldo-Jureša, Dragica

    2005-01-01

    A 44-year-old diabetic man with isolated septic arthritis of the left acromioclavicular joint (A–C) caused by Staphylococcus aureus is described. He was admitted to the Department of Rheumatology with clinical symptoms of left shoulder arthritis and fever. Laboratory findings showed leukocytosis, elevated levels of erythrocyte sedimentation rate and C-reactive protein, all indicating septic arthritis. Blood culture was positive for Staphylococcus aureus. Left A–C joint x-ray and ultrasonograp...

  6. Changes in Septic Tank Effluent Due to Water Softener Use

    OpenAIRE

    Hogan, Patrick Lynn

    2012-01-01

    The compatibility of home water softeners and septic tanks is of concern for the on-site wastewater treatment community. Research has shown that high sodium levels in activated sludge plants can lead to deflocculation and poor effluent quality. Therefore, it is logical to assume that high sodium levels that result from the exchange of calcium and magnesium for sodium in home softeners could give rise to poor effluent quality from septic tanks, leading to shortened lives of drain fields. Addit...

  7. An Unusual Case of Septic Arthritis of the Hip.

    Science.gov (United States)

    Ray, Ujjwayini; Dutta, Soma; Sutradhar, Arpita

    2016-11-01

    Non-typhoidal Salmonella, particularly Salmonella enterica serovar typhimurium is food borne pathogen causing mild self-limiting diarrhoea in healthy adults. It can occasionally cause extraintestinal focal infection in susceptible patients. Salmonella, as the aetiological agent of osteomyelitis and septic arthritis is rare and has been mostly reported in patients with sickle cell disease or thalassaemia. We report a case of septic arthritis by Salmonellatyphimurium in an immunocompromised patient who was successfully treated following timely isolation and identification of the aetiological agent.

  8. The intensive care medicine research agenda on septic shock

    DEFF Research Database (Denmark)

    Perner, Anders; Gordon, Anthony C; Angus, Derek C

    2017-01-01

    Septic shock remains a global health challenge with millions of cases every year, high rates of mortality and morbidity, impaired quality of life among survivors and relatives, and high resource use both in developed and developing nations. Care and outcomes are improving through organisational...... and translational work. In this review, international experts summarize the current position of clinical research in septic shock and propose a research agenda to advance this field....

  9. Non activated protein C supplementation in septic pediatric hematological patients

    Directory of Open Access Journals (Sweden)

    Teresa Perillo

    2016-06-01

    Full Text Available The purpose of the study was to examine safety and efficacy of non-activated Protein C (PC supplementation in our cohort of septic pediatric hematological patients. We conducted a retrospective study of 22 septic patients receiving human plasma-derived PC concentrate from 2008 to 2015 at our Pediatric Oncology Center (Bari, Italy. The Surviving sepsis campaign definitions for sepsis, severe sepsis and septic shock were used to define the patients’ septic status. For each patient, we calculated Lansky performance status scale (LPSS and a risk score defined the Hematologic risk score (HRS that we created in 2007. Patients were defined as High risk for severe sepsis/septic shock in case of HRS>3. HRS10% PC concentration decrease within 12 hours from the first evaluation. All patients received 80 U/kg/day PC, intravenously, every twenty-four hours. No drug-related adverse event was observed. The observed sepsis-related mortality rate in our cohort was 9%. PC supplementation in our cohort appeared to be safe, and, probably due to prompt PC administration, we observed an overall mortality that was much lower than expected mortality in cancer severe septic patients.

  10. Racial differences in vasopressor requirements for septic shock.

    Science.gov (United States)

    Bauman, Zachary M; Killu, Keith F; Rech, Megan A; Bernabei-Combs, Jenna L; Gassner, Marika Y; Coba, Victor E; Tovbin, Alina; Kunkel, Patti L; Mlynarek, Mark E

    2014-03-01

    The objective of this study was to compare vasopressor requirements between African American (AA) patients and white patients in septic shock. This was a retrospective cohort review conducted over a 2-year period measuring total and mean dosage of various vasopressors used between two racial groups during the treatment of patients admitted with septic shock. The study included patients admitted to the intensive care unit with septic shock at an 805-bed tertiary, academic center. All septic shock patients were managed with vasopressors. Vasopressor selection, dosage, and duration were at the discretion of the treating physician. Total, mean, and duration of vasopressor dosing requirements were obtained for study participants. Comorbidities, prehospitalization antihypertensive medication requirements, intravenous fluids given during the septic shock phase, and source of infection were analyzed. One hundred fifty-nine patients with septic shock were analyzed, of which 96 (60.4%) were AAs (P shock were treated with higher doses of NE and required longer duration of NE administration compared with white patients.

  11. Neutralisation of peritoneal IL-17A markedly improves the prognosis of severe septic mice by decreasing neutrophil infiltration and proinflammatory cytokines.

    Directory of Open Access Journals (Sweden)

    Jinbao Li

    Full Text Available PURPOSE: The current study aimed to elucidate the role of peritoneal fluid IL-17A in septic mice, and the effects of intraperitoneal or intravenous blockade of the IL-17A pathway by anti-IL17A antibody on survival, plasma, and peritoneal cavity cytokine profile in a murine caecal ligation and puncture (CLP sepsis model. The main source of peritoneal fluid IL-17A in septic mice was identified. METHODS: Male C57BL/6 mice that underwent severe CLP or sham surgery were intraperitoneally or intravenously administered anti-IL17A antibodies or isotype antibodies. The survival rates were observed. IL-17A, TNF-α, and IL-6 cytokine levels were measured by ELISA. Surface and intracellular IL-17A immunofluorescence stains were detected by flow cytometry to identify the IL-17A-producing cells. RESULTS: The IL-17A level was elevated much higher and earlier in peritoneal fluid than in the blood of the CLP mice. The intraperitoneal IL-17A blockade more significantly protects against CLP-induced mortality than intravenous blockade because of decreased TNF-α and IL-6 levels both in peritoneal fluid and blood, neutrophil infiltration in the peritoneal cavity, and lung injury. γδ T lymphocytes were identified to be the main source of IL-17A in the peritoneal fluid of septic mice. CONCLUSIONS: The earlier and higher elevated IL-17A derived from γδ T cells in peritoneal fluid plays a critical role during polymicrobial severe sepsis and effect of intraperitoneal IL-17A antibody administration superior to intravenous administration on survival of severe CLP-induced septic mice. The intraperitoneal blockade of IL-17A decreases proinflammatory cytokine production, neutrophil infiltration, and lung injury, thereby improving septic mice survival, which provides a new potential therapy target for sepsis.

  12. Septic and nonseptic olecranon bursitis. Utility of the surface temperature probe in the early differentiation of septic and nonseptic cases.

    Science.gov (United States)

    Smith, D L; McAfee, J H; Lucas, L M; Kumar, K L; Romney, D M

    1989-07-01

    Forty-six consecutive cases of olecranon bursitis were prospectively analyzed during a 1-year period. Eleven cases were septic; 35 cases were nonseptic. In addition to bursal fluid analysis, the surface temperature over the involved olecranon bursa and the contralateral (control) olecranon process was obtained by using a surface temperature probe. We compared the temperature difference between the involved and control sides in all septic and nonseptic cases. In nonseptic cases, the mean surface temperature difference was 0.7 degree C vs 3.7 degrees C in septic cases. In all septic cases, the temperature difference was 2.2 degrees C or greater (range, 2.2 degrees C to 5.1 degrees C; SD, 1.1). Use of the surface probe temperature difference proved 100% sensitive and 94% specific in discriminating septic from nonseptic cases. It seems to be more helpful than the bursal fluid leukocyte count, the predominant cell type, or Gram's stain in the early differentiation of septic and nonseptic olecranon bursitis.

  13. [Pneumococcal septic arthritis in HIV infection].

    Science.gov (United States)

    Trivalle, C; Cremieux, A C; Carbon, C

    1995-11-04

    Infections due to pneumococci are frequent in patients infected with the human immunodeficiency virus (HIV), but joint infections are rare. We observed two cases of septic arthritis due to pneumococci in two non-haemophilic HIV seropositive patients. In the first case, a 31-year old drug addict who had undergone splenectomy, developed hip joint infection during an episode of meningitis due to pneumococci. The germ was moderately sensitive to ampicillin. The second case involved the knee joint in a 29-year-old woman who developed pneumococcal pneumonia after a trip to Zaire. In both cases, joint infection developed after antibiotics had been initiated, and in the first case, after the infection appear to be under control. This would be similar to "post-infectious" arthritis described in gonococcal and meningococcal infections. In HIV positive patients, joint infections are rare compared with other types of immunodepression, but can be observed in all stages of the disease. A total of 75 cases have been reported in the literature, including 8 cases due to pneumococci. These joint infections could be another argument in favour of anti-pneumococcal vaccination in HIV positive patients.

  14. Limited use of antiseptics in septic surgery.

    Science.gov (United States)

    Röhner, Eric; Hoff, Paula; Pfitzner, Tilman; Seeger, Joern Bengt; Buttgereit, Frank; Perka, Carsten; Matziolis, Georg

    2012-10-01

    In septic joint surgery, treatment with antiseptics is a standard procedure. Postinfectious degeneration of cartilage often results in early arthritis that necessitates joint replacement, even in young patients. It is still unclear whether antiseptics have only a toxic effect on chondrocytes or also induce late cell death through apoptosis. We hypothesized that commonly used antiseptics (polyhexanide, hydrogen peroxide, and chlorhexidine) induce different stages of apoptosis on human chondrocytes. Human chondrocytes were isolated and cultured. Polyhexanide, hydrogen peroxide, and chlorhexidine were added to the monolayer cultures. Early and late apoptotic cells were analyzed using flow cytometric detection of Annexin V, active caspases, and 7AAD, and fluorescence microscopy using Annexin V and propidium iodide staining. Flow cytometric analysis revealed an increase of Annexin V and active caspases expression of human chondrocytes after incubation with polyhexanide, hydrogen peroxide, and chlorhexidine. Fluorescence microscopy demonstrated a high number of apoptotic cells. Our data show that polyhexanide and chlorhexidine only promote the early stages of apoptosis without any differences in toxicity. Conversely, hydrogen peroxide induces early and later stages of apoptosis on primary human chondrocytes in vitro.

  15. [Agranulocytosis and septic shock after metamizole use].

    Science.gov (United States)

    Oude Munnik, Thijs H; Annink-Smoors, Marjon; Hom, Harold W; Sportel, Esther T

    2016-01-01

    Metamizole is an analgesic, the orally administered form of which was withdrawn in the Netherlands in 1989 due to an unacceptably high incidence of agranulocytosis. However, later studies showed a much lower incidence and since 2013 the use of metamizole has been recommended by the national guideline on postoperative pain. A 58-year-old woman was referred by her general practitioner to our hospital with suspected diverticulitis. Three days previously the patient had returned from a four-week period of rehabilitation at a German spa following hip replacement surgery. She had been using metamizole since the operation. Within hours of admission, the patient developed septic shock and was transferred to the intensive care unit. Laboratory tests revealed severe neutropenia of 0.2 × 10(9)/l. Treatment consisted of filgrastim, piperacillin/tazobactam and haemodynamic support. After five days the patient was sufficiently recovered to return to the ward. Metamizole-related agranulocytosis is rare but potentially life-threatening. This condition is expected to occur more frequently as the use of metamizole in the Netherlands increases.

  16. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo

    DEFF Research Database (Denmark)

    Ale, Marcel Tutor; Maruyama, Hiroko; Tamauchi, Hidekazu

    2011-01-01

    Fucoidan is known to exhibit crucial biological activities, including anti-tumor activity. In this study, we examined the influence of crude fucoidan extracted from Sargassum sp. (MTA) and Fucus vesiculosus (SIG) on Lewis lung carcinoma cells (LCC) and melanoma B16 cells (MC). In vitro studies were...

  17. Murine Lung Cancer Increases CD4+ T Cell Apoptosis and Decreases Gut Proliferative Capacity in Sepsis.

    Directory of Open Access Journals (Sweden)

    John D Lyons

    Full Text Available Mortality is significantly higher in septic patients with cancer than in septic patients without a history of cancer. We have previously described a model of pancreatic cancer followed by sepsis from Pseudomonas aeruginosa pneumonia in which cancer septic mice have higher mortality than previously healthy septic mice, associated with increased gut epithelial apoptosis and decreased T cell apoptosis. The purpose of this study was to determine whether this represents a common host response by creating a new model in which both the type of cancer and the model of sepsis are altered.C57Bl/6 mice received an injection of 250,000 cells of the lung cancer line LLC-1 into their right thigh and were followed three weeks for development of palpable tumors. Mice with cancer and mice without cancer were then subjected to cecal ligation and puncture and sacrificed 24 hours after the onset of sepsis or followed 7 days for survival.Cancer septic mice had a higher mortality than previously healthy septic mice (60% vs. 18%, p = 0.003. Cancer septic mice had decreased number and frequency of splenic CD4+ lymphocytes secondary to increased apoptosis without changes in splenic CD8+ numbers. Intestinal proliferation was also decreased in cancer septic mice. Cancer septic mice had a higher bacterial burden in the peritoneal cavity, but this was not associated with alterations in local cytokine, neutrophil or dendritic cell responses. Cancer septic mice had biochemical evidence of worsened renal function, but there was no histologic evidence of renal injury.Animals with cancer have a significantly higher mortality than previously healthy animals following sepsis. The potential mechanisms associated with this elevated mortality differ significantly based upon the model of cancer and sepsis utilized. While lymphocyte apoptosis and intestinal integrity are both altered by the combination of cancer and sepsis, the patterns of these alterations vary greatly depending on

  18. Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação histopatológica e de apoptose celular em pulmões preservados com solução de baixo potássio dextrana vs. solução histidina-triptofano-cetoglutarato An experimental rat model of ex vivo lung perfusion for the assessment of lungs regarding histopathological findings and apoptosis: low-potassium dextran vs. histidine-tryptophan-ketoglutarate

    Directory of Open Access Journals (Sweden)

    Edson Azevedo Simões

    2012-08-01

    Full Text Available OBJETIVO: Comparar os achados histopatológicos e de apoptose em pulmões de ratos preservados em soluções low-potassium dextran (LPD, baixo potássio dextrana, histidine-tryptophan-ketoglutarate (HTK, histidina-triptofano-cetoglutarato ou salina normal (SN em 6 h e 12 h de isquemia pela utilização de um modelo experimental de perfusão pulmonar ex vivo. MÉTODOS: Sessenta ratos Wistar foram anestesiados, randomizados e submetidos à perfusão anterógrada pela artéria pulmonar com uma das soluções preservadoras. Após a extração, os blocos cardiopulmonares foram preservados por 6 ou 12 h a 4ºC, sendo então reperfundidos com sangue homólogo em um sistema de perfusão ex vivo durante 60 min. Ao final da reperfusão, fragmentos do lobo médio foram extraídos e processados para histopatologia, sendo avaliados os seguintes parâmetros: congestão, edema alveolar, hemorragia alveolar, hemorragia, infiltrado inflamatório e infiltrado intersticial. O grau de apoptose foi avaliado pelo método TdT-mediated dUTP nick end labeling. RESULTADOS: A histopatologia demonstrou que todos os pulmões preservados com SN apresentaram edema alveolar após 12 h de isquemia. Não houve diferenças em relação ao grau de apoptose nos grupos estudados. CONCLUSÕES: No presente estudo, os achados histopatológicos e de apoptose foram semelhantes com o uso das soluções LPD e HTK, enquanto a presença de edema foi significativamente maior com o uso de SN.OBJECTIVE: To compare histopathological findings and the degree of apoptosis among rat lungs preserved with low-potassium dextran (LPD solution, histidine-tryptophan-ketoglutarate (HTK solution, or normal saline (NS at two ischemia periods (6 h and 12 h using an experimental rat model of ex vivo lung perfusion. METHODS: Sixty Wistar rats were anesthetized, randomized, and submitted to antegrade perfusion via pulmonary artery with one of the preservation solutions. Following en bloc extraction, the heart-lung

  19. Mitochondrial dysfunction in peripheral blood mononuclear cells in pediatric septic shock.

    Science.gov (United States)

    Weiss, Scott L; Selak, Mary A; Tuluc, Florin; Perales Villarroel, Jose; Nadkarni, Vinay M; Deutschman, Clifford S; Becker, Lance B

    2015-01-01

    Mitochondrial dysfunction in peripheral blood mononuclear cells has been linked to immune dysregulation and organ failure in adult sepsis, but pediatric data are limited. We hypothesized that pediatric septic shock patients exhibit mitochondrial dysfunction within peripheral blood mononuclear cells which in turn correlates with global organ injury. Prospective observational study. Academic PICU. Thirteen pediatric patients with septic shock and greater than or equal to two organ failures and 11 PICU controls without sepsis or organ failure. Ex vivo measurements of mitochondrial oxygen consumption and membrane potential (ΔΨm) were performed in intact peripheral blood mononuclear cells on day 1-2 and day 5-7 of septic illness and in controls. The Pediatric Logistic Organ Dysfunction score, inotrope score, and organ failure-free days were determined from medical records. Spare respiratory capacity, an index of bioenergetic reserve, was lower in septic peripheral blood mononuclear cells on day 1-2 (median, 1.81; interquartile range, 0.52-2.09 pmol O2/s/10 cells) compared with controls (5.55; 2.80-7.21; p = 0.03). Spare respiratory capacity normalized by day 5-7. Patients with sepsis on day 1-2 exhibited a higher ratio of LEAK to maximal respiration than controls (17% vs Pediatric Logistic Organ Dysfunction score, inotrope score, or organ failure-free days (all p > 0.05). Although there was a weak overall association between ΔΨm on day 1-2 and organ failure-free days (Spearman ρ = 0.56, p = 0.06), patients with sepsis with normal organ function by day 7 exhibited higher ΔΨm on day 1-2 compared with patients with organ failure for more than 7 days (p = 0.04). Mitochondrial dysfunction was present in peripheral blood mononuclear cells in pediatric sepsis, evidenced by decreased bioenergetic reserve and increased uncoupling. Mitochondrial membrane potential, but not respiration, was associated with duration of organ injury.

  20. "Immunonutrition" Has Failed to Improve Peritonitis-Induced Septic Shock in Rodents.

    Directory of Open Access Journals (Sweden)

    Julie Boisramé-Helms

    Full Text Available Immunonutrition in sepsis, including n-3 poly-unsaturated fatty acids (PUFAs or L-arginine supplementation, is a controversial issue that has yielded a great number of studies for the last thirty-five years, and the conclusions regarding the quantity and quality of this support in patients are deceiving. The aim of the present experimental study is to investigate the effects of a pretreatment with enteral nutrition enriched with n-3 PUFAs or L-arginine on vascular dysfunctions, inflammation and oxidative stress during septic shock in rats.Rats were fed with enteral Peptamen® HN (HN group, Peptamen® AF containing n-3 PUFAs (AF group or Peptamen® AF enriched with L-arginine (AFA group. On day 4, peritonitis by cecal ligation and puncture (CLP was performed. Rats were resuscitated (H18 once septic shock was established. After a 4-hour resuscitation, vessels and organs were harvested to assess inflammation, superoxide anion, nitric oxide and prostacyclin levels. Ex-vivo vascular reactivity was also performed.Compared to CLP-AF or CLP-HN groups, 47.6% of CLP-AFA rats died before the beginning of hemodynamic measurements (vs. 8.0% and 20.0% respectively, p<0.05. AF and AFA rats required significantly increased norepinephrine infusion rates to reach the mean arterial pressure objective, compared to CLP-HN rats. Both CLP-AF and CLP-AFA reduced mesenteric resistance arterial contractility, decreased vascular oxidative stress, but increased NF-κB (0.40±0.15 in CLP-AF and 0.69±0.06 in CLP-AFA vs. 0.09±0.03 in SHAM rats and 0.30±0.06 in CLP-HN, ß-actin ratio, p<0.05 and pIκB expression (0.60±0.03 in CLP-AF and 0.94±0.15 in CLP-AFA vs. 0.04±0.01 in SHAM rats and 0.56±0.07 in CLP-HN, ß-actin ratio, p<0.05, nitric oxide and prostacyclin production in septic rats.Although n-3 PUFAs or L-arginine supplementation exhibited an antioxidant effect, it worsened the septic shock-induced vascular dysfunction. Furthermore, mortality was higher after L

  1. Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway*

    Science.gov (United States)

    Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu

    2015-01-01

    Objectives: Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Design: Experimental animal investigation. Setting: University research laboratory. Subjects: Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20–25 g. Interventions: We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Measurements and Main Results: Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10

  2. Xenon Protects Against Septic Acute Kidney Injury via miR-21 Target Signaling Pathway.

    Science.gov (United States)

    Jia, Ping; Teng, Jie; Zou, Jianzhou; Fang, Yi; Wu, Xie; Liang, Mingyu; Ding, Xiaoqiang

    2015-07-01

    Septic acute kidney injury is one of the most common and life-threatening complications in critically ill patients, and there is no approved effective treatment. We have shown xenon provides renoprotection against ischemia-reperfusion injury and nephrotoxicity in rodents via inhibiting apoptosis. Here, we studied the effects of xenon preconditioning on septic acute kidney injury and its mechanism. Experimental animal investigation. University research laboratory. Experiments were performed with male C57BL/6 mice, 10 weeks of age, weighing 20-25 g. We induced septic acute kidney injury by a single intraperitoneal injection of Escherichia coli lipopolysaccharide at a dose of 20 mg/kg. Mice were exposed for 2 hours to either 70% xenon or 70% nitrogen, 24 hours before the onset of septic acute kidney injury. In vivo knockdown of miR-21 was performed using locked nucleic acid-modified anti-miR, the role of miR-21 in renal protection conferred by the xenon preconditioning was examined, and miR-21 signaling pathways were analyzed. Xenon preconditioning provided morphologic and functional renoprotection, characterized by attenuation of renal tubular damage, apoptosis, and a reduction in inflammation. Furthermore, xenon treatment significantly upregulated the expression of miR-21 in kidney, suppressed proinflammatory factor programmed cell death protein 4 expression and nuclear factor-κB activity, and increased interleukin-10 production. Meanwhile, xenon preconditioning also suppressed the expression of proapoptotic protein phosphatase and tensin homolog deleted on chromosome 10, activating protein kinase B signaling pathway, subsequently increasing the expression of antiapoptotic B-cell lymphoma-2, and inhibiting caspase-3 activity. Knockdown of miR-21 upregulated its target effectors programmed cell death protein 4 and phosphatase and tensin homolog deleted on chromosome 10 expression, resulted in an increase in apoptosis, and exacerbated lipopolysaccharide

  3. Application of voxelised numerical phantoms linked to the M.C.N.P. Monte Carlo code to the realistic measurement in vivo of actinides in the lungs and contaminated wounds; Application des fantomes numeriques voxelises associes au code Monte Carlo MCNP a la mesure in vivo realiste des actinides dans les poumons et les plaies contaminees

    Energy Technology Data Exchange (ETDEWEB)

    Noelle, P

    2006-12-15

    In vivo lung counting, one of the preferred methods for monitoring people exposed to the risk of actinide inhalation, is nevertheless limited by the use of physical calibration phantoms which, for technical reasons, can only provide a rough representation of human tissue. A new approach to in vivo measurements has been developed to take advantage of advances in medical imaging and computing; this consists of numerical phantoms based on tomographic images (CT) or magnetic resonance images (R.M.I.) combined with Monte Carlo computing techniques. Under laboratory implementation of this innovative method using specific software called O.E.D.I.P.E., the main thrust of this thesis was to provide answers to the following question: what do numerical phantoms and new techniques like O.E.D.I.P.E. contribute to the improvement in calibration of low-energy in vivo counting systems? After a few developments of the O.E.D.I.P.E. interface, the numerical method was validated for systems composed of four germanium detectors, the most widespread configuration in radio bioassay laboratories (a good match was found, with less than 10% variation). This study represents the first step towards a person-specific numerical calibration of counting systems, which will improve assessment of the activity retained. A second stage focusing on an exhaustive evaluation of uncertainties encountered in in vivo lung counting was possible thanks to the approach offered by the previously-validated O.E.D.I.P.E. software. It was shown that the uncertainties suggested by experiments in a previous study were underestimated, notably morphological differences between the physical phantom and the measured person. Some improvements in the measurement procedure were then proposed, particularly new bio-metric equations specific to French measurement configurations that allow a more sensible choice of the calibration phantom, directly assessing the thickness of the torso plate to be added to the Livermore phantom

  4. Late Sequelae of Hip Septic Arthritis in Children

    Directory of Open Access Journals (Sweden)

    Shirin Mardookhpour

    2012-07-01

    Full Text Available Septic arthritis of the hip in children has multiple sequelae and may result in severe disability. Significant morbidity can be prevented by early recognition and treatment. The authors reviewed 13 children with 14 hips with sequelae of septic arthritis of the hip. All of children had history of hip septic arthritis before age of 4 years. Six were male subjects, and 7 were female subjects. We evaluated the history, clinical findings and radiographs of all children who had been treated at the Imam Khomeini hospital between 1986 and 2001 for septic arthritis of the hip. Final results of operations in patients include range of motion, presence or absence pain, joint stability, limb-length discrepancy were assessed. Three hips had mild pain in usual daily activities and one patient with cerebral palsy experienced hip instability. Most of patients (80% had flexion contracture about 10-15 degrees .Final results showed average limb length discrepancy was about 2.8 cm. Septic arthritis of the hip in children may result in a spectrum of residual problems and the significant complications can be averted by early detection and treatment. Treatment in younger age cause better outcome.

  5. Septic wastewater treatment using recycled rubber particles as biofiltration media.

    Science.gov (United States)

    Oh, Jin Hwan; Park, Jaeyoung; Ellis, Timothy G

    2014-01-01

    Performance of the laboratory-scale recycled rubber particles (RRP) biofilter was compared to a conventional gravel system and a peat biofilter for treatment of septic tank effluent. During the study, the RRP biofilter provided similar or better performance than other systems in terms of organic removal and hydraulic capacity. After the start-up period, RRP biofilter achieved removal efficiencies for BOD5, total suspended solids (TSS), ammonia nitrogen of 96%, 93%, and 90%, respectively, over the range of hydraulic loading rates of 57-204 L/m2/d. On the other hand, the peat biofilter failed hydraulically and the gravel system showed high TSS concentrations in the effluent. RRP provided high surface area and sufficient time for biological treatment. In addition, RRP was observed to provide ammonia adsorption capacity. The results showed that RRP has the potential to be used as substitutes for natural aggregate such as gravel in septic system drainfields. The RRP biofilter can be used as alternative septic systems for the sites where an existing septic system has failed or site conditions, such as high groundwater table or small lot size, are not suitable for the installation of conventional septic systems.

  6. Gender differences in septic intensive care unit patients.

    Science.gov (United States)

    Campanelli, Francesco; Landoni, Giovanni; Cabrini, Luca; Zangrillo, Alberto

    2017-12-13

    The world population is mostly male at birth, although there is a shift in predominance over 55 years of age with more females than males. Male gender was recently hypothesized to be a risk factor for sepsis and septic shock; the reasons and the consequences of this odd discrepancy are yet a matter of debate. We investigated the percentage of males and females in a large number of trials performed on septic adult patients admitted to Intensive Care Units. We analysed all the multicentre randomized controlled trials ever published in peer-reviewed Journals reporting a significant effect on mortality in intensive care unit septic adult patients; furthermore, we retrieved all the manuscripts dealing with sepsis or septic shock patients published in the last 3 years in the three medical Journals with the highest impact factor. We analysed data from 12 multicentre randomized controlled trials (for a total of 5080 patients, 61% males) and from further 22 trials published in the New England Journal of Medicine, the Lancet, and the Journal of the American Medical Association (for a total of 493,066 patients, 54% males). Data on gender ratio in survivors were not available. Data from 34 large studies on 498,146 septic adult patients clearly showed a prevalence of males despite the expected female predominance. Further studies are required to explain the reasons, to evaluate if a difference is present in survival rate, and to identify gender-tailored preventive measures and treatments.

  7. In vivo activation of a T helper 2-driven innate immune response in lung fibrosis induced by multi-walled carbon nanotubes.

    Science.gov (United States)

    Dong, Jie; Ma, Qiang

    2016-09-01

    Pulmonary exposure to certain forms of carbon nanotubes (CNT) induces fibrosing lesions in the lungs that manifest an acute inflammation followed by chronic interstitial fibrosis. The mechanism of CNT-induced fibrogenesis is largely unknown. The biphasic development with drastically distinct pathologic manifestations suggests a junction of acute-to-chronic transition. Here we analyzed the molecular pathways and regulators underlying the pathologic development of CNT-induced lung fibrosis. Mice were exposed to multi-walled CNT (MWCNT; XNRI MWNT-7, Mitsui; 40 μg) by pharyngeal aspiration for 7 days along with vehicle and carbonaceous controls. Genome-wide microarray analyses of the lungs identified a range of differentially expressed genes that potentially function in the acute-to-chronic transition through pathways involving immune and inflammatory regulation, responses to stress and extracellular stimuli, and cell migration and adhesion. In particular, a T helper 2 (Th2)-driven innate immune response was significantly enriched. We then demonstrated that MWCNT induced the expression of Th2 cytokines interleukin (IL)-4 and IL-13, and a panel of signature downstream genes, such as Il4i1, Chia, and Ccl11/Eotaxin, time dependently. Induction of Th2 cytokines took place in CD4+ T lymphocytes indicating activation of Th2 cells. Furthermore, induction involved activation of a Th2 cell-specific signaling pathway through phosphorylation of STAT6 and up-regulation of GATA-3 to mediate the transcription of Th2 target genes. Our study uncovers activation of a Th2-driven immune/inflammatory response during pulmonary fibrosis development induced by MWCNT. The findings provide novel insights into the molecular events that control the transition from an acute inflammatory response to chronic fibrosis through Th2 functions in CNT-exposed lungs.

  8. Arthroscopic management of native shoulder septic arthritis.

    Science.gov (United States)

    Abdel, Matthew P; Perry, Kevin I; Morrey, Mark E; Steinmann, Scott P; Sperling, John W; Cass, Joseph R

    2013-03-01

    There is little information on the results of arthroscopic treatment of native shoulder sepsis. Therefore, the purpose of this study was to determine the presentation, preoperative indices, intraoperative findings, and outcomes related to native shoulder sepsis treated with arthroscopy. We retrospectively reviewed 50 consecutive native shoulders with septic arthritis between 1994 and 2008. Patients (75% male) were an average age of 66 years. Four patients had bilateral involvement. All underwent arthroscopic irrigation and debridement. The mean follow-up was 31 months (range, 1-185 months). Patients were immunocompromised in 57% of cases. The mean preoperative values (normal reference ranges) included white blood cell count, 13 × 10(9)/L (3.5-10.5 × 10(9)/L); erythrocyte sedimentation rate, 66 mm/h (0-29 mm/h), and C-creative protein, 83 mg/L (0-10 mg/L). The average aspiration cell count was 110,988, with a mean differential of 87% neutrophils. The most common organisms were methicillin-susceptible Staphylococcus aureus (44%). Repeat irrigation and debridement was required within the first month in 16 of 50 shoulders (32%). Within 1 year, 17% of patients had died. Final Gächter staging was I or II for 32 shoulders and III or IV for 18 shoulders. Most patients with native shoulder sepsis are elderly and immunocompromised and present with increased inflammatory markers and a supporting aspiration cell count. Patients and surgeons must be aware that after initial arthroscopy, 1 in 3 patients will require additional surgical intervention, whether anticipated or not. Level IV, Case Series, Treatment Study. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  9. Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis.

    Science.gov (United States)

    O'Brien, Andrew J; Villani, Linda A; Broadfield, Lindsay A; Houde, Vanessa P; Galic, Sandra; Blandino, Giovanni; Kemp, Bruce E; Tsakiridis, Theodoros; Muti, Paola; Steinberg, Gregory R

    2015-07-15

    Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin (100 μM) and eliminated in mouse embryonic fibroblasts (MEFs) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted. © 2015 Authors; published by Portland Press Limited.

  10. Attenuation of the DNA Damage Response by Transforming Growth Factor-Beta Inhibitors Enhances Radiation Sensitivity of Non–Small-Cell Lung Cancer Cells In Vitro and In Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Du, Shisuo; Bouquet, Sophie; Lo, Chen-Hao; Pellicciotta, Ilenia; Bolourchi, Shiva [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Parry, Renate [Varian Medical Systems, Palo Alto, California (United States); Barcellos-Hoff, Mary Helen, E-mail: mhbarcellos-hoff@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States)

    2015-01-01

    Purpose: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non–small-cell lung carcinoma (NSCLC) cells in vitro and in vivo. Methods and Materials: TGF-β–mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure. The DNA damage response was assessed by ataxia telangiectasia mutated (ATM) or Trp53 protein phosphorylation, γH2AX foci formation, or comet assay in irradiated cells. Radiation sensitivity was determined by clonogenic assay. Mice bearing syngeneic subcutaneous LLC tumors were treated with 5 fractions of 6 Gy and/or neutralizing or control antibody. Results: The NCI-H1299, A549, and LLC NSCLC cell lines pretreated with LY364947 before radiation exposure exhibited compromised DNA damage response, indicated by decreased ATM and p53 phosphorylation, reduced γH2AX foci, and increased radiosensitivity. The NCI-H292 cells were unresponsive. Transforming growth factor-β signaling inhibition in irradiated LLC cells resulted in unresolved DNA damage. Subcutaneous LLC tumors in mice treated with TGF-β neutralizing antibody exhibited fewer γH2AX foci after irradiation and significantly greater tumor growth delay in combination with fractionated radiation. Conclusions: Inhibition of TGF-β before radiation attenuated DNA damage recognition and increased radiosensitivity in most NSCLC cells in vitro and promoted radiation-induced tumor control in vivo. These data support the rationale for concurrent TGF-β inhibition and RT to provide therapeutic benefit in NSCLC.

  11. Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Tripti Singh

    Full Text Available Lung cancer remains the leading cause of cancer-related deaths worldwide, and non-small cell lung cancer (NSCLC represents approximately 80% of total lung cancer cases. The use of non-toxic dietary phytochemicals can be considered as a chemotherapeutic strategy for the management of the NSCLC. Here, we report that grape seed proanthocyanidins (GSPs induce apoptosis of NSCLC cells, A549 and H1299, in vitro which is mediated through increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic proteins Bcl2 and Bcl-xl, disruption of mitochondrial membrane potential, and activation of caspases 9, 3 and poly (ADP-ribose polymerase (PARP. Pre-treatment of A549 and H1299 cells with the caspase-3 inhibitor (z-DEVD-fmk significantly blocked the GSPs-induced apoptosis of these cells confirmed that GSPs-induced apoptosis is mediated through activation of caspases-3. Treatments of A549 and H1299 cells with GSPs resulted in an increase in G1 arrest. G0/G1 phase of the cell cycle is known to be controlled by cyclin dependent kinases (Cdk, cyclin-dependent kinase inhibitors (Cdki and cyclins. Our western blot analyses showed that GSPs-induced G1 cell cycle arrest was mediated through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27, and a simultaneous decrease in the levels of Cdk2, Cdk4, Cdk6 and cyclins. Further, administration of 50, 100 or 200 mg GSPs/kg body weight of mice by oral gavage (5 d/week markedly inhibited the growth of s.c. A549 and H1299 lung tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death, increased expression of Bax, reduced expression of anti-apoptotic proteins and activation of caspase-3 in tumor xenograft cells. Based on the data obtained in animal study, human equivalent dose of GSPs was calculated, which seems affordable and attainable. Together, these results suggest that GSPs may represent a potential therapeutic agent for the non

  12. Growth kinetics and in vivo radiosensitivity in nude mice of two subpopulations derived from a single human small cell carcinoma of the lung

    DEFF Research Database (Denmark)

    Spang-Thomsen, M; Clerici, M; Engelholm, S A

    1986-01-01

    , and by the cell cycle distribution changes monitored by FCM. The results showed that the tumors differed in the in vivo radiosensitivity despite similarities in the growth kinetics. The results support the concept that difference in sensitivity among tumor subpopulations is an important reason for therapeutic...

  13. Metabolomics as a Novel Approach for Early Diagnosis of Pediatric Septic Shock and Its Mortality

    OpenAIRE

    Mickiewicz, Beata; Vogel, Hans J.; Wong, Hector R.; Winston, Brent W.

    2013-01-01

    Rationale: Septic shock is a significant cause of morbidity and mortality in the pediatric population. Early recognition of septic shock and appropriate treatment increase survival rate; thus, developing new diagnostic tools may improve patients’ outcomes.

  14. Similar Microcirculatory Alterations in Patients with Normodynamic and Hyperdynamic Septic Shock

    NARCIS (Netherlands)

    Edul, Vanina S. Kanoore; Ince, Can; Vazquez, Alejandro Risso; Rubatto, Paolo N.; Espinoza, Emilio D. Valenzuela; Welsh, Sebastián; Enrico, Carolina; Dubin, Arnaldo

    2016-01-01

    Rationale: In normodynamic septic shock, the quantitative assessment of sublingual microcirculation has shown decreases in perfused vascular density and red blood cell velocity. However, no studies have been performed in hyperdynamic septic shock. Objectives: To characterize the microcirculatory

  15. Role of echocardiography in reducing shock reversal time in pediatric septic shock: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ahmed A. EL‐Nawawy

    2018-01-01

    Conclusion: Serial echocardiography provided crucial data for early recognition of septic myocardial dysfunction and hypovolemia that was not apparent on clinical assessment, allowing a timely management and resulting in shock reversal time reduction among children with septic shock.

  16. Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo.

    Science.gov (United States)

    Singh, Tripti; Prasad, Ram; Katiyar, Santosh K

    2013-01-01

    Non-small-cell lung cancer (NSCLC) represents approximately 80% of all types of lung cancer. Here, we report the chemotherapeutic effect of honokiol, a phytochemical from Magnolia grandiflora, on NSCLC cells and the molecular mechanisms underlying these effects using in vitro and in vivo models. Treatment of NSCLC cells (A549, H1299, H460 and H226) with honokiol (20, 40 and 60 µM) inhibited histone deacetylase (HDAC) activity, reduced the levels of class I HDAC proteins and enhanced histone acetyltransferase activity in a dose-dependent manner. These effects of honokiol were associated with a significant reduction in the viability of NSCLC cells. Concomitant treatment of cells with a proteasome inhibitor, MG132, prevented honokiol-induced degradation of class I HDACs, suggesting that honokiol reduced the levels of HDACs in NSCLC cells through proteasomal degradation. Valproic acid, an inhibitor of HDACs, exhibited a similar pattern of reduced viability and induction of death of NSCLC cells. Treatment of A549 and H1299 cells with honokiol resulted in an increase in G 1 phase arrest, and a decrease in the levels of cyclin D1, D2 and cyclin dependent kinases. Further, administration of honokiol by oral gavage significantly inhibited the growth of subcutaneous A549 and H1299 tumor xenografts in athymic nude mice, which was associated with the induction of apoptotic cell death and marked inhibition of class I HDACs proteins and HDAC activity in the tumor xenograft tissues. Together, our study provides new insights into the role of class I HDACs in the chemotherapeutic effects of honokiol on lung cancer cells.

  17. Septic systems as hot-spots of pollutants in the environment: Fate and mass balance of micropollutants in septic drainfields.

    Science.gov (United States)

    Yang, Yun-Ya; Toor, Gurpal S; Wilson, P Chris; Williams, Clinton F

    2016-10-01

    Septic systems, a common type of onsite wastewater treatment systems, can be an important source of micropollutants in the environment. We investigated the fate and mass balance of 17 micropollutants, including wastewater markers, hormones, pharmaceuticals and personal care products (PPCPs) in the drainfield of a septic system. Drainfields were replicated in lysimeters (1.5m length, 0.9m width, 0.9m height) and managed similar to the field practice. In each lysimeter, a drip line dispersed 9L of septic tank effluent (STE) per day (equivalent to 32.29L/m(2) per day). Fourteen micropollutants in the STE and 12 in the leachate from drainfields were detected over eight months. Concentrations of most micropollutants in the leachate were low (85% of the added micropollutants except for sucralose were attenuated in the drainfield. We discovered that sorption was the key mechanism for retention of carbamazepine and partially for sulfamethoxazole, whereas microbial degradation likely attenuated acetaminophen in the drainfield. This data suggests that sorption and microbial degradation limited transport of micropollutants from the drainfields. However, the leaching of small amounts of micropollutants indicate that septic systems are hot-spots of micropollutants in the environment and a better understanding of micropollutants in septic systems is needed to protect groundwater quality. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Dispatch and prehospital transport for acute septic patients

    DEFF Research Database (Denmark)

    Pedersen, Peter Bank; Henriksen, Daniel Pilsgaard; Mikkelsen, Søren

    2017-01-01

    with a suboptimal mode of transport. Patients with severe sepsis or septic shock suffer from highly time dependent conditions but they present with a wide range of symptoms, which might be difficult to identify in the dispatch system. The aim of the study is to investigate the modes of prehospital transport among...... acute admitted patients with sepsis, severe sepsis and septic shock. METHODS: We included all adult patients (≥15 years) presenting to an acute medical unit at Odense University Hospital with a first-time admission of community-acquired sepsis between September 2010-August 2011. Cases and prehospital...... (36.3%) had sepsis, 1,071 (62.5%) severe sepsis, and 21 (1.2%) septic shock. In the group of sepsis patients, 390 (62.8%) arrived without public prehospital transport, 197 (31.7%) were transported by ambulance, and 34 (5.5%) were assisted by MECU. In the group of severe sepsis patients, the same...

  19. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

    2014-01-01

    BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established. METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care...... unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay...... were similar in the two intervention groups. CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion...

  20. Septic arthritis in a native knee due to Corynebacterium striatum.

    Science.gov (United States)

    Molina Collada, Juan; Rico Nieto, Alicia; Díaz de Bustamante Ussia, Macarena; Balsa Criado, Alejandro

    2017-03-07

    We describe a case of septic arthritis in a native knee due to Corynebacterium striatum, gram-positive bacilli that are usually commensal organisms of skin and mucosal membranes, but are seldom implicated in native septic arthritis. An 84-year-old man with Corynebacterium striatum septic arthritis of his native left knee and no response to conventional antibiotic therapy. Thus, the patient was allowed to take dalbavancin for compassionate use, with an excellent clinical outcome. This case emphasizes de role of Corynebacterium striatum in native joint infections and highlights the importance of early detection and appropriate treatment in improving the clinical outcome. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  1. The majority of patients in septic shock are transfused with fresh-frozen plasma

    DEFF Research Database (Denmark)

    Reiter, Nanna; Wesche, Nikolaj; Perner, Anders

    2013-01-01

    Fresh-frozen plasma (FFP) transfusion may be widely used in patients in septic shock, but the use is not well-described. Our aim was to describe the current use of FFP transfusion in medical patients with septic shock.......Fresh-frozen plasma (FFP) transfusion may be widely used in patients in septic shock, but the use is not well-described. Our aim was to describe the current use of FFP transfusion in medical patients with septic shock....

  2. Control groups in recent septic shock trials: a systematic review.

    Science.gov (United States)

    Pettilä, Ville; Hjortrup, Peter Buhl; Jakob, Stephan M; Wilkman, Erika; Perner, Anders; Takala, Jukka

    2016-12-01

    The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials. We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting. A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care. Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

  3. Septic arthritis and bursitis: emergency ultrasound can facilitate diagnosis.

    Science.gov (United States)

    Costantino, Thomas G; Roemer, Benjamin; Leber, Ernest H

    2007-04-01

    This article reports the case of a 52-year-old woman with septic arthritis and bursitis of her shoulder. Due to a minor musculoskeletal injury and lack of fever, the diagnosis was missed on her first Emergency Department visit. Sonographic guidance of the shoulder arthrocentesis led to successful aspiration of the larger fluid collection in the subacromial bursa and allowed the diagnosis and treatment to proceed more rapidly. Septic arthritis is a challenging clinical diagnosis, and when it occurs in more difficult to aspirate joints, the diagnosis can become more challenging still. Ultrasound provides a means for the emergency physician to establish the diagnosis more readily.

  4. A natural chalcone induces apoptosis in lung cancer cells: 3D-QSAR, docking and an in vivo/vitro assay

    OpenAIRE

    Chen, Gang; Zhou, Di; Li, Xue-Zheng; Jiang, Zhe; Tan, Chengyu; Wei, Xiu-Yan; Ling, Junhong; Jing, Jing; Liu, Fen; Li, Ning

    2017-01-01

    This study was to study the antitumor effect of lonchocarpin (34) from traditional herbal medicine Pongamia pinnata (L.) Pierre and to reveal the underlying mechanism. The cytotoxic activities of lonchocarpin were evaluated in 10 lung cancer cell lines and it exhibited 97.5% activity at a dose of 100??M in the H292 cell line. A field-based quantitative structure-activity relationship (3D-QSAR) study of 37 flavonoids from P. pinnata was also performed, and the results obtained showed that the ...

  5. Bilateral Acromioclavicular Septic Arthritis as an Initial Presentation of Streptococcus pneumoniae Endocarditis

    Directory of Open Access Journals (Sweden)

    Neda Hashemi-Sadraei

    2014-01-01

    Full Text Available Infective endocarditis (IE is infrequently associated with septic arthritis. Moreover, septic arthritis of the acromioclavicular (AC joint is rarely reported in the literature. We report a case of Streptococcus pneumoniae IE in a patient who presented with bilateral AC joint septic arthritis and we review the literature on the topic.

  6. Bilateral Acromioclavicular Septic Arthritis as an Initial Presentation of Streptococcus pneumoniae Endocarditis

    OpenAIRE

    Hashemi-Sadraei, Neda; Gupta, Rohan; Machicado, Jorge D.; Govindu, Rukma

    2014-01-01

    Infective endocarditis (IE) is infrequently associated with septic arthritis. Moreover, septic arthritis of the acromioclavicular (AC) joint is rarely reported in the literature. We report a case of Streptococcus pneumoniae IE in a patient who presented with bilateral AC joint septic arthritis and we review the literature on the topic.

  7. The impact of septic systems density and nearness to spring water ...

    African Journals Online (AJOL)

    The improper use of onsite sanitation facilities such as latrines and septic systems may lead to groundwater contamination. It is true that drain field of septic system located too close to water point, and or over population of the septic systems in a small area can lead to pollution of groundwater. Our study investigated the ...

  8. Salidroside ameliorates sepsis-induced acute lung injury and mortality via downregulating NF-κB and HMGB1 pathways through the upregulation of SIRT1.

    Science.gov (United States)

    Lan, Kuo-Cheng; Chao, Sung-Chuan; Wu, Hsiao-Yi; Chiang, Chia-Lien; Wang, Ching-Chia; Liu, Shing-Hwa; Weng, Te-I

    2017-09-20

    Sepsis is a life-threatening medical condition. Salidroside, a substance isolated from Rhodiola rosea, possesses antioxidant and anti-inflammatory properties. The effect and mechanism of salidroside on sepsis-induced acute lung injury still remains to be well clarified. Here, we investigated the effect and mechanism of salidroside on septic mouse models and explored the role of salidroside-upregulated SIRT1. Salidroside inhibited the inflammatory responses and HMGB1 productions in bacterial lipopolysaccharide (LPS)-treated macrophages and mice. Salidroside could also reverse the decreased SIRT1 protein expression in LPS-treated macrophages and mice. Salidroside also alleviated the sepsis-induced lung edema, lipid peroxidation, and histopathological changes and the mortality, and improved the lung PaO2/FiO2 ratio in cecal ligation and puncture (CLP)-induced septic mice. Salidroside significantly decreased the serum TNF-α, IL-6, NO, and HMGB1 productions, pulmonary inducible NO synthase (iNOS) and phosphorylated NF-κB-p65 protein expressions, and pulmonary HMGB1 nuclear translocation in CLP septic mice. Moreover, sepsis decreased the SIRT1 protein expression in the lungs of CLP septic mice. Salidroside significantly upregulated the SIRT1 expression and inhibited the inflammatory responses in CLP septic mouse lungs. These results suggest that salidroside protects against sepsis-induced acute lung injury and mortality, which might be through the SIRT1-mediated repression of NF-κB activation and HMGB1 nucleocytoplasmic translocation.

  9. Ativação da proteína TGFbetaI latente em pulmão irradiado in vivo Latent TGFbeta1 activation in the lung irradiated in vivo

    Directory of Open Access Journals (Sweden)

    MARCOS DUARTE MATTOS

    2002-12-01

    Full Text Available OBJETIVO: Investigar no pulmão, por imunohistoquímica, a localização das proteínas TGFbeta1 latente e TGFbeta1 ativa, se ocorre ativação radioinduzida da proteína TGFbeta1 latente e a distribuição das fibras colágenas em diversos períodos de tempo após irradiação. MÉTODOS: 32 camundongos isogênicos (C57BL foram divididos em dois grupos: GI (não irradiado com 12 animais e GII (irradiado com 20 animais. Os animais do GII receberam radiação gama (telecobaltoterapia, 60Co, com rendimento de 0,97Gy/min, dose única de 7Gy em corpo inteiro. Os camundongos dos grupos I e II foram sacrificados por estiramento cervical nos períodos de 1, 14, 30 e 90 dias após irradiação. RESULTADOS: Os pulmões irradiados apresentaram: 1 congestão vascular e espessamento dos septos alveolares aos 30 dias e mais intensamente aos 90 dias depois da irradiação; 2 aumento significante da deposição de colágeno em todos os períodos de tempo após irradiação; 3 fraca ativação da proteína TGFbeta1 latente em um dia e intensa aos 14 dias depois da irradiação em brônquios e alvéolos. Nossos resultados sugerem que células dos brônquios e alvéolos podem participar do complexo mecanismo de fibrose pulmonar radioinduzida atuando como fontes da proteína TGFbeta1 ativa.PURPOSE: assess the latent and active TGFb1 localization in the lung, whether or not radiation induces latent TGFbeta1 activation, and the distribution of collagen fibers in the irradiated lung. METHODS: Thirty two C57BL mice were randomly assigned in two groups: GI (non irradiated animals and GII (irradiated animals. The mice from GII received a single whole ¾ body radiation dose of 7Gy, using a 60Co source at a dose rate of 0.97 Gy/min. They were sacrificed by cervical dislocation at 1, 14, 30 and 90 days after radiation. RESULTS: The irradiated lungs showed: 1 vascular congestion and thickness of the alveolar septa 30 days and more intense 90 days after irradiation; 2

  10. Lung cancer

    Science.gov (United States)

    ... it is called metastatic cancer to the lung . Causes Lung cancer is the deadliest type of cancer for both ... under age 45. Cigarette smoking is the leading cause of lung cancer. The more cigarettes you smoke per day and ...

  11. Lung surgery

    Science.gov (United States)

    ... cavity, particularly after trauma Surgery to remove small balloon-like tissues (blebs) that cause lung collapse ( pneumothorax ) ... this surgery include: Failure of the lung to expand Injury to the lungs or blood vessels Need ...

  12. Microcirculatory monitoring in septic patients: Where do we stand?

    NARCIS (Netherlands)

    Gruartmoner, G.; Mesquida, J.; Ince, C.

    2017-01-01

    Microcirculatory alterations play a pivotal role in sepsis-related morbidity and mortality. However, since the microcirculation has been a "black box", current hemodynamic management of septic patients is still guided by nnacrocirculatory parameters. In the last decades, the development of several

  13. Septic arthritis and osteomyelitis due to Bordetella petrii.

    Science.gov (United States)

    Nogi, Masayuki; Bankowski, Matthew J; Pien, Francis D

    2015-03-01

    A case of Bordetella petrii septic arthritis and osteomyelitis in an elbow resulted from a dirt bike accident in Hawaii. Two months of intravenous antibiotics and repeated surgeries were required to cure this infection. Our case, and literature review, suggests that extended-spectrum penicillins, tetracycline, and trimethoprim-sulfamethoxazole are good treatment options. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Pattern of Microbial Flora in Septic Incomplete Abortion in Port ...

    African Journals Online (AJOL)

    Alasia Datonye

    ABSTRACT. Background: Septic abortion occurs when there is colonization of the upper genital tract by micro organisms following termination of pregnancy usually before the age of viability. This can result from ascending infections from the lower genital tract or direct inoculation of micro organisms from contaminated and ...

  15. Pattern of Microbial Flora in Septic Incomplete Abortion in Port ...

    African Journals Online (AJOL)

    Background: Septic abortion occurs when there is colonization of the upper genital tract by micro organisms following termination of pregnancy usually before the age of viability. This can result from ascending infections from the lower genital tract or direct inoculation of micro organisms from contaminated and poorly ...

  16. Actinomyces pyogenes septic arthritis in a diabetic farmer.

    LENUS (Irish Health Repository)

    Lynch, M

    2012-02-03

    We report a case of septic arthritis and osteomyelitis of the left ankle due to Actinomyces pyogenes in a diabetic farmer. Few confirmed human cases of A. pyogenes infection have been reported, partly because of inadequate identification of this bacterium. Bacteriological characteristics of the organism, which resembles Arcanobacterium haemolyticum, are described with a review of previous case reports.

  17. Enhanced attenuation of septic system phosphate in noncalcareous sediments.

    Science.gov (United States)

    Robertson, W D

    2003-01-01

    Review of phosphate behavior in four mature septic system plumes on similar textured sand has revealed a strong correlation between carbonate mineral content and phosphate concentrations. A plume on calcareous sand (Cambridge site, 27 wt % CaCO3 equiv.) has proximal zone PO4 concentrations (4.8 mg/L P average) that are about 75% of the septic tank effluent value, whereas three plumes on noncalcareous sand (Muskoka, L. Joseph, and Nobel sites, effluent values. Phosphate attenuation at the noncalcareous sites appears to be an indirect result of the development of acidic conditions (site average pH 3.5 to 5.9) and elevated Al concentrations (up to 24 mg/L), which subsequently causes the precipitation of Al-P minerals such as variscite (AlPO4 x 2H2O). This is supported by scanning electron microscope analyses, which show the widespread occurrence of (Al+P)--rich secondary mineral coatings on sand grains below the infiltration beds. All of these septic systems are more than 10 years old, indicating that these attenuation reactions have substantial longevity. A field lysimeter experiment demonstrated that this reaction sequence can be readily incorporated into engineered waste water treatment systems. We feel this important P removal mechanism has not been adequately recognized, particularly for its potential significance in reducing P loading from septic systems in lakeshore environments.

  18. Endogenous IL-10 protects mice from death during septic peritonitis

    NARCIS (Netherlands)

    van der Poll, T.; Marchant, A.; Buurman, W. A.; Berman, L.; Keogh, C. V.; Lazarus, D. D.; Nguyen, L.; Goldman, M.; Moldawer, L. L.; Lowry, S. F.

    1995-01-01

    IL-10 production during endotoxic shock is part of a protective mechanism that involves IL-10-induced inhibition of TNF synthesis. We sought to determine the role of IL-10 in septic peritonitis induced by cecal ligation and puncture (CLP). CLP led to a rapid induction of IL-10 mRNA in various organs

  19. Nocardia Septic Arthritis Complicating an Anterior Cruciate Ligament Repair

    OpenAIRE

    Yong, Elaine X. L.; Cheong, Elaine Y.L.; Boutlis, Craig S.; Chen, Darren B.; Liu, Eunice Y.-T.; McKew, Genevieve L.

    2015-01-01

    Nocardia infection following anterior cruciate ligament (ACL) allograft reconstruction is a rare occurrence. We report a case of Nocardia infection of an allograft ACL reconstruction and septic arthritis of the knee joint due to an organism most similar to the novel Nocardia species Nocardia aobensis.

  20. Childhood Pyogenic Septic Arthritis as Seen in a Teaching Hospital ...

    African Journals Online (AJOL)

    Its pattern of presentation that varies from and within subregions has implications on the early recognition, treatment, and outcome. ..... MUA* + physiotherapy. 1. 2.3. Total. 44. 100. *MUA: Manipulation under anesthesia ... Septic shock. 4. 9.09. Joint stiffness. 4. 9.09. Pathologic dislocation (hip). 2. 4.55. Osteonecrosis. 1.

  1. Septic hip dislocations in children in a developing country | Ngom ...

    African Journals Online (AJOL)

    Purpose: To report on a radiological issue and therapeutic aspects encountered in septic hip dislocations in a developing country. Patients and Methods: Nineteen children among whom 11 boys and 8 girls aged on average 5.3-years old presented 7 recent and 12 late hip dislocations. Those dislocations were distributed ...

  2. Retainment of the antimicrobial agent triclosan in a septic tank

    DEFF Research Database (Denmark)

    Kirjanova, Ala; Rimeika, Mindaugas; Vollertsen, Jes

    2014-01-01

    Laboratory experiments were conducted to investigate the fate of the antimicrobial agent triclosan (TCS) in a conventional septic tank. The main mechanism of TCS removal from wastewater was identified to be rapid TCS sorption to suspended particles followed by settling of these particles...

  3. Childhood Pyogenic Septic Arthritis as Seen in a Teaching Hospital ...

    African Journals Online (AJOL)

    2017-05-18

    May 18, 2017 ... osteomyelitis in the metaphyseal ends of long bones, penetrating and open joint injuries as well as surgical instrumentations.[4,5] Irreversible damage to the articular cartilage by bacteria toxins, proteases from the synovial cells, and chondrocytes in addition to accumulated pus. Introduction. Septic arthritis ...

  4. Septic Abortion Managed in a Tertiary Hospital in West Bengal

    African Journals Online (AJOL)

    endotoxic shock or jaundice or acute renal failure. Statistical analysis was done by using Epi Info™ software (Version 3.5.1,. CDC) after proper arrangement of all the data in tabular form and presented as simple percentage. Results: During the period,. 1297 cases of abortion were admitted among which 107 were septic ...

  5. Adrenal insufficiency in critically ill septic patients at Dr George ...

    African Journals Online (AJOL)

    Rationale: Adrenal insufficiency occurs with varying frequency in critically ill patients. It is usually associated with a high mortality and poor clinical outcome. Objective: To determine the incidence of adrenal failure in patients with severe sepsis and septic shock admitted to our intensive care unit. Design: Prospective ...

  6. Norepinephrine in septic shock : when and how much?

    NARCIS (Netherlands)

    Hamzaoui, Olfa; Scheeren, Thomas W L; Teboul, Jean-Louis

    Purpose of reviewNorepinephrine is the first-line agent recommended during resuscitation of septic shock to correct hypotension due to depressed vascular tone. Important clinical issues are the best timing to start norepinephrine, the optimal blood pressure target, and the best therapeutic options

  7. Adrenal insufficiency in critically ill septic patients at Dr George ...

    African Journals Online (AJOL)

    Adele

    patients with septic shock.5 It is important to recognize these patients since this disorder has a high mortality if untreated.6. The most common cause of adrenal insufficiency in critically ill patients is sepsis and the systemic inflammatory response syndrome (SIRS).5,7 This is presumably due to the circulating suppressive ...

  8. Septic Arthritis of The Hip Joint presenting as Acute Abdomen ...

    African Journals Online (AJOL)

    Septic arthritis of the hip joint in two children, originally thought to be cases of acute abdomen is presented. In one case, the discovery of extra-peritoneal purulent fluid at surgery, obviated the need for laparotomy and in the other, the true nature of the disease became apparent one week after laparotomy. These cases ...

  9. Nocardia Septic Arthritis Complicating an Anterior Cruciate Ligament Repair.

    Science.gov (United States)

    Yong, Elaine X L; Cheong, Elaine Y L; Boutlis, Craig S; Chen, Darren B; Liu, Eunice Y-T; McKew, Genevieve L

    2015-08-01

    Nocardia infection following anterior cruciate ligament (ACL) allograft reconstruction is a rare occurrence. We report a case of Nocardia infection of an allograft ACL reconstruction and septic arthritis of the knee joint due to an organism most similar to the novel Nocardia species Nocardia aobensis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Pylephlebitis and Crohn's disease: A rare case of septic shock.

    Science.gov (United States)

    Scaringi, Stefano; Giudici, Francesco; Gabbani, Giacomo; Zambonin, Daniela; Morelli, Marco; Carrà, Rossella; Bechi, Paolo

    2017-08-10

    Troncular pylephlebitis, defined as septic thrombophlebitis of the portal vein, is usually secondary to suppurative infection from the regions drained by the portal system. Therefore, pylephlebitis can occur from the portal vein main tributaries. The occurrence of mesenteric pylephlebitis in Crohn's disease is extremely rare. We describe a case of septic shock due to mesenteric pylephlebitis in a 47 years old male affected with Crohn's disease. The patient was admitted to the emergency department after he had been complained from 3h of a peri-umbilical abdominal pain associated to fever and shivering quickly followed by a severe hypotension. His medical history included histologically confirmed ileal Crohn's disease diagnosed 4 years before and treated with mesalamine only. Computed tomography scan confirmed the mesenteric pylephlebitis diagnosis. After medical therapy with antibiotics and systemic nutrition, the patient was successfully operated to treat his ileal Crohn's disease. In our case, the quick onset of a septic shock was not due to a peritonitis complicating a Crohn's disease, but to a rare condition not needing an urgent surgical resolution. This report shows that, even in Crohn's disease, once diagnosis is performed, antibiotic therapy associated to enteral and parenteral nutrition can lead to a complete clinical remission of mesenteric pylephlebitis, mandatory to perform an elective surgery. This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn's disease patient who is not showing clinical signs of peritonitis. Copyright © 2017. Published by Elsevier Ltd.

  11. A Rational Approach to Septic Tank Design | Nnaji | Nigerian ...

    African Journals Online (AJOL)

    A new approach to the design of septic tanks was developed based on a number of critical parameters, namely: residual detention time, minimum residual detention time, residual depth and minimum residual depth. This method involved rst specifying a desired desludging interval. This interval was then substituted in a ...

  12. Congenital candidiasis presenting as septic shock without rash

    Science.gov (United States)

    Carmo, Kathryn Browning; Evans, Nick; Isaacs, David

    2009-01-01

    Congenital candidiasis is rare and often benign. This report describes the case of twins born at 32 weeks of gestation with different manifestations of congenital candidiasis. One twin was born well though neutropenic, and died from overwhelming sepsis with septic shock at 22 h. The other twin presented with a delayed onset of rash at 2 days, remained well and survived. PMID:21686407

  13. In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue.

    OpenAIRE

    Baumgarth, N.; Kelso, A

    1996-01-01

    Influenza virus infection induces the local production of gamma interferon (IFN-gamma) by T cells and non-T cells in the respiratory tract. To elucidate the possible functions of this cytokine, the humoral and local cellular immune responses to influenza virus were studied in BALB/c mice with or without in vivo neutralization of IFN-gamma by using monoclonal antibodies. Neutralization of IFN-gamma led to a significant reduction in virus-specific titers of immunoglobulins G2a and G3 in serum b...

  14. Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study

    DEFF Research Database (Denmark)

    Varis, Elina; Pettilä, Ville; Poukkanen, Meri

    2017-01-01

    Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock...... surrogate endpoints for mortality in septic shock patients....

  15. Mortality predictors in renal transplant recipients with severe sepsis and septic shock.

    Directory of Open Access Journals (Sweden)

    Mônica Andrade de Carvalho

    Full Text Available INTRODUCTION: The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU with severe sepsis and septic shock. METHODS: Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality. RESULTS: A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51 ± 13 years (males, 115 [60.5%], and the median APACHE II was 20 (16-23. The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6-2.3] years. The lung was the most common infection site (59.5%. Upon ICU admission, 16.4% of the patients had ≤ 1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥ 2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7-19.6; p = 0.004, delta SOFA 24 h (OR = 1.7; 95% CI, 1.2-2.3; p = 0.001, mechanical ventilation (OR = 30; 95% CI, 8.8-102.2; p<0.0001, hematologic dysfunction (OR = 6.8; 95% CI, 2.0-22.6; p = 0.002, admission from the ward (OR = 3.4; 95% CI, 1.2-9.7; p = 0.02 and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9-16.6; p = 0.002. CONCLUSIONS: Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the

  16. Clinical characteristics and outcomes of community-acquired methicillin-resistant Staphylococcus aureus septic arthritis

    Directory of Open Access Journals (Sweden)

    Sian Yik Lim

    2017-01-01

    Full Text Available Objective: We investigated the clinical characteristics, treatment patterns and outcomes of community-acquired methicillin resistant Staphylococcus aureus (CA-MRSA septic arthritis. Methods: This was a retrospective chart review of CA-MRSA septic arthritis in a tertiary care hospital from 2000-2013. We compared CA-MRSA septic arthritis cases with HA-MRSA septic arthritis cases to identify important differences between the two groups. Results: We identified 11 cases of CA-MRSA septic arthritis and 34 cases of hospital-acquired methicillin-resistant SA (HA-MRSA septic arthritis. Community-acquired methicillin-resistant Staphylococcus aureus caused 25% of the MRSA septic arthritis cases. Community-acquired methicillin-resistant Staphylococcus aureus septic arthritis occurred in younger patients with fewer comorbidities or risk factors. There was no difference in initial presentation between CA-MRSA and HA-MRSA. Community-acquired methicillin-resistant Staphylococcus aureus patients were less likely to be treated with appropriate antibiotics initially. Community-acquired methicillin-resistant Staphylococcus aureus septic arthritis was associated with increased morbidity with a high percentage of patients developing poor joint outcomes or osteomyelitis complications.  Community-acquired methicillin-resistant Staphylococcus aureus septic arthritis was also associated with increased utilization of health care resources due to long hospital stays, high readmissions rates, and increased requirements for rehabilitation facility placement and home health support. There was no difference in mortality, poor joint outcome, readmissions, and osteomyelitis complications between CA-MRSA septic arthritis and HA-MRSA septic arthritis. Conclusions: Community-acquired methicillin-resistant Staphylococcus aureus septic arthritis is associated with increased morbidity and health care resource utilization. Increased awareness into CA-MRSA as a cause of septic

  17. Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models.

    Science.gov (United States)

    Shin, Woo-Young; Shim, Do-Wan; Kim, Myong-Ki; Sun, Xiao; Koppula, Sushruta; Yu, Sang-Hyeun; Kim, Han-Bi; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

    2017-06-09

    Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1β secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders. Copyright © 2017. Published by Elsevier B.V.

  18. Septic-embolic and septic-metabolic brain abscess; Septisch-embolischer und septisch-metastatischer Hirnabszess

    Energy Technology Data Exchange (ETDEWEB)

    Weber, W.; Henkes, H.; Kuehne, D. [Alfried-Krupp-Krankenhaus Essen (Germany). Klinik fuer Radiologie und Neuroradiologie; Felber, S. [Universitaetsklinik Innsbruck (Austria). Klinische Abt. der Radiologie I; Jaenisch, W. [Freie Univ. Berlin (Germany). Inst. fuer Neuropathologie; Woitalla, D. [Bochum Univ. (Germany). St. Josef-Hospital

    2000-11-01

    The hematogeneous spread of bacteria, fungi and protozoa may also reach the brain vessels, which happens mostly through septic emboli. >From such an embolus a metastatic focal encephalitis and later a septic-embolic brain abscess may arise. The most frequently underlying infections that may cause septic emboli are bacterial endocarditis as well as bacterial infections of artificial heart valve prostheses. Congenital heart malformations with a right-to-left shunt also play here a certain role. Basically, however, all septic conditions and bacteriemias may cause septic-embolic brain abscesses. They occur frequently as multiple lesions. MRI is superior to CT in depicting the different stages of evolution from focal encephalitis, through the hardly encapsulated early abscess, to the formation of a membrane and later a dense fibrous capsule. The medical treatment of a brain abscess requires properly performed CT or MRI follow-up examinations in order to realize early enough a possible growing of such a lesion. (orig.) [German] Die haemoatogene Ausbreitung von Bakterien, Pilzen oder Protozoen bis in die Hirngefaesse erfolgt meist durch eine septische Embolie. Es entstehen eine metastatische Herdenzephalitis und im weiteren Verlauf daraus ein septisch-embolischer Hirnabszess. Die haeufigste Grunderkrankung die zu septischen Embolien fuehrt, ist die bakterielle Endokarditis sowie die bakterielle Infektion von Herzklappenprothesen. Eine besondere Bedeutung kommt hier den angeborenen kardialen Fehlbildungen mit Rechts-Links-Shunt zu. Grundsaetzlich koennen jedoch alle Bakteriaemien zu septisch-embolischen Hirnabszessen fuehren. Septisch-embolische Hirnabszesse treten aufgrund ihres Entstehungsmechanismus haeufig multipel auf. Die CT und besser noch die MRT erlauben die Darstellung aller Entwicklungsstadien von der Herdenzephalitis ueber den kaum abgegrenzten Abszess, die Membranbildung bis zur Entstehung einer dicken, die eitergefuellte Hoehle allseits umgebenden

  19. The synergistic antitumor effects of all-trans retinoic acid and C-phycocyanin on the lung cancer A549 cells in vitro and in vivo.

    Science.gov (United States)

    Li, Bing; Gao, Mei-Hua; Chu, Xian-Ming; Teng, Lei; Lv, Cong-Yi; Yang, Peng; Yin, Qi-Feng

    2015-02-15

    The anticancer effects and mechanism of all-trans retinoic acid (ATRA), C-phycocyanin (C-PC) or ATRA+C-PC on the growth of A549 cells were studied in in vitro and in vivo experiments. The effects of C-PC and ATRA on the growth of A549 cells were determined. The expression of CDK-4 and caspase-3, and the cellular apoptosis levels were detected. The tumor model was established by subcutaneous injection of A549 cells to the left axilla of the NU/NU mice. The weights of tumor and the spleen were tested. The viabilities of T-cells and spleen cells, TNF levels, the expression of Bcl-2 protein and Cyclin D1 gene were examined. Results showed both C-PC and ATRA could inhibit the growth of tumor cells in vivo and in vitro. ATRA+C-PC cooperatively showed a higher antitumor activity. The dosage of ATRA was reduced when it was administered with C-PC together, and the toxicity was reduced as well. ATRA+C-PC could decrease CDK-4 but increase caspase-3 protein expression level and induce cell apoptosis. ATRA alone could lower the activities of T lymphocytes and spleen weights, but the combination with C-PC could effectively promote viability of T cells and spleen. C-PC+ATRA could up-regulate TNF, and down-regulate Bcl-2 and Cyclin D1 gene. The combination might inhibit tumor growth by inhibiting the progress of cell cycle, inducing cell apoptosis and enhancing the body immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Evolving Concepts in Lung Carcinogenesis

    Science.gov (United States)

    Gomperts, Brigitte N.; Spira, Avrum; Massion, Pierre P.; Walser, Tonya C.; Wistuba, Ignacio I.; Minna, John D.; Dubinett, Steven M.

    2012-01-01

    Lung carcinogenesis is a complex, stepwise process that involves the acquisition of genetic mutations and epigenetic changes that alter cellular processes, such as proliferation, differentiation, invasion, and metastasis. Here, we review some of the latest concepts in the pathogenesis of lung cancer and highlight the roles of inflammation, the “field of cancerization,” and lung cancer stem cells in the initiation of the disease. Furthermore, we review how high throughput genomics, transcriptomics, epigenomics, and proteomics are advancing the study of lung carcinogenesis. Finally, we reflect on the potential of current in vitro and in vivo models of lung carcinogenesis to advance the field and on the areas of investigation where major breakthroughs will lead to the identification of novel chemoprevention strategies and therapies for lung cancer. PMID:21500122

  1. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Dirk Schädler

    Full Text Available We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure.This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment, or no hemoperfusion (control. Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7.97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15. Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7% compared to the control group (26.0%; p = 0.039. The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9% when compared to the control group (16.3%. After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19.In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

  2. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: A randomized controlled trial.

    Science.gov (United States)

    Schädler, Dirk; Pausch, Christine; Heise, Daniel; Meier-Hellmann, Andreas; Brederlau, Jörg; Weiler, Norbert; Marx, Gernot; Putensen, Christian; Spies, Claudia; Jörres, Achim; Quintel, Michael; Engel, Christoph; Kellum, John A; Kuhlmann, Martin K

    2017-01-01

    We report on the effect of hemoadsorption therapy to reduce cytokines in septic patients with respiratory failure. This was a randomized, controlled, open-label, multicenter trial. Mechanically ventilated patients with severe sepsis or septic shock and acute lung injury or acute respiratory distress syndrome were eligible for study inclusion. Patients were randomly assigned to either therapy with CytoSorb hemoperfusion for 6 hours per day for up to 7 consecutive days (treatment), or no hemoperfusion (control). Primary outcome was change in normalized IL-6-serum concentrations during study day 1 and 7. 97 of the 100 randomized patients were analyzed. We were not able to detect differences in systemic plasma IL-6 levels between the two groups (n = 75; p = 0.15). Significant IL-6 elimination, averaging between 5 and 18% per blood pass throughout the entire treatment period was recorded. In the unadjusted analysis, 60-day-mortality was significantly higher in the treatment group (44.7%) compared to the control group (26.0%; p = 0.039). The proportion of patients receiving renal replacement therapy at the time of enrollment was higher in the treatment group (31.9%) when compared to the control group (16.3%). After adjustment for patient morbidity and baseline imbalances, no association of hemoperfusion with mortality was found (p = 0.19). In this patient population with predominantly septic shock and multiple organ failure, hemoadsorption removed IL-6 but this did not lead to lower plasma IL-6-levels. We did not detect statistically significant differences in the secondary outcomes multiple organ dysfunction score, ventilation time and time course of oxygenation.

  3. Medical image of the week: septic emboli

    Directory of Open Access Journals (Sweden)

    Malakkla N

    2014-09-01

    Full Text Available No abstract available. Article truncated at 150 words. A 46-year-old man was admitted with altered mental status. His past medical history included HIV/AIDS on HAART therapy, hepatitis B and C, non-Hodgkin's lymphoma (NHL, deep venous thrombosis with insertion of an inferior vena caval filter, and poly-substance abuse. Vitals revealed fever and tachycardia. On exam, he was lethargic and confused, and had bilateral crackles on lung auscultation. Computerized axial tomography (CT of the head was unremarkable and chest X-ray revealed patchy nodular infiltrates in the right upper lobe and bilateral lower lobes. Work up for an infectious cause was initiated including opportunistic infections and he was started on empiric antibiotics for pneumonia. On Day 2, his roommate who came to visit him, revealed that he was recently admitted in another hospital for headache and flu-like symptoms, and discharged with a peripherally inserted central catheter (PICC in place as he was scheduled for a positron emission tomography (PET the next ...

  4. N-terminal-pro-brain natriuretic peptide elevations in the course of septic and non-septic shock reflect systolic left ventricular dysfunction assessed by transpulmonary thermodilution

    Directory of Open Access Journals (Sweden)

    A.B. Johan Groeneveld

    2016-03-01

    Conclusions: In septic and non-septic shock, NT-proBNP elevations reflect systolic left ventricular dysfunction and are associated with a poor outcome. They may help recognition of cardiac dysfunction in shock and its management when invasive hemodynamic monitoring is not yet instituted.

  5. 24-Methyl-Cholesta-5,24(28-Diene-3β,19-diol-7β-Monoacetate Inhibits Human Small Cell Lung Cancer Growth In Vitro and In Vivo via Apoptosis Induction

    Directory of Open Access Journals (Sweden)

    Ting-Wen Chung

    2017-07-01

    Full Text Available 24-methyl-cholesta-5,24(28-diene-3β,19-diol-7β-monoacetate (MeCDDA is a natural steroid compound isolated from a wild-type soft coral (Nephthea erecta. The present study aimed to investigate the anti-small cell lung cancer (SCLC effects of MeCDDA in vitro and in vivo, as well as to elucidate its underlying mechanism. Our results indicated that H1688 and H146 cells show relevant sensitivity to MeCDDA, and the exposure to MeCDDA in SCLC cells caused dose-dependent growth inhibitory responses. In addition, MeCDDA treatment promoted cell apoptosis and increased the activities of caspases in H1688 cells, reducing the mitochondrial membrane potential and stimulating the release of cytochrome c into the cytosol. Along with the increase in Bax expression and reduction in Bcl-2, the MeCDDA treatment also significantly decreased Akt and mTOR phosphorylation. Finally, MeCDDA treatment in the mouse xenograft model of H1688 cells exhibited significant inhibition of tumor growth, corroborating MeCDDA as a potential pre-clinical candidate for the treatment of SCLC. Overall, our results demonstrate that the cytotoxic effects of MeCDDA towards H1688 and H146 cells, possibly through the activation of the mitochondrial apoptotic pathway and inhibition of the PI3K/Akt/mTOR pathway, merit further studies for its possible clinical application in chemotherapy.

  6. Comparison of prognostic value of N-terminal pro-brain natriuretic peptide in septic and non-septic intensive care patients.

    Science.gov (United States)

    Ozcan, Namik; Ozcan, Ayse; Kaymak, Cetin; Basar, Hulya; Kotanoglu, Mustafa; Kose, Bektas

    2017-03-01

    The aim of this study is to compare the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in septic and non-septic intensive care patients. Fifty consecutive patients admitted to the intensive care unit (ICU) were enrolled in either the septic or non-septic group according to the criteria in the International Sepsis Definitions Conference in 2001. Demographic and clinical data, procalcitonin and lactate levels at admission, and death within 28 days were registered. Five blood samples were collected from all patients for NT-proBNP measurements. Septic patients had higher APACHE II (19 (16.00-24.25) vs. 16 (13.00-18.25)), and SOFA (8 (5-10) vs. 6 (4-7)) scores (p care patients.

  7. Initial resuscitation and management of pediatric septic shock.

    Science.gov (United States)

    Martin, K; Weiss, S L

    2015-04-01

    The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function; 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications; and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock.

  8. Aquatic Plant/microbial Filters for Treating Septic Tank Effluent

    Science.gov (United States)

    Wolverton, B. C.

    1988-01-01

    The use of natural biological processes for treating many types of wastewater have been developed by NASA at the John C. Stennis Space Center, NSTL, Mississippi, during the past 15 years. The simplest form of this technology involves the use of aquatic plant/marsh filters for treatment of septic tank effluent. Septic tank effluent from single home units can be treated to advanced secondary levels and beyond by using a 37.2 sq m (400 sq ft) surface area washed gravel filter. This filter is generally 0.3 m (1 ft) deep with a surface cover of approximately 0.15 m (6 in.) of gravel. The plants in this filter are usually aesthetic or ornamental such as calla lily (Zantedeschia aethiopica), canna lily (Canna flaccida), elephant ear (Colocasia esculenta), and water iris (Iris pseudacorus).

  9. Diagnostics of septic arthritis in the sternoclavicular region

    DEFF Research Database (Denmark)

    Bodker, Tina; Tottrup, Mikkel; Petersen, Klaus Kjaer

    2013-01-01

    Background: Septic arthritis in the sternoclavicular (SC) region is rare and may be difficult to diagnose clinically and radiologically. It mainly affects immunocompromised persons, and can clinically be misinterpreted as tumor and rheumatic disorders. Lacking radiological reference standard......, a multimodality approach may contribute to a prolonged diagnostic process. Purpose: To describe the diagnostics of septic arthritis in the SC region. Material and Methods: Between 2001 and 2011 10 patients with Staphylococcus infection in the SC region were investigated in our institution. Clinical, biochemical......, radiological, and microbiological findings were studied retrospectively; all CT and MR examinations were re-evaluated. Results: Initial radiography in nine patients and ultrasonography in six patients were inconclusive resulting in supplementary MRI and/or CT. Five patients examined by MRI were immediately...

  10. Septic pericarditis and myocardial abscess in an English Springer spaniel.

    Science.gov (United States)

    Fraga Veloso, Gemma; Fraga Manteiga, Eduardo; Trehy, Mary; Freeman, Alistair; McConnell, J Fraser; Dukes McEwan, Joanna

    2014-03-01

    Septic pericarditis and myocardial abscess are rare conditions in dogs. They are usually caused by foreign bodies, penetrating wounds, systemic infections or extension of local infections such as endocarditis, pleuritis or pulmonary infections to the myocardial tissue. Here we report a septic pericardial effusion and myocardial abscess in a young English Springer spaniel presenting with a long history of pyrexia and lethargy. No cause could clearly be identified although a penetrating injury or dissolving foreign body was highly suspected. The patient was successfully treated with a surgical approach in combination with broad spectrum antibacterials resulting in resolution of clinical signs without recurrence of the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. State Waste Discharge Permit application: 400 Area Septic System

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    As part of the Hanford Federal Facility Agreement and Consent Order negotiations, the US Department of Energy, Richland Operations Office, the US Environmental Protection Agency, and the Washington State Department of Ecology agreed that liquid effluent discharges to the ground on the Hanford Site which affects groundwater or has the potential to affect groundwater would be subject to permitting under the structure of Chapter 173-216 (or 173-218 where applicable) of the Washington Administrative Code, the State Waste Discharge Permit Program. This document constitutes the State Waste Discharge Permit application for the 400 Area Septic System. The influent to the system is domestic waste water. Although the 400 Area Septic System is not a Public Owned Treatment Works, the Public Owned Treatment Works application is more applicable than the application for industrial waste water. Therefore, the State Waste Discharge Permit application for Public Owned Treatment Works Discharges to Land was used.

  12. Microcirculatory monitoring in septic patients: Where do we stand?

    Science.gov (United States)

    Gruartmoner, G; Mesquida, J; Ince, C

    Microcirculatory alterations play a pivotal role in sepsis-related morbidity and mortality. However, since the microcirculation has been a "black box", current hemodynamic management of septic patients is still guided by macrocirculatory parameters. In the last decades, the development of several technologies has shed some light on microcirculatory evaluation and monitoring, and the possibility of incorporating microcirculatory variables to clinical practice no longer seems to be beyond reach. The present review provides a brief summary of the current technologies for microcirculatory evaluation, and attempts to explore the potential role and benefits of their integration to the resuscitation process in critically ill septic patients. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  13. Arthroscopy of septic carpitis in donkeys (Equus asinus).

    Science.gov (United States)

    Elkasapy, A H; AbdelGalil, A I; Al-Akraa, A M; Ibrahim, I M; Ismail, S F

    2014-01-01

    Experimental septic arthritis was induced in the radiocarpal joint of 18 donkeys by intra-articular injection of Staphylococcus aureus (3-4X10(6) CFU). The inoculated animals were divided into three groups (6 donkeys in each group). The arthroscopic examination was carried out before induction of septic carpitis and 3 days (group I), 14 days (group II), and 28 days (group III) after induction of infection. The arthroscopic examination of group I revealed hyperemia of synovial membrane and hypertrophied villi. In group II, severe hyperemia of synovial membrane, hypertrophied villi, pannus in the joint cavity and beginning of articular cartilage erosion were found. In group III, severe hyperemia of synovial membrane, hypertrophied villi and more prominent articular cartilage erosion were present.

  14. Arthroscopy of septic carpitis in donkeys (Equus asinus

    Directory of Open Access Journals (Sweden)

    A.H. Elkasapy

    2014-11-01

    Full Text Available Experimental septic arthritis was induced in the radiocarpal joint of 18 donkeys by intra-articular injection of Staphylococcus aureus (3-4X106 CFU. The inoculated animals were divided into three groups (6 donkeys in each group. The arthroscopic examination was carried out before induction of septic carpitis and 3 days (group I, 14 days (group II, and 28 days (group III after induction of infection. The arthroscopic examination of group I revealed hyperemia of synovial membrane and hypertrophied villi. In group II, severe hyperemia of synovial membrane, hypertrophied villi, pannus in the joint cavity and beginning of articular cartilage erosion were found. In group III, severe hyperemia of synovial membrane, hypertrophied villi and more prominent articular cartilage erosion were present.

  15. Corticosteroids and Pediatric Septic Shock Outcomes: A Risk Stratified Analysis

    Science.gov (United States)

    Atkinson, Sarah J.; Cvijanovich, Natalie Z.; Thomas, Neal J.; Allen, Geoffrey L.; Anas, Nick; Bigham, Michael T.; Hall, Mark; Freishtat, Robert J.; Sen, Anita; Meyer, Keith; Checchia, Paul A.; Shanley, Thomas P.; Nowak, Jeffrey; Quasney, Michael; Weiss, Scott L.; Banschbach, Sharon; Beckman, Eileen; Howard, Kelli; Frank, Erin; Harmon, Kelli; Lahni, Patrick; Lindsell, Christopher J.; Wong, Hector R.

    2014-01-01

    Background The potential benefits of corticosteroids for septic shock may depend on initial mortality risk. Objective We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk. Methods We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression was used to model the effects of corticosteroids on 28-day mortality and complicated course, defined as death within 28 days or persistence of two or more organ failures at 7 days. Results Subjects who received corticosteroids had greater organ failure burden, higher illness severity, higher mortality, and a greater requirement for vasoactive medications, compared to subjects who did not receive corticosteroids. PERSEVERE-based mortality risk did not differ between the two groups. For the entire cohort, corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI 1.3–4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1–2.5, p = 0.012). Within each PERSEVERE-based stratum, corticosteroid administration was not associated with improved outcomes. Similarly, corticosteroid administration was not associated with improved outcomes among patients with no comorbidities, nor in groups of patients stratified by PRISM. Conclusions Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort. PMID:25386653

  16. Corticosteroids and pediatric septic shock outcomes: a risk stratified analysis.

    Science.gov (United States)

    Atkinson, Sarah J; Cvijanovich, Natalie Z; Thomas, Neal J; Allen, Geoffrey L; Anas, Nick; Bigham, Michael T; Hall, Mark; Freishtat, Robert J; Sen, Anita; Meyer, Keith; Checchia, Paul A; Shanley, Thomas P; Nowak, Jeffrey; Quasney, Michael; Weiss, Scott L; Banschbach, Sharon; Beckman, Eileen; Howard, Kelli; Frank, Erin; Harmon, Kelli; Lahni, Patrick; Lindsell, Christopher J; Wong, Hector R

    2014-01-01

    The potential benefits of corticosteroids for septic shock may depend on initial mortality risk. We determined associations between corticosteroids and outcomes in children with septic shock who were stratified by initial mortality risk. We conducted a retrospective analysis of an ongoing, multi-center pediatric septic shock clinical and biological database. Using a validated biomarker-based stratification tool (PERSEVERE), 496 subjects were stratified into three initial mortality risk strata (low, intermediate, and high). Subjects receiving corticosteroids during the initial 7 days of admission (n = 252) were compared to subjects who did not receive corticosteroids (n = 244). Logistic regression was used to model the effects of corticosteroids on 28-day mortality and complicated course, defined as death within 28 days or persistence of two or more organ failures at 7 days. Subjects who received corticosteroids had greater organ failure burden, higher illness severity, higher mortality, and a greater requirement for vasoactive medications, compared to subjects who did not receive corticosteroids. PERSEVERE-based mortality risk did not differ between the two groups. For the entire cohort, corticosteroids were associated with increased risk of mortality (OR 2.3, 95% CI 1.3-4.0, p = 0.004) and a complicated course (OR 1.7, 95% CI 1.1-2.5, p = 0.012). Within each PERSEVERE-based stratum, corticosteroid administration was not associated with improved outcomes. Similarly, corticosteroid administration was not associated with improved outcomes among patients with no comorbidities, nor in groups of patients stratified by PRISM. Risk stratified analysis failed to demonstrate any benefit from corticosteroids in this pediatric septic shock cohort.

  17. Continuation of Statin Therapy and Vasopressor Use in Septic Shock.

    Science.gov (United States)

    Zechmeister, Carrie; Hurren, Jeff; McNorton, Kelly

    2015-07-01

    Studies have evaluated the use of statins in sepsis; however, no human studies have explored their effect on vasopressor requirements in septic shock. The primary objective was to determine the effect of prehospital statin continuation on duration of vasopressor therapy in patients with septic shock. Secondary objectives included maximum and average vasopressor dose and in-hospital mortality. This was a retrospective, institutional board-approved, observational cohort study in a community teaching hospital; 119 adult intensive care unit (ICU) patients with an ICD-9 code for septic shock and prehospital statin therapy were evaluated. Multivariate analyses were performed to address confounders. Of the 1229 patients screened, 119 (10%) met inclusion criteria; 73 patients (61%) had a statin continued within 24 hours of ICU admission. Crude analysis demonstrated no difference in vasopressor duration in the statin versus no statin group (3.3 vs 4.8 days; P = 0.21). There was no difference in either maximum (17.9 ± 16.1 vs 23.8 ± 21.7 µg/min norepinephrine equivalents [NEQs]; P = 0.1) or average vasopressor dose (9.5 ± 8.4 vs 12.1 ± 11.5 µg/min NEQ; P = 0.17). There was a decrease in mortality in the statin patients (43% vs 67 %; P = 0.05). On adjustment for potential confounders, there was no difference in any outcome, with a persistent trend toward lower mortality in the statin group. Continuation of prehospital statin therapy decreased neither duration nor dose of vasopressors in patients with septic shock but yielded a trend toward decreased mortality. © The Author(s) 2015.

  18. Microbial diversity of septic tank effluent and a soil biomat.

    Science.gov (United States)

    Tomaras, Jill; Sahl, Jason W; Siegrist, Robert L; Spear, John R

    2009-05-01

    Microbial diversity of septic tank effluent (STE) and the biomat that is formed as a result of STE infiltration on soil were characterized by 16S rRNA gene sequence analysis. Results indicate that microbial communities are different within control soil, STE, and the biomat and that microbes found in STE are not found in the biomat. The development of a stable soil biomat appears to provide the best on-site water treatment or protection for subsequent groundwater interactions of STE.

  19. [Fluid balance and acute kidney injury in septic shock].

    Science.gov (United States)

    Martínez-García, Jesús Javier; León-Sicairos, Nidia Maribel; Canizalez-Román, Adrián; García-Arellano, Bianca Azucena

    In patients with septic shock, excessive fluid administration can lead to increased morbidity and mortality. The aim of this study was to evaluate the association between fluid balance, acute kidney injury and mortality in patients with septic shock. A study of cases and controls was conducted in a Pediatric Intensive Care Unit. The fluid balance in the first 72h and the presence of acute kidney injury was compared in patients diagnosed with septic shock who died against patients who survived the same condition. Univariate and multivariate analyses were performed. Forty-five cases and forty-five controls were included in the analysis. Mortality was associated with Pediatric Risk of Mortality (PRISM III) ≥ 26 points (OR 7.5, 95% CI 2.8-18.7; p=0.000), Pediatric Logistic Organ Dysfunction (PELOD) ≥ 24 points (OR 11.0, 95% CI 4.1-29.4; p=0.000), creatinine ≥ 0.65mg/dl (OR 5.6, 95% CI 2.2-13.9; p=0.000), lactate ≥ 2.5 mmol/l (OR 2.5, 95% CI 1.1-5.9; p=0.033), SvO2 9% in 72h (OR 4.3, 95% CI 1.6-11.7; p=0.003), acute kidney injury (OR 5.7, 95% CI: 2.2-15.1; p=0.000). In the multivariate model, the values of PRISM ≥26 and PELOD ≥24 points were significant. In patients who died due to septic shock, the multivariate model showed an association with PRISM ≥26 and PELOD ≥24 and a trend toward association with SvO2 9%. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  20. Systemic inflammatory response syndrome: a case of septic shock

    Directory of Open Access Journals (Sweden)

    Nicolò Gentiloni Silveri

    2008-09-01

    Full Text Available An elderly, diabetic male, with severe sepsis, swiftly treated with antibiotics that were efficacious in vitro against the E. Coli isolated in his blood, rapidly slides into multiple organ dysfunction syndrome and dies of septic shock after a month in intensive care, despite receiving appropriate pain relief and aetiopathogenetic therapy. This event provides us with the opportunity to take a new look at systemic inflammatory response syndrome and a critical review of the relative therapy

  1. Molecular mechanisms involved in the pathogenesis of septic shock.

    Science.gov (United States)

    López-Bojórquez, Lucia Nikolaia; Dehesa, Alejandro Zentella; Reyes-Terán, Gustavo

    2004-01-01

    Pathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as well as the enzymes and genes involved in the cellular activation that precedes this condition. The most important molecular aspects are discussed, ranging from the cytokines involved and their respective transduction pathways to the cellular mechanisms related to accelerated catabolism and multi-organic failure.

  2. Bacillus pumilus Septic Arthritis in a Healthy Child.

    Science.gov (United States)

    Shivamurthy, V M; Gantt, Soren; Reilly, Christopher; Tilley, Peter; Guzman, Jaime; Tucker, Lori

    2016-01-01

    We report a case of septic arthritis caused by a Bacillus species, B. pumilus, occurring in a healthy child. This organism rarely causes serious infections and has only been described in newborns and immunocompromised individuals or as a skin infection. This child developed an indolent joint swelling after a minor skin injury, and symptoms were initially thought most consistent with chronic arthritis. The case demonstrates that clinicians should consider joint infection in children presenting with acute monoarticular swelling, even without prominent systemic features.

  3. Is this septic shock? A rare case of distributive shock

    OpenAIRE

    Val-Flores,Luis Silva; Fior,Alberto; Santos, Ana; Reis, Lu?s; Bento, Lu?s

    2014-01-01

    The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration - a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also...

  4. Is this septic shock? A rare case of distributive shock.

    Science.gov (United States)

    Val-Flores, Luis Silva; Fior, Alberto; Santos, Ana; Reis, Luís; Bento, Luís

    2014-01-01

    The authors report a rare case of shock in a patient without significant clinical history, admitted to the intensive care unit for suspected septic shock. The patient was initially treated with fluid therapy without improvement. A hypothesis of systemic capillary leak syndrome was postulated following the confirmation of severe hypoalbuminemia, hypotension, and hemoconcentration--a combination of three symptoms typical of the disease. The authors discussed the differential diagnosis and also conducted a review of the diagnosis and treatment of the disease.

  5. Arthroscopic treatment of septic arthritis of the knee in children.

    Science.gov (United States)

    Agout, C; Lakhal, W; Fournier, J; de Bodman, C; Bonnard, C

    2015-12-01

    Childhood septic arthritis of the knee is a serious disease that can impair growth and cause serious functional sequelae. There are few data on arthroscopic treatment in children, and series were always less than 20 cases. The objective of this study was to assess clinical and radiographic results of arthroscopic drainage combined with antibiotic therapy for the treatment of childhood septic arthritis of the knee. The hypothesis was that arthroscopic treatment is also effective in children. A retrospective study, conducted between January 2003 and December 2012, included patients under 15 years of age with septic arthritis of the knee treated by arthroscopic drainage with a minimum of 2 years' follow-up. Fifty-six patients, with a mean age at surgery of 3.4 years (range, 3 months to 12 years), were included. Staphylococcus aureus was the most common causative organism. Two patients (3.6%) had recurrence, successfully treated by repeat arthroscopic drainage. Mean Lysholm score was 96.9 (range, 70-100) and mean KOOS-Child pain, symptoms, daily life, sports and quality of life scores were respectively 97 (81-100), 95 (75-100), 98 (89-100), 93 (71-100) and 95 (70-100) at a mean 65 months' follow-up. Ranges of motion were normal. Radiology found no joint damage. Arthroscopic drainage combined with antibiotic treatment is a simple and effective treatment for childhood septic arthritis of the knee and is for our reference attitude. It can also be indicated in case of recurrence. IV, retrospective study. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Clinical presentation and treatment of septic arthritis in children.

    Science.gov (United States)

    Moro-Lago, I; Talavera, G; Moraleda, L; González-Morán, G

    The aim of this study is to determine the epidemiological features, clinical presentation, and treatment of children with septic arthritis. A retrospective review was conducted on a total of 141 children with septic arthritis treated in Hospital Universitario La Paz (Madrid) between the years 2000 to 2013. The patient data collected included, the joint affected, the clinical presentation, the laboratory results, the appearance, Gram stain result, and the joint fluid culture, as well as the imaging tests and the treatment. Most (94%) of the patients were less than 2 years-old. The most common location was the knee (52%), followed by the hip (21%). The septic arthritis was confirmed in 53%. No type of fever was initially observed in 49% of them, and 18% had an ESR (mm/h) or CRP (mg/l) less than 30 in the initial laboratory analysis. The joint fluid was purulent in 45% and turbid in 12%. The Gram stain showed bacteria in 4%. The fluid culture was positive in 17%. Staphylococcus aureus was the most common pathogen found, followed by Streptococcus agalactiae, Streptococcus pneumoniae, and Kingella kingae. Antibiotic treatment was intravenous administration for 7 days, followed by 21 days orally. Surgery was performed in 18% of cases. The diagnosis was only confirmed in 53% of the patients. Some of the confirmed septic arthritis did not present with the classical clinical/analytical signs, demonstrating that the traumatologist or paediatrician requires a high initial level of clinical suspicion of the disease. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. An Experimental Study on Effects of Distilled White-ginseng Herbal Acupuncture on A549 human ephithelial lung cancer cell in vitro and implanted Sarcoma-180 in vivo

    Directory of Open Access Journals (Sweden)

    Jong-Seong We

    2004-12-01

    Full Text Available Objectives : In order to investigate effects and immune improvement of distilled white-ginseng herbal extract, expression of Cox-1, Cox-2, and mRNA of Bcl-2 and Bax were analyzed in A549 cell in vivo. Survival time and expression of cytokine mRNA were measured for the mice with Sarcoma-180 induced abdominal cancer. Methods : Balb/c mouse was treated with distilled white-ginseng Herbal Acupuncture at Wisu(BL21 and Chung-wan(CV12 to investigate anti-cancer effects and immune response. Results : 1. For expression of mRNA of Cox-1 using RT-PCR, the control group and the experiment groups show significant increase. For Cox-2, both experiment groups and the normal group showed significant decrease. For Bcl-2, experiment groups showed slight decrease compared to the control group. For Bax, no significant changes were shown between the control group and experiment groups. 2.For survival time, all of experiment groups didn't show significant differences. 3.For IL-2 productivity using Flow cytometry, experiment group I didn't show any significance, For IL-4, all of experiment groups showed slight decrease compared to the control group. 4. For IL-2 productivity using ELISA, experiment groupI showed slight decrease compared to the control group, experiment group II didn't show any significance. 5.For expression of cytokine mRNA using RT-PCR, significant increase of IL-2 and IL-4 were witnessed in the experiment groupI compared to the control group. Significant decrease of IL-10 was shown in all of experiment groups compared to the control group. Conclusion : According to the results, we can expect that distilled white-ginseng Herbal Acupuncture may be further effects in anti-cancer and immune improvement if increasing concentration.

  8. Genome-wide expression profiling in pediatric septic shock.

    Science.gov (United States)

    Wong, Hector R

    2013-04-01

    For nearly a decade, our research group has had the privilege of developing and mining a multicenter, microarray-based, genome-wide expression database of critically ill children (≤10 y of age) with septic shock. Using bioinformatic and systems biology approaches, the expression data generated through this discovery-oriented, exploratory approach have been leveraged for a variety of objectives, which are reviewed here. Fundamental observations include widespread repression of gene programs corresponding to the adaptive immune system and biologically significant differential patterns of gene expression across developmental age groups. The data have also identified gene expression-based subclasses of pediatric septic shock having clinically relevant phenotypic differences. The data have also been leveraged for the discovery of novel therapeutic targets, as well as for the discovery and development of novel stratification and diagnostic biomarkers. Almost a decade of genome-wide expression profiling in pediatric septic shock is now demonstrating tangible results. The studies have progressed from an initial discovery-oriented and exploratory phase to a new phase in which the data are being translated and applied to address several areas of clinical need.

  9. Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.

    Science.gov (United States)

    Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Grunwell, Jocelyn R; Opoka, Amy; Wong, Hector R

    2017-04-01

    Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock. We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. The primary outcome variable was complicated course, defined as 28-day mortality or the persistence of two or more organ failures 7 days after a septic shock diagnosis. We used logistic regression to test for an association between corticosteroid exposure and outcome, within genotype group, and adjusted for illness severity. Multiple PICUs in the United States. Standard care. There were no differences in outcome when comparing the various genotype groups. Among patients homozygous for the wild-type glucocorticoid receptor allele, corticosteroids were independently associated with increased odds of complicated course (odds ratio, 2.30; 95% CI, 1.01-5.21; p = 0.047). Based on these glucocorticoid receptor polymorphisms, we could not detect a beneficial effect of corticosteroids among any genotype group. Among children homozygous for the wild-type allele, corticosteroids were independently associated with increased odds of poor outcome.

  10. CE: Managing Sepsis and Septic Shock: Current Guidelines and Definitions.

    Science.gov (United States)

    Makic, Mary Beth Flynn; Bridges, Elizabeth

    2018-02-01

    : Sepsis is a leading cause of critical illness and hospital mortality. Early recognition and intervention are essential for the survival of patients with this syndrome. In 2002, the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM) launched the Surviving Sepsis Campaign (SSC) to reduce overall patient morbidity and mortality from sepsis and septic shock by driving practice initiatives based on current best evidence. The SSC guidelines have been updated every four years, with the most recent update completed in 2016. The new guidelines have increased the focus on early identification of infection, risks for sepsis and septic shock, rapid antibiotic administration, and aggressive fluid resuscitation to restore tissue perfusion.In 2014, the SCCM and the ESICM convened a task force of specialists to reexamine the definitions of terms used to identify patients along the sepsis continuum. In 2016, this task force published the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). The new definitions and recommendations included tools, based on an updated understanding of the pathobiology of sepsis, that can be used to predict adverse outcomes in patients with infection.This article discusses the new SSC treatment guidelines, changes in the sepsis bundle interventions, and the Sepsis-3 definitions and tools, all of which enable nurses to improve patient outcomes through timely collaborative action.

  11. Bacteria removal in septic effluent: influence of biofilm and protozoa.

    Science.gov (United States)

    Chabaud, Sylvaine; Andres, Yves; Lakel, Abdel; Le Cloirec, Pierre

    2006-09-01

    Numerous biological, physical and chemical parameters are involved in the retention and removal of bacteria in wastewater treatment systems. Biological parameters, such as biofilms and protozoa grazing activity, are often mentioned but few studies provide a better understanding of their influence. In this study, the effect of bacterivorous protozoa on pathogenic indicator bacteria removal was investigated in septic effluent and in the presence of a biofilm coating glass slides. Endogenous bacteria from septic effluent were quantified. First, bacteria removal was compared between septic effluents treated or not with an inhibitor of protozoa (cycloheximide). The mortality rates were 10 times lower in treated effluent (96 CFU mL(-1) d(-1)) than in untreated effluent (1100 CFU mL(-1) d(-1)). Secondly, the efficiency of bacteria removal was studied (i) with a biofilm surface and active protozoa, (ii) with a biofilm surface and inactivated protozoa, (iii) with a clean surface. Protozoa in the presence of a biofilm were responsible for 60% of bacteria removal. Biofilm without protozoa and a clean surface each removed similar quantities of bacteria. Grazing by protozoa could be an important biological mechanism for bacterial elimination in wastewater treatment systems.

  12. How Do I Integrate Hemodynamic Variables When Managing Septic Shock?

    Directory of Open Access Journals (Sweden)

    Olfa Hamzaoui

    2016-11-01

    Full Text Available Hemodynamic management of sepsis-induced circulatory failure is complex since this pathological state includes multiple cardiovascular derangements that can vary from patient to patient according to the degree of hypovolemia, of vascular tone depression, of myocardial depression and of microvascular dysfunction. The treatment of the sepsis-induced circulatory failure is thus not univocal and should be adapted on an individual basis. As physical examination is insufficient to obtain a comprehensive picture of the hemodynamic status, numerous hemodynamic variables more or less invasively collected, have been proposed to well assess the severity of each component of the circulatory failure and to monitor the response to therapy. In this article, we first describe the hemodynamic variables, which are the most relevant to be used, emphasizing on their physiological meaning, their validation and their limitations in patients with septic shock. We then proposed a general approach for managing patients with septic shock by describing the logical steps that need to be followed in order to select and deliver the most appropriate therapies. This therapeutic approach is essentially based on knowledge of physiology, of pathophysiology of sepsis, and of published data from clinical studies that addressed the issue of hemodynamic management of septic shock.

  13. Experimental models of sepsis and septic shock: an overview

    Directory of Open Access Journals (Sweden)

    Garrido Alejandra G.

    2004-01-01

    Full Text Available Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

  14. The Yin/Yan of CCL2: a minor role in neutrophil anti-tumor activity in vitro but a major role on the outgrowth of metastatic breast cancer lesions in the lung in vivo.

    Science.gov (United States)

    Lavender, Nicole; Yang, Jinming; Chen, Sheau-Chiann; Sai, Jiqing; Johnson, C Andrew; Owens, Philip; Ayers, Gregory D; Richmond, Ann

    2017-01-31

    The role of the chemokine CCL2 in breast cancer is controversial. While CCL2 recruits and activates pro-tumor macrophages, it is also reported to enhance neutrophil-mediated anti-tumor activity. Moreover, loss of CCL2 in early development enhances breast cancer progression. To clarify these conflicting findings, we examined the ability of CCL2 to alter naïve and tumor entrained neutrophil production of ROS, release of granzyme-B, and killing of tumor cells in multiple mouse models of breast cancer. CCL2 was delivered intranasally in mice to elevate CCL2 levels in the lung and effects on seeding and growth of breast tumor cells were evaluated. The TCGA data base was queried for relationship between CCL2 expression and relapse free survival of breast cancer patients and compared to subsets of breast cancer patients. Even though each of the tumor cell lines studied produced approximately equal amounts of CCL2, exogenous delivery of CCL2 to co-cultures of breast tumor cells and neutrophils enhanced the ability of tumor-entrained neutrophils (TEN) to kill the less aggressive 67NR variant of 4T1 breast cancer cells. However, exogenous CCL2 did not enhance naïve or TEN neutrophil killing of more aggressive 4T1 or PyMT breast tumor cells. Moreover, this anti-tumor activity was not observed in vivo. Intranasal delivery of CCL2 to BALB/c mice markedly enhanced seeding and outgrowth of 67NR cells in the lung and increased the recruitment of CD4+ T cells and CD8+ central memory T cells into lungs of tumor bearing mice. There was no significant increase in the recruitment of CD19+ B cells, or F4/80+, Ly6G+ and CD11c + myeloid cells. CCL2 had an equal effect on CD206+ and MHCII+ populations of macrophages, thus balancing the pro- and anti-tumor macrophage cell population. Analysis of the relationship between CCL2 levels and relapse free survival in humans revealed that overall survival is not significantly different between high CCL2 expressing and low CCL2 expressing

  15. Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients.

    Science.gov (United States)

    Mariano, Filippo; Morselli, Maurizio; Bergamo, Daniela; Hollo, Zsuzsanna; Scella, Sandro; Maio, Mariella; Tetta, Ciro; Dellavalle, Ambrogio; Stella, Maurizio; Triolo, Giorgio

    2011-12-01

    Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF). An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06-0.12) mmol/L (Time 0) and 0.23 (0.18-0.31) mmol/L during treatment; median sieving coefficient for citrate was 0.95 (0.88-1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r = 0.85 and 0.78, respectively). Median citrate load entering in the patients' bloodstream was 13.60 (9.1-19.6, n = 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51€), saving costs could be potentially relevant with more extended use of citrate anticoagulation. In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.

  16. Serum free cortisol fraction in healthy and septic neonatal foals.

    Science.gov (United States)

    Hart, K A; Barton, M H; Ferguson, D C; Berghaus, R; Slovis, N M; Heusner, G L; Hurley, D J

    2011-01-01

    Relative cortisol insufficiency occurs in septic foals and impacts survival. Serum free (biologically available) cortisol concentration might be a better indicator of physiologic cortisol status than serum total cortisol concentration in foals. In septic foals, (1) low free cortisol concentration correlates with disease severity and survival and (2) predicts disease severity and outcome better than total cortisol concentration. Fifty-one septic foals; 11 healthy foals; 6 healthy horses. In this prospective clinical study, foals meeting criteria for sepsis at admission were enrolled. University-owned animals served as healthy controls. Basal and cosyntropin-stimulated total cortisol concentration and percent free cortisol (% free cortisol) were determined by chemiluminescent immunoassay and ultrafiltration/ligand-binding methods, respectively. Group data were compared by ANOVA, Mann-Whitney U-tests, and receiver operator characteristic curves. Significance was set at P cortisol was highest in healthy foals at birth (58 ± 8% mean ± SD), and was higher (P ≤ .004) in healthy foals of all ages (33 ± 6 to 58 ± 8%) than in adult horses (7 ± 3%). Cosyntropin-stimulated total and free cortisol concentrations were lower (P ≤ .03) in foals with shock (total = 6.2 ± 8.1 μg/dL; free = 3.5 ± 4.8 μg/dL versus total = 10.8 ± 6.0 μg/dL; free = 6.9 ± 3.3 μg/dL in foals without shock) and in nonsurvivors (total = 3.8 ± 6.9 μg/dL; free = 1.9 ± 3.9 μg/dL versus total = 9.1 ± 7.7 μg/dL; free = 5.5 ± 4.4 μg/dL in survivors). Free cortisol was no better than total cortisol at predicting disease severity or outcome in septic foals. Serum free cortisol is impacted by age and illness in the horse. There is no advantage to measuring free over total cortisol in septic foals. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  17. Role of circulating soluble chemokines in septic shock.

    Science.gov (United States)

    de Pablo, R; Monserrat, J; Prieto, A; Alvarez-Mon, M

    2013-11-01

    Chemokines are a large superfamily of small proteins that function not only in leukocyte trafficking, but are also necessary for linkage between innate and adaptive immunity. Little is known about their role in septic shock. We hypothesized that serum levels of the most important chemokines are related to organ failure, disease severity and outcome. A prospective observational study was carried out. Surgical-clinical Intensive Care Unit. Ninety-two patients diagnosed with septic shock using international criteria. Forty patients were excluded due to acquired immunity disturbances. Samples from 36 healthy controls were also analyzed. None. In 46% of the patients who suffered acute respiratory distress syndrome (ARDS), IL-8 levels were higher than in patients without ARDS (499.9±194.1 vs. 190.8±91.7 pg/ml; P=.039). This molecule was also higher in 36% of the patients with sepsis-induced acute renal failure (ARF) (453.3±181.6 vs. 201.3±95.9 pg/ml; P=.049). Coagulopathy was found in 19% of the septic shock patients with elevated serum IL-8 levels (635.8±292.3 vs. 218.7±87.0 pg/ml; P=.010), elevated MIP-1α (91.4±27.3 vs. 58.8±11.1 pg/ml; P=.044), and low circulating RANTES levels (8162.2±6321.0 vs. 18781.8±11.1 pg/ml; P=.027). No significant differences were found between survivors and non-survivors at any time of follow-up. Upon admission to the ICU, IL-8 is a reliable biomarker of sepsis-induced AFR, ARDS and coagulopathy. Altered circulating MIP-1α and RANTES levels are also found in patients with septic shock and coagulopathy. However, chemokines do not appear to be good biomarkers of mortality in septic shock. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  18. DIAGNOSTICS AND TREATMENT OF THE SEPSIS AND SEPTIC SHOCK IN CHILDREN

    Directory of Open Access Journals (Sweden)

    R.F. Tepaev

    2010-01-01

    Full Text Available Sepsis is one of the leading causes of mortality in children. Timely diagnosis is the most important condition of successful therapy for sepsis. The work provides modern recommendations for diagnosis of the systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, sets out key guidelines for administering and treating severe sepsis and septic shock in children. Key words: systemic inflammatory response syndrome, sepsis, septic shock, children. (Pediatric Pharmacology. – 2010; 7(5:24-29

  19. Arthroscopic Treatment of Septic Arthritis of the Elbow in a 4-Year-Old Girl

    Directory of Open Access Journals (Sweden)

    Masashi Koide

    2015-01-01

    Full Text Available Pediatric septic arthritis is uncommon and has been traditionally treated by joint aspiration or open arthrotomy. There are some reports about arthroscopic surgery in pediatric septic arthritis of the knee, hip, and shoulder. However, there is no report for the case of elbow. We report a case of pediatric septic arthritis of elbow treated with arthroscopically with good clinical condition at 3-year follow-up. This paper is based on a report first published in Japanese (Tojo (2012.

  20. Restricting volumes of resuscitation fluid in adults with septic shock after initial management

    DEFF Research Database (Denmark)

    Hjortrup, Peter B; Haase, Nicolai; Bundgaard, Helle

    2016-01-01

    PURPOSE: We assessed the effects of a protocol restricting resuscitation fluid vs. a standard care protocol after initial resuscitation in intensive care unit (ICU) patients with septic shock. METHODS: We randomised 151 adult patients with septic shock who had received initial fluid resuscitation...... patients with septic shock. The patient-centred outcomes all pointed towards benefit with fluid restriction, but our trial was not powered to show differences in these exploratory outcomes. TRIAL REGISTRATION: NCT02079402....

  1. Clinical efficacy of nitroglycerin in patients with septic shock with ARDS

    Directory of Open Access Journals (Sweden)

    Li-ping LIU

    2015-10-01

    Full Text Available Objective To evaluate the clinical efficacy of nitroglycerin in patients with septic shock with ARDS, and explore its possible mechanism. Methods From January 2013 to January 2014, patients with septic shock with ARDS were included in the study in the department of critical care medicine in our hospital. Patients who met the criteria were randomly divided into the control group and the nitroglycerin group. The standard treatment was given in control group, and nitroglycerin 0.5-1.0mg/h was given in nitroglycerin group on basis of standard treatment. Monitoring indexes were recorded at 0, 6, 24 and 72h, including general condition, APACHE Ⅱ score, hemodynamic indexes (HR, MAP, CVP, CI, SVRI, PAWP, PAP, Lac, volume of fluid resuscitation, quantity of vasopressor drugs, ventilator condition (PH, PO2, PCO2, RR, PEEP, VT, FiO2, oxygenation index, airway resistance, lung compliance, mechanical ventilation time, ICU stay time, hospital follow-up, 28-day follow-up, immune index (CD4+/CD8+, inflammatory markers (CRP, PCT, IL-6, WBC. Results Forty-three patients were included in this study, with 21 in control group and 22 in nitroglycerin group. At 24 and 72h after the treatment, APACHEⅡ score, heart rate, pulmonary artery pressure (PAP, lactic acid and dopamine, norepinephrine, respiratory rate (RR, inspired oxygen concentration (FiO2, airway resistance, C reactive protein (CRP, procalcitonin (PCT, interleukin-6 (IL-6, white blood cell count (WBC significantly decreased as compared with those at 0 and 6 h, and these parameters in nitroglycerin group were lower than these in the control group at the 72h (P<0.05; at the same time, those indexes such as peripheral vascular resistance index (SVRI, pH value, arterial partial pressure of oxygen (PaO2, tidal volume (VT, lung compliance, oxygenation index, CD4+/CD8+ more significantly increased in the treatment group at 24 and 72h than those at 0 and 6h, especially at 72h, and these values were

  2. A novel method for a fast diagnosis of septic arthritis using mid infrared and deported spectroscopy.

    Science.gov (United States)

    Albert, Jean-David; Monbet, Valérie; Jolivet-Gougeon, Anne; Fatih, Nadia; Le Corvec, Maëna; Seck, Malik; Charpentier, Frédéric; Coiffier, Guillaume; Boussard-Pledel, Catherine; Bureau, Bruno; Guggenbuhl, Pascal; Loréal, Olivier

    2016-05-01

    To assess the ability of mid infrared deported spectroscopy to discriminate synovial fluids samples of septic arthritis patients from other causes of joint effusion. Synovial fluids obtained from patients with clinically suspected arthritis were collected, analysed and classified according to standard diagnostic procedures as septic or non-septic. A spectroscopic analysis on synovial fluid samples was then performed using a coiled optical fiber made with chalcogenide glass. After a factorial analysis of the normalized spectra and the computation of a Fisher test used to select the most relevant components, a logistic regression model was fitted, allowing to attribute a score between 0 - non-septic -, and 1 - septic. In a first phase, we analysed the synovial fluids from 122 different synovial fluids including 6 septic arthritis among arthritis of various origins. Septic synovial fluids were identified with a sensitivity of 95.8% and a specificity of 93.9% and an AUROC of 0.977. The analysis of an independent set of samples (n=42, including two septic arthritis) gave similar values. Our data strongly supports the interest of mid infrared deported spectroscopy, which could be used potentially at point of care, for a rapid and easy diagnosis of septic arthritis. Now, the precision of the diagnosis must be evaluated through a multicentric study on a larger panel of patients. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  3. Effects of fluid restriction on measures of circulatory efficacy in adults with septic shock

    DEFF Research Database (Denmark)

    Hjortrup, P. B.; Haase, Nicolai; Wetterslev, Jørn

    2017-01-01

    BACKGROUND: The haemodynamic consequences of fluid resuscitation in septic shock have not been fully elucidated. Therefore, we assessed circulatory effects in the first 24 h of restriction of resuscitation fluid as compared to standard care in intensive care unit (ICU) patients with septic shock....... METHODS: This was a post-hoc analysis of the multicentre CLASSIC randomised trial in which patients with septic shock, who had received the initial fluid resuscitation, were randomised to a protocol restricting resuscitation fluid or a standard care protocol in nine ICUs. The highest plasma lactate...... of restriction of resuscitation fluid as compared with standard care in adults with septic shock who had received initial resuscitation....

  4. Acute Disseminated Melioidosis Presenting with Septic Arthritis and Diffuse Pulmonary Consolidation in an Otherwise Healthy Adult: A Case Report

    Directory of Open Access Journals (Sweden)

    Hai Sherng Lee

    2015-03-01

    Full Text Available Background: Melioidosis is an infectious disease caused by Burkholderia pseudomallei. It is most prevalent in South-East Asia, northern Australia, and the Indian subcontinent. Septic arthritis is a rare manifestation of melioidosis. Melioidosis is usually found in patients with diabetes, heavy alcohol use, or chronic lung disease. Results: We report a case of melioidosis in an otherwise healthy 44-year-old male, who presented with acute painful left knee swelling, high-grade fever associated with chills, rigors and night sweats, and a productive cough. Examination revealed active synovitis with effusion involving his left knee, ankle and elbow joints and scattered crackles over both lung fields. Chest X-ray showed diffuse pulmonary consolidation. Abdominal ultrasound showed splenic micro-abscesses. The diagnosis was made based on a positive blood culture for Burkholderia pseudomallei. He was started on appropriate antibiotics and responded well, becoming afebrile after 48 hours, while his joint effusions disappeared after one week. A repeat chest X-ray after two weeks of intensive antibiotic therapy showed marked improvement. At the time of writing, he was under uneventful outpatient follow-up and still had 12 weeks to complete his course of antibiotics. Conclusion: Septic arthritis only occurs in 4% of patients with melioidosis. When there is diffuse pulmonary involvement, melioidosis may mimic disseminated tuberculosis, other acute disseminated or focal sepsis syndromes, and systemic vasculitis syndromes. This case is relevant for medical literature as melioidosis is emerging and is expanding its known territories worldwide. It should be considered early in the differential diagnoses of patients presenting with constitutional symptoms in endemic areas, so that treatment can be started early to reduce its high mortality and morbidity.

  5. [Extensive burns complicated with infective endocarditis and septic pulmonary embolism: case report and literature review].

    Science.gov (United States)

    Li, T S; Qi, Y; Wang, Y; Wang, Y X; Liu, F Y; Dai, L; Xia, G G

    2016-10-12

    Objective: To improve the clinical recognition of infective endocarditis (IE) and septic pulmonary embolism (SPE) in patients with extensive burns. Methods: A case of large area burn complicated with IE and SPE confirmed by blood cultures and echocardiography was described. A literature review was performed with "burn" and "infective endocarditis" as the Chinese key words in Wanfang database; with "burn" and "infective endocarditis" as Mesh terms in PubMed. Results: The patient was a 37-year-old male with large area burn, who presented with fever and hemoptysis. Blood cultures were positive for methicillin resistant Staphylococcus aureus (MRSA). Echocardiography disclosed vegetations located in the tricuspid valve. Multiple wedge-shaped lesions were found on chest CT. From January 1978 to December 2015, 26 related articles were retrieved and 134 burned patients complicated with endocarditis were reported, of which, 97 cases were IE and 1 case with SPE. Of the 134 cases, 120 cases were dead, 12 cases cured and 2 cases unknown. The mortality was 89.6%. Conclusions: There was a high mortality of burned patients complicated with IE. SPE should be considered for patients with multiple peripheral nodules in both lungs and a positive blood culture. Combination and prolonged anti-infective therapy may increase the treatment success and reduce the risk of recurrence.

  6. Vertebral Osteomyelitis and Septic Arthritis Associated With Staphylococcus hyicus in a Juvenile Peregrine Falcon ( Falco peregrinus ).

    Science.gov (United States)

    Maier, Kristina; Fischer, Dominik; Hartmann, Antje; Kershaw, Olivia; Prenger-Berninghoff, Ellen; Pendl, Helene; Schmidt, Martin J; Lierz, Michael

    2015-09-01

    A 6-week-old, parent-reared peregrine falcon ( Falco peregrinus ) was presented with spastic hypertonus of its hind limbs of unknown origin and duration. Radiologic examination revealed smooth periosteal reactions ventrally at thoracic vertebrae 5 to 7. Contrast-enhanced computed tomography identified the swelling as inflammation; antibiotic, antimycotic, anti-inflammatory, and analgesic treatments were initiated, and vitamins and minerals were supplemented. Because the bird's condition did not improve after 10 days, it was euthanatized and submitted for postmortem examination. On histopathologic examination, chronic, active osteomyelitis was diagnosed in thoracic vertebrae 5 to 7, and chronic, active arthritis was present in both the right shoulder and left elbow joints. Staphylococcus hyicus was isolated from these 3 locations, as well as from lungs and liver, indicating a chronic septic staphylococcosis. Although infections with Staphylococcus species are occasional causes of vertebral osteomyelitis in juvenile poultry with active growth plates, it is only sporadically reported in raptors and companion birds. This case report is the first description of the clinical features and diagnostic and pathologic findings in a juvenile peregrine falcon with hematogenous osteomyelitis and arthritis associated with septicemia caused by S hyicus.

  7. Cathelicidin peptide sheep myeloid antimicrobial peptide-29 prevents endotoxin-induced mortality in rat models of septic shock.

    Science.gov (United States)

    Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; D'Amato, Giuseppina; Circo, Raffaella; Orlando, Fiorenza; Skerlavaj, Barbara; Silvestri, Carmela; Saba, Vittorio; Zanetti, Margherita; Scalise, Giorgio

    2004-01-15

    The present study was designed to investigate the antiendotoxin activity and therapeutic efficacy of sheep myeloid antimicrobial peptide (SMAP)-29, a cathelicidin-derived peptide. The in vitro ability of SMAP-29 to bind LPS from Escherichia coli 0111:B4 was determined using a sensitive limulus chromogenic assay. Two rat models of septic shock were performed: (1) rats were injected intraperitoneally with 1 mg E. coli 0111:B4 LPS and (2) intraabdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg/kg SMAP-29, 1 mg/kg polymyxin B or 20 mg/kg imipenem. The main outcome measures were: abdominal exudate and plasma bacterial growth, plasma endotoxin and tumor necrosis factor-alpha concentrations, and lethality. The in vitro study showed that SMAP-29 completely inhibited the LPS procoagulant activity at approximately 10 microM peptide concentration. The in vivo experiments showed that all compounds reduced the lethality when compared with control animals. SMAP-29 achieved a substantial decrease in endotoxin and tumor necrosis factor-alpha plasma concentrations when compared with imipenem and saline treatment and exhibited a slightly lower antimicrobial activity than imipenem. No statistically significant differences were noted between SMAP-29 and polymyxin B. SMAP-29, because of its double antiendotoxin and antimicrobial activities, could be an interesting compound for septic shock treatment.

  8. Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU

    DEFF Research Database (Denmark)

    Holst, Lars B; Haase, Nicolai; Wetterslev, Jørn

    2013-01-01

    BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS: The Transfusion...... Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin...

  9. What Is Lung Cancer?

    Science.gov (United States)

    ... Shareable Graphics Infographics “African-American Men and Lung Cancer” “Lung Cancer Is the Biggest Cancer Killer in Both ... starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may spread ...

  10. Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites.

    Science.gov (United States)

    Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

    2013-07-07

    To investigate the benefits of probiotics treatment in septic rats. The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P probiotics treated group compared with septic model group (33.3% vs 100.0%, P probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P Probiotics improve survival of septic rats by suppressing these conditioned pathogens.

  11. Probiotics improve survival of septic rats by suppressing conditioned pathogens in ascites

    Science.gov (United States)

    Liu, Da-Quan; Gao, Qiao-Ying; Liu, Hong-Bin; Li, Dong-Hua; Wu, Shang-Wei

    2013-01-01

    AIM: To investigate the benefits of probiotics treatment in septic rats. METHODS: The septic rats were induced by cecal ligation and puncture. The animals of control, septic model and probiotics treated groups were treated with vehicle and mixed probiotics, respectively. The mixture of probiotics included Bifidobacterium longum, Lactobacillus bulgaricus and Streptococcus thermophilus. We observed the survival of septic rats using different amounts of mixed probiotics. We also detected the bacterial population in ascites and blood of experimental sepsis using cultivation and real-time polymerase chain reaction. The severity of mucosal inflammation in colonic tissues was determined. RESULTS: Probiotics treatment improved survival of the rats significantly and this effect was dose dependent. The survival rate was 30% for vehicle-treated septic model group. However, 1 and 1/4 doses of probiotics treatment increased survival rate significantly compared with septic model group (80% and 55% vs 30%, P probiotics treated group compared with septic model group (5.20 ± 0.57 vs 9.81 ± 0.67, P probiotics treated group compared with septic model group (33.3% vs 100.0%, P probiotics treated group were decreased significantly compared with that of septic model group (3.93 ± 0.73 vs 8.80 ± 0.83, P probiotics treatment, there was a decrease in the scores of inflammatory cell infiltration into the intestinal mucosa in septic animals (1.50 ± 0.25 vs 2.88 ± 0.14, P Probiotics improve survival of septic rats by suppressing these conditioned pathogens. PMID:23840152

  12. In aqua vivo EPID dosimetry

    NARCIS (Netherlands)

    Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Ígor; Pecharromán-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; van Herk, Marcel; Mijnheer, Ben J.

    2012-01-01

    At the Netherlands Cancer Institute--Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the

  13. Multidrug resistant bacteria isolated from septic arthritis in horses

    Directory of Open Access Journals (Sweden)

    Rodrigo G. Motta

    Full Text Available ABSTRACT: Septic arthritis is a debilitating joint infectious disease of equines that requires early diagnosis and immediate therapeutic intervention to prevent degenerative effects on the articular cartilage, as well as loss of athletic ability and work performance of the animals. Few studies have investigated the etiological complexity of this disease, as well as multidrug resistance of isolates. In this study, 60 horses with arthritis had synovial fluid samples aseptically collected, and tested by microbiological culture and in vitro susceptibility test (disk diffusion using nine antimicrobials belonging to six different pharmacological groups. Bacteria were isolated in 45 (75.0% samples, as follows: Streptococcus equi subsp. equi (11=18.3%, Escherichia coli (9=15.0%, Staphylococcus aureus (6=10.0%, Streptococcus equi subsp. zooepidemicus (5=8.3%, Staphylococcus intermedius (2=3.3%, Proteus vulgaris (2=3.3%, Trueperella pyogenes (2=3.3%, Pseudomonas aeruginosa (2=3.3%, Klebsiella pneumoniae (1=1.7%, Rhodococcus equi (1=1.7%, Staphylococcus epidermidis (1=1.7%, Klebsiella oxytoca (1=1.7%, Nocardia asteroides (1=1.7%, and Enterobacter cloacae (1=1.7%. Ceftiofur was the most effective drug (>70% efficacy against the pathogens in the disk diffusion test. In contrast, high resistance rate (>70% resistance was observed to penicillin (42.2%, enrofloxacin (33.3%, and amikacin (31.2%. Eleven (24.4% isolates were resistant to three or more different pharmacological groups and were considered multidrug resistant strains. The present study emphasizes the etiological complexity of equine septic arthritis, and highlights the need to institute treatment based on the in vitro susceptibility pattern, due to the multidrug resistance of isolates. According to the available literature, this is the first report in Brazil on the investigation of the etiology. of the septic arthritis in a great number of horses associated with multidrug resistance of the isolates.

  14. Therapy-resistant septic olecranon bursitis due to Mycobacterium gordonae.

    Science.gov (United States)

    Konrads, Christian; Rückl, Kilian; El Tabbakh, Mohammed; Rudert, Maximilian; Kircher, Stefan; Plumhoff, Piet

    2016-01-01

    Septic olecranon bursitis due to atypical mycobacteria is rare. An insidious beginning can delay diagnosis and treatment. Antibacterial therapy recommendations are not well-defined for bursitis caused by atypical mycobacteria. We present a rare case of olecranon bursitis caused by Mycobacterium gordonae, reporting our experiences regarding pathogen identification and antibiotic therapy, which differs from regimes used in common septic bursitis mostly caused by staphylococcus aureus. A 35-year-old male with bursitis olecrani received open bursectomy. Microbiological culture did not reveal bacteria. Due to wound healing complications revision surgery was performed four weeks postoperatively. Finally, Mycobacterium gordonae was identified by PCR and an antibiogram could be developed. A triple antimicrobial combination therapy with Rifampicin, Clarithromycin, and Ethambutol was administered systemically for 12 months. The patient was followed-up for 24 months. After the second operation with pathogen identification and antibiotic combination therapy the wound healed without any additional complications. At last follow-up 24 months after the first surgery with bursectomy and 23 months after revision surgery with debridement, the patient was still pain free with no significant clinical findings or tenderness to touch at the operation site. Elbow range of motion was full. As septic bursitis can be caused by many different and sometimes rare and difficult to identify bacteria, intraoperative probes should be taken and histopathological and microbiological analysis should be conducted, including PCR. In a young man with olecranon bursitis due to Mycobacterium gordonae surgical treatment and an antibiotic combination therapy showed a good clinical outcome after one and two years. © The Authors, published by EDP Sciences, 2016.

  15. SURGICAL TREATMENT OF CHILDREN WITH CONSEQUENCES OF INFANTILE SEPTIC ARTHRITIS

    Directory of Open Access Journals (Sweden)

    M. P. Teplenky

    2017-01-01

    Full Text Available Introduction. The consequences of infantile septic arthritis are quite diverse and can manifest themselves as a damage to the growth zone, deformation and destruction of the articular components, and violation of the articular relationships. To treat this pathology, technically complex and traumatic surgical interventions are used. The purpose of this work is to analyze the medium-term results of the use of these methods in the treatment of children with septic coxitis consequences.Material and methods. The outcomes of treatment for 37 children with consequences of septic coxitis using Ilizarov apparatus were analyzed. Average age of patients at the time of the surgery was 8.2±0.5 years (from 6 to 10 years. Follow up period was from 3 to 10 years (average 4.7 years. Functional outcomes were assessed by C.L. Colton, radiologic indices — by E. Severin score and J. Kruczynski.Results. Patients were distributed into three groups according to anatomical features. Functional outcomes of patients in the 1st group: good (12–15 points — 3 joints, satisfactory (9–11 points — 5 joints, unsatisfactory (8 points — 1 joint. X-ray findings of patients in the 1st group according to J. Kruczynski criteria: good — 5 joints, satisfactory — 4 joints; by E. Severin criteria: Ia — 1, Ib –1, IIa — 2, IIb — 3, III — 2. Functional outcomes of patients in the 2nd group: good (12–14 points — 10 joints, satisfactory (9–11 points — 8 joints. Distribution in the second group by J. Kruczynski criteria: good — 9, satisfactory — 9; by E. Severin criteria: IIa — 14, IIb — 4. Distribution of functional outcomes in the 3rd group in accordance with C.L. Colton criteria: good (12–15 points — 3 joints, satisfactory (9–11 points — 7 joints. Distribution in the third group according to J. Kruczynski criteria: good — 4, satisfactory — 6; by E. Severin criteria: IIa — 5, IIb — 4, III — 1.Conclusion. The use of the presented

  16. Septic arthritis of the ankle due to Salmonella enteritidis.

    LENUS (Irish Health Repository)

    Dineen, Patrick F

    2011-06-01

    Salmonella septic arthritis in healthy, immunocompetent patients is extremely rare. We present the case of a 70-year-old man who presented with a one-day history of painful swelling of his ankle from which was aspirated pus which subsequently grew Salmonella enteritidis. There was no history of trauma or symptoms consistent with Salmonella enterocolitis. Our patient recovered fully after two weeks on intravenous ceftriaxone and six weeks on oral ciprofloxacin. Salmonella is a notifiable disease in the European Union and the United States of America, and is associated with outbreaks as a result of food contamination. The nature of Salmonella arthritis and its appropriate management are outlined.

  17. A Case of Polyarticular Pasteurella multocida Septic Arthritis

    Directory of Open Access Journals (Sweden)

    Sarah Nitoslawski

    2016-01-01

    Full Text Available A 76-year-old man with a history of osteoarthritis presents with right leg erythema and inability to weight-bear and pain in his right shoulder. Synovial fluid cell count of the knee and shoulder showed abundant neutrophils, and cultures of the knee showed growth of Pasteurella multocida. The patient owned four cats with which he had frequent contact, but history and physical examination elicited no evidence of scratches or bites. This case highlights the invasive potential of Pasteurella multocida in an immunocompetent individual and its capacity to cause septic arthritis in the setting of frequent animal contact.

  18. Acute glyco-metabolic decompensation during septic shock

    Directory of Open Access Journals (Sweden)

    Maria Marta Cravino

    2010-09-01

    Full Text Available Hyper-glycemy is commonly described as a complication in patients affected by septic states, regardless of their having had diabetes. Numerous studies also record the presence of glyco-metabolic decompensations in patients affected by leukemia and lymphoma treated with chemotherapy. The case under study interesting and peculiar as there is no mention of glycemy levels so high to be not suitable for life. It is interesting also the patient's good therapeutical response, their marrow aplasia status and general poor health condition notwithstanding.

  19. Bacillus pumilus Septic Arthritis in a Healthy Child

    Directory of Open Access Journals (Sweden)

    V. M. Shivamurthy

    2016-01-01

    Full Text Available We report a case of septic arthritis caused by a Bacillus species, B. pumilus, occurring in a healthy child. This organism rarely causes serious infections and has only been described in newborns and immunocompromised individuals or as a skin infection. This child developed an indolent joint swelling after a minor skin injury, and symptoms were initially thought most consistent with chronic arthritis. The case demonstrates that clinicians should consider joint infection in children presenting with acute monoarticular swelling, even without prominent systemic features.

  20. Lumbar facet septic arthritis. Report of two cases

    Directory of Open Access Journals (Sweden)

    Juan Manuel Velasco

    2017-02-01

    Full Text Available We report two cases with isolated septic arthritis of a lumbar facet after a non articular infection, and sepsis. Being a rarity, it is a condition that goes frequently unnoticed, unless taken into account directly. If it is not treated on time, it can leave serious sequelae. The treatment may vary, according to the time of diagnosis. It might have a good response to antibiotic therapy alone, or it may be necessary to associate surgical drainage.

  1. Lung emphysema induced by cigarette smoke: Studies in mice

    NARCIS (Netherlands)

    Eijl, Teunis Jan Ahasuerus van

    2006-01-01

    The experiments described in this thesis were designed to shed some more light on the mechanisms underlying cigarette smoke-induced lung emphysema. We used elastase instillation to induce lung emphysema, and subsequently perfused the lungs ex-vivo with buffer at a range of flows to measure changes

  2. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Shankar-Hari, Manu; Phillips, Gary S.; Levy, Mitchell L.; Seymour, Christopher W.; Liu, Vincent X.; Deutschman, Clifford S.; Angus, Derek C.; Rubenfeld, Gordon D.; Singer, Mervyn; Angus, Derek; Annane, Djilalli; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon; Chiche, Jean-Daniel; Coopersmith, Craig; Deutschman, Cliff; Hotchkiss, Richard; Levy, Mitchell; Marshall, John; Martin, Greg; Opal, Steve; Rubenfeld, Gordon; Seymour, Christopher; van der Poll, Tom; Vincent, Jean-Louis

    2016-01-01

    IMPORTANCE Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition. OBJECTIVE To develop a new definition and clinical criteria for identifying

  3. Do septic systems contribute micropollutants and their transformation products to shallow groundwater?

    Science.gov (United States)

    Septic systems may contribute micropollutants to shallow groundwater and surface water. We constructed two in situ conventional drainfields (drip dispersal and gravel trench) and an advanced drainfield of septic systems to investigate the fate and transport of micropollutants to shallow groundwater....

  4. Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality.

    Science.gov (United States)

    Mickiewicz, Beata; Vogel, Hans J; Wong, Hector R; Winston, Brent W

    2013-05-01

    Septic shock is a significant cause of morbidity and mortality in the pediatric population. Early recognition of septic shock and appropriate treatment increase survival rate; thus, developing new diagnostic tools may improve patients' outcomes. To determine whether a metabolomics approach could be useful in the diagnosis and prognosis of septic shock in pediatric intensive care unit (PICUs). Serum samples were collected from 60 patients with septic shock, 40 PICU patients with systemic inflammatory response syndrome (not suspected of having an infection), and 40 healthy children. Proton nuclear magnetic resonance spectroscopy spectra were analyzed and quantified using targeted profiling methodology. Multivariate statistical analysis was applied to detect specific patterns in metabolic profiles and to highlight differences between patient samples. Supervised analysis afforded good predictive models and managed to separate patient populations. Some of the metabolite concentrations identified in serum samples changed markedly, indicating their influence on the separation between patient groups. These metabolites represent a composite biopattern of the pediatric metabolic response to septic shock and might be considered as the basis for a biomarker panel for the diagnosis of septic shock and its mortality in PICU. Our results indicate that nuclear magnetic resonance metabolite profiling might serve as a promising approach for the diagnosis and prediction of mortality in septic shock in a pediatric population and that quantitative metabolomics methods can be applied in the clinical evaluations of pediatric septic shock.

  5. Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.

    Science.gov (United States)

    Wong, Hector R; Cvijanovich, Natalie Z; Allen, Geoffrey L; Thomas, Neal J; Freishtat, Robert J; Anas, Nick; Meyer, Keith; Checchia, Paul A; Weiss, Scott L; Shanley, Thomas P; Bigham, Michael T; Banschbach, Sharon; Beckman, Eileen; Harmon, Kelli; Zimmerman, Jerry J

    2014-04-15

    Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects. To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock. We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis. The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects. Notably, the degree of down-regulation was significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway. Administration of corticosteroids in pediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.

  6. SEPTIC TANK SETBACK DISTANCES: A WAY TO MINIMIZE VIRUS CONTAMINATION OF DRINKING WATER

    Science.gov (United States)

    Septic tanks are the most frequently reported causes of contamination in ground-water disease outbreaks associated with the consumption of untreated ground water in the United States. The placement of septic tanks is generally controlled by county-wide or state-wide regulations, ...

  7. Effect of temperature on anaerobic treatment of black water in UASB-septic tank systems

    NARCIS (Netherlands)

    Luostarinen, S.; Sanders, W.T.M.; Kujawa-Roeleveld, K.; Zeeman, G.

    2007-01-01

    The effect of northern European seasonal temperature changes and low temperature on the performance of upflow anaerobic sludge blanket (UASB)-septic tanks treating black water was studied. Three UASB-septic tanks were monitored with different operational parameters and at different temperatures. The

  8. Diabetic Septic Foot Lesions in El Obeid, Western Sudan | El Bushra ...

    African Journals Online (AJOL)

    Objectives: To study the magnitude, presentations and outcomes of diabetic septic foot lesions in El Obeid, Western Sudan. Patients and Methods: The records of 86 diabetic patients with septic foot lesions admitted to the wards of the University Surgical Unit at El Obeid Teaching Hospital, Western Sudan during the years ...

  9. Refractory septic shock in children: a European Society of Paediatric and Neonatal Intensive Care definition

    NARCIS (Netherlands)

    Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J. G.|info:eu-repo/dai/nl/085432083; Javouhey, Etienne; Peters, Mark J.; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

    2016-01-01

    Purpose Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and

  10. Initial fluid resuscitation of patients with septic shock in the intensive care unit

    DEFF Research Database (Denmark)

    Carlsen, Sarah; Perner, A

    2011-01-01

    Fluid is the mainstay of resuscitation of patients with septic shock, but the optimal composition and volume are unknown. Our aim was to evaluate the current initial fluid resuscitation practice in patients with septic shock in the intensive care unit (ICU) and patient characteristics and outcome...

  11. Lactate concentrations in the rectal lumen in patients in early septic shock

    DEFF Research Database (Denmark)

    Ibsen, Michael; Tenhunen, J.; Wiis, J.

    2010-01-01

    Previously, we observed that rectal luminal lactate was higher in non-survivors compared with survivors of severe sepsis or septic shock persisting >24 h. The present study was initiated to further investigate this tentative association between rectal luminal lactate and mortality in a larger...... population of patients in early septic shock....

  12. Consecutive daily measurements of luminal concentrations of lactate in the rectum in septic shock patients

    DEFF Research Database (Denmark)

    Ibsen, Michael; Wiis, Jørgen; Waldau, Tina

    2012-01-01

    In a recent study we found no difference in the concentrations of luminal lactate in the rectum between nonsurvivors and survivors in early septic shock (......In a recent study we found no difference in the concentrations of luminal lactate in the rectum between nonsurvivors and survivors in early septic shock (...

  13. A holistic approach for perfusion assessment in septic shock: Basic foundations and clinical applications

    NARCIS (Netherlands)

    Hernández Poblete, G.W.

    2013-01-01

    A fundamental challenge in septic shock resuscitation is to evaluate tissue perfusion. In this thesis, we review the basic foundations for the development of a comprehensive and holistic model for perfusion assessment in septic shock, and outline its application to evaluate the impact of

  14. Survivors of septic shock caused by Neisseria meningitidis in childhood : Psychosocial outcomes in young adulthood

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    2011-01-01

    Objective: To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. Design: A cross-sectional study. Setting: The psychological investigation took place in the department of Child and

  15. Refractory septic shock in children : a European Society of Paediatric and Neonatal Intensive Care definition

    NARCIS (Netherlands)

    Morin, Luc; Ray, Samiran; Wilson, Clare; Remy, Solenn; Benissa, Mohamed Rida; Jansen, Nicolaas J. G.; Javouhey, Etienne; Peters, Mark J.; Kneyber, Martin; De Luca, Daniele; Nadel, Simon; Schlapbach, Luregn Jan; Maclaren, Graeme; Tissieres, Pierre

    2016-01-01

    Although overall paediatric septic shock mortality is decreasing, refractory septic shock (RSS) is still associated with high mortality. A definition for RSS is urgently needed to facilitate earlier identification and treatment. We aim to establish a European society of paediatric and neonatal

  16. The impact of septic systems density and nearness to spring water ...

    African Journals Online (AJOL)

    account

    septic systems density and nearness to water points on spring water quality. Samples from 15 spring wells were analysed for pH, nitrate and faecal coliform contamination. Locations and distances of spring from septic systems were determined using global positioning system (GPS) device and ArcGIS software, respectively.

  17. Fusobacterium necrophorum presenting as isolated lung nodules

    Directory of Open Access Journals (Sweden)

    Rajiv Sonti

    2015-01-01

    Full Text Available Fusobacterium necrophorum causes Lemierre's syndrome - a dramatic and distinct condition beginning with pharyngitis before proceeding to internal jugular vein septic thrombophlebitis and respiratory tract infection in otherwise healthy individuals. It is rare, but by far the most common pathway to parenchymal lung disease with this organism. Here we describe we a 34 year old healthy lady who was nontoxic without any antecedent illness who presented with lung nodules due to fusobacterium necrophorum as the sole manifestation of disease. Leading diagnostic consideration prior to culture data was pulmonary vasculitis. Identifying her disease process was a somewhat chance occurrence, and it began to resolve prior to antibiotic therapy. Though it would be difficult to recommend keen awareness of this organism given its rarity, it is important to consider that its scope may be broader than traditionally considered.

  18. Identification of pediatric septic shock subclasses based on genome-wide expression profiling

    Directory of Open Access Journals (Sweden)

    Monaco Marie

    2009-07-01

    Full Text Available Abstract Background Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results Three putative subclasses (subclasses A, B, and C were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, P Conclusion Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.

  19. A cluster of septic olecranon bursitis in association with infantry training.

    Science.gov (United States)

    Wasserzug, O; Balicer, R D; Boxman, J; Klement, E; Ambar, R; Zimhony, O

    2011-01-01

    Septic olecranon bursitis (OB) is caused primarily by Staphylococcus aureus (SA) usually in association with occupations involving trauma to the elbows. An outbreak of septic OB was identified in an infantry platoon. The severity of the injury to the skin overlying the elbows was scored and compared to a parallel platoon of the same unit. All soldiers were tested for SA carriage and pulse field gel electrophoresis (PFGE) was performed on available isolates. Nine cases of septic OB were identified only in platoon A. The significant risk factor for septic OB was a moderately or severely injured elbow (RR = 3.86). SA was isolated from the anterior nares and elbows of 29/36 (80.6%) of the soldiers in the unit (platoons A + B); however, this did not account for the difference in morbidity between the two platoons. This is the first report of a cluster of septic OB in association with intense infantry training.

  20. Infectious Etiologies and Patient Outcomes in Pediatric Septic Shock.

    Science.gov (United States)

    Ames, Stefanie G; Workman, Jennifer K; Olson, Jared A; Korgenski, E Kent; Masotti, Susan; Knackstedt, Elizabeth D; Bratton, Susan L; Larsen, Gitte Y

    2017-03-01

    Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. We evaluated a retrospective cohort of children (age shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in ≤1 hour and (2) receipt of appropriate antibiotics in ≤1 hour. The primary outcome was development of new or progressive multiple system organ dysfunction syndrome (NP-MODS). The secondary outcome was mortality. Among 321 patients admitted to intensive care, 48% (n = 153) received empiric antibiotics in ≤1 hour. These patients were more ill at presentation with significantly greater median pediatric index of mortality 2 (PIM2) scores and were more likely to receive recommended resuscitation in the ED (61% vs 14%); however, rates of NP-MODS (9% vs 12%) and hospital mortality (7% vs 4%) were similar to those treated later. Early, appropriate antibiotics were administered to 33% (n = 67) of patients with identified or suspected bacterial infection. These patients had significantly greater PIM2 scores but similar rates of NP-MODS (15% vs 15%) and hospital mortality (10% vs 6%) to those treated later. Critically ill children with septic shock treated in a children's hospital ED who received antibiotics in ≤1 hour were significantly more severely ill than those treated later, but they did not have increased risk of NP-MODS or death.

  1. [Septic abortion. Complications and therapeutic considerations (author's transl)].

    Science.gov (United States)

    Cañas, E; Cararach, V; Fortuny, A

    1980-01-25

    A study is presented on the incidence and complications of septic abortion in a group of patients admited on the 1st. Obstetric and Gynecologic Clinic of the University of Barcelona during a period of 5 years (1971-1975). Abortion is the cause of admision of 20,2% of patients in the gynecology ward and represents the 12,3% of the overall number of patients during the same period. In 7,8% of the patients admited because of abortion we found the criteria for establishing the diagnosis of septic complication and in 15,2% of those extrapelvic involvement is found, mainly endotoxic shock, acute renal failure and difuse peritonitis. Endocervical cultures were positive in 73% of cases and in 65,7% gram negative germs were isolated, being the most common E. coli. The different clinical patterns are discussed in cases in which anaerobics are implicated and the diagnostic and therapeutic aproaches in the different complications are reviewed particularly in concern to the indications of surgery when this may be the only lifesaving procedure.

  2. Simvastatin prevents lipopolysaccharide-induced septic shock in rats.

    Science.gov (United States)

    Yu, Li; Da, Xing-Wen; Wu, Xiao-Ling; He, Ao-di; Long, Ding

    2017-04-01

    Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis. Herein, we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock. In our study, rats were divided into a saline group, an LPS group and an LPS plus simvastatin group. Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg), with variations in left ventricular pressure recorded throughout. Ninety min after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated from the whole blood using separating medium. The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1). In addition, mesentery microcirculations of inlet diameter, outlet diameter and blood flow rate were measured in all three groups. The results indicated that simvastatin significantly promoted heart systolic function and increased the level of uPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group. Moreover, simvastatin reversed the LPS-induced inhibition of mesentery microcirculation. Taken together, it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.

  3. Necrotizing Fasciitis Secondary to Aeromonas Infection Presenting with Septic Shock

    Directory of Open Access Journals (Sweden)

    Nikhil Bhatia

    2017-01-01

    Full Text Available This report describes a case of necrotizing fasciitis presenting with septic shock due to an Aeromonas infection. The patient cut his foot while mowing the lawn and then spent time in a pool with black mold. He began feeling ill and developed swelling and a quarter-sized black area on his right lower extremity. Despite being hemodynamically unstable with systolic blood pressure in the low 70s, the patient was transferred to our facility from outside hospital 100 miles away. Upon arriving to facility, the patient appeared to be septic and the infected area of skin had grown. Irrigation and debridement were performed and appropriate antibiotic therapy was given; however, the patient subsequently died on hospital day 8. On review of the literature, cases of necrotizing fasciitis due to Aeromonas infection have been treated successfully with the aforementioned therapy; however, there is high mortality associated with these infections, many times related to a delayed diagnosis. Our patient also had multiple poor prognostic factors including hepatic dysfunction and immunosuppression.

  4. First diagnosis of septic arthritis in a dinosaur

    Science.gov (United States)

    Anné, Jennifer; Hedrick, Brandon P.; Schein, Jason P.

    2016-08-01

    Identification and interpretation of pathologies in the fossil record allows for unique insights into the life histories of extinct organisms. However, the rarity of such finds limits not only the sample size for palaeopathologic studies, but also the types of analyses that may be performed. In this study, we present the first occurrence of a palaeopathology in a vertebrate from the Mesozoic of the East Coast of North America (Appalachia), a pathologic ulna and radius of an indeterminate hadrosaur from the Navesink Formation (New Jersey). X-ray microtomography allowed for both detailed and more accurate diagnosis of the pathologic condition as well as virtual conservation of the specimen. Based on extant archosaurian comparisons, the hadrosaur was diagnosed with severe septic arthritis affecting the proximal ulna and radius. Diagnosis was based on erosion of the joint and highly reactive periosteal bone growth and fusion of the elements. To the best of our knowledge, this is the first recorded account of septic arthritis in dinosaurs. The severity of the pathology suggests the animal suffered with this condition for some time before death. Unfortunately, only the ulna and radius were found. Thus, the extent to which the condition spread to other parts of the body is unknown.

  5. Septic hip dislocations in children in a developing country

    Directory of Open Access Journals (Sweden)

    Gabriel Ngom

    2011-01-01

    Full Text Available Purpose: To report on a radiological issue and therapeutic aspects encountered in septic hip dislocations in a developing country. Patients and Methods: Nineteen children among whom 11 boys and 8 girls aged on average 5.3-years old presented 7 recent and 12 late hip dislocations. Those dislocations were distributed into in category 1: dislocations without associated lesion; category 2: dislocations associated with minor lesions; category 3: dislocations associated with major lesion. Ten children who presented an elevated erythrocyte sedimentation rate (ESR received antibiotics. An arthrotomy was performed in children with a recent dislocation. Traction was performed in all children with an average duration of 5 weeks. The results were considered good, intermediate or bad using two parameters: ESR and reduction of dislocation. Results: 2 category 1 dislocations, 6 category 2 dislocations and 11 category 3 dislocations were noted. As concerns the recent dislocations, there were 2 category 1 dislocations and 5 category 2 dislocations. For late dislocations, 1 category 2 and 11 category 3 dislocations were recorded. There were 8 good results and 11 bad results. The good results concerned 7 recent dislocations and one late dislocation. The bad results concerned exclusively late dislocations. Conclusion: In children with septic hip dislocations, the good results concern almost exclusively recent dislocations but arthrotomy and immobilization must be done early.

  6. Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum.

    Science.gov (United States)

    Wong, Hector R; Cvijanovich, Natalie; Allen, Geoffrey L; Lin, Richard; Anas, Nick; Meyer, Keith; Freishtat, Robert J; Monaco, Marie; Odoms, Kelli; Sakthivel, Bhuvaneswari; Shanley, Thomas P

    2009-05-01

    To advance our biological understanding of pediatric septic shock, we measured the genome-level expression profiles of critically ill children representing the systemic inflammatory response syndrome (SIRS), sepsis, and septic shock spectrum. Prospective observational study involving microarray-based bioinformatics. Multiple pediatric intensive care units in the United States. Children shock on day 1. The available day 3 samples included 20 patients still meeting sepsis criteria, 39 patients still meeting septic shock criteria, and 24 patients meeting the exclusive day 3 category, SIRS resolved. None other than standard care. Longitudinal analyses were focused on gene expression relative to control samples and patients having paired day 1 and day 3 samples. The longitudinal analysis focused on up-regulated genes revealed common patterns of up-regulated gene expression, primarily corresponding to inflammation and innate immunity, across all patient groups on day 1. These patterns of up-regulated gene expression persisted on day 3 in patients with septic shock, but not to the same degree in the other patient classes. The longitudinal analysis focused on down-regulated genes demonstrated gene repression corresponding to adaptive immunity-specific signaling pathways and was most prominent in patients with septic shock on days 1 and 3. Gene network analyses based on direct comparisons across the SIRS, sepsis, and septic shock spectrum, and all available patients in the database, demonstrated unique repression of gene networks in patients with septic shock corresponding to major histocompatibility complex antigen presentation. Finally, analyses focused on repression of genes corresponding to zinc-related biology demonstrated that this pattern of gene repression is unique to patients with septic shock. Although some common patterns of gene expression exist across the pediatric SIRS, sepsis, and septic shock spectrum, septic shock is particularly characterized by

  7. Septic Arthritis of the Wrist: Incidence, Risk Factors, and Predictors of Infection.

    Science.gov (United States)

    Jennings, John D; Zielinski, Elizabeth; Tosti, Rick; Ilyas, Asif M

    2017-05-01

    Septic arthritis of the wrist can result in permanent damage to the joint, making timely diagnosis crucial to initiate empiric antibiotics and surgical intervention. Although septic arthritis is routinely included in the differential diagnosis of atraumatic wrist pain, the incidence is unknown. Unlike large joints, there is no consensus on cell count values considered pathognomonic for wrist septic arthritis. The goal of this retrospective study was to determine the incidence of wrist septic arthritis and to identify the clinical, serum, and joint fluid values that predict infection. The records of patients who presented to a single urban hospital with a swollen, painful wrist without trauma during a 10-year period were reviewed. For patients who had a joint fluid analysis, the records were examined for history as well as demographic and laboratory data. Joint fluid analysis consisted of cell count, Gram stain, and cultures. Of 892 patients who met the inclusion criteria, 1.5% had wrist septic arthritis. Variables associated with septic arthritis included serum white blood cell count above 11,000/µL, core temperature above 100.4°F within 24 hours of aspiration, history of intravenous drug abuse, and smoking. No joint cell count analysis predicted septic arthritis, although patients with septic wrists had an elevated joint white blood cell count above 97,000/µL. Wrist septic arthritis is uncommon; however, objective factors can help identify patients at risk. Because joint cell count analysis cannot reliably predict a septic wrist, priority for joint aspirations with limited fluid should be given instead to Gram stain, culture, and crystal analysis. [Orthopedics. 2017; 40(3):e526-e531.]. Copyright 2017, SLACK Incorporated.

  8. [Altered hepatic expression of selenoprotein S1 in septic mouse induced by LPS attack].

    Science.gov (United States)

    Su, Mao-sheng; He, Lei; Yao, Yong-ming; Yu, Yan; Wu, Yao; Dong, Jia-hong

    2010-07-13

    To investigate the change of selenoprotein S1 (SEPS1) hepatic expression in septic mouse induced by LPS attack. The septic murine model induced by LPS attack was established. Ten mice were randomly selected as control group from 84 BALB/c mice and others as septic group. The mice were sacrificed after anesthesia in control group and 10 mg/kg LPS was injected intraperitoneally into septic group mice. Liver and blood samples were taken at 6, 12, 24, 48, 72 and 96 h after LPS injection. Ten mice were randomly selected at each time point. The levels of blood ALT, AST, LDH and liver IL-6, TNF-α were detected. And the SEPS1 expression was simultaneously detected by Western blot. There was liver damage in septic group compared with normal control group. The levels of ALT, AST and LDH markedly increased. And all peaked at 24 h. The levels were (99 ± 11), (299 ± 48) and (1523 ± 131) U/L respectively (versus level at zero hour, P 8239) ng/L, P < 0.05]. Western blot showed that SEPS1 protein expression markedly increased simultaneously in liver of septic mouse. And the peak value was reached at 24 h post-injury. Then there was a gradual decrease and normal level returned at 72 h. Immunohistochemical results showed that SEPS1 protein expression in liver of septic mouse also markedly increased. And the peak value was reached at 24 h post-injury. Pathologic results showed that liver lesion was apparent in septic mouse and it was the worst during 6-12 h. Liver damage to different extents may be induced by LPS attack in septic mouse. The levels of IL-6 and TNF-α markedly increase. The SEPS1 protein expression in liver of septic mouse is also markedly elevated. And it peaks at 24 h post-injury and returns to normal at 72 h.

  9. [The hemodynamic characteristics of septic shock and relationship with syndrome types of traditional Chinese medicine].

    Science.gov (United States)

    He, Jianzhuo; Wang, Lei; Yin, Xin; Guo, Liheng; Zhang, Minzhou

    2016-02-01

    To observe hemodynamic characteristics and the correlation with syndrome types of traditional Chinese medicine (TCM) in patients with septic shock, so as to direct the treatment based on syndrome differentiation. A prospective observation was conducted. Sixty-eight patients with septic shock admitted to the Department of Critical Care Medicine of Dade Road General Hospital of Guangdong Hospital of TCM from January 2013 to July 2015 were enrolled. Pulse indicating continuous cardiac output (PiCCO) was used to monitor the hemodynamic changes, including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), global end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), maximum rate of the increase in pressure (dPmax) and systemic vascular resistance index (SVRI), for assessment of hemodynamics. According to the CI, the patients were divided into two groups , i.e. high CI group (CI ≥ 50.0 mL×s(-1)×m(-2), n = 34) and low CI group (CI types were investigated, the correlation between the TCM syndrome factors and hemodynamic parameters was analyzed. The patients were divided into survival group and death group, and clinical parameters and hemodynamic characteristics were compared between two groups. The acute physiology and chronic health evaluation II (APACHEII) score and blood glucose of low CI group were higher than those of high CI group [APACHEII score: 24.4±7.2 vs. 19.8±7.4, t = -2.279, P = 0.023; blood glucose (mmol/L): 9.7 (7.7, 14.6) vs. 6.7 (5.6, 10.0), Z = -2.257, P = 0.024], CI and GEDVI were lowered [CI (mL×s(-1)×m(-2)): 36.7±8.3 vs. 68.4±16.7, t = 10.285, P = 0.000; GEDVI (mL/m(2)): 689.0 (566.0, 883.8) vs. 838.5 (692.8, 1?247.3), Z = -2.711, P = 0.007], while SVRI was increased [kPa×s×L(-1)×m(-2): 248.7 (202.1, 324.5) vs. 143.4 (102.7, 171.4), Z = -5.336, P = 0.000]. Accompanied symptoms were found to occur more commonly in septic shock patients, and the most common syndrome elements

  10. Bench-to-bedside review: Vasopressin in the management of septic shock

    Science.gov (United States)

    2011-01-01

    This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 μg/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse

  11. Lung Cancer

    Science.gov (United States)

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  12. Lung cancer

    OpenAIRE

    Neville, Alan J

    2009-01-01

    Lung cancer is the leading cause of cancer deaths in both men and women, with 80-90% of cases caused by smoking. Small cell lung cancer accounts for 20% of all cases, and is usually treated with chemotherapy. Adenocarcinoma is the main non-small cell pathology, and is treated initially with surgery.

  13. Lung cancer

    OpenAIRE

    Neville, Alan J; Kuruvilla, Mridula Sara

    2010-01-01

    Lung cancer is the leading cause of cancer deaths in both men and women, with 80% to 90% of cases caused by smoking. Small cell lung cancer accounts for 20% of all cases, and is usually treated with chemotherapy. Adenocarcinoma is the main non-small cell pathology, and is treated initially with surgery.

  14. Lung Cancer Screening

    Science.gov (United States)

    ... factors increase or decrease the risk of lung cancer. Lung cancer is a disease in which malignant (cancer) ... following PDQ summaries for more information about lung cancer: Lung Cancer Prevention Non-Small Cell Lung Cancer Treatment ...

  15. Value of Serum Cholinesterase Activity in the Diagnosis of Septic Shock Due to Bacterial Infections.

    Science.gov (United States)

    Bahloul, Mabrouk; Baccouch, Najeh; Chtara, Kamilia; Turki, Mouna; Turki, Olfa; Hamida, Chokri Ben; Chelly, Hedi; Ayedi, Fatma; Chaari, Anis; Bouaziz, Mounir

    2017-06-01

    We aimed to investigate whether serum cholinesterase (SChE) activity can be helpful for the diagnosis of septic shock and to evaluate its usefulness in comparison with procalcitonin (PCT) and C-reactive protein (CRP). A prospective single-blinded study conducted in an intensive care unit of university hospital. Patients were classified as having cardiogenic shock, septic shock, or hemorrhagic shock. We also included a control group without neither hemodynamic instability nor sepsis. For all included patients, SChE, PCT, and CRP were simultaneously sampled. The comparison of sepsis markers between all groups showed that the mean values of PCT and CRP were significantly higher in patients with septic shock. However, SChE activity was significantly lower in this group. The SChE activity was found to be more accurate than PCT and CRP for the diagnosis of septic shock. In fact, an SChE activity ≤ 4000 UI/L predicted the diagnosis of septic shock with a sensitivity of 78%, a specificity of 89%, a predictive negative value of 97%, and a predictive positive value of 65%. However, the prognostic value of SChE activity was poor in multivariate analysis. The SChE activity level was significantly decreased in patients with septic shock. However, its prognostic value is poor. Our results suggest that SChE activity is useful for the diagnosis of septic shock. Further studies are warranted to confirm our findings.

  16. Micropollutants in groundwater from septic systems: Transformations, transport mechanisms, and human health risk assessment.

    Science.gov (United States)

    Yang, Yun-Ya; Toor, Gurpal S; Wilson, P Chris; Williams, Clinton F

    2017-10-15

    Septic systems may contribute micropollutants to shallow groundwater and surface water. We constructed two in situ conventional drainfields (drip dispersal and gravel trench) and an advanced drainfield of septic systems to investigate the fate and transport of micropollutants to shallow groundwater. Unsaturated soil-water and groundwater samples were collected, over 32 sampling events (January 2013 to June 2014), from the drainfields (0.31-1.07 m deep) and piezometers (3.1-3.4 m deep). In addition to soil-water and groundwater, effluent samples collected from the septic tank were also analyzed for 20 selected micropollutants, including wastewater markers, hormones, pharmaceuticals and personal care products (PPCPs), a plasticizer, and their transformation products. The removal efficiencies of micropollutants from septic tank effluent to groundwater were similar among three septic systems and were 51-89% for sucralose and 53->99% for other micropollutants. Even with high removal rates within the drainfields, six PPCPs and sucralose with concentrations ranging from groundwater, respectively. The human health risk assessment showed that the risk to human health due to consumption of groundwater is negligible for the micropollutants monitored in the study. A better understanding of ecotoxicological effects of micropollutant mixtures from septic systems to ecosystem and human health is warranted for the long-term sustainability of septic systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Comparative Analysis of Direct Hospital Care Costs between Aseptic and Two-Stage Septic Knee Revision

    Science.gov (United States)

    Kasch, Richard; Merk, Sebastian; Assmann, Grit; Lahm, Andreas; Napp, Matthias; Merk, Harry; Flessa, Steffen

    2017-01-01

    Background The most common intermediate and long-term complications of total knee arthroplasty (TKA) include aseptic and septic failure of prosthetic joints. These complications cause suffering, and their management is expensive. In the future the number of revision TKA will increase, which involves a greater financial burden. Little concrete data about direct costs for aseptic and two-stage septic knee revisions with an in depth-analysis of septic explantation and implantation is available. Questions/Purposes A retrospective consecutive analysis of the major partial costs involved in revision TKA for aseptic and septic failure was undertaken to compare 1) demographic and clinical characteristics, and 2) variable direct costs (from a hospital department’s perspective) between patients who underwent single-stage aseptic and two-stage septic revision of TKA in a hospital providing maximum care. We separately analyze the explantation and implantation procedures in septic revision cases and identify the major cost drivers of knee revision operations. Methods A total of 106 consecutive patients (71 aseptic and 35 septic) was included. All direct costs of diagnosis, surgery, and treatment from the hospital department’s perspective were calculated as real purchase prices. Personnel involvement was calculated in units of minutes. Results Aseptic versus septic revisions differed significantly in terms of length of hospital stay (15.2 vs. 39.9 days), number of reported secondary diagnoses (6.3 vs. 9.8) and incision-suture time (108.3 min vs. 193.2 min). The management of septic revision TKA was significantly more expensive than that of aseptic failure ($12,223.79 vs. $6,749.43) (p financial loss for the operating department. PMID:28107366

  18. Obturator Internus Abscess with Ipsilateral Septic Hip Arthritis.

    Science.gov (United States)

    Park, Sang Hyun; Kim, Joo Yong; Kong, Gyu Min; Roh, Sang Myung

    2016-11-01

    Obturator internus muscle (OIM) abscess is an uncommon condition often mistaken for bacterial infection of the hip joint. If the OIM abscess is accompanied by a septic hip, it becomes more difficult to make a diagnosis. Surgical drainage of OIM abscess is difficult because it is located at a deep part of the pelvic cavity. Therefore, intravenous antibiotic therapy or image-guided aspiration were used as a treatment method instead of surgical drainage. When drainage of the abscess was inadequate, prolonged antibiotic treatment was necessary. Here, we report a 12-year boy with abscess in the OIM and ipsilateral pyogenic arthritis of the hip which was accompanied by acute osteomyelitis of the triradiate cartilage of the acetabulum. The patient was successfully treated by surgical drainage of the abscess using the Stoppa approach and arthroscopic irrigation of the hip joint. Staphylococcus aureuswas the causative organism which was sensitive to oxacillin.

  19. Septic arthritis due to tubercular and Aspergillus co-infection

    Directory of Open Access Journals (Sweden)

    Mukesh Kumar

    2016-01-01

    Full Text Available Aspergillus septic arthritis is a rare and serious medical and surgical problem. It occurs mainly in immunocompromised patients. Aspergillus fumigatus is the most common causative organism followed by Aspergillus flavus. The most common site affected is knee followed by shoulder, ankle, wrist, hip and sacroiliac joint. Debridement and voriconazole are primary treatment of articular aspergilosis. To the best of our knowledge, there are no reported cases of co-infection of tuberculosis (TB and Aspergillus infecting joints. We report a case of co-infection of TB and A. flavus of hip and knee of a 60-year-old male, with type 2 diabetes mellitus. He was treated with debridement, intravenous voriconazole, and antitubercular drugs.

  20. Hyperkalemia induced pseudo-myocardial infarction in septic shock

    Directory of Open Access Journals (Sweden)

    S E Pothiawala

    2014-01-01

    Full Text Available Hyperkalemia is an acute life-threatening disorder presenting to the emergency department. Patients with hyperkalemia may manifest characteristic electrocardiographic changes including tented T waves, widening of the QRS complex and loss of P waves, sine wave pattern and eventually asystole. There have been only few reports of hyperkalemia causing ST segment elevation on electrocardiogram simulating an acute myocardial infarction. This case describes pseudo-myocardial infarction due to hyperkalemia and septic shock. Rapid determination of serum potassium levels by bedside blood gas analyzers serves to be a useful guide. ST segment elevation related to hyperkalemia will resolve with successful reduction of the serum potassium levels by appropriate therapy. It is important for physicians to be aware of this condition as this will aid in initiating correct therapy and prevent the patient from unnecessary interventions and the associated risk of complications.

  1. Primary Retroperitoneal Abscess Complicated with Septic Arthritis of the Hip

    Directory of Open Access Journals (Sweden)

    Chuan-Nan Su

    2006-01-01

    Full Text Available Primary retroperitoneal abscess complicated with septic arthritis of the hip is an unusual disease. The insidious and occult nature of abscess coexistent with arthritis causes diagnostic delays, prolonged sepsis, and considerably higher morbidity and mortality. We herein present a case of gouty arthritis and avascular necrosis of the femoral head in a 41-year-old woman who complained of fever, right flank pain, body weight loss, swelling over her right lower limb, and 2 weeks of pain in the right hip. The computed tomographic scan showed a huge abscess (about 32 × 10 × 8 cm over the right posterior pararenal space, with swelling of the right psoas, iliac, and obturator muscles. During surgery, the abscess was drained and sequestrectomy of the right hip was performed. Cultures of pus from the retroperitoneum and right hip showed Escherichia coli and Staphylococcus aureus. We review the literature and discuss possible causes.

  2. Paecilomyces lilacinus septic olecranon bursitis in an immunocompetent host.

    Science.gov (United States)

    Schweitzer, Karl M; Richard, Marc J; Leversedge, Fraser J; Ruch, David S

    2012-05-01

    Paecilomyces lilacinus is a filamentous fungus that is a rare cause of infection in immunocompromised human hosts. We present a case of lilacinus septic olecranon bursitis in an otherwise healthy 78-year-old male. This patient's case was complicated by wound breakdown after bursectomy and appropriate anti-fungal treatment, requiring a local soft tissue rearrangement. This case demonstrates the need for appropriate and timely medical and surgical treatment in infections involving lilacinus, which are not isolated solely to systemically immunocompromised and medically-ill patient populations. In cases where the patient is systemically immumocompromised or has been rendered locally immunocompromised, it is essential to obtain a full culture work-up, including fungi.

  3. Septic Bursitis in an 8-Year-Old Boy

    Directory of Open Access Journals (Sweden)

    Panagiotis Kratimenos

    2014-01-01

    Full Text Available Background. The prepatellar bursa can become inflamed owing to repeated trauma. Prepatellar bursitis is extremely rare in children. Methods. We report the case of an 8-year-old boy who was treated for an erythematous, swollen, and severely painful right knee, fever, inability to bear weight on the leg, and purulent material draining from a puncture wound. We describe the differential diagnosis for tender swollen knee, including infection, gout, rheumatoid arthritis, and osteoarthritis. If untreated, prepatellar bursitis can progress to patellar osteomyelitis. Results. Wound cultures grew Streptococcus pyogenes, with the infection resolving with amoxicillin. Conclusions. A high index of suspicion is necessary in children presenting with prepatellar bursitis to prevent potentially devastating sequelae of infection of the septic joint.

  4. Accuracy of spiral CT and 3D reconstruction in the detection of acute pulmonary embolism - development of an animal model using porcine lungs and technical specimens. Development of an animal model using porcine lungs and technical specimens; Diagnostik der akuten Lungenembolie mittels Spiral-CT und 3D-Rekonstruktion. Entwicklung eines Tiermodells und technischer Probekoerper im Ex-vivo-Experiment

    Energy Technology Data Exchange (ETDEWEB)

    Ries, B.G. [Klinik und Poliklinik fuer Radiologie, Univ. Mainz (Germany); Klinik fuer Radiologische Diagnostik, RWTH Aachen (Germany); Kauczor, H.U.; Thelen, M. [Klinik und Poliklinik fuer Radiologie, Univ. Mainz (Germany); Konerding, M.A. [Anatomisches Inst., Mainz Univ (Germany)

    2001-02-01

    Purpose: To develop a model for simulation the CT morphologic situation of acute pulmonary embolism, to evaluate the accuracy of spiral CT and 3D reconstruction in the detection of artificial emboli and to investigate the influence of the orientation of emboli depending on z-axis orientation. Materials and Methods: Standardized artificial emboli made of wax and of defined size and shape were positioned into the pulmonary arteries of porcine lungs. Castings of the embolized pulmonary arterial trees were made by injection of a special opaque resin. After performance of spiral CT the data sets of the emboli and the pulmonary arteries were post-processed. The 3D segmentations were compared with the anatomic preparation to evaluate the accuracy of spiral CT/3D reconstruction-technique. Technical specimens simulating CT-morphology of acute embolized vessels underwent spiral CT in six different positions with respect to the z-axis. The CT data were reconstructed using a standardized and a contrastadapted method with interactive correction. The 3D emboli were analysed under qualitative aspects, and measurements of their extent were done. Results: In nearly 91%, there was complete agreement between CT and the corresponding findings at the anatomical preparation. Measurements of the 3D reconstructed technical specimens showed discrepancies of shape and size in dependence of the size of the original preparation, orientation and reconstruction technique. Overestimation up to 4 mm and underestimation to 2,2 mm were observed. Measurements of preparations with heights from 14 to 26 mm showed variances of {+-}1,5 mm ({proportional_to}6-11%). Conclusion: The presented models are suitable to simulate CT morphology of acute pulmonary embolism under ex-vivo conditions. Accuracy in the detection of artificial emboli using spiral CT/3D reconstruction is affected by localization, size and orientation of the emboli and the reconstruction technique. (orig.) [German] Ziel: Die Entwicklung

  5. Central venous oxygen saturation for the diagnosis of low cardiac output in septic shock patients

    DEFF Research Database (Denmark)

    Perner, A; Haase, N; Wiis, J

    2010-01-01

    Simple diagnostic tests are needed to screen septic patients for low cardiac output because intervention is recommended in these patients. We assessed the diagnostic value of central venous oxygen saturation in the superior vena cava (ScvO(2)) for detecting low cardiac output in patients with sep...... with septic shock.......Simple diagnostic tests are needed to screen septic patients for low cardiac output because intervention is recommended in these patients. We assessed the diagnostic value of central venous oxygen saturation in the superior vena cava (ScvO(2)) for detecting low cardiac output in patients...

  6. Maximally effective dosing regimens of meropenem in patients with septic shock

    DEFF Research Database (Denmark)

    Sjövall, Fredrik; Alobaid, Abdulaziz S; Wallis, Steven C

    2018-01-01

    Objectives: To use a population pharmacokinetic approach to define maximally effective meropenem dosing recommendations for treatment of Acinetobacter baumannii and Pseudomonas aeruginosa infections in a large cohort of patients with septic shock. Methods: Adult patients with septic shock...... was required for both empirical and targeted treatment. In patients with a CL CR of ≤ 100 mL/min, successful concentration targets could be reached with intermittent dosing of 1000 mg/8 h. Conclusions: In patients with septic shock and possible augmented renal clearance, doses should be increased and...

  7. Septic arthritis: what is the role for the rheumatologist?

    Directory of Open Access Journals (Sweden)

    V. Carraro

    2011-09-01

    Full Text Available Septic arthritis (SA is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA. Predisposing factors are immunosuppressive and corticosteroids therapy and RA “itself”. The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor α (TNFα antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficultto- access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.

  8. Effects of aeration on water quality from septic system leachfields.

    Science.gov (United States)

    Potts, David A; Görres, Josef H; Nicosia, Erika L; Amador, José A

    2004-01-01

    We conducted a pilot-scale study at a research facility in southeastern Connecticut to assess the effects of leachfield aeration on removal of nutrients and pathogens from septic system effluent. Treatments consisted of lysimeters periodically aerated to maintain a headspace O(2) concentration of 0.209 mol mol(-1) (AIR) or vented to an adjacent leachfield trench (LEACH) and were replicated three times. All lysimeters were dosed with effluent from a septic tank for 24 mo at a rate of 12 cm d(-1) and subsequently for 2 mo at 4 cm d(-1). LEACH lysimeters had developed a clogging mat, or biomat, 20 mo before the beginning of our study. The level of aeration in the AIR treatment was held constant regardless of loading rate. No conventional biomat developed in the AIR treatment, whereas a biomat was present in the LEACH lysimeters. The headspace of LEACH lysimeters was considerably depleted in O(2) and enriched in CH(4), CO(2), and H(2)S relative to AIR lysimeters. Drainage water from AIR lysimeters was saturated with O(2) and had significantly lower pH, five-day biological oxygen demand (BOD(5)), and ammonium, and higher levels of nitrate and sulfate than LEACH lysimeters regardless of dosing rate. By contrast, significantly lower levels of total N and fecal coliform bacteria were observed in AIR than in LEACH lysimeters only at the higher dosing rate. No significant differences in total P removal were observed. Our results suggest that aeration may improve the removal of nitrogen, BOD(5), and fecal coliforms in leachfield soil, even in the absence of a biomat.

  9. Septic complication following porous hydroxyapatite cranioplasty: prosthesis retention management.

    Science.gov (United States)

    Iaccarino, Corrado; Mattogno, Pier P; Zanotti, Bruno; Bellocchi, Silvio; Verlicchi, Angela; Viaroli, Edoardo; Pastorello, Giulia; SGULò, Francesco; Ghadirpour, Reza; Servadei, Franco

    2016-05-13

    After failing of autologous cranioplasty or when the bone flap is unavailable, the alloplastic (heterologous) materials are the choice for cranial reconstruction. No agreement has been reported about the material with a significant lower risk of septic complications. This is due to extremely heterogeneous prognostic factors related not only to the material used but also to the surgical procedures and/or to the timing of the procedure. More attention should be focused on the material whose characteristic could enable a delay in bacterial colonization, where an antibiotic therapy could be effective, without need of prosthesis removal. Four cases of severe septic complication following cranioplasty with porous hydroxyapatite (HA) prosthesis are presented. Patients were conservatively treated, without heterologous bone flap removal. All of our patients presented reasons for delaying HA cranioplasty removal: Patients 1, 3 and 4 had an associated shunted hydrocephalus and the need for non- removing the prosthesis was related to the predictable recurrence of overshunting and/or sinking skin flap syndrome. In case 4 the revision surgery would have also damaged the microvascular flap with latissimus dorsi muscle used by plastic surgeon for skin reconstruction. In case 2 the patient refused revision surgery. In all cases systemic and/or radiological signs of infection were observed. In Case 2 the infective process surrounded completely the HA prosthesis, while it was located in the epidural region in Case 1 and 4. In Case 3 a surgical curettage of the infected wound was performed over the HA prosthesis. Following prosthesis retention management with antibiotic therapy, all patients revealed systemic and/or radiological signs of sepsis resolution at follow-up. The possibility to avoid a prosthesis removal with effective antibiotic treatment is mainly due to the combination of three factors: targeted antibiotic therapy, good anatomical area revascularization (resulting of an

  10. [SEPTIC SHOCK IN PATIENT WITH SEVERE HEAD TRAUMA].

    Science.gov (United States)

    Sichev, A A; Tabasaransky, T Φ; Savin, I A; Gorachev, A S; Tenedieva, V D; Abramov, T A; Oshorov, A V; Polupan, A A; Mazkovsky, I V; Gavrilov, A G; Potapov, A A

    2015-01-01

    The clinical observation illustrates the role of screening of inflammatory markers and advanced hemodynamic monitoring in optimization of the treatment of the patient with severe traumatic brain injury (sTBI). The level of consciousness by the Glasgow Coma Scale at admission was 5 points. From the first day of stay the patient suffered hyperthermia to 39,0° C° The diagnosis of the aspiration pneumonia was determined by radiological signs, bronchoscopy and inflammatory blood markers, C-reactive protein, leukocytosis. From the second day the constant infusion of norepinephrine was necessary to maintain mean ABP above 80 mmHg. On the 10th day the patient's condition deteriorated sharply. Developed hyperthermia to 40, 2° and cardiovascular collapse (in spite of the high level of norepinephrine support a sharp decline in ABP up to 49/20 mmHg). Invasive advanced hemodynamic PiCCO monitoring (transpulmonary thermodilution) was started Septic shock was suspected. Standard laboratory tests did not meet the criteria for septic shock. Witnessed a slight increase in CRP and procalcitonin (PCT) was within normal limits. Diagnostic search was supplemented by a study of interleukins (IL-6 and IL-2R) in the blood plasma. The significant increase in their values, was regarded as the initial manifestations of the systemic inflammatory response. Sepsis was confirmed. The extended antibiotic therapy started Continuous Veno-Venous hemofiltration was used as part of treatment of the inflammatory-toxic condition. In two days of the therapy the patient's condition has stabilized, the patient recovered consciousness in the form of opening the eyes, simple instructions. At discharge, the patient's condition according to the Glasgow outcome scale was estimated at 4 points.

  11. Arthroscopic Treatment of Septic Arthritis in Very Young Children.

    Science.gov (United States)

    Thompson, Rachel M; Gourineni, Prasad

    2017-01-01

    Arthroscopic lavage is a well-established, minimally invasive treatment for septic arthritis (SA) in adults, but the use of arthroscopy in the pediatric population is typically restricted to sports injuries and deformity. Previous research on arthroscopic lavage of septic joints in the pediatric population has been limited to case reports and small case series of older children. As such, we aimed to evaluate the safety and efficacy of arthroscopic treatment of SA in various joints in very young children. Between 2011 and 2015, 24 children (aged 3 wk to 6 y) were treated for SA with arthroscopic lavage. A single portal was adequate for both inflow and outflow in most cases. A second portal was used in all knees and in other joints for synovectomy, when indicated. Drains were placed through the portal site and remained in place for 2 to 3 days. Antibiotics were managed by the infectious disease service. Nine hips, 9 knees, 4 ankles, and 2 shoulders were included. Portal placement, visualization, and adequate lavage were straight forward in all joints. There was 1 transient femoral nerve palsy and no other arthroscopy-associated complications (iatrogenic damage, difficult drain placement, or conversion to open). Two patients required repeat arthroscopic lavage for disease eradication, one of which required a second admission. A third patient underwent open irrigation following arthroscopic lavage with a resultant 1.125 average procedures per subject. At final follow-up (2 to 49 mo, average 16 mo), no recurrence of infection or decreased range of motion was noted. Arthroscopic lavage appears to be a safe, quick, and effective alternative to open arthrotomy for the treatment of SA in very young children. It is feasible in any large joint even in the infantile population, allowing for improved visualization and irrigation with little soft-tissue dissection and morbidity. Our relatively simple technique and positive results should encourage regular use of arthroscopic

  12. Effects of Early Continuous Venovenous Hemofiltration on E-Selectin, Hemodynamic Stability, and Ventilatory Function in Patients with Septic-Shock-Induced Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    Jian-biao Meng

    2016-01-01

    Full Text Available Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS (not acute kidney injury, AKI with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n=24 and a non-ECVVH group (n=27. Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2 ratio, extravascular lung water index (EVLWI, and E-selectin level were not significantly different between groups (all P>0.05. Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all P<0.05 at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU were shorter in ECVVH group (all P<0.05, but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI, treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU.

  13. Hypoxia in models of lung cancer

    DEFF Research Database (Denmark)

    Graves, Edward E; Vilalta, Marta; Cecic, Ivana K

    2010-01-01

    PURPOSE: To efficiently translate experimental methods from bench to bedside, it is imperative that laboratory models of cancer mimic human disease as closely as possible. In this study, we sought to compare patterns of hypoxia in several standard and emerging mouse models of lung cancer...... to establish the appropriateness of each for evaluating the role of oxygen in lung cancer progression and therapeutic response. EXPERIMENTAL DESIGN: Subcutaneous and orthotopic human A549 lung carcinomas growing in nude mice as well as spontaneous K-ras or Myc-induced lung tumors grown in situ......H2AX foci in vitro and in vivo. Finally, our findings were compared with oxygen electrode measurements of human lung cancers. RESULTS: Minimal fluoroazomycin arabinoside and pimonidazole accumulation was seen in tumors growing within the lungs, whereas subcutaneous tumors showed substantial trapping...

  14. In aqua vivo EPID dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Igor; Pecharroman-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; Herk, Marcel J.; Mijnheer, Ben van [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands)

    2012-01-15

    Purpose: At the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital in vivo dosimetry using an electronic portal imaging device (EPID) has been implemented for almost all high-energy photon treatments of cancer with curative intent. Lung cancer treatments were initially excluded, because the original back-projection dose-reconstruction algorithm uses water-based scatter-correction kernels and therefore does not account for tissue inhomogeneities accurately. The aim of this study was to test a new method, in aqua vivo EPID dosimetry, for fast dose verification of lung cancer irradiations during actual patient treatment. Methods: The key feature of our method is the dose reconstruction in the patient from EPID images, obtained during the actual treatment, whereby the images have been converted to a situation as if the patient consisted entirely of water; hence, the method is termed in aqua vivo. This is done by multiplying the measured in vivo EPID image with the ratio of two digitally reconstructed transmission images for the unit-density and inhomogeneous tissue situation. For dose verification, a comparison is made with the calculated dose distribution with the inhomogeneity correction switched off. IMRT treatment verification is performed for each beam in 2D using a 2D {gamma} evaluation, while for the verification of volumetric-modulated arc therapy (VMAT) treatments in 3D a 3D {gamma} evaluation is applied using the same parameters (3%, 3 mm). The method was tested using two inhomogeneous phantoms simulating a tumor in lung and measuring its sensitivity for patient positioning errors. Subsequently five IMRT and five VMAT clinical lung cancer treatments were investigated, using both the conventional back-projection algorithm and the in aqua vivo method. The verification results of the in aqua vivo method were statistically analyzed for 751 lung cancer patients treated with IMRT and 50 lung cancer patients treated with VMAT. Results: The improvements by

  15. Lung Transplant

    Science.gov (United States)

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  16. Analysis of PD-1 expression in the monocyte subsets from non-septic and septic preterm neonates.

    Directory of Open Access Journals (Sweden)

    Magdalena Zasada

    Full Text Available Programmed death-1 (PD-1 receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW, and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL. PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical by flow cytometry. In case of late-onset sepsis (LOS, the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome.

  17. Lung allocation.

    Science.gov (United States)

    Gottlieb, Jens

    2017-08-01

    Shortage of donor lungs in most western countries and broadening of indications for lung transplantation (LTx) has led increased waiting list mortality in the past. Usually donor lungs and recipients are matched by size as measured by total lung capacity and blood type in first order. In some countries regional allocation comes first, in other countries a national wait list exists and some nations are organized in supranational allocation systems. Organ distribution should respect the ethical principles of equity, justice, beneficence and utility. Generally, top priority on the list should be given to patients with the least amount of time to live but outcome is an important factor to consider to avoid futile transplantations. Installation of an urgency status will decrease mortality of the sickest candidates on the waitlist unless the proportion of patients on urgency status will be too high. Urgency can be determined by clinical judgment (so called center decision), an audit process or objectively by a score system. Among the 3,500 transplants performed worldwide annually, approximately 60% are allocated by lung allocation score (LAS) (US, Germany, the Netherlands). With the LAS a model for survival prediction after lung transplantation and wait list survival probability was created. Clinical experience in the US since 2005 and in Germany since 2011 favourable reports regarding effects on waiting list outflow, transplant activity and outcomes have been published. Future perspectives will focus on broader geographic sharing, updating and further development of the LAS.

  18. Septic shock: recognizing and managing this life-threatening condition in pediatric patients.

    Science.gov (United States)

    Silverman, Adam M

    2015-04-01

    Septic shock is a relatively rare but life-threatening condition in pediatric patients that can often be difficult to recognize in the emergency department. Once recognized, the emphasis of therapy is to reverse deficits in cellular respiration by increasing oxygen and other substrate delivery to tissue beds. Providing oxygen, improving tissue perfusion through augmentation of cardiac output, and administering antibiotics in a timely manner have all been shown to significantly improve outcomes in children with septic shock. Goal-directed therapy is relatively straightforward, emphasizes the need for effective surveillance and timely recognition of this disease process, and has the potential to significantly reduce morbidity and mortality. This review discusses how to identify specific populations at the greatest risk for septic shock, lays out the essential components of goal-directed therapy, examines potential pitfalls in management, and distinguishes additional ways that emergency clinicians can avoid the devastating consequences of septic shock in pediatric patients.

  19. The use of recombinant factor VIIa in a pediatric septic shock patient with disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    Ronaldo Arkader

    2008-03-01

    Full Text Available This is a report on a pediatric patient with septic shock and disseminated intravascular coagulation, who developed life-threatening bleeding which was successfully treated with recombinant factor VIIa.

  20. Acute septic arthritis of the acromioclavicular joint caused by Haemophilus parainfluenzae: a rare causative origin.

    Science.gov (United States)

    Hong, Myong-Joo; Kim, Yeon-Dong; Ham, Hyang-Do

    2015-04-01

    Septic arthritis of the acromioclavicular (AC) joint is a rare entity with symptoms that include erythema, swelling, and tenderness over the AC joint, fever, and limitation of shoulder motion with pain. In previous reports, Staphylococcus and Streptococcus species have been mentioned as common causative organisms. Haemophilus parainfluenzae is a normal inhabitant of the oral cavity, respiratory tract, gastrointestinal tract, and urogenital tract. However, it sometimes causes opportunistic infections leading to septic arthritis and osteomyelitis. AC joint infection associated with H.parainfluenzae is very rare, and only one case has been reported in the literature. Moreover, septic arthritis in immunocompetent patients is also very rare. Here, we report the case of a healthy patient with H. parainfluenzae-related septic arthritis of the AC joint.

  1. Oxidative stress and 'monocyte reprogramming' in septic patients with acute kidney injury requiring CRRT.

    Science.gov (United States)

    Silva, Sandra; de Cal, Massimo; Cruz, Dinna; Lentini, Paolo; Corradi, Valentina; Gallo, Giampiero; Salvatori, Gabriella; Verbine, Anton; Pogoshyan, Lusine; Nalesso, Federico; Brendolan, Alessandra; Piccinni, Pasquale; Ronco, Claudio

    2008-01-01

    Oxidative stress (OS) and monocyte HLA-DR expression are known to be predictive of mortality in sepsis; nevertheless, limited information exists regarding sepsis with acute kidney injury (AKI). The aim of the study was to correlate these markers with outcome in septic patients with AKI requiring continuous renal replacement therapy (CRRT). Advanced oxidation protein products (AOPP) were measured in 32 patients on days 1, 3, 7, 14, 21, and 28. In 14 we assessed the percentage of monocytes expressing HLA-DR (%DR+) and the HLA-DR mean fluorescence intensity (MFI). 20 healthy volunteers, 17 septic patients without AKI and 20 septic AKI patients not treated by CRRT were used for comparison. The mortality rate was 59%. Septic CRRT patients had higher AOPP and lower %DR+ (p CRRT. However, this study was not able to confirm the usefulness of these markers in predicting survival in this subset of patients. Copyright 2008 S. Karger AG, Basel.

  2. Association between sympathoadrenal activation, fibrinolysis, and endothelial damage in septic patients

    DEFF Research Database (Denmark)

    Johansson, Pär I; Haase, Nicolai; Perner, Anders

    2014-01-01

    for Severe Sepsis/Septic Shock trial who were expected not to receive catecholamines at screening preintervention (baseline) and had baseline blood sampled. Clinical, outcome data, and measurements of plasma concentration (p-) biomarkers reflecting sympathoadrenal activation, endothelial activation......PURPOSE: The purpose of this study is to investigate potential associations between sympathoadrenal activation and/or vasopressor/inotropic therapy and endothelial activation, damage, and coagulopathy in septic patients. MATERIALS AND METHODS: Septic patients included in the Scandinavian Starch......). CONCLUSIONS: In septic patients, endogenous noradrenaline was independently associated with biomarkers of endothelial activation, damage, fibrinolysis and mortality, comparable with findings in trauma and myocardial infarction patients. The catecholamine surge in critical illness may contribute to balance...

  3. Induced hypothermia in patients with septic shock and respiratory failure (CASS)

    DEFF Research Database (Denmark)

    Itenov, Theis Skovsgaard; Johansen, Maria Egede; Bestle, Morten

    2018-01-01

    -dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70...... died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce...... mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation....

  4. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016

    NARCIS (Netherlands)

    Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; de Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuck; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip

    2017-01-01

    Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012!' Design: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings

  5. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

    NARCIS (Netherlands)

    Singer, Mervyn; Deutschman, Clifford S.; Seymour, Christopher Warren; Shankar-Hari, Manu; Annane, Djillali; Bauer, Michael; Bellomo, Rinaldo; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig M.; Hotchkiss, Richard S.; Levy, Mitchell M.; Marshall, John C.; Martin, Greg S.; Opal, Steven M.; Rubenfeld, Gordon D.; van der Poll, Tom; Vincent, Jean-Louis; Angus, Derek C.

    2016-01-01

    IMPORTANCE Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need

  6. Group A Streptococcus Septic Shock after Surgical Abortion: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Stephanie C. Tardieu

    2017-01-01

    Full Text Available Group A Streptococcus (GAS causing puerperal sepsis is a leading cause of maternal mortality worldwide. Although rare, GAS infection is a relatively significant public health concern because of its propensity to evolve rapidly into septic shock, streptococcal toxic shock syndrome, and death. We report the case of a 27-year-old patient who presented with GAS septic shock after undergoing a surgical termination of pregnancy and was treated successfully and recovered without sequelae. GAS septic shock should always be included in the differential diagnosis of any patient who develops sepsis after a surgical abortion. Patients with GAS septic shock have a rapid clinical decline and need aggressive fluid management, early initiation of broad-spectrum antibiotics, and rapid surgical intervention.

  7. High-performance detection and early prediction of septic shock for alcohol-use disorder patients

    Directory of Open Access Journals (Sweden)

    Jacob Calvert

    2016-06-01

    Conclusions: Analysis of the higher order correlations and trends between relevant clinical measurements using the InSight algorithm leads to more accurate detection and prediction of septic shock, even in cases where diagnosis may be confounded by AUD.

  8. Pylephlebitis and Crohn’s disease: A rare case of septic shock

    Directory of Open Access Journals (Sweden)

    Stefano Scaringi

    2017-01-01

    Conclusion: This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn’s disease patient who is not showing clinical signs of peritonitis.

  9. STRUCTURAL CHANGES OF THE HEART DURING SEVERE SEPSIS OR SEPTIC SHOCK

    NARCIS (Netherlands)

    Smeding, Lonneke; Plotz, Frans B.; Groeneveld, A. B. Johan; Kneyber, Martin C. J.

    Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to

  10. Septic olecranon and prepatellar bursitis in hockey players: a report of three cases.

    Science.gov (United States)

    Tuff, Taylor; Chrobak, Karen

    2016-12-01

    Septic bursitis (SB) is an important differential diagnosis in athletes presenting with an acute subcutaneous swelling of the elbow or knee. Prompt recognition is essential to minimize recovery time and prevent the spread of infection. Due to the significant overlap in clinical features, it is often difficult to differentiate SB from non-septic bursitis (NSB) without bursal aspirate analysis. SB is commonly not considered unless the bursitis is accompanied by a local skin lesion or fever. This study describes two cases of septic olecranon bursitis and one case of septic prepatellar bursitis in adult hockey players presenting to a sports medicine clinic. None of the cases presented with an observable skin lesion and only one case developed a fever. It is therefore essential that clinicians maintain a high index of suspicion and monitor for signs of progression when presented with an acute bursitis even in the absence of these features.

  11. Beta-lactam dosing in critically ill patients with septic shock and continuous renal replacement therapy

    National Research Council Canada - National Science Library

    Ulldemolins, Marta; Vaquer, Sergi; Llauradó-Serra, Mireia; Pontes, Caridad; Calvo, Gonzalo; Soy, Dolors; Martín-Loeches, Ignacio

    2014-01-01

    .... This article aims to describe the current clinical scenario for beta-lactam dosing in critically ill patients with septic shock and CRRT, to highlight the sources of variability among the different...

  12. Hospital Mortality of Septic Acute Kidney Injury Requiring Renal Replacement Therapy in the Postoperative Elderly

    Directory of Open Access Journals (Sweden)

    Wei-Lun Liu

    2012-06-01

    Conclusions: The hospital mortality of postoperative elderly patients with septic AKI was more than 60% and was not affected by age. Mechanical ventilator use was the major risk factor and prognostic factor for elderly patients in this clinical setting.

  13. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study

    NARCIS (Netherlands)

    Hernandez, Glenn; Pedreros, Cesar; Veas, Enrique; Bruhn, Alejandro; Romero, Carlos; Rovegno, Maximiliano; Neira, Rodolfo; Bravo, Sebastian; Castro, Ricardo; Kattan, Eduardo; Ince, Can

    2012-01-01

    Purpose: Perfusion assessment during septic shock resuscitation is difficult and usually complex determinations. Capillary refill time (CRT) and central-to-toe temperature difference (Tc-toe) have been proposed as objective reproducible parameters to evaluate peripheral perfusion. The comparative

  14. Multimodal monitoring for hemodynamic categorization and management of pediatric septic shock: a pilot observational study*.

    Science.gov (United States)

    Ranjit, Suchitra; Aram, Gnanam; Kissoon, Niranjan; Ali, Mhd Kashif; Natraj, Rajeshwari; Shresti, Sharad; Jayakumar, Indira; Gandhi, Deepika

    2014-01-01

    To evaluate the cardiovascular aberrations using multimodal monitoring in fluid refractory pediatric septic shock and describe the clinical characteristics of septic myocardial dysfunction. Prospective observational study of patients with unresolved septic shock after infusion of 40 mL/kg fluid in the first hour. Two tertiary care referral Indian PICUs. Patients aged 1 month to 16 years who had fluid refractory septic shock. Changes in therapy were based on findings of clinical assessment, bedside echocardiography, and invasive blood pressure monitoring within 6 hours of recognition of septic shock. Over a 4-year period, 48 patients remained in septic shock despite at least 40 mL/kg fluid infusion. On clinical examination, 21 patients had cold shock and 27 had warm shock. Forty-one patients (85.5%) had vasodilatory shock on invasive blood pressure; these included 14 patients who initially presented with cold shock. The commonest echocardiography findings were impaired left ± right ventricular function in 19 patients (39.6%) and hypovolemia in 16 patients (33%). Three patients who had normal myocardial function on day 1 developed secondary septic myocardial dysfunction on day 3. Echocardio graphy, along with invasive arterial pressure monitoring, allowed fluid, inotropy, and pressors to be titrated more precisely in 87.5% of patients. Shock resolved in 46 of 48 patients (96%) and 44 patients (91.6%) survived to discharge. Bedside echocardiography provided crucial information leading to the recognition of septic myocardial dysfunction and uncorrected hypovolemia that was not apparent on clinical assessment. With invasive blood pressure monitoring, echocardiography affords a simple noninvasive tool to determine the cause of low cardiac output and the physiological basis for adjustment of therapy in patients who remain in shock despite 40 mL/kg fluid.

  15. Hemodynamic Analysis of Pediatric Septic Shock and Cardiogenic Shock Using Transpulmonary Thermodilution

    OpenAIRE

    En-Pei Lee; Shao-Hsuan Hsia; Jainn-Jim Lin; Oi-Wa Chan; Jung Lee; Chia-Ying Lin; Han-Ping Wu

    2017-01-01

    Septic shock and cardiogenic shock are the two most common types of shock in children admitted to pediatric intensive care units (PICUs). The aim of the study was to investigate which hemodynamic variables were associated with mortality in children with shock. We retrospectively analyzed 50 children with shock (37 septic shock cases and 13 cardiogenic shock cases) in the PICU and monitored their hemodynamics using transpulmonary thermodilution from 2003 to 2016. Clinical factors were analyzed...

  16. Differential expression of the Nrf2-linked genes in pediatric septic shock.

    Science.gov (United States)

    Grunwell, Jocelyn R; Weiss, Scott L; Cvijanovich, Natalie Z; Allen, Geoffrey L; Thomas, Neal J; Freishtat, Robert J; Anas, Nick; Meyer, Keith; Checchia, Paul A; Shanley, Thomas P; Bigham, Michael T; Fitzgerald, Julie; Howard, Kelli; Frank, Erin; Harmon, Kelli; Wong, Hector R

    2015-09-17

    Experimental data from animal models of sepsis support a role for a transcription factor, nuclear erythroid-related factor 2 p45-related factor 2 (Nrf2), as a master regulator of antioxidant and detoxifying genes and intermediary metabolism during stress. Prior analysis of a pediatric septic shock transcriptomic database showed that the Nrf2 response is a top 5 upregulated signaling pathway in early pediatric septic shock. We conducted a focused analysis of 267 Nrf2-linked genes using a multicenter, genome-wide expression database of 180 children with septic shock 10 years of age or younger and 53 healthy controls. The analysis involved RNA isolated from whole blood within 24 h of pediatric intensive care unit admission for septic shock and a false discovery rate of 5 %. We compared differentially expressed genes from (1) patients with septic shock and healthy controls and (2) across validated gene expression-based subclasses of pediatric septic shock (endotypes A and B) using several bioinformatic methods. We found upregulation of 123 Nrf2-linked genes in children with septic shock. The top gene network represented by these genes contained primarily enzymes with oxidoreductase activity involved in cellular lipid metabolism that were highly connected to the peroxisome proliferator activated receptor and the retinoic acid receptor families. Endotype A, which had higher organ failure burden and mortality, exhibited a greater downregulation of Nrf2-linked genes than endotype B, with 92 genes differentially regulated between endotypes. Our findings indicate that Nrf2-linked genes may contribute to alterations in oxidative signaling and intermediary metabolism in pediatric septic shock.

  17. A case of Candida orthopsilosis associated septic arthritis in a patient with Systemic Lupus Erythematosus (SLE

    Directory of Open Access Journals (Sweden)

    Orville D. Heslop

    2015-03-01

    Full Text Available We report a case of persistent Candida orthopsilosis associated septic arthritis. Repeated isolation of C. orthopsilosis from tissue and joint fluid was confirmed by identification of the ITS region of the rRNA gene using a Candida-Specific Luminex based assay and gene sequencing of the D1/D2 regions. This was the first case of C. orthopsilosis associated septic arthritis reported in Jamaica and in the literature.

  18. Candida septic arthritis with rice body formation: A case report and review of literature

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Yu Mi; Cho, Hyun Yee; Lee, Sheen Woo; Hwang, Yun Mi; Kim, Young Kyu [Gachon University, Gil Hospital, Incheon (Korea, Republic of)

    2013-06-15

    Rice body formation in a joint or bursa is a rare condition, and is usually associated with rheumatoid arthritis or tuberculous arthritis. Here we describe a case of multiple rice body formation in a shoulder joint and in adjacent bursae, which was confirmed to be due to septic arthritis by Candida species. To the best of our knowledge, rice body formation in Candida septic arthritis in an immune-competent patient has not been previously reported.

  19. Severe Osteomyelitis and Septic Arthritis due to Serratia marcescens in an Immunocompetent Patient

    OpenAIRE

    Hiba Hadid; Muhammad Usman; Sudeep Thapa

    2015-01-01

    Septic arthritis and osteomyelitis due to Serratia marcescens in immunocompetent patients without risk factors are extremely rare. Here, we report a case of septic arthritis and severe adjacent osteomyelitis of the tibia due to Serratia marcescens in a diabetic community-dweller patient. The patient had no contact with healthcare workers or facilities and had no chronic disease except for poorly controlled diabetes. Without predisposing risk factors, this type of infection is extremely rare, ...

  20. Severe Osteomyelitis and Septic Arthritis due to Serratia marcescens in an Immunocompetent Patient.

    Science.gov (United States)

    Hadid, Hiba; Usman, Muhammad; Thapa, Sudeep

    2015-01-01

    Septic arthritis and osteomyelitis due to Serratia marcescens in immunocompetent patients without risk factors are extremely rare. Here, we report a case of septic arthritis and severe adjacent osteomyelitis of the tibia due to Serratia marcescens in a diabetic community-dweller patient. The patient had no contact with healthcare workers or facilities and had no chronic disease except for poorly controlled diabetes. Without predisposing risk factors, this type of infection is extremely rare, even in diabetics.

  1. Severe Osteomyelitis and Septic Arthritis due to Serratia marcescens in an Immunocompetent Patient

    Directory of Open Access Journals (Sweden)

    Hiba Hadid

    2015-01-01

    Full Text Available Septic arthritis and osteomyelitis due to Serratia marcescens in immunocompetent patients without risk factors are extremely rare. Here, we report a case of septic arthritis and severe adjacent osteomyelitis of the tibia due to Serratia marcescens in a diabetic community-dweller patient. The patient had no contact with healthcare workers or facilities and had no chronic disease except for poorly controlled diabetes. Without predisposing risk factors, this type of infection is extremely rare, even in diabetics.

  2. Septic arthritis and acute rheumatic fever in children: the diagnostic value of serological inflammatory markers.

    Science.gov (United States)

    Mistry, Raakhi M; Lennon, Diana; Boyle, Matthew J; Chivers, Karel; Frampton, Chris; Nicholson, Ross; Crawford, Haemish

    2015-01-01

    Joint pain and raised inflammatory markers are features of both acute rheumatic fever (ARF) and septic arthritis, often posing a diagnostic challenge to clinicians. Important differences in the presenting serological inflammatory marker profile may assist patient diagnosis, however, as clinical experience suggests that ARF is associated with a higher erythrocyte sedimentation rate (ESR), whereas other serological markers may be similarly elevated in these 2 conditions. The goal of this study was to determine the diagnostic value of serological inflammatory markers and white cell count (WCC) in children presenting with acute joint pain secondary to ARF or septic arthritis. Data were obtained from the Auckland regional rheumatic fever database and hospital computer records between 2005 and 2012. Records of all patients under the age of 16 years who were admitted with a new diagnosis of ARF or septic arthritis were analyzed. The diagnosis of ARF was defined on the basis of the New Zealand modification of the Jones Criteria, and the diagnosis of septic arthritis was defined on the basis of joint fluid cytology and culture. Baseline characteristics, serological inflammatory markers, and serum WCC were compared between the ARF and septic arthritis patient groups. Children with ARF displayed significantly higher ESR, higher serum C-reactive protein, and lower serum WCC than children with septic arthritis on presentation to hospital. In children presenting with monoarthritis, an ESR>64.5, serum WCCmedication before hospital presentation, and 74% of these children (25/34) had abnormal echocardiograms on admission. ARF and septic arthritis are important diagnoses to consider in children presenting with acute joint pain in New Zealand. A significant proportion of patients with ARF initially present with acute monoarthritis. Serological inflammatory markers and WCC on presentation differ significantly between children with ARF and septic arthritis.

  3. FDG-PET/CT for differentiating between aseptic and septic delayed union in the lower extremity.

    Science.gov (United States)

    van Vliet, Kirsten E; de Jong, Vincent M; Termaat, M Frank; Schepers, Tim; van Eck-Smit, Berthe L F; Goslings, J Carel; Schep, Niels W L

    2017-09-27

    (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) has proven to have a high diagnostic accuracy for the detection of bone infections. In patients with delayed union it may be clinically important to differentiate between aseptic and septic delayed union. The aim of this study was to evaluate the efficacy and to assess the optimal diagnostic accuracy of FDG-PET/CT in differentiating between aseptic and septic delayed union in the lower extremity. This is a retrospective study of consecutive patients who underwent FDG-PET/CT scanning for suspicion of septic delayed union of the lower extremity. Diagnosis of aseptic delayed union or septic delayed union was made based on surgical deep cultures following PET/CT scanning and information on clinical follow-up. FDG-uptake values were measured at the fractured site by use of the maximum standardized uptake value (SUVmax). Sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were calculated at various SUVmax cut-off points. A total of 30 patients were included; 13 patients with aseptic delayed unions and 17 patients with septic delayed unions. Mean SUVmax in aseptic delayed union patients was 3.23 (SD ± 1.21). Mean SUVmax in septic delayed union patients was 4.77 (SD ± 1.87). A cut-off SUVmax set at 4.0 showed sensitivity, specificity and diagnostic accuracy of FDG-PET/CT were 65, 77 and 70% to differentiate between aseptic and septic delayed union, respectively. Using a semi-quantitative measure (SUVmax) for interpretation of FDG-PET/CT imaging seems to be a promising tool for the discrimination between aseptic and septic delayed union.

  4. COLLOIDS IN SEPTIC TANK EFFLUENT AND THEIR INFLUENCE ON FILTER PERMEABILITY

    OpenAIRE

    Marcin Spychała; Jakub Nieć; Natalia Walczak; Anna Marciniak

    2015-01-01

    The aim of the study was to evaluate the content of colloids in septic tank effluent and their impact on textile filter permeability. Measurements were performed on septic tank effluent without suspended solids but containing colloids and without colloids - including only dissolved substances (filtered by micro-filters and centrifuged). The study was conducted on unclogged and clogged textile filter coupons. During the study the following measurements were determined: turbidity, chemical oxyg...

  5. Mettre au point un vaccin contre la septicémie hémorragique chez ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    12 janv. 2018 ... Photo: Markus Kostner / Banque mondiale. Le fardeau de la septicémie hémorragique pour les petits exploitants. La septicémie hémorragique est une maladie bactérienne aiguë et souvent mortelle touchant principalement les bovins et les buffles en Asie et en Afrique. La bactérie responsable est ...

  6. Severe Sepsis and Septic Shock Associated with Chikungunya Fever in an Adolescent.

    Science.gov (United States)

    Sharma, Pradeep Kumar; Kumar, Maneesh; Bhandari, Neha; Kushwaha, Anand

    2018-01-06

    Chikungunya is usually a benign disease, and little is known on the occurrence of severe clinical complications. We describe a 12-year-old boy with rapid onset septic shock and multi-organ failure associated with chikungunya fever. Severe sepsis and septic shock can be associated with chikungunya. © The Author(s) [2018]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Application of fluorescent and vibration spectroscopy for septic serum human albumin structure deformation during pathology

    Science.gov (United States)

    Zyubin, A.; Konstantinova, E.; Slezhkin, V.; Matveeva, K.; Samusev, I.; Bryukhanov, V.

    2017-12-01

    In this paper we perform results of conformational analysis of septic human serum albumin (HSA) carried out by Raman spectroscopy (RS), infrared (IR) spectroscopy and fluorescent spectroscopy. The main vibrational groups were identified and analyzed for septic HSA and its health control. Comparison between Raman and IR results were done. Fluorescent spectral changes of Trp-214 group were analyzed. Application of Raman, IR spectroscopy, fluorescent spectroscopy for conformational changes study of HSA during pathology were shown.

  8. Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids.

    Science.gov (United States)

    Wong, Hector R; Atkinson, Sarah J; Cvijanovich, Natalie Z; Anas, Nick; Allen, Geoffrey L; Thomas, Neal J; Bigham, Michael T; Weiss, Scott L; Fitzgerald, Julie C; Checchia, Paul A; Meyer, Keith; Quasney, Michael; Hall, Mark; Gedeit, Rainer; Freishtat, Robert J; Nowak, Jeffrey; Raj, Shekhar S; Gertz, Shira; Lindsell, Christopher J

    2016-10-01

    Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids. We conducted a secondary analysis of 288 previously published pediatric subjects with septic shock. For prognostic enrichment, each study subject was assigned a baseline mortality probability using the pediatric sepsis biomarker risk model. For predictive enrichment, each study subject was allocated to one of two septic shock endotypes, based on a 100-gene signature reflecting adaptive immunity and glucocorticoid receptor signaling. The primary study endpoint was complicated course, defined as the persistence of two or more organ failures at day 7 of septic shock or 28-day mortality. We used logistic regression to test for an association between corticosteroids and complicated course within endotype. Among endotype B subjects at intermediate to high pediatric sepsis biomarker risk model-based risk of mortality, corticosteroids were independently associated with more than a 10-fold reduction in the risk of a complicated course (relative risk, 0.09; 95% CI, 0.01-0.54; p = 0.007). A combination of prognostic and predictive strategies based on serum protein and messenger RNA biomarkers can identify a subgroup of children with septic shock who may be more likely to benefit from corticosteroids. Prospective validation of these strategies and the existence of this subgroup are warranted.

  9. Prognostic factors in the survival of patients with blood disorders recovering from septic shock.

    Science.gov (United States)

    Waszczuk-Gajda, Anna; Wiktor Jedrzejczak, Wieslaw

    2017-06-01

    Septic shock is one of the major direct causes of death in patients in hematology departments. The knowledge about clinical outcomes and factors associated with negative outcome in these patients can be important and useful for physicians to identify the patients who are most likely to benefit from ICU therapy. We retrospectively analyzed records of 214 episodes of septic shock in patients with different blood diseases hospitalized between 1998 and 2011 in the Department of Hematology, Oncology and Internal Medicine, the Medical University of Warsaw, Poland. Direct survival with resolution of septic shock was 46%. Among these survivors, 75% continued to live at 30 days, 49% at 6 months, and 12% at 5 years after shock resolution. It was found that the most important prognostic factors for direct (short-term) mortality were multiorgan failure, lack of concordance of empiric antibiotic treatment with results of in vitro sensitivity testing, the Karnofsky score below 60%, presence of more than two comorbidities. Long-term prognosis (3-year follow-up) was affected by multiple factors with the most significant being Karnofsky score, higher organ failure score, hematologic disease relapse or resistance to treatment. Septic shock in patients with blood disorders treated in the hematology ward was associated with very high risk of mortality in all periods after its completion. However, although the results of treatment of septic shock in patients with blood diseases are poor, they were comparable to the results of treatment of septic shock in mixed populations treated in intensive care units.

  10. Site-specific changes in cytokine response to septic dose of lipopolysaccharide in ovariectomized female rats.

    Science.gov (United States)

    Iwasa, T; Matsuzaki, T; Gereltsetseg, G; Munkhzaya, M; Tungalagsurv, A; Murakami, M; Yamasaki, M; Yamamoto, Y; Kuwahara, A; Kato, T; Yasui, T; Irahara, M

    2014-08-01

    The immune response is altered according to hormonal and metabolic status. Obesity increases the inflammatory and fever response, whereas loss of gonadal steroid decreases behavioral response to immune stress. However, the immune systems of ovariectomized animals exhibiting obesity and gonadal steroid deficiency, particularly under septic conditions, have not been fully examined. In the present study, we evaluated the ovariectomy-induced changes of central and peripheral immune responses to life-threatening septic stimulus. Ovariectomized rats showed heavier body weight and lighter uterine weight when compared with gonadally intact rats. Fever response to septic dose of lipopolysaccharide (LPS) in ovariectomized rats was less evident when compared with that in gonadally intact rats. In addition, under LPS-injected septic conditions, hypothalamic gene levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and serum protein levels of IL-1β and TNF-α in ovariectomized rats were lower than those in gonadally intact rats. On the other hand, IL-6 levels in visceral fat under septic conditions were higher in ovariectomized rats than in gonadally intact rats. These findings indicate that ovariectomy-induced site-specific changes in cytokine response under septic conditions. As hypothalamic, but not peripheral, pro-inflammatory cytokines are directly involved in the fever response, the attenuation of fever response observed in ovariectomized rats may be caused by a reduction in central cytokine responses.

  11. Epidemiology of septic arthritis of the knee at Hospital das Clinicas, Universidade de Sao Paulo

    Directory of Open Access Journals (Sweden)

    Camilo Partezani Helito

    Full Text Available Background: Septic arthritis is an infrequent disease although very important due to the possibility of disastrous outcomes if treatment is not adequately established. Adequate information concerning the epidemiology of septic arthritis is still lacking due to the uncommon nature of the disease as well as the struggle to establish a correct case-definition. Objective: To epidemiologically characterize the population seen at Hospital das Clínicas, University of São Paulo with a diagnosis of septic arthritis between 2006 and 2011. Methods: Sixty-one patients diagnosed with septic arthritis of the knee between 2006 and 2011 were retrospectively evaluated. The patients' clinical and epidemiological characteristics, the microorganisms that caused the infection and the patients' treatment and evolution were analyzed. Results: Septic arthritis of the knee was more common among men, with distribution across a variety of age ranges. Most diagnoses were made through positive synovial fluid cultures. The most prevalent clinical comorbidities were systemic arterial hypertension and diabetes mellitus, and the most commonly reported joint disease was osteoarthritis. Staphylococcus aureus was the prevailing pathogen. Fever was present in 36% of the cases. All patients presented elevation in inflammatory tests. Gram staining was positive in only 50.8% of the synovial fluid samples analyzed. Six patients presented complications and unfavorable evolution of their condition. Conclusion: S. aureus is still the most common pathogen in acute knee infections in our environment. Gram staining, absence of fever and normal leukocyte count cannot be used to rule out septic arthritis.

  12. Asymmetric dimethylarginine and L-arginine levels in neonatal sepsis and septic shock.

    Science.gov (United States)

    Aydemir, Ozge; Ozcan, Beyza; Yucel, Husniye; Bas, Ahmet Yagmur; Demirel, Nihal

    2015-05-01

    Nitric oxide (NO) formed by the enzyme NO synthase (NOS) from L-arginine, is an important mediator for pathogen elimination. Being a potent vasodilator NO is implicated in hypotension and decreased organ perfusion in sepsis. Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor. We investigated ADMA and L-arginine levels in neonatal sepsis and their relation to disease severity. A prospective controlled study was conducted including 31 neonates with sepsis and 20 controls. Serum ADMA and L-arginine levels were measured within 24 h of sepsis diagnosis. Clinical and laboratory data including clinical risk index for babies (CRIB) score, presence of septic shock, organ dysfunction and death were recorded. L-arginine and ADMA levels were higher in neonates with sepsis compared to controls (p = 0.029 and p = 0.001, respectively). Neonates with septic shock had higher ADMA levels compared to septic neonates without shock (p = 0.026) and controls (p neonates with septic shock compared to septic neonates without shock (p = 0.012) and controls (p neonatal sepsis and even higher levels are observed in septic shock.

  13. Septic shoulder presenting as a shoulder dislocation in the pediatric patient: a case report.

    Science.gov (United States)

    Maguire, Kathleen J; Otsuka, Norman Y

    2017-05-01

    Shoulder dislocation is relatively uncommon in the younger pediatric population. Because of the relative strength of the surrounding soft tissue structures of the shoulder compared with the proximal humeral physis, subluxation or dislocation resulting from a traumatic event or application of force is rare and instead a proximal humeral physeal injury occurs. Case presentation - We present a 5-year-old male who presented to the office with post-traumatic left shoulder pain for about 1 week. Radiographs of the left shoulder indicated inferior subluxation of the humeral head. He was ultimately diagnosed and treated for a septic shoulder. Septic arthritis of the glenohumeral joint accounts for about 3% of all septic arthritis cases. About half of the pediatric patients with a septic arthritis will present with a concomitant osteomyelitis about the joint involved. Widening of the glenohumeral joint and subluxation clinically as well as radiographically have been described in cases of large joint effusions because of an increase in intra-articular fluid in adults. This inferior subluxation is often noted without a frank dislocation. The case described in this report is unique in that this is the first to describe a pediatric septic shoulder presenting as a shoulder subluxation. Given the rarity of pediatric shoulder dislocations and subluxations, the pediatric orthopaedist and pediatrician should maintain a suspicion for a septic joint. Level V.

  14. Lower mitochondrial dysfunction in survivor septic patients with mitochondrial DNA haplogroup JT.

    Science.gov (United States)

    Lorente, Leonardo; Martín, María M; López-Gallardo, Ester; Ferreres, José; Solé-Violán, Jordi; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro; Montoya, Julio; Ruiz-Pesini, Eduardo

    2017-10-17

    The comparison on mitochondrial function between severe septic patients and healthy control subjects according to mitochondrial deoxyribonucleic acid (mtDNA) haplogroup has not been previously reported; and this was the objective of the current study. Prospective, multicenter, observational study. We obtained blood samples from 198 severe septic patients at days 1, 4 and 8 of severe sepsis diagnosis and from 96 sex- and age-matched healthy controls to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The endpoint of the study was 30-day mortality. We included 198 severe septic patients (38 with mtDNA haplogroup JT and 160 with mtDNA haplogroup non-JT) and 96 healthy control subjects (16 with mtDNA haplogroup JT and 80 with mtDNA haplogroup non-JT). We have no found statistically significant differences in platelet CIV specific activity between healthy controls and survivor severe septic patients with mtDNA haplogroup JT at days 1, 4 and 8 of severe sepsis diagnosis; and the remaining severe septic patients showed lower platelet CIV specific activity than healthy controls with the same mtDNA haplogroup. The new finding of our study was that survivor severe septic patients and healthy controls with mtDNA haplogroup JT showed no different platelet Civ specific activity. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  15. Divergent results induced by different types of septic shock in transglutaminase 2 knockout mice.

    Science.gov (United States)

    Yoo, Hyun; Ahn, Eu-Ree; Kim, Se-Jin; Lee, Seon-Hyeong; Oh, Seung Hyun; Kim, Soo-Youl

    2013-01-01

    Acute sepsis can be induced by cytokines such as TNF-α and biological products such as LPS. All of these agents cause systemic inflammation, which is characterized by hemodynamic shock and liver toxicity. However, the outcomes of different septic shock models were totally opposite in transglutaminase 2 knockout (TGase 2(-/-)) mice. The aim of our study was to clarify the role of TGase 2 in liver injury. Therefore, we explored the role of TGase 2 in liver damage using two different stress models: LPS-induced endotoxic shock and TNF-α/actinomycin D (ActD)-induced sepsis. TNF-α-dependent septic shock resulted in increased liver damage in TGase 2(-/-) mice compared with wild-type (WT) mice, and was accompanied by increased levels of caspase 3 and cathepsin D (CTSD) in the damaged liver. Conversely, LPS-induced septic shock resulted in ablation of inflammatory endotoxic shock in TGase 2(-/-) mice and decreased liver injury. We found that TGase 2 protected liver tissue from TNF-α-dependent septic shock by reducing the expression of caspase 3 and CTSD. However, TGase 2 differently participated in increased the hemodynamic shock in LPS-induced septic shock through macrophage activation rather than protecting direct liver damage. Therefore, these findings demonstrate that septic shock caused by different agents may induce different results in TGase 2(-/-) mice depending on the primary target organs affected.

  16. Retrospective evaluation of recurrent secondary septic peritonitis in dogs (2000-2011): 41 cases.

    Science.gov (United States)

    Barfield, Dominic M; Tivers, Michael S; Holahan, Matthew; Welch, Kristin; House, Arthur; Adamantos, Sophie E

    2016-01-01

    To describe the clinical characteristics of recurrent septic peritonitis in dogs. Multicenter retrospective observational study. Client-owned dogs with recurrent septic peritonitis. Three university emergency and referral hospitals. None. Medical records from 3 veterinary university teaching hospitals were reviewed and data were collected using a standardized data collection sheet for all cases of septic peritonitis during the study period (2000-2011). Forty one dogs met the inclusion criteria for recurrent peritonitis. All dogs underwent relaparotomy. The original cause of septic peritonitis in these cases included previous surgery for gastrointestinal foreign body removal (n = 26), gastrointestinal neoplasia (n = 3), gastric or duodenal ulceration (n = 3), biliary tract leakage (n = 2), and single instance for each of the following: penetrating foreign body, hernia strangulation, intussusception, mesenteric volvulus, infection of the laparotomy incision, prostatic abscess, and trauma. Eighteen animals survived to discharge. There was no difference detected between survivors and nonsurvivors with recurrent peritonitis in terms of inciting cause, serum albumin concentration, surgical management, or provision of appropriate initial antimicrobials. The survival rate for dogs having recurrent peritonitis was 43.9% (18/41 dogs). This retrospective study did not identify any significant prognostic indicators for dogs with recurrent peritonitis and that the mortality rate for dogs having more than one surgery for septic peritonitis is similar to that reported for a single surgery for septic peritonitis. ©Veterinary Emergency and Critical Care Society 2015.

  17. Horseshoe lung with left lung hypoplasia.

    OpenAIRE

    Ersöz, A; Soncul, H; Gökgöz, L; Kalaycioğlu, S; Tunaoğlu, S; Kaptanoğlu, M; Yener, A

    1992-01-01

    Horseshoe lung is an uncommon congenital malformation in which the bases of the right and the left lungs are fused to each other by a narrow isthmus posterior to the cardiac apex. So far 22 cases have been described: most of these were associated with right lung hypoplasia and the scimitar syndrome. A horseshoe lung anomaly with left lung hypoplasia is described.

  18. Lung Oxidative Damage by Hypoxia

    Directory of Open Access Journals (Sweden)

    O. F. Araneda

    2012-01-01

    Full Text Available One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described.

  19. From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective

    Directory of Open Access Journals (Sweden)

    Ginsburg I

    2017-02-01

    Full Text Available Isaac Ginsburg,1 Peter Vernon van Heerden,2 Erez Koren1 1Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, 2General Intensive Care Unit, Hadassah University Hospital, Jerusalem, Israel Abstract: This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders Keywords: histones, sepsis, septic shock

  20. Selenium Effect on Oxidative Stress Factors in Septic Rats

    Directory of Open Access Journals (Sweden)

    Elmira Zolali

    2014-05-01

    Full Text Available Purpose: Severe oxidative stress is an important event that occurs in patients with sepsis. The body has extensive and multiple defense mechanisms against the reactive oxygen species (ROS produced during inflammation and sepsis. One of these mechanisms includes a group of enzymes that utilize selenium as their cofactor. The purpose of this study is investigating of Selenium effect on oxidative stress factors in animal model of sepsis. Methods: Sepsis was induced by caecal ligation and puncture (CLP method. 30 Male Wistar rats were divided into following groups: sham group; CLP group; 100 μg/kg Selenium- treated CLP group. 12 hours after inducing sepsis animals were killed and lungs were removed. One of the lungs was frozen in liquid nitrogen and kept at -70°C for enzymatic activity analysis and the other was kept in formalin 10% until tissue section preparation performed for histopathological studies. Results: The Myeloperoxidase (MPO activity was decreased in Selenium- treated CLP group. Inflammation score of lung tissue was lowered in Selenium- treated CLP group, but it wasn’t statically significant. Level of glutathione peroxidase (GPx was higher in CLP and Selenium- treated CLP groups. Conclusion: It seems that Selenium has protective effect on lung inflammation during acute lung injury. Also it may improve some stress oxidative profile during CLP model of sepsis.