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Sample records for acute pulmonary injury

  1. Acute kidney injury in patients with pulmonary embolism

    PubMed Central

    Chang, Chih-Hsiang; Fu, Chung-Ming; Fan, Pei-Chun; Chen, Shao-Wei; Chang, Su-Wei; Mao, Chun-Tai; Tian, Ya-Chung; Chen, Yung-Chang; Chu, Pao-Hsien; Chen, Tien-Hsing

    2017-01-01

    Abstract Acute kidney injury (AKI) is overlooked in patients with pulmonary embolism (PE). Risk factors for and long-term outcomes of this complication remain unknown. This study evaluated the predictors and prognosis of AKI in patients with PE. This retrospective cohort study used Taiwan's National Health Insurance Research Database. We enrolled a total of 7588 patients who were admitted to a hospital for PE from January1997 to December 2011 and administered anticoagulation or thrombolytic agents. All demographic data, risk factors, and outcomes were analyzed. AKI was diagnosed in 372 (4.9%) patients. Multivariate logistic regression analysis revealed pre-existing chronic kidney disease, hypertension, diabetes mellitus, massive PE, anemia, and sepsis as independent risk factors for AKI. In the long-term follow-up, the survival rate was similar in the AKI and non-AKI groups. Careful risk factor screening and intensive intervention in patients with AKI might yield outcomes similar to those in patients without AKI. PMID:28248851

  2. [Prognostication of acute-pancreatitis-associated pulmonary injury based on determination of cytokines levels].

    PubMed

    Fedorkiv, M B; Hudz, I M; Shevchuk, I M

    2013-07-01

    The results of examination of 68 patients, admitted to hospital for an acute pancreatitis during 48 h from its occurrence, were analyzed. In all the patients the cytokines (IL-8, IL-10, TNF-alpha) content was determined in the blood, using immunoenzymal analysis. Algorithm of prognostication of an acute pancreatitis-associated pulmonary injury, basing on determination of the cytokines contents, was elaborated.

  3. Pulmonary function test findings in patients with acute inhalation injury caused by smoke bombs

    PubMed Central

    Cao, Lu; Zhang, Xin-Gang; Wang, Jian-Guo; Wang, Han-Bin; Chen, Yi-Bing; Zhao, Da-Hui; Shi, Wen-Fang

    2016-01-01

    Background This study aimed to determine the effects of smoke bomb-induced acute inhalation injury on pulmonary function at different stages of lung injury. Methods We performed pulmonary function tests (PFTs) in 15 patients with acute inhalation injury from days 3 to 180 after smoke inhalation. We measured the trace element zinc in whole blood on days 4 and 17, and correlations of zinc levels with PFTs were performed. Results In the acute stage of lung injury (day 3), 3 of 11 patients with mild symptoms had normal pulmonary function and 8 patients with restrictive ventilatory dysfunction and reduced diffusing capacity. Some patients also had mild obstructive ventilatory dysfunction (5 patients) and a decline in small airway function (6 patients). For patients with severe symptoms, PFT results showed moderate to severe restrictive ventilatory dysfunction and reduced diffusing capacity. PaCO2 was significantly higher (P=0.047) in patients with reduced small airway function compared with those with normal small airway function. Whole blood zinc levels in the convalescence stage (day 17) were significantly lower than those in the acute stage (day 4). Zinc in the acute stage was negatively correlated with DLCO/VA on days 3, 10, and 46 (r=−0.633, −0.676, and −0.675 respectively, P<0.05). Conclusions Smoke inhalation injury mainly causes restrictive ventilatory dysfunction and reduced diffusing capacity, and causes mild obstructive ventilatory dysfunction and small airway function decline in some patients. Zinc is negatively correlated with DLCO/VA. Zinc levels may be able to predict prognosis and indicate the degree of lung injury. PMID:28066595

  4. Rosiglitazone dampens pulmonary inflammation in a porcine model of acute lung injury.

    PubMed

    Mirakaj, Valbona; Mutz, Christian; Vagts, Dierk; Henes, Janek; Haeberle, Helene A; Husung, Susanne; König, Tony; Nöldge-Schomburg, Gabriele; Rosenberger, Peter

    2014-08-01

    The hallmarks of acute lung injury (ALI) are the compromised alveolar-capillary barrier and the extravasation of leukocytes into the alveolar space. Given the fact that the peroxisome proliferator-activated receptor-γ agonist rosiglitazone holds significant anti-inflammatory properties, we aimed to evaluate whether rosiglitazone could dampen these hallmarks of local pulmonary inflammation in a porcine model of lung injury. For this purpose, we used a model of lipopolysaccharide (LPS, 50 μg/kg)-induced ALI. One hundred twenty minutes following the infusion of LPS, we started the exposure to rosiglitazone through inhalation or infusion. We found that intravenous rosiglitazone significantly controlled local pulmonary inflammation as determined through the expression of cytokines within the alveolar compartment. Furthermore, we found a significant reduction of the protein concentration and neutrophil activity within the alveolar space. In summary, we therefore conclude that the treatment with rosiglitazone might dampen local pulmonary inflammation during the initial stages of ALI.

  5. Effect of partial liquid ventilation on pulmonary vascular permeability and edema after experimental acute lung injury.

    PubMed

    Lange, N R; Kozlowski, J K; Gust, R; Shapiro, S D; Schuster, D P

    2000-07-01

    We evaluated the effects of partial liquid ventilation (PLV) with two different dosages of the perfluorocarbon LiquiVent (perflubron) on pulmonary vascular permeability and edema formation after oleic acid (OA)-induced acute lung injury in dogs. We used imaging with positron emission tomography to measure fractional pulmonary blood flow, lung water concentration (LWC), and the pulmonary transcapillary escape rate (PTCER) of (68)Ga-labeled transferrin at 5 and 21 h after lung injury in five dogs undergoing conventional mechanical ventilation (CMV), five dogs undergoing low-dose PLV (perflubron at 10 ml/kg), and four dogs undergoing high dose PLV (perflubron at 30 ml/kg). A positive end-expiratory pressure of 7.5 cm H(2)O was used in all dogs. After OA (0.08 ml/kg)- induced lung injury, there were no significant differences or trends for PTCER or LWC at any time when the PLV groups were compared with the CMV group. However, lung tissue myeloperoxidase activity was significantly lower in the combined PLV group than in the CMV group (p = 0.016). We conclude that after OA-induced lung injury, the addition of PLV to CMV does not directly attenuate pulmonary vascular leak or lung water accumulation. Rather, the benefits of such treatment may be due to modifications of the inflammatory response.

  6. Regulation of S1P receptors and sphingosine kinases expression in acute pulmonary endothelial cell injury

    PubMed Central

    Liu, Huiying; Zhang, Zili; Li, Puyuan; Yuan, Xin; Zheng, Jing; Liu, Jinwen

    2016-01-01

    Background Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) is a severe clinical syndrome with mortality rate as high as 30–40%. There is no treatment yet to improve pulmonary endothelial barrier function in patients with severe pulmonary edema. Developing therapies to protect endothelial barrier integrity and stabilizing gas exchange is getting more and more attention. Sphingosine-1-phosphate (S1P) is able to enhance the resistance of endothelial cell barrier. S1P at physiological concentrations plays an important role in maintaining endothelial barrier function. Proliferation, regeneration and anti-inflammatory activity that mesenchymal stem cells (MSCs) exhibit make it possible to regulate the homeostatic control of S1P. Methods By building a pulmonary endothelial cell model of acute injury, we investigated the regulation of S1P receptors and sphingosine kinases expression by MSCs during the treatment of acute lung injury using RT-PCR, and investigated the HPAECs Micro-electronics impedance using Real Time Cellular Analysis. Results It was found that the down-regulation of TNF-α expression was more significant when MSC was used in combination with S1P. The combination effection mainly worked on S1PR2, S1PR3 and SphK2. The results show that when MSCs were used in combination with S1P, the selectivity of S1P receptors was increased and the homeostatic control of S1P concentration was improved through regulation of expression of S1P metabolic enzymes. Discussions The study found that, as a potential treatment, MSCs could work on multiple S1P related genes simultaneously. When it was used in combination with S1P, the expression regulation result of related genes was not simply the superposition of each other, but more significant outcome was obtained. This study establishes the experimental basis for further exploring the efficacy of improving endothelial barrier function in acute lung injury, using MSCs in combination with S1P and their

  7. Effect of inhaled nitric oxide on pulmonary hemodynamics after acute lung injury in dogs

    SciTech Connect

    Romand, J.A.; Pinsky, M.R.; Firestone, L.; Zar, H.A.; Lancaster, J.R. Jr. )

    1994-03-01

    Increased pulmonary vascular resistance (PVR) and mismatch in ventilation-to-perfusion ratio characterize acute lung injury (ALI). Pulmonary arterial pressure (Ppa) decreases when nitric oxide (NO) is inhaled during hypoxic pulmonary vasoconstriction (HPV); thus NO inhalation may reduce PVR and improve gas exchange in ALI. The authors studied the hemodynamic and gas exchange effects of NO inhalation during HPV and then ALI in eight anesthetized open-chest mechanically ventilated dogs. Right atrial pressure, Ppa, and left ventricular and arterial pressures were measured, and cardiac output was estimated by an aortic flow probe. Shunt and dead space were also estimated. The effect of 5-min exposures to 0, 17, 28, 47, and 0 ppm inhaled NO was recorded during hyperoxia, hypoxia, and oleic acid-induced ALI. During ALI, partial [beta]-adrenergic blockage (propanolol, 0.15 mg/kg iv) was induced and 74 ppm NO was inhaled. Nitrosylhemoglobin (NO-Hb) and methemoglobin (MetHb) levels were measured. During hyperoxia, NO inhalation had no measurable effects. Hypoxia increased Ppa and calculated PVR, both of which decreased with 17 ppm NO. ALI decreased arterial Po[sub 2] and increased airway pressure, shunt, and dead space ventilation. Ppa and PVR were greater during ALI than during hyperoxia. NO inhalation had no measurable effect during ALI before or after [beta]-adrenergic blockage. MetHb remained low, and NO-Hb was unmeasurable. Bolus infusion of nitroglycerin (15 [mu]g) induced an immediate decrease in Ppa and PVR during ALI. Short-term NO inhalation does not affect PVR or gas exchange in dogs with oleic acid-induced ALI, nor does it increase NO-Hb or MetHb. In contrast, NO can diminish hypoxia-induced elevations in pulmonary vascular tone. These data suggest that NO inhalation selectively dilates the pulmonary circulation and specifically reduces HPV but not oleic acid-induced increases in pulmonary vasomotor tone. 28 refs., 3 figs., 2 tabs.

  8. Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury

    PubMed Central

    Yabuuchi, Nozomi; Sagata, Masataka; Saigo, Chika; Yoneda, Go; Yamamoto, Yuko; Nomura, Yui; Nishi, Kazuhiko; Fujino, Rika; Jono, Hirofumi; Saito, Hideyuki

    2016-01-01

    High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr), blood urea nitrogen (BUN) and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk. PMID:28025487

  9. Indoxyl Sulfate as a Mediator Involved in Dysregulation of Pulmonary Aquaporin-5 in Acute Lung Injury Caused by Acute Kidney Injury.

    PubMed

    Yabuuchi, Nozomi; Sagata, Masataka; Saigo, Chika; Yoneda, Go; Yamamoto, Yuko; Nomura, Yui; Nishi, Kazuhiko; Fujino, Rika; Jono, Hirofumi; Saito, Hideyuki

    2016-12-23

    High mortality of acute kidney injury (AKI) is associated with acute lung injury (ALI), which is a typical complication of AKI. Although it is suggested that dysregulation of lung salt and water channels following AKI plays a pivotal role in ALI, the mechanism of its dysregulation has not been elucidated. Here, we examined the involvement of a typical oxidative stress-inducing uremic toxin, indoxyl sulfate (IS), in the dysregulation of the pulmonary predominant water channel, aquaporin 5 (AQP-5), in bilateral nephrectomy (BNx)-induced AKI model rats. BNx evoked AKI with the increases in serum creatinine (SCr), blood urea nitrogen (BUN) and serum IS levels and exhibited thickening of interstitial tissue in the lung. Administration of AST-120, clinically-used oral spherical adsorptive carbon beads, resulted in a significant decrease in serum IS level and thickening of interstitial tissue, which was accompanied with the decreases in IS accumulation in various tissues, especially lung. Interestingly, a significant decrease in AQP-5 expression of lung was observed in BNx rats. Moreover, the BNx-induced decrease in pulmonary AQP-5 protein expression was markedly restored by oral administration of AST-120. These results suggest that BNx-induced AKI causes dysregulation of pulmonary AQP-5 expression, in which IS could play a toxico-physiological role as a mediator involved in renopulmonary crosstalk.

  10. The role of leptin in the development of pulmonary neutrophilia in infection and Acute Lung Injury

    PubMed Central

    Ubags, Niki D.; Vernooy, Juanita H.; Burg, Elianne; Hayes, Catherine; Bement, Jenna; Dilli, Estee; Zabeau, Lennart; Abraham, Edward; Poch, Katie R.; Nick, Jerry A.; Dienz, Oliver; Zuñiga, Joaquin; Wargo, Matthew J.; Mizgerd, Joseph P.; Tavernier, Jan; Rincón, Mercedes; Poynter, Matthew E.; Wouters, Emiel F.M.; Suratt, Benjamin T.

    2014-01-01

    Objective One of the hallmarks of severe pneumonia and associated Acute Lung Injury (ALI) is neutrophil recruitment to the lung. Leptin is thought to be up-regulated in the lung following injury and to exert diverse effects on leukocytes, influencing both chemotaxis and survival. We hypothesized that pulmonary leptin contributes directly to the development of pulmonary neutrophilia during pneumonia and ALI. Design Controlled human and murine in vivo and ex vivo experimental studies. Settings Research laboratory of a university hospital. Subjects Healthy human volunteers and subjects hospitalized with bacterial and H1N1 pneumonia. C57Bl/6 and db/db mice were also used. Interventions Lung samples from patients and mice with either bacterial or H1N1 pneumonia and associated ALI were immunostained for leptin. Human bronchoalveolar-lavage (BAL) samples obtained after lipopolysaccharide (LPS)-induced lung injury were assayed for leptin. C57Bl/6 mice were examined after oropharyngeal aspiration of recombinant leptin alone or in combination with E.coli- or K.pneumonia-induced pneumonia. Leptin-resistant (db/db) mice were also examined using the E.coli model. BAL neutrophilia and cytokine levels were measured. Leptin-induced chemotaxis was examined in human blood- and murine marrow-derived neutrophils in vitro. Measurements and Main Results Injured human and murine lung tissue showed leptin induction compared to normal lung, as did human BAL following LPS instillation. BAL neutrophilia in uninjured and infected mice was increased and lung bacterial-load decreased by airway leptin administration, whereas BAL neutrophilia in infected leptin-resistant mice was decreased. In sterile lung injury by LPS, leptin also appeared to decrease airspace neutrophil apoptosis. Both human and murine neutrophils migrated towards leptin in vitro, and this required intact signaling through the JAK2/PI3K pathway. Conclusion We demonstrate that pulmonary leptin is induced in injured human and

  11. Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury.

    PubMed

    Hu, Yue; Lou, Jian; Mao, Yuan-Yuan; Lai, Tian-Wen; Liu, Li-Yao; Zhu, Chen; Zhang, Chao; Liu, Juan; Li, Yu-Yan; Zhang, Fan; Li, Wen; Ying, Song-Min; Chen, Zhi-Hua; Shen, Hua-Hao

    2016-12-01

    MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of MTOR or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of Mtor in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.

  12. VEGF‐D promotes pulmonary oedema in hyperoxic acute lung injury

    PubMed Central

    Sato, Teruhiko; Paquet‐Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J; Yuan, Yinan; Zhang, You‐Fang; Fox, Stephen B; Hibbs, Margaret L; Wilkinson‐Berka, Jennifer L; Williams, Richard A; Stacker, Steven A; Sly, Peter D

    2016-01-01

    Abstract Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF‐D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF‐D in pathological oedema was unknown. To address these issues, we exposed Vegfd‐deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd‐deficient mice was substantially reduced compared to wild‐type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf‐d and its receptor Vegfr‐3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild‐type mice, indicating that components of the Vegf‐d signalling pathway are up‐regulated in hyperoxia. Importantly, VEGF‐D and its receptors were co‐localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF‐D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf‐d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF‐D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:26924464

  13. Acute pulmonary oedema.

    PubMed

    Powell, Jessica; Graham, David; O'Reilly, Sarah; Punton, Gillian

    2016-02-03

    Acute pulmonary oedema is a distressing and life-threatening illness that is associated with a sudden onset of symptoms. For the best possible patient outcomes, it is essential that nurses in all clinical areas are equipped to accurately recognise, assess and manage patients with acute pulmonary oedema. This article outlines the pathophysiology of acute cardiogenic and non-cardiogenic pulmonary oedema, and suggests a systematic approach to the recognition and management of its most serious manifestations. Long-term care and symptom recognition are discussed and suggestions for ongoing patient self-management are provided.

  14. The anesthetic agent sevoflurane attenuates pulmonary acute lung injury by modulating apoptotic pathways

    PubMed Central

    Wang, L.; Ye, Y.; Su, H.B.; Yang, J.P.

    2017-01-01

    The objective of this study was to evaluate lung protection by the volatile anesthetic sevoflurane (SEVO), which inhibits apoptosis. Male Sprague-Dawley rats (250–280 g; n=18) were randomly divided into three groups. The LPS group received 5 mg/kg endotoxin (lipopolysaccharide), which induced acute lung injury (ALI). The control (CTRL) group received normal saline and the SEVO group received sevoflurane (2.5%) for 30 min after ALI was induced by 5 mg/kg LPS. Samples were collected for analysis 12 h after LPS. Lung injury was assessed by pathological observations and tissue wet to dry weight (W/D) ratios. Apoptotic index (AI) was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and electron microscopy. Caspase-3 and cleaved-caspase-3 protein levels were determined by immunocytochemistry and western blotting, respectively. Bcl-xl levels were measured by western blotting and Bcl-2 levels by quantitative real-time polymerase chain reaction and western blotting. In the LPS group, W/D ratios, AI values, caspase-3 and cleaved-caspase-3 levels were significantly higher than in the CTRL group and lung injury was more severe. In the SEVO group, W/D ratios, AI, caspase-3 and cleaved-caspase-3 were lower than in the LPS group. Bcl-2 and Bcl-xl expression were higher than in the LPS group and lung injury was attenuated. Sevoflurane inhalation protected the lungs from injury by regulating caspase-3 activation and Bcl-xl and Bcl-2 expression to inhibit excessive cell apoptosis, and such apoptosis might be important in the pathogenesis of LPS-induced ALI. PMID:28225890

  15. Clara Cell Protein (CC16), a Marker of Lung Epithelial Injury, Is Decreased in Plasma and Pulmonary Edema Fluid From Patients With Acute Lung Injury

    PubMed Central

    Kropski, Jonathan A.; Fremont, Richard D.; Calfee, Carolyn S.; Ware, Lorraine B.

    2009-01-01

    Background: Acute lung injury (ALI) and ARDS are common clinical syndromes that are underdiagnosed. Clara cell secretory protein (CC16) is an antiinflammatory protein secreted by the Clara cells of the distal respiratory epithelium that has been proposed as a biomarker of lung epithelial injury. We tested the diagnostic and prognostic utility of CC16 in patients with non–trauma-related ALI/ARDS compared to a control group of patients with acute cardiogenic pulmonary edema (CPE). Methods: Plasma and pulmonary edema fluid samples were obtained from medical and surgical patients with ALI/ARDS or CPE requiring intubation for mechanical ventilation. The etiology of pulmonary edema was determined using consensus clinical criteria for ALI/ARDS and CPE and the edema fluid-to-plasma protein ratio. Plasma and edema fluid CC16 levels were measured by sandwich enzyme-linked immunosorbent assay. CC16 levels were log transformed for analysis, and comparisons were made by the Student t test or χ2 as appropriate. Results: Compared to patients with CPE (n = 9), patients with ALI/ARDS (n = 23) had lower median CC16 levels in plasma (22 ng/mL [interquartile range (IQR), 9 to 44 ng/mL] vs 55 ng/mL [IQR, 18 to 123 ng/mL], respectively; p = 0.053) and pulmonary edema fluid (1,950 ng/mL [IQR, 1,780 to 4,024 ng/mL] vs 4,835 ng/mL [IQR, 2,006 to 6,350 ng/mL], respectively; p = 0.044). Relative to total pulmonary edema fluid protein concentration, the median CC16 level was significantly lower in patients with ALI/ARDS (45 ng CC16/mg total protein [IQR, 4 to 64 ng CC16/mg total protein] vs 120 ng CC16/mg total protein [IQR, 87 to 257 ng CC16/mg total protein], respectively; p = 0.005). Neither plasma nor edema fluid CC16 levels predicted mortality, the number of days of unassisted ventilation, or ICU length of stay. Conclusion: CC16 is a promising diagnostic biomarker for helping to discriminate ALI from CPE. Larger scale validation is warranted to better characterize the utility of CC16

  16. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  17. Acute Inhalation Injury

    PubMed Central

    Gorguner, Metin; Akgun, Metin

    2010-01-01

    Inhaled substances may cause injury in pulmonary epithelium at various levels of respiratory tract, leading from simple symptoms to severe disease. Acute inhalation injury (AII) is not uncommon condition. There are certain high risk groups but AII may occur at various places including home or workplace. Environmental exposure is also possible. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances and chemical properties may affect disease severity as well as its location. Although AII cases may recover in a few days but AII may cause long-term complications, even death. We aimed to discuss the effects of short-term exposures (minutes to hours) to toxic substances on the lungs. PMID:25610115

  18. Acute Intraoperative Pulmonary Aspiration.

    PubMed

    Nason, Katie S

    2015-08-01

    Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk, and immediate management options by the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical.

  19. Roger S. Mitchell lecture. Uses of expression microarrays in studies of pulmonary fibrosis, asthma, acute lung injury, and emphysema.

    PubMed

    Sheppard, Dean

    2002-03-01

    Expression microarrays are a powerful tool that could provide new information about the molecular pathways regulating common lung diseases. To exemplify how this tool can be useful, selected examples of informative experiments are reviewed. In studies relevant to asthma, the cytokine interleukin-13 has been shown to produce many of the phenotypic features of this disease, but the cellular targets in the airways and the molecular pathways activated are largely unknown. We have used microarrays to begin to dissect the different transcriptional responses of primary lung cells to this cytokine. In experiments designed to identify global transcriptional programs responsible for regulating lung inflammation and pulmonary fibrosis, we performed microarray experiments on lung tissue from wild-type mice and mice lacking a member of the integrin family know to be involved in activation of latent transforming growth factor (TGF)-beta. In addition to identifying distinct cluster of genes involved in each of these processes, these studies led to the identification of novel pathways by which TGF-beta can regulate acute lung injury and emphysema. Together, these examples demonstrate how careful application and thorough analysis of expression microarrays can facilitate the discovery of novel molecular targets for intervening in common lung diseases.

  20. Effects of short-term propofol and dexmedetomidine on pulmonary morphofunction and biological markers in experimental mild acute lung injury.

    PubMed

    Cavalcanti, Vinícius; Santos, Cintia Lourenço; Samary, Cynthia Santos; Araújo, Mariana Neves; Heil, Luciana Boavista Barros; Morales, Marcelo Marcos; Silva, Pedro Leme; Pelosi, Paolo; Fernandes, Fatima Carneiro; Villela, Nivaldo; Rocco, Patricia Rieken Macedo

    2014-11-01

    We evaluated whether the short-term use of dexmedetomidine and propofol may attenuate inflammatory response and improve lung morphofunction in experimental acute lung injury (ALI). Thirty-six Wistar rats were randomly divided into five groups. Control (C) and ALI animals received sterile saline solution and Escherichia coli lipopolysaccharide by intraperitoneal injection respectively. After 24h, ALI animals were randomly treated with dexmedetomidine, propofol, or thiopental sodium for 1h. Propofol reduced static lung elastance and resistive pressure and was associated with less alveolar collapse compared to thiopental sodium and dexmedetomidine. Dexmedetomidine improved oxygenation, but did not modify lung mechanics or histology. Propofol was associated with lower IL (interleukin)-6 and IL-1β expression, whereas dexmedetomidine led to reduced inducible nitric oxide (iNOS) and increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression in lung tissue compared to thiopental sodium. In conclusion, in this model of mild ALI, short-term use of dexmedetomidine and propofol led to different functional effects and activation of biological markers associated with pulmonary inflammation.

  1. A numerical model of the respiratory modulation of pulmonary shunt and PaO2 oscillations for acute lung injury.

    PubMed

    Beda, Alessandro; Jandre, Frederico C; Giannella-Neto, Antonio

    2010-03-01

    It is an accepted hypothesis that the amplitude of the respiratory-related oscillations of arterial partial pressure of oxygen (DeltaPaO2) is primarily modulated by fluctuations of pulmonary shunt (Deltas), the latter generated mainly by cyclic alveolar collapse/reopening, when present. A better understanding of the relationship between DeltaPaO2, Deltas, and cyclic alveolar collapse/reopening can have clinical relevance for minimizing the severe lung damage that the latter can cause, for example during mechanical ventilation (MV) of patients with acute lung injury (ALI). To this aim, we numerically simulated the effect of such a relationship on an animal model of ALI under MV, using a combination of a model of lung gas exchange during tidal ventilation with a model of time dependence of shunt on alveolar collapse/opening. The results showed that: (a) the model could adequately replicate published experimental results regarding the complex dependence of DeltaPaO2 on respiratory frequency, driving pressure (DeltaP), and positive end-expiratory pressure (PEEP), while simpler models could not; (b) such a replication strongly depends on the value of the model parameters, especially of the speed of alveolar collapse/reopening; (c) the relationship between DeltaPaO2 and Deltas was overall markedly nonlinear, but approximately linear for PEEP>or=6 cmH2O, with very large DeltaPaO2 associated with relatively small Deltas.

  2. Role of Cardiovascular Disease-associated iron overload in Libby amphibole-induced acute pulmonary injury and inflammation

    EPA Science Inventory

    Pulmonary toxicity induced by asbestos is thought to be mediated through redox-cycling of fiber-bound and bioavailable iron (Fe). We hypothesized that Libby amphibole (LA)-induced cute lung injury will be exacerbated in rat models of cardiovascular disease (CVD)-associated Fe-ove...

  3. Deep venous thrombosis and pulmonary embolism in patients with acute spinal cord injury: a comparison with nonparalyzed patients immobilized due to spinal fractures

    SciTech Connect

    Myllynen, P.; Kammonen, M.; Rokkanen, P.; Boestman, O.L.; Lalla, M.; Laasonen, E.

    1985-06-01

    The occurrence of deep venous thrombosis (DVT) was studied in the series of 23 consecutive patients with acute spinal cord injury and 14 immobilized patients with spinal fractures without paralysis. The incidence of DVT in paralyzed patients was 100% as detected by the /sup 125/I-labeled fibrinogen test and confirmed by contrast venography, and 64% as detected by repeated clinical examinations and confirmed by contrast venography. The respective incidence of DVT in nonparalyzed patients with spinal fractures was 0%. The diagnosis of DVT was reached earlier with the radiofibrinogen test than with the clinical followup (5 days vs. 25 days). Two of the 23 paralyzed patients (9%) developed nonfatal clinical pulmonary embolism (PE). There were no differences in the values of routine coagulation tests. The result justifies prophylactic anticoagulant therapy in all cases of spinal cord injury during the acute post-traumatic phase.

  4. Acute kidney injury during pregnancy.

    PubMed

    Van Hook, James W

    2014-12-01

    Acute kidney injury complicates the care of a relatively small number of pregnant and postpartum women. Several pregnancy-related disorders such as preeclampsia and thrombotic microangiopathies may produce acute kidney injury. Prerenal azotemia is another common cause of acute kidney injury in pregnancy. This manuscript will review pregnancy-associated acute kidney injury from a renal functional perspective. Pathophysiology of acute kidney injury will be reviewed. Specific conditions causing acute kidney injury and treatments will be compared.

  5. Time course of respiratory mechanics and pulmonary structural remodelling in acute lung injury.

    PubMed

    Rocco, Patricia R M; Facchinetti, Livia D; Ferreira, Halina C; Negri, Elnara M; Capelozzi, Vera L; Faffe, Debora S; Zin, Walter A

    2004-10-12

    The aim of this study was to evaluate the time course of in vivo and in vitro respiratory mechanics and examine whether these parameters could reflect the temporal changes in lung parenchyma remodelling in paraquat (PQ)-induced lung injury. Measurements were done 1, 3 and 8 weeks after the intraperitoneal (i.p.) injection of saline (control) or paraquat (7mgkg(-1)) in rats. Airway and tissue resistances increased from control in PQ1 and PQ3 and returned to control values in PQ8, in accordance with the magnitude of bronchoconstriction. Viscoelastic/inhomogeneous pressure, tissue elastance, the number of polymorphonuclear cells, and collagen fibre content in lung parenchyma increased in PQ1 and remained elevated in PQ3 and PQ8. Static elastance increased in PQ1, returned to control values after 3 weeks, and was correlated with the volume fraction of collapsed alveoli. In conclusion, there is a restoration of normal alveolar-capillary lung units with a gradual improvement in airway and tissue resistances and static elastance. However, the on-going fibrotic process kept elevated tissue elastance and viscoelastic/inhomogeneous pressure.

  6. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

    Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

  7. [Acute radiation injury].

    PubMed

    Saito, Tsutomu

    2012-03-01

    Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.

  8. Landiolol hydrochloride ameliorates acute lung injury in a rat model of early sepsis through the suppression of elevated levels of pulmonary endothelin-1.

    PubMed

    Matsuishi, Yujiro; Jesmin, Subrina; Kawano, Satoru; Hideaki, Sakuramoto; Shimojo, Nobutake; Mowa, Chishimba Nathan; Akhtar, Shila; Zaedi, Sohel; Khatun, Tanzila; Tsunoda, Yoshiya; Kiwamoto, Takumi; Hizawa, Nobuyuki; Inoue, Yoshiaki; Mizutani, Taro

    2016-12-01

    Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-α and IL-6 but [PaO2] was significantly decreased. LPS also induced a significant increase in levels of pulmonary ET-1 and ET-A receptor, but levels of ET-B receptor, which has vasodilating effects, were remarkably diminished. Further, LPS administration upregulated the pulmonary expression of HIF-1α. Finally, the treatment of LPS-administered rats with landiolol for 3h ameliorated and prevented ALI, normalized the altered levels of pulmonary ET-1 and ET-A receptors. Landiolol also induced significant down-regulation of ET-B receptor in lung tissues in the early hours (phase) of sepsis. However, Landiolol treatment had no effect on the up-regulated inflammatory mediators (TNF-α, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1α also remained unchanged after landiolol treatment. Collectively, these data led us to conclude that landiolol may ameliorate sepsis-induced ALI via the pulmonary ET system.

  9. Combined effect of low-dose nitric oxide gas inhalation with partial liquid ventilation on hemodynamics, pulmonary function, and gas exchange in acute lung injury of newborn piglets.

    PubMed Central

    Choi, Chang Won; Hwang, Jong Hee; Chang, Yun Sil; Park, Won Soon

    2003-01-01

    We conducted a randomized animal study to determine whether there is a cumulative effect on hemodynamics, pulmonary function, and gas exchange when low-dose nitric oxide (NO) is added to partial liquid ventilation (PLV) in acute lung injury. Eighteen newborn piglets were saline-lavaged repeatedly, and randomly divided into two groups: PLV with perfluorocarbon group (n=8) and lavage only (control) group (n=10). Perfluorodecalin (30 mL/kg) was instilled into the endotracheal tube for 30 min, followed by 5-10 mL/kg/hr. Fifteen minutes after the completion of perfluorodecalin dosing, NO (10 ppm) was added to the inspiratory gas in an "on/off" manner. Perfluorodecalin instillation produced a significant improvement in gas exchange, pulmonary mechanics, shunt, and pulmonary arterial pressure (PAP). The addition of NO produced a further significant improvement in PaO2 and PAP. The "on/off" response to NO was seen apparently in PAP, PaO2, dynamic compliance, and shunt. All the variables in control group were remained at near the after-lavage levels without significant improvements until the end of the experiment. We concluded that NO might have a cumulative effect on gas exchange when combined with PLV, and this might be attributable to deceased PAP and V/Q mismatching. PMID:14676437

  10. Pulmonary Thromboembolectomy for Acute Pulmonary Thromboembolism

    PubMed Central

    Yi, Inho; Cho, Kyu Seok; Kim, Bum Shik; Kim, Soo-Cheol; Kim, Dae Hyun; Kim, Jung-Heon; Youn, Hyo Chul

    2011-01-01

    Background Acute pulmonary thromboembolism is fatal because of abruptly occurring hypoxemia and right ventricular failure. There are several treatment modalities, including anticoagulation, thrombolytics, ECMO (extracorporeal membrane oxygenator), and thromboembolectomy, for managing acute pulmonary thromboembolism. Materials and Methods Medical records from January 1999 to December 2004 at our institution were retrospectively reviewed for pulmonary thromboembolectomy. There were 7 patients (4 men and 3 women), who underwent a total of 8 operations because one patient had post-operative recurrent emboli and underwent reoperation. Surgery was indicatedfor mild hypoxemia and performed with CPB (cardiopulmonary bypass) in a beating heart state. Results The patients had several symptoms, such as dyspnea, chest discomfort, and palpitation. Four patients had deep vein thromboembolisms and 3 had psychotic problems, specifically schizophrenia. Post-operative complications included hemothorax, pleural effusion, and pericardial effusion. There were two hospital deaths, one each by brain death and right heart failure. Conclusion Emergency operation should be performed when medical treatments are no longer effective. PMID:22263185

  11. Vitamin D/VDR signaling attenuates lipopolysaccharide‑induced acute lung injury by maintaining the integrity of the pulmonary epithelial barrier.

    PubMed

    Shi, Yong-Yan; Liu, Tian-Jing; Fu, Jian-Hua; Xu, Wei; Wu, Lin-Lin; Hou, A-Na; Xue, Xin-Dong

    2016-02-01

    Vitamin D and its receptor have a protective effect on epithelial barriers in various tissues. Low levels of vitamin D are associated with numerous pulmonary diseases, including acute lung injury (ALI) and acute respiratory distress syndrome. The present study investigated whether the vitamin D/vitamin D receptor (VDR) pathway may ameliorate lipopolysaccharide (LPS)‑induced ALI through maintaining the integrity of the alveolar epithelial barrier. This was investigated by exposing wild‑type (WT) and VDR knockout C57BL/6J mice to LPS, then comparing the healthy and LPS‑treated mice lungs and bronchoalveolar lavage fluid (BALF). More specifically, lung histology, mRNA levels of proinflammatory cytokines and chemokines, and protein expression levels of tight junction proteins were determined. In addition, a vitamin D analog (paricalcitol) was administered to WT mice in order to investigate the effect of vitamin D on the alveolar epithelial barrier following exposure to LPS. VDR knockout mice exhibited severe lung injuries (P<0.001), increased alveolar permeability [demonstrated by a higher wet‑dry ratio of lung weight (P<0.05), greater expression levels of BALF protein (P<0.001) and fluorescein isothiocyanate‑conjugated 4 kDa dextran (P<0.001) leakage into the alveolar space], elevated proinflammatory cytokine and chemokine mRNA levels, as demonstrated by reverse transcription‑quantitative polymerase chain reaction (P<0.05), and decreased protein and mRNA expression levels of occludin (P<0.01) and zonula occludens‑1 (ZO‑1; P<0.01) compared with WT mice. Paricalcitol treatment partially inhibited these pathological changes in WT mice by maintaining the mRNA and protein expression levels of occludin (P<0.01) and ZO‑1 (P<0.05). A lack of VDRs in the pulmonary epithelial barrier appeared to compromise its defense, leading to more severe LPS‑induced lung injury. Furthermore, vitamin D treatment alleviated LPS‑induced lung injury and preserved alveolar

  12. Sympathetic crashing acute pulmonary edema

    PubMed Central

    Agrawal, Naman; Kumar, Akshay; Aggarwal, Praveen; Jamshed, Nayer

    2016-01-01

    Sympathetic crashing acute pulmonary edema (SCAPE) is the extreme end of the spectrum of acute pulmonary edema. It is important to understand this disease as it is relatively common in the emergency department (ED) and has better outcomes when managed appropriately. The patients have an abrupt redistribution of fluid in the lungs, and when treated promptly and effectively, these patients will rapidly recover. Noninvasive ventilation and intravenous nitrates are the mainstay of treatment which should be started within minutes of the patient's arrival to the ED. Use of morphine and intravenous loop diuretics, although popular, has poor scientific evidence. PMID:28149030

  13. Sympathetic crashing acute pulmonary edema.

    PubMed

    Agrawal, Naman; Kumar, Akshay; Aggarwal, Praveen; Jamshed, Nayer

    2016-12-01

    Sympathetic crashing acute pulmonary edema (SCAPE) is the extreme end of the spectrum of acute pulmonary edema. It is important to understand this disease as it is relatively common in the emergency department (ED) and has better outcomes when managed appropriately. The patients have an abrupt redistribution of fluid in the lungs, and when treated promptly and effectively, these patients will rapidly recover. Noninvasive ventilation and intravenous nitrates are the mainstay of treatment which should be started within minutes of the patient's arrival to the ED. Use of morphine and intravenous loop diuretics, although popular, has poor scientific evidence.

  14. The pathogenesis of pulmonary edema in acute pancreatitis.

    PubMed Central

    Warshaw, A L; Lesser, P B; Rie, M; Cullen, D J

    1975-01-01

    Acute pulmonary edema appeared 3 or more days after the onset of acute pancreatitis in 7 patients, an approximate incidence of 8%. The severity of pancreatitis in these patients was characterized by massive requirements for intravenous colloid and by marked hypocalcemia. In addition, at least 5 of the 7 patients had very high serum levels of triglycerides at the time of hospital admission. Hemodynamic studies during pulmonary edema showed normal central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance. Cardiac index was appropriately elevated. Respiratory treatment, consisting of endotracheal intubation and controlled ventilation with PEEP, was successful in allowing reversal of the pulmonary injury and recovery of respiratory function within 1-2 weeks in all cases. Two patients died later from pancreatic abscesses. The findings indicate that a distinct form of pulmonary injury may occur in acute pancreatitis, characterized by loss of integrity of the alveolar-capilllary membrane, leading to pulmonary edema. The mechanism of injury is not known but may be caused by circulating free fatty acids, phospholipase A, or vasoactive substances. The pulmonary membrane lesion appears to heal during the period of intensive respiratory support. Images Fig. 1. PMID:1101836

  15. Pathophysiology of pulmonary complications of acute pancreatitis

    PubMed Central

    Browne, George W; Pitchumoni, CS

    2006-01-01

    Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, IL-8, fMet-leu-phe (a bacterial wall product), nitric oxide, substance P, and macrophage inhibitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines. PMID:17131469

  16. [Acute Kidney Injury].

    PubMed

    Brix, Silke; Stahl, Rolf

    2017-02-01

    Acute kidney injury (AKI) is an important part of renal diseases and a common clinical problem. AKI is an acute decline in renal function. Due to a lack of therapeutic options, prevention and optimal management of patients with AKI are the most important strategies. Although seldom the sole cause of patients' death, AKI is associated with a significant increase in mortality. Our objective is to draw the attention towards the prevention of AKI of non-renal causes.

  17. Acute injuries in orienteerers.

    PubMed

    Kujala, U M; Nylund, T; Taimela, S

    1995-02-01

    The aim of this study was to characterize the type and severeity of acute injuries occurring in Finnish orienteerers in 1987 to 1991. The study is based on the orienteering license insurance records accounting for 2189 orienteering injuries during 69268 person-years of exposure in active orienteerers. Of these orienteerers, 73.0% were male; 73.5% (N = 1608) of all injuries occurred in males, so the injury rate was similar in males and females. The rate was highest in orienteerers 20 to 24 years of age and lowest in children. Injuries occurred most commonly during May to September (78.9% or all injuries), the months which include the orienteering competition season, and were more common during competitions (59.8%) than during training. A high number of the injuries occurred during weekends (58.9% of injuries) including 68.1% of all competition injuries and 44.9% of all training injuries. The lower limbs were involved in 1611 (73.6%) of cases, the ankle (28.7%) and the knee (23.2%) being the two most common injury locations. Sprains, strains and contusions were the most common injuries. Wounds were proportionally more common in males than in females while ankle sprains were more common in females. Fractures, seven open and 94 closed, accounted for 4.6% of injuries; they were most common in the hand/wrist/forearm (N = 44) and ankle (N = 16), and were more frequent during competition (62.3%) than during training. The most important areas for preventive measures seem to be the ankle and the knee.

  18. microRNA-1246 mediates lipopolysaccharide-induced pulmonary endothelial cell apoptosis and acute lung injury by targeting angiotensin-converting enzyme 2

    PubMed Central

    Fang, Yue; Gao, Fengying; Hao, Jing; Liu, Zhenwei

    2017-01-01

    In this study, we aimed to identify potential microRNA (miRNA) regulators of angiotensin-converting enzyme 2 (ACE2) and to explore their roles in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The expression of predicted miRNA regulators of ACE2 was examined in LPS-exposed pulmonary microvascular endothelial cells (PMVECs). Gain- and loss-of-function studies were performed to determine the functions of candidate miRNAs in LPS-induced PMVEC apoptosis and inflammatory response. The roles of the miRNAs in LPS-induced lung inflammation and permeability were investigated in a mouse model. Notably, LPS (1 μg/mL) significantly induced the expression of miR-1246 in PMVECs. ACE2 was validated as a target gene of miR-1246. Silencing of miR-1246 prevented LPS-induced inhibition of ACE2, which was accompanied by reduced apoptosis and production of IL-1β and TNF-α. In contrast, ectopic expression of miR-1246 triggered apoptosis in PMVECs and promoted IL-1β and TNF-α release. MiR-1246-mediated apoptosis of PMVECs was impaired by overexpression of ACE2. Depletion of miR-1246 attenuated lung inflammation, neutrophil infiltration, and vascular permeability and restored pulmonary expression of ACE2 in LPS-exposed mice. Taken together, miR-1246 meditates LPS-induced pulmonary endothelial cell apoptosis in vitro and ALI in mouse models, which are, at least partially, ascribed to repression of ACE2. PMID:28386354

  19. Effects of reduced tidal volume ventilation on pulmonary function in mice before and after acute lung injury.

    PubMed

    Thammanomai, Apiradee; Majumdar, Arnab; Bartolák-Suki, Erzsébet; Suki, Béla

    2007-11-01

    We investigated the influence of load impedance on ventilator performance and the resulting effects of reduced tidal volume (Vt) on lung physiology during a 30-min ventilation of normal mice and 10 min of additional ventilation following lavage-induced injury at two positive end-expiratory pressure (PEEP) levels. Respiratory mechanics were regularly monitored, and the lavage fluid was tested for the soluble E-cadherin, an epithelial cell adhesion molecule, and surfactant protein (SP) B. The results showed that, due to the load dependence of the delivered Vt from the small-animal ventilator: 1) uncontrolled ventilation in normal mice resulted in a lower delivered Vt (6 ml/kg at 3-cmH(2)O PEEP and 7 ml/kg at 6-cmH(2)O PEEP) than the prescribed Vt (8 ml/kg); 2) at 3-cmH(2)O PEEP, uncontrolled ventilation in normal mice led to an increase in lung parenchymal functional heterogeneity, a reduction of SP-B, and an increase in E-cadherin; 3) at 6-cmH(2)O PEEP, ventilation mode had less influence on these parameters; and 4) in a lavage model of acute respiratory distress syndrome, delivered Vt decreased to 4 ml/kg from the prescribed 8 ml/kg, which resulted in severely compromised lung function characterized by increases in lung elastance, airway resistance, and alveolar tissue heterogeneity. Furthermore, the low Vt ventilation also resulted in poor survival rate independent of PEEP. These results highlight the importance of delivering appropriate Vt to both the normal and injured lungs. By leaving the Vt uncompensated, it can significantly alter physiological and biological responses in mice.

  20. PULMONARY INJURY AND INFLAMMATION FROM REPEATED EXPOSURE TO SOLUBLE COMPONENTS AND SOLID PARTICULATE MATTER (PM)

    EPA Science Inventory

    Pulmonary injury from acute exposures to PM and the role of soluble versus insoluble PM have received considerable attention; however, their long-term impacts are less well understood. This study compared pulmonary injury and inflammatory responses from repeated exposure to solub...

  1. Dexmedetomidine alleviates pulmonary edema by upregulating AQP1 and AQP5 expression in rats with acute lung injury induced by lipopolysaccharide.

    PubMed

    Jiang, Yuan-xu; Dai, Zhong-liang; Zhang, Xue-ping; Zhao, Wei; Huang, Qiang; Gao, Li-kun

    2015-10-01

    This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS). Male Wistar rats were randomly divided into five groups: normal saline control (NS) group, receiving intravenous 0.9% normal saline (5 mL/kg); LPS group, receiving intravenous LPS (10 mg/kg); small-dose dexmedetomidine (S) group, treated with a small dose of dexmedetomidine (0.5 μg · kg(-1) · h(-1)); medium-dose dexmedetomidine (M) group, treated with a medium dose of dexmedetomidine (2.5 μg · kg(-1) · h(-1)); high-dose dexmedetomidine (H) group, treated with a high dose of dexmedetomidine (5 μg · kg(-1) · h(-1)). The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the lungs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio (W/D). The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in the lung tissues were assessed by enzyme- linked immunosorbent assay (ELISA). The mRNA and protein expression levels of aquaporin-1 (AQP1) and aquaporin-5 (AQP5) were detected by RT-PCR, immunohistochemistry, and Western blotting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group (P<0.01). The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group (P<0.01). Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.

  2. Acute Ozone (O3) Exposure Enhances Aortic Contraction in Healthy Rats while Exacerbating Pulmonary Injury in Diabetics

    EPA Science Inventory

    Air pollution exposure affects health adversely in individuals with type 2 diabetes (T2D) and diet induced obesity (DIO). We hypothesized that T2D and DIO would exacerbate O3 induced pulmonary responses and alter arterial reactivity. Male Wistar and Goto Kakizaki (GK) rats, a l...

  3. Acute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II Diabetes

    EPA Science Inventory

    Abstract for Society of Toxicology, March 22-25, 2015, San Diego, CAAcute Ozone (O3) Exposure Accelerates Diet-Induced Pulmonary Injury and Metabolic Alterations in a Rat Model of Type II DiabetesS.J. Snow1,3, D. Miller2, V. Bass2, M. Schladweiler3, A. Ledbetter3, J. Richards3, C...

  4. Acute hand injuries in athletes.

    PubMed

    Rosenbaum, Yoseph A; Awan, Hisham M

    2017-03-22

    Hand and wrist injuries in athletes are common, representing between 3 and 25% of all sports injuries. As many as a quarter of all sports injuries involve the hand or wrist. We review the recent literature regarding acute hand injuries in athletes based on the structures involved - bone, muscle/tendon, ligament, and neurovascular - including diagnosis and pathophysiology of these injuries, focusing on athlete-specific facets of treatment, and when available, opinions on return to play.

  5. Acute Kidney Injury

    PubMed Central

    Zuk, Anna; Bonventre, Joseph V.

    2016-01-01

    Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD). PMID:26768243

  6. Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome

    PubMed Central

    Wu, Chaomin; Evans, Colin E.; Dai, Zhiyu; Huang, Xiaojia; Zhang, Xianming; Jin, Hua; Hu, Guochang; Song, Yuanlin; Zhao, You-Yang

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3–5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients. PMID:28333981

  7. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    EPA Science Inventory

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  8. Experimental pulmonary inflammatory injury in the monkey.

    PubMed Central

    Revak, S D; Rice, C L; Schraufstätter, I U; Halsey, W A; Bohl, B P; Clancy, R M; Cochrane, C G

    1985-01-01

    by the return to full activity of four out of five BAL samples after their incubation with the reducing agent dithiothreitol in the presence of methionine sulfoxide peptide reductase. The specific activity of catalase in the BAL fluids of animals given 3-amino, 1,2,4 triazole (AT) 1 h before lavaging showed drops from 0.97 in untreated monkeys to 0.04 in FNLP-treated and 0.49 in PMA-treated monkeys. MPO levels also fell in the AT-treated injured animals from 16.59 to 0.85 delta OD/min X ml in FNLP animals in the absence and presence of AT, and 30.47 to 0.60 delta OD/min X ml in PMA-treated animals. Inhibition of MPO by AT was shown in vitro to be H2O2 dependent. Total glutathione levels in the BAL fluids did not change appreciably after FNLP or PMA treatment. These studies present substantial evidence of the generation of both proteases and oxidants during the establishment of acute pulmonary inflammatory injury in an experimental primate model. Images PMID:2995448

  9. Lung transcriptional profiling: insights into the mechanisms of ozone-induced pulmonary injury in Wistar Kyoto rats

    EPA Science Inventory

    Acute ozone-induced pulmonary injury and inflammation are well characterized in rats; however, mechanistic understanding of the pathways involved is limited. We hypothesized that acute exposure of healthy rats to ozone will cause transcriptional alterations, and comprehensive ana...

  10. Surgical management of penetrating pulmonary injuries

    PubMed Central

    Petrone, Patrizio; Asensio, Juan A

    2009-01-01

    Chest injuries were reported as early as 3000 BC in the Edwin Smith Surgical Papyrus. Ancient Greek chronicles reveal that they had anatomic knowledge of the thoracic structures. Even in the ancient world, most of the therapeutic modalities for chest wounds and traumatic pulmonary injuries were developed during wartime. The majority of lung injuries can be managed non-operatively, but pulmonary injuries that require operative surgical intervention can be quite challenging. Recent progress in treating severe pulmonary injuries has relied on finding shorter and simpler lung-sparing techniques. The applicability of stapled pulmonary tractotomy was confirmed as a safe and valuable procedure. Advancement in technology have revolutionized thoracic surgery and ushered in the era of video-assisted thoracoscopic surgery (VATS), providing an alternative method for accurate and direct evaluation of the lung parenchyma, mediastinum, and diaphragmatic injuries. The aim of this article is to describe the incidence of the penetrating pulmonary injuries, the ultimate techniques used in its operative management, as well as the diagnosis, complications, and morbidity and mortality. PMID:19236703

  11. World Trade Center Health Program; Addition of New-Onset Chronic Obstructive Pulmonary Disease and WTC-Related Acute Traumatic Injury to the List of WTC-Related Health Conditions. Final rule.

    PubMed

    2016-07-05

    The World Trade Center (WTC) Health Program conducted a review of published, peer-reviewed epidemiologic studies regarding potential evidence of chronic obstructive pulmonary disease (COPD) and acute traumatic injury among individuals who were responders to or survivors of the September 11, 2001, terrorist attacks. The Administrator of the WTC Health Program (Administrator) found that these studies provide substantial evidence to support a causal association between each of these health conditions and 9/11 exposures. As a result, the Administrator is publishing a final rule to add both new-onset COPD and WTC-related acute traumatic injury to the List of WTC-Related Health Conditions eligible for treatment coverage in the WTC Health Program.

  12. Autophagy in Acute Kidney Injury

    PubMed Central

    Livingston, Man J.; Dong, Zheng

    2014-01-01

    Acute kidney injury is a major kidney disease associated with poor clinical outcomes. The pathogenesis of acute kidney injury is multifactorial and is characterized by tubular cell injury and death. Recent studies have demonstrated autophagy induction in proximal tubular cells during acute kidney injury. The regulatory mechanisms of tubular cell autophagy are poorly understood; however, some recent findings have set up a foundation for further investigation. Although autophagy may promote cell death under certain experimental conditions, pharmacological and autophagy-related gene knockout studies have established a renoprotective role for autophagy in acute kidney injury. The mechanisms by which autophagy protects cells from injury and how, possibly, its pro-survival role switches to pro-death under certain conditions are discussed. Further research is expected to help us understand the regulatory network of tubular cell autophagy, define its precise roles in specific context of acute kidney injury, and identify autophagy-targeting strategies for the prevention and treatment of acute kidney injury. PMID:24485026

  13. [Acute pulmonary edema secondary to acute upper airway obstruction].

    PubMed

    Sánchez-Ortega, J L; Carpintero-Moreno, F; Olivares-López, A; Borrás-Rubio, E; Alvarez-López, M J; García-Izquierdo, A

    1992-01-01

    We report a 72 years old woman with mild arterial hypertension and no other pathological history who presented an acute pulmonary edema due to acute obstruction of the upper airway secondary to vocal chord paralysis developing during the immediate postoperative phase of thyroidectomy. The acute pulmonary edema resolved after application of tracheal reintubation, mechanical ventilation controlled with end expiratory positive pressure, diuretics, morphine, and liquid restriction. We discuss the possible etiopathogenic possibilities of this infrequent clinical picture and we suggest that all patients who suffered and acute obstruction of the upper airways require a careful clinical surveillance in order to prevent the development of the pulmonary syndrome.

  14. Pulmonary microRNA expression profiling in an immature piglet model of cardiopulmonary bypass-induced acute lung injury.

    PubMed

    Li, Wenlei; Ma, Kai; Zhang, Sen; Zhang, Hao; Liu, Jinping; Wang, Xu; Li, Shoujun

    2015-04-01

    After surgery performed under cardiopulmonary bypass (CPB), severe lung injury often occurs in infants. MicroRNAs (miRNAs) are potentially involved in diverse pathophysiological processes via regulation of gene expression. The objective of this study was to investigate differentially expressed miRNAs and their potential target genes in immature piglet lungs in response to CPB. Fourteen piglets aged 18.6 ± 0.5 days were equally divided into two groups that underwent sham sternotomy or CPB. The duration of aortic cross-clamping was 2 h, followed by 2 h reperfusion. Lung injury was evaluated by lung function indices, levels of cytokines, and histological changes. We applied miRNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analysis to determine miRNA expression. Meanwhile, qRT-PCR and enzyme-linked immunosorbent assay were used for validation of predicted mRNA targets. The deterioration of lung function and histopathological changes revealed the piglets' lungs were greatly impaired due to CPB. The levels of tumor necrosis factor alpha, interleukin 6, and interleukin 10 increased in the lung tissue after CPB. Using miRNA microarray, statistically significant differences were found in the levels of 16 miRNAs in the CPB group. Up-regulation of miR-21 was verified by PCR. We also observed down-regulation in the levels of miR-127, miR-145, and miR-204, which were correlated with increases in the expression of the products of their potential target genes PIK3CG, PTGS2, ACE, and IL6R in the CPB group, suggesting a potential role for miRNA in the regulation of inflammatory response. Our results show that CPB induces severe lung injury and dynamic changes in miRNA expression in piglet lungs. Moreover, the changes in miRNA levels and target gene expression may provide a basis for understanding the pathogenesis of CPB-induced injury to immature lungs.

  15. Transfusion related acute lung injury presenting with acute dyspnoea: a case report

    PubMed Central

    Haji, Altaf Gauhar; Sharma, Shekhar; Vijaykumar, DK; Paul, Jerry

    2008-01-01

    Introduction Transfusion-related acute lung injury is emerging as a common cause of transfusion-related adverse events. However, awareness about this entity in the medical fraternity is low and it, consequently, remains a very under-reported and often an under-diagnosed complication of transfusion therapy. Case presentation We report a case of a 46-year old woman who developed acute respiratory and hemodynamic instability following a single unit blood transfusion in the postoperative period. Investigation results were non-specific and a diagnosis of transfusion-related acute lung injury was made after excluding other possible causes of acute lung injury. She responded to symptomatic management with ventilatory and vasopressor support and recovered completely over the next 72 hours. Conclusion The diagnosis of transfusion-related acute lung injury relies on excluding other causes of acute pulmonary edema following transfusion, such as sepsis, volume overload, and cardiogenic pulmonary edema. All plasma containing blood products have been implicated in transfusion-related acute lung injury, with the majority being linked to whole blood, packed red blood cells, platelets, and fresh-frozen plasma. The pathogenesis of transfusion-related acute lung injury may be explained by a "two-hit" hypothesis, involving priming of the inflammatory machinery and then activation of this primed mechanism. Treatment is supportive, with prognosis being substantially better than for most other causes of acute lung injury. PMID:18957111

  16. Neonatal Acute Kidney Injury.

    PubMed

    Selewski, David T; Charlton, Jennifer R; Jetton, Jennifer G; Guillet, Ronnie; Mhanna, Maroun J; Askenazi, David J; Kent, Alison L

    2015-08-01

    In recent years, there have been significant advancements in our understanding of acute kidney injury (AKI) and its impact on outcomes across medicine. Research based on single-center cohorts suggests that neonatal AKI is very common and associated with poor outcomes. In this state-of-the-art review on neonatal AKI, we highlight the unique aspects of neonatal renal physiology, definition, risk factors, epidemiology, outcomes, evaluation, and management of AKI in neonates. The changes in renal function with gestational and chronologic age are described. We put forth and describe the neonatal modified Kidney Diseases: Improving Global Outcomes AKI criteria and provide the rationale for its use as the standardized definition of neonatal AKI. We discuss risk factors for neonatal AKI and suggest which patient populations may warrant closer surveillance, including neonates <1500 g, infants who experience perinatal asphyxia, near term/ term infants with low Apgar scores, those treated with extracorporeal membrane oxygenation, and those requiring cardiac surgery. We provide recommendations for the evaluation and treatment of these patients, including medications and renal replacement therapies. We discuss the need for long-term follow-up of neonates with AKI to identify those children who will go on to develop chronic kidney disease. This review highlights the deficits in our understanding of neonatal AKI that require further investigation. In an effort to begin to address these needs, the Neonatal Kidney Collaborative was formed in 2014 with the goal of better understanding neonatal AKI, beginning to answer critical questions, and improving outcomes in these vulnerable populations.

  17. Safety and Efficacy of Combined Extracorporeal Co2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study*

    PubMed Central

    Castanier, Matthias; Signouret, Thomas; Soundaravelou, Rettinavelou; Lepidi, Anne; Seghboyan, Jean-Marie

    2015-01-01

    Objective: To assess the safety and efficacy of combining extracorporeal Co2 removal with continuous renal replacement therapy in patients presenting with acute respiratory distress syndrome and acute kidney injury. Design: Prospective human observational study. Settings: Patients received volume-controlled mechanical ventilation according to the acute respiratory distress syndrome net protocol. Continuous venovenous hemofiltration therapy was titrated to maintain maximum blood flow and an effluent flow of 45 mL/kg/h with 33% predilution. Patients: Eleven patients presenting with both acute respiratory distress syndrome and acute kidney injury required renal replacement therapy. Interventions: A membrane oxygenator (0.65 m2) was inserted within the hemofiltration circuit, either upstream (n = 7) or downstream (n = 5) of the hemofilter. Baseline corresponded to tidal volume 6 mL/kg of predicted body weight without extracorporeal Co2 removal. The primary endpoint was 20% reduction in Paco2 at 20 minutes after extracorporeal Co2 removal initiation. Tidal volume was subsequently reduced to 4 mL/kg for the remaining 72 hours. Measurements and Main Results: Twelve combined therapies were conducted in the 11 patients. Age was 70 ± 9 years, Simplified Acute Physiology Score II was 69 ± 13, Sequential Organ Failure Assessment score was 14 ± 4, lung injury score was 3 ± 0.5, and Pao2/Fio2 was 135 ± 41. Adding extracorporeal Co2 removal at tidal volume 6 mL/kg decreased Paco2 by 21% (95% CI, 17–25%), from 47 ± 11 to 37 ± 8 Torr (p < 0.001). Lowering tidal volume to 4 mL/kg reduced minute ventilation from 7.8 ± 1.5 to 5.2 ± 1.1 L/min and plateau pressure from 25 ± 4 to 21 ± 3 cm H2O and raised Paco2 from 37 ± 8 to 48 ± 10 Torr (all p < 0.001). On an average of both positions, the oxygenator’s blood flow was 410 ± 30 mL/min and the Co2 removal rate was 83 ± 20 mL/min. The oxygenator blood flow (p <0.001) and the Co2 removal rate (p = 0.083) were higher when

  18. Acute injuries in Taekwondo.

    PubMed

    Schlüter-Brust, K; Leistenschneider, P; Dargel, J; Springorum, H P; Eysel, P; Michael, J W-P

    2011-08-01

    Although Taekwondo is becoming an increasingly popular sport, there is a lack of reliable epidemiologic data on Taekwondo injuries. To perform an epidemiologic study on the variety of types of injury in professional and amateur Taekwondo athletes and to find a relation between Taekwondo style, skill level, weight-class and warm-up routine and the occurrence of injuries, we analysed the injury data using a 7-page questionnaire from a total of 356 Taekwondo athletes who were randomly selected. Overall, we registered a total of 2,164 injuries in 356 athletes. Most traumas were contusions and sprains in the lower extremities. Professional Taekwondo athletes have an increased risk of injury in comparison to recreational athletes. Taekwondo style, weight class and tournament frequency have an influence on the athlete's injury profile. Warm-up routines were found to have a positive effect on injury rates. Overall, Taekwondo may be considered a rather benign activity, if injuries during Taekwondo tournaments can be avoided. If not, Taekwondo can result in serious musculoskeletal problems.

  19. The effect of composition, size, and solubility on acute pulmonary injury in rats following exposure to Mexico city ambient particulate matter samples.

    PubMed

    Snow, Samantha J; De Vizcaya-Ruiz, Andrea; Osornio-Vargas, Alvaro; Thomas, Ronald F; Schladweiler, Mette C; McGee, John; Kodavanti, Urmila P

    2014-01-01

    Particulate matter (PM)-associated metals can contribute to adverse cardiopulmonary effects following exposure to air pollution. The aim of this study was to investigate how variation in the composition and size of ambient PM collected from two distinct regions in Mexico City relates to toxicity differences. Male Wistar Kyoto rats (14 wk) were intratracheally instilled with chemically characterized PM10 and PM2.5 from the north and PM10 from the south of Mexico City (3 mg/kg). Both water-soluble and acid-leachable fractions contained several metals, with levels generally higher in PM10 South. The insoluble and total, but not soluble, fractions of all PM induced pulmonary damage that was indicated by significant increases in neutrophilic inflammation, and several lung injury biomarkers including total protein, albumin, lactate dehydrogenase activity, and γ-glutamyl transferase activity 24 and 72 h postexposure. PM10 North and PM2.5 North also significantly decreased levels of the antioxidant ascorbic acid. Elevation in lung mRNA biomarkers of inflammation (tumor necrosis factor [TNF]-α and macrophage inflammatory protein [MIP]-2), oxidative stress (heme oxygenase [HO]-1, lectin-like oxidized low-density lipoprotein receptor [LOX]-1, and inducibile nitric oxide synthase [iNOS]), and thrombosis (tissue factor [TF] and plasminogen activator inhibitor [PAI]-1), as well as reduced levels of fibrinolytic protein tissue plasminogen activator (tPA), further indicated pulmonary injury following PM exposure. These responses were more pronounced with PM10 South (PM10 South > PM10 North > PM2.5 North), which contained higher levels of redox-active transition metals that may have contributed to specific differences in selected lung gene markers. These findings provide evidence that surface chemistry of the PM core and not the water-soluble fraction played an important role in regulating in vivo pulmonary toxicity responses to Mexico City PM.

  20. [Positive end-expiratory pressure : adjustment in acute lung injury].

    PubMed

    Bruells, C S; Dembinski, R

    2012-04-01

    Treatment of patients suffering from acute lung injury is a challenge for the treating physician. In recent years ventilation of patients with acute hypoxic lung injury has changed fundamentally. Besides the use of low tidal volumes, the most beneficial setting of positive end-expiratory pressure (PEEP) has been in the focus of researchers. The findings allow adaption of treatment to milder forms of acute lung injury and severe forms. Additionally computed tomography techniques to assess the pulmonary situation and recruitment potential as well as bed-side techniques to adjust PEEP on the ward have been modified and improved. This review gives an outline of recent developments in PEEP adjustment for patients suffering from acute hypoxic and hypercapnic lung injury and explains the fundamental pathophysiology necessary as a basis for correct treatment.

  1. Alveolar edema fluid clearance and acute lung injury.

    PubMed

    Berthiaume, Yves; Matthay, Michael A

    2007-12-15

    Although lung-protective ventilation strategies have substantially reduced mortality of acute lung injury patients there is still a need for new therapies that can further decrease mortality in patients with acute lung injury. Studies of epithelial ion and fluid transport across the distal pulmonary epithelia have provided important new concepts regarding potential new therapies for acute lung injury. Overall, there is convincing evidence that the alveolar epithelium is not only a tight epithelial barrier that resists the movement of edema fluid into the alveoli, but it is also actively involved in the transport of ions and solutes, a process that is essential for edema fluid clearance and the resolution of acute lung injury. The objective of this article is to consider some areas of recent progress in the field of alveolar fluid transport under normal and pathologic conditions. Vectorial ion transport across the alveolar and distal airway epithelia is the primary determinant of alveolar fluid clearance. The general paradigm is that active Na(+) and Cl(-) transport drives net alveolar fluid clearance, as demonstrated in several different species, including the human lung. Although these transport processes can be impaired in severe lung injury, multiple experimental studies suggest that upregulation of Na(+) and Cl(-) transport might be an effective therapy in acute lung injury. We will review mechanisms involved in pharmacological modulation of ion transport in lung injury with a special focus on the use of beta-adrenergic agonists which has generated considerable interest and is a promising therapy for clinical acute lung injury.

  2. Acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  3. Low Tidal Volume Ventilation in Patients Without Acute Lung Injury.

    PubMed

    Tang, Weibing; Wang, Zhi; Liu, Ye; Zhu, Jing

    2015-05-01

    Acute respiratory distress syndrome is a life threatening respiratory condition characterized by breakdown of the alveolar-capillary barrier, leading to flooding of the alveolar space producing the classical chest radiograph of bilateral pulmonary infiltrates. In this study, we employed lung protective ventilation strategies in patients without acute lung injury (ALI) to determine whether mechanical ventilation with lower tidal volume would provide more clinical benefits to patients without ALI.

  4. [Acute pulmonary edema as a nursing emergency].

    PubMed

    Navarro Aldana, M C

    2001-01-01

    The presence of Acute Pulmonary Edema represents a severe emergency condition that requires immediate and efficient treatment; otherwise, imminent death of the patient occurs. Therefore it is of utter importance to perform frequent reviews of the literature to keep up with the newest procedures to warrant the best quality nursing care of our patients. This article reviews the physiopathology, clinical manifestations, and medical treatment of the Acute Pulmonary Edema, emphasizing on the nursing aspects of the treatment and pointing out the need to treat the predisposing cardiac alteration as soon as possible.

  5. Acute lung injury in fulminant hepatic failure following paracetamol poisoning.

    PubMed Central

    Baudouin, S. V.; Howdle, P.; O'Grady, J. G.; Webster, N. R.

    1995-01-01

    BACKGROUND--There is little information on the incidence of acute lung injury or changes in the pulmonary circulation in acute liver failure. The aim of this study was to record the incidence of acute lung injury in fulminant hepatic failure caused by paracetamol poisoning, to document the associated pulmonary circulatory changes, and to assess the impact of lung injury on patient outcome. METHODS--The degree of lung injury was retrospectively assessed by a standard scoring system (modified from Murray) in all patients with fulminant hepatic failure caused by paracetamol poisoning, admitted to the intensive care unit over a one year period. The severity of liver failure and illness, other organ system failure, and patient outcome were also analysed. RESULTS--Twenty four patients with paracetamol-induced liver failure were admitted and nine developed lung injury of whom eight (33%) had severe injury (Murray score > 2.5). In two patients hypoxaemia contributed to death. Patients with lung injury had higher median encephalopathy grades (4 v 2 in the non-injured group) and APACHE II scores (29 v 16). Circulatory failure, requiring vasoconstrictor support, occurred in all patients with lung injury but in only 40% of those without. Cerebral oedema, as detected by abnormal rises in intracranial pressure, also occurred in all patients with lung injury but in only 27% of the non-injured patients. The incidence of renal failure requiring renal replacement therapy was similar in both groups (67% and 47%). Pulmonary artery occlusion pressures were normal in the lung injury group. Cardiac output was high (median 11.2 1/min), systemic vascular resistance low (median 503 dynes/s/cm-5), and pulmonary vascular resistance low (median 70 dynes/s/cm-5), but not significantly different from the group without lung injury. Mortality was much higher in the lung injury group than in the non-injured group (89% v 13%). CONCLUSIONS--Acute lung injury was common in patients with paracetamol

  6. L-arginine attenuates acute lung injury after smoke inhalation and burn injury in sheep.

    PubMed

    Murakami, Kazunori; Enkhbaatar, Perenlei; Yu, Yong-Ming; Traber, Lillian D; Cox, Robert A; Hawkins, Hal K; Tompkins, Ronald G; Herndon, David; Traber, Daniel L

    2007-10-01

    Thermal injury results in reduced plasma levels of arginine (Arg). With reduced Arg availability, NOS produces superoxide instead of NO. We hypothesized that Arg supplementation after burn and smoke inhalation (B + S) injury would attenuate the acute insult to the lungs and, thus, protect pulmonary function. Seventeen Suffolk ewes (n = 17) were randomly divided into three groups: (1) sham injury group (n = 6), (2) B + S injury plus saline treatment (n = 6), and (3) B + S injury plus L-ARG infusion at 57 mg.kg(-1).h(-1) (n = 5). Burn and smoke inhalation injury was induced by standardized procedures, including a 40% area full thickness flame burn combined with 48 breaths of smoke from burning cottons. All animals were immediately resuscitated by Ringer solution and supported by mechanical ventilation for 48 h, during which various variables of pulmonary function were monitored. The results demonstrated that Arg treatment attenuated the decline of plasma Arg concentration after B + S injury. A higher plasma Arg concentration was associated with a less decline in Pao2/Fio2 ratio and a reduced extent of airway obstruction after B + S injury. Histopathological examinations also indicated a remarkably reduced histopathological scores associated with B + S injury. Nitrotyrosine stain in lung tissue was positive after B + S injury, but was significantly reduced in the group with Arg. Therefore, L-Arg supplementation improved gas exchange and pulmonary function in ovine after B + S injury via its, at least in part, effect on reduction of oxidative stress through the peroxynitrite pathway.

  7. [Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock].

    PubMed

    Sánchez Marteles, Marta; Urrutia, Agustín

    2014-03-01

    Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

  8. An uncommon cause of acute pulmonary edema.

    PubMed

    Nepal, Santosh; Giri, Smith; Bhusal, Mohan; Siwakoti, Krishmita; Pathak, Ranjan

    2016-09-01

    Acute cardiogenic pulmonary edema secondary to catecholamine-induced cardiomyopathy is a very uncommon and fatal initial presentation of pheochromocytoma. However, with early clinical suspicion and aggressive management, the condition is reversible. This case report describes a patient who presented with hypertension, dyspnea, and cough with bloody streaks, and who recovered within 48 hours after appropriate treatment.

  9. Acute Exacerbations of Idiopathic Pulmonary Fibrosis

    PubMed Central

    Collard, Harold R.; Moore, Bethany B.; Flaherty, Kevin R.; Brown, Kevin K.; Kaner, Robert J.; King, Talmadge E.; Lasky, Joseph A.; Loyd, James E.; Noth, Imre; Olman, Mitchell A.; Raghu, Ganesh; Roman, Jesse; Ryu, Jay H.; Zisman, David A.; Hunninghake, Gary W.; Colby, Thomas V.; Egan, Jim J.; Hansell, David M.; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kondoh, Yasuhiro; Lynch, David A.; Müller-Quernheim, Joachim; Myers, Jeffrey L.; Nicholson, Andrew G.; Selman, Moisés; Toews, Galen B.; Wells, Athol U.; Martinez, Fernando J.

    2007-01-01

    The natural history of idiopathic pulmonary fibrosis (IPF) has been characterized as a steady, predictable decline in lung function over time. Recent evidence suggests that some patients may experience a more precipitous course, with periods of relative stability followed by acute deteriorations in respiratory status. Many of these acute deteriorations are of unknown etiology and have been termed acute exacerbations of IPF. This perspective is the result of an international effort to summarize the current state of knowledge regarding acute exacerbations of IPF. Acute exacerbations of IPF are defined as acute, clinically significant deteriorations of unidentifiable cause in patients with underlying IPF. Proposed diagnostic criteria include subjective worsening over 30 days or less, new bilateral radiographic opacities, and the absence of infection or another identifiable etiology. The potential pathobiological roles of infection, disordered cell biology, coagulation, and genetics are discussed, and future research directions are proposed. PMID:17585107

  10. Sepsis and Acute Kidney Injury.

    PubMed

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  11. Sepsis and Acute Kidney Injury

    PubMed Central

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-01-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically “Risk-Injury-Failure-Loss-Endstage” (RIFLE), “Acute Kidney Injury Netwok” (AKIN) and “The Kidney Disease/ Improving Global Outcomes” (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also “cell cycle arrest” molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated. PMID:27366441

  12. Nitric oxide and hyperoxic acute lung injury

    PubMed Central

    Liu, Wen-wu; Han, Cui-hong; Zhang, Pei-xi; Zheng, Juan; Liu, Kan; Sun, Xue-jun

    2016-01-01

    Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI. PMID:27867474

  13. Transfusion-related acute lung injury.

    PubMed

    Federico, Anne

    2009-02-01

    Approximately one person in 5,000 will experience an episode of transfusion-related acute lung injury (TRALI) in conjunction with the transfusion of whole blood or blood components. Its hallmarks include hypoxemia, dyspnea, fever, hypotension, and bilateral pulmonary edema (noncardiogenic). The mortality for reported cases is 16.3%. The incidence and mortality may be even higher than estimated because of under-recognition and under-reporting. Although TRALI was identified as a clinical entity in the 1980s, a lack of consensus regarding a definition was present until 2004. An exact cause has yet to be identified; however, there are two theories regarding the etiology: the "antibody" and the "two-hit" theories. These theories involve both donor and recipient factors. Further education and research are needed to assist in the development of strategies for the prevention and treatment of TRALI.

  14. Pathophysiology of Acute Kidney Injury

    PubMed Central

    Basile, David P.; Anderson, Melissa D.; Sutton, Timothy A.

    2014-01-01

    Acute kidney injury (AKI) is the leading cause of nephrology consultation and is associated with high mortality rates. The primary causes of AKI include ischemia, hypoxia or nephrotoxicity. An underlying feature is a rapid decline in GFR usually associated with decreases in renal blood flow. Inflammation represents an important additional component of AKI leading to the extension phase of injury, which may be associated with insensitivity to vasodilator therapy. It is suggested that targeting the extension phase represents an area potential of treatment with the greatest possible impact. The underlying basis of renal injury appears to be impaired energetics of the highly metabolically active nephron segments (i.e., proximal tubules and thick ascending limb) in the renal outer medulla, which can trigger conversion from transient hypoxia to intrinsic renal failure. Injury to kidney cells can be lethal or sublethal. Sublethal injury represents an important component in AKI, as it may profoundly influence GFR and renal blood flow. The nature of the recovery response is mediated by the degree to which sublethal cells can restore normal function and promote regeneration. The successful recovery from AKI depends on the degree to which these repair processes ensue and these may be compromised in elderly or CKD patients. Recent data suggest that AKI represents a potential link to CKD in surviving patients. Finally, earlier diagnosis of AKI represents an important area in treating patients with AKI that has spawned increased awareness of the potential that biomarkers of AKI may play in the future. PMID:23798302

  15. Surgical embolectomy for acute massive pulmonary embolism

    PubMed Central

    Yavuz, Senol; Toktas, Faruk; Goncu, Tugrul; Eris, Cuneyt; Gucu, Arif; Ay, Derih; Erdolu, Burak; Tenekecioglu, Erhan; Karaagac, Kemal; Vural, Hakan; Ozyazicioglu, Ahmet

    2014-01-01

    Objective: Acute massive pulmonary embolism (PE) is associated with significant mortality rate despite diagnostic and therapeutic advances. The aim of this study was to analyze our clinical outcomes of patients with acute massive PE who underwent emergency surgical pulmonary embolectomy. Methods: This retrospective study included 13 consecutive patients undergoing emergency surgical pulmonary embolectomy for acute massive PE at our institution from March 2000 to November 2013. The medical records of all patients were reviewed for demograhic and preoperative data and postoperative outcomes. All patients presented with cardiogenic shock with severe right ventricular dysfunction confirmed by echocardiography, where 4 (30.8%) of the patients experienced cardiac arrest requiring cardiopulmonary resuscitation before surgery. Results: The mean age of patients was 61.8 ± 14 years (range, 38 to 82 years) with 8 (61.5%) males. The most common risk factors for PE was the history of prior deep venous thrombosis (n = 9, 69.2%). There were 3 (23.1%) in-hospital deaths including operative mortality of 7.7% (n = 1). Ten (76.9%) patients survived and were discharged from the hospital. The mean follow-up was 25 months; follow-up was 100% complete in surviving patients. There was one case (7.7%) of late death 12 months after surgery due to renal carcinoma. Postoperative echocardiographic pressure measurements demonstrated a significant reduction (P < 0.001). At final follow-up, all patients were in New York Heart Association class I and no readmission for a recurrent of PE was observed. Conclusion: Surgical pulmonary embolectomy is a reasonable option and could be performed with acceptable results, if it is performed early in patients with acute massive PE who have not reached the profound cardiogenic shock or cardiac arrest. PMID:25664045

  16. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  17. Variability in Ozone-Induced Pulmonary Injury and Inflammation in Healthy and Cardiovascular Compromised Rat Models

    EPA Science Inventory

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure depe...

  18. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

    EPA Science Inventory

    Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

  19. [Transfusion-related acute lung injury (TRALI)].

    PubMed

    Schweisfurth, H; Sopivnik, I; Moog, R

    2014-09-01

    Transfusion-related acute lung injury (TRALI) is primarily caused by transfusion of fresh frozen plasma or platelet concentrates and occurs by definition within 6 hours after transfusion with acute shortness of breath, hypoxemia and radiographically detectable bilateral infiltrates of the lung. Mostly leucocyte antibodies in the plasma of the blood donor (immunogenic TRALI) are responsible. Apart from antibodies, other substances such as biologically active lipids, mainly arising from the storage of platelet and red blood cell concentrates, can activate neutrophilic granulocytes and trigger a non-immunogenic TRALI. Pathophysiologically, granulocytes in the capillaries of the lung vessels release oxygen radicals and enzymes which damage the endothelial cells and cause pulmonary edema. Therapeutically, nasal oxygen administration may be sufficient. In severe cases, mechanical ventilation, invasive hemodynamic monitoring and fluid intake are required. Diuretics should be avoided. The administration of glucocorticoids is controversial. Antibody-related TRALI reactions occurred mainly after transfusion of fresh frozen plasma, which had been obtained from womenimmunized during pregnancy against leukocyte antigens. Therefore, in Germany, since 2009 only plasma from female donors without a history of prior or current pregnancy or negative testing for antibodies against HLA I, II or HNA has been used with the result that since then no TRALI-related death has been registered.

  20. Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery

    PubMed Central

    Fadel, Fatina I.; Mohamed, Mohamed Farouk; Habib, Sonia A.; Ibrahim, Mona H.; Sleem, Zeinab S.; Bazaraa, Hafez M.; Soliman, Mohamed M.A.

    2012-01-01

    Introduction Cardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery. Material and methods The study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: patients who suffered AKI grades II and III; and group II: patients who did not develop AKI or at risk. Peripheral venous blood was withdrawn pre- and post-operatively for serial measurements of NGAL and creatinine. Statistical analysis was performed using Statistical Package for Social Sciences version 14. Results Mean plasma NGAL levels showed highly significant elevations in group I patients at 2, 12, and 24 h after surgery (p < 0.0001) compared to group II. Significant correlations were found between NGAL and creatinine at different time intervals. Highly significant correlations (p < 0.0001) were found between plasma NGAL and AKI at 2, 12 and 24 h after surgery. A cut-off level of 100 ng/ml at 2 h, and 125 ng/ml at 12 h post-operatively both recorded the highest accuracy, being 95% accurate, with sensitivity of 100% and 89.5% respectively, and specificity of 90.5% and 100% respectively. Conclusions This study showed that plasma NGAL could be used as an early biomarker for detection of AKI following CPB. We recommend further studies on a wider scale to validate the current study results. PMID:22661997

  1. Rock Climbing Injuries: Acute and Chronic Repetitive Trauma.

    PubMed

    Chang, Connie Y; Torriani, Martin; Huang, Ambrose J

    2016-01-01

    Rock climbing has increased in popularity as a sport, and specific injuries related to its practice are becoming more common. Chronic repetitive injuries are more common than acute injuries, although acute injuries tend to be more severe. We review both acute and chronic upper and lower extremity injuries. Understanding the injury pattern in rock climbers is important for accurate diagnosis.

  2. Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using ...

  3. Glyphosate Poisoning with Acute Pulmonary Edema

    PubMed Central

    Thakur, Darshana Sudip; Khot, Rajashree; Joshi, P. P.; Pandharipande, Madhuri; Nagpure, Keshav

    2014-01-01

    GlySH-surfactant herbicide (GlySH), one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The US Environmental Protection Agency (EPA) states that ‘GlySH’ is of relatively low oral and acute dermal toxicity. It does not have anticholinesterase effect and no organophosphate-like central nervous system (CNS) effects. The clinical features range from skin and throat irritation to hypotension and death. Severe GlySH-surfactant poisoning is manifested by gastroenteritis, respiratory disturbances, altered mental status, hypotension refractory to the treatment, renal failure, and shock.[1] GlySH intoxication has a case fatality rate 3.2–29.3%. Pulmonary toxicity and renal toxicity seem to be responsible for mortality. Metabolic acidosis, abnormal chest X-ray, arrhythmias, and elevated serum creatinine levels are useful prognostic factors for predicting GlySH mortality.[2] There is no antidote and the mainstay of treatment for systemic toxicity is decontamination and aggressive supportive therapy. We report a case of acute pulmonary edema, which is a rare but severe manifestation of oral GlySH poisoning, where patient survived with aggressive supportive therapy. PMID:25948977

  4. Hypoxia-induced pulmonary arterial hypertension augments lung injury and airway reactivity caused by ozone exposure.

    PubMed

    Zychowski, Katherine E; Lucas, Selita N; Sanchez, Bethany; Herbert, Guy; Campen, Matthew J

    2016-08-15

    Ozone (O3)-related cardiorespiratory effects are a growing public health concern. Ground level O3 can exacerbate pre-existing respiratory conditions; however, research regarding therapeutic interventions to reduce O3-induced lung injury is limited. In patients with chronic obstructive pulmonary disease, hypoxia-associated pulmonary hypertension (HPH) is a frequent comorbidity that is difficult to treat clinically, yet associated with increased mortality and frequency of exacerbations. In this study, we hypothesized that established HPH would confer vulnerability to acute O3 pulmonary toxicity. Additionally, we tested whether improvement of pulmonary endothelial barrier integrity via rho-kinase inhibition could mitigate pulmonary inflammation and injury. To determine if O3 exacerbated HPH, male C57BL/6 mice were subject to either 3 weeks continuous normoxia (20.9% O2) or hypoxia (10.0% O2), followed by a 4-h exposure to either 1ppm O3 or filtered air (FA). As an additional experimental intervention fasudil (20mg/kg) was administered intraperitoneally prior to and after O3 exposures. As expected, hypoxia significantly increased right ventricular pressure and hypertrophy. O3 exposure in normoxic mice caused lung inflammation but not injury, as indicated by increased cellularity and edema in the lung. However, in hypoxic mice, O3 exposure led to increased inflammation and edema, along with a profound increase in airway hyperresponsiveness to methacholine. Fasudil administration resulted in reduced O3-induced lung injury via the enhancement of pulmonary endothelial barrier integrity. These results indicate that increased pulmonary vascular pressure may enhance lung injury, inflammation and edema when exposed to pollutants, and that enhancement of pulmonary endothelial barrier integrity may alleviate such vulnerability.

  5. Acute myocardial injury caused by Sydney funnel-web spider (Atrax robustus) envenoming.

    PubMed

    Isbister, G K; Warner, G

    2003-12-01

    A 67-year-old female suffered envenoming by a Sydney funnel-web spider (Atrax robustus), complicated by ST elevation and elevated troponin levels consistent with an acute myocardial injury. She was treated primarily with funnel-web spider antivenom, admission to intensive care and initial respiratory support for acute pulmonary oedema. The mechanism by which funnel-web spider envenomation caused myocardial injury is unclear but follow-up nuclear studies in the patient demonstrated that she had minimal atherosclerotic disease.

  6. Hepatic cryoablation-induced acute lung injury: histopathologic findings.

    PubMed

    Washington, K; Debelak, J P; Gobbell, C; Sztipanovits, D R; Shyr, Y; Olson, S; Chapman, W C

    2001-01-01

    We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-kappaB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P<0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo

  7. Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II.

    PubMed

    Wu, Zhiyong; Wang, Zhiwei; Dai, Feifeng; Liu, Huagang; Ren, Wei; Chang, Jinxing; Li, Bowen

    2016-01-01

    Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement.

  8. Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II

    PubMed Central

    Wang, Zhiwei; Dai, Feifeng; Liu, Huagang; Ren, Wei; Chang, Jinxing; Li, Bowen

    2016-01-01

    Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (PMVECs) were divided into control group, AngII group, AngII+PP2 (Src kinase inhibitor) group, and PP2 group. PP2 was used to inhibit the phosphorylation of Y685-VE-cadherin. Pathological changes, infiltration of macrophages and neutrophils, and pulmonary microvascular permeability were used to determine the pulmonary microvascular endothelial barrier function. Flow cytometry was used to determine the apoptosis of PMVECs, and immunofluorescence was used to determine the skeletal arrangement. Transendothelial resistance was used to detect the permeability of endothelial barrier. Phosphorylation of Y685-VE-cadherin was significantly reduced after AngII stimulation (P < 0.05), together with skeletal rearrangement, and elevation of endothelial permeability which finally induced endothelial barrier injury. After PP2 interference, the phosphorylation of Y685-VE-cadherin was further reduced and the endothelial permeability was further elevated. These data indicated that AngII could induce pulmonary injury by triggering endothelial barrier injury, and such process may be related to the dephosphorylation of Y685-VE-cadherin and the endothelial skeletal rearrangement. PMID:28119542

  9. Age-related differences in pulmonary effects of acute and ...

    EPA Pesticide Factsheets

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects.Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers ofpulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that ado

  10. Pathophysiology of ischaemic acute kidney injury.

    PubMed

    Kanagasundaram, Nigel Suren

    2015-03-01

    Acute kidney injury is common, dangerous and costly, affecting around one in five patients emergency admissions to hospital. Although survival decreases as disease worsens, it is now apparent that even modest degrees of dysfunction are not only associated with higher mortality but are an independent risk factor for death. This review focuses on the pathophysiology of acute kidney injury secondary to ischaemia - its commonest aetiology. The haemodynamic disturbances, endothelial injury, epithelial cell injury and immunological mechanisms underpinning its initiation and extension will be discussed along with the considerable and complex interplay between these factors that lead to an intense, pro-inflammatory state. Mechanisms of tubular recovery will be discussed but also the pathophysiology of abnormal repair with its direct consequences for long-term renal function. Finally, the concept of 'organ cross-talk' will be introduced as a potential explanation for the higher mortality observed with acute kidney injury that might be deemed modest in conventional biochemical terms.

  11. Acute pulmonary oedema on the Ruwenzori mountain range.

    PubMed Central

    Naeije, R; Mélot, C

    1990-01-01

    A 40 year old man had an episode of severe pulmonary oedema at 4000-5000 m during the ascent of the Margherita peak (5109 m) of Mount Stanley on the Ruwenzori. He had taken acetazolamide and high dose dexamethasone to treat symptoms of acute mountain sickness. Six years before he had been studied by right heart catheterisation as a healthy volunteer during hypoxic breathing at sea level. His pulmonary vascular reactivity had been within the normal range for 32 healthy subjects. This man had high altitude pulmonary oedema despite currently recommended treatments for acute mountain sickness and normal pulmonary vascular reactivity to hypoxia at sea level. PMID:2271350

  12. Prognostic Scores for Acute Pulmonary Embolism.

    PubMed

    Morillo, Raquel; Moores, Lisa; Jiménez, David

    2017-02-06

    Rapid and accurate risk stratification is critical in determining the optimal treatment strategy for patients with acute pulmonary embolism (PE). Early identification of patients with normal blood pressure and a favorable prognosis (low-risk PE) might select a subset of patients for outpatient treatment, which is associated with reduced cost and improved patient satisfaction, and has been shown to be effective and safe. Alternatively, identification of normotensive patients deemed as having a high risk for PE-related adverse clinical events (intermediate-high-risk PE) might select a subset of patients for close observation and consideration of escalation of therapy. Clinical prognostic scores have been gaining importance in the classification of patients into these categories. They should be derived and validated following strict methodological standards, and their use in clinical practice should be encouraged.

  13. Drug-induced pulmonary edema and acute respiratory distress syndrome.

    PubMed

    Lee-Chiong, Teofilo; Matthay, Richard A

    2004-03-01

    Noncardiogenic pulmonary edema, and, to a lesser extent, acute respiratory distress syndrome (ARDS), are common clinical manifestations of drug-induced lung diseases. Clinical features and radiographic appearances are generally indistinguishable from other causes of pulmonary edema and ARDS. Typical manifestations include dyspnea, chest discomfort, tachypnea, and hypoxemia. Chest radiographs commonly reveal interstitial and alveolar filling infiltrates. Unlike pulmonary edema that is due to congestive heart failure, cardiomegaly and pulmonary vascular redistribution are generally absent in cases that are drug-related. Rare cases of drug-induced myocarditis with heart failure and pulmonary edema have been described. Results from laboratory evaluation and respiratory function tests are nonspecific.

  14. Pulmonary Injury after Combined Exposures to Low-Dose Low-LET Radiation and Fungal Spores

    PubMed Central

    Marples, B.; Downing, L.; Sawarynski, K. E.; Finkelstein, J. N.; Williams, J. P.; Martinez, A. A.; Wilson, G. D.; Sims, M. D.

    2013-01-01

    Exposure to infectious microbes is a likely confounder after a nuclear terrorism event. In combination with radiation, morbidity and mortality from an infection may increase significantly. Pulmonary damage after low-dose low-LET irradiation is characterized by an initial diffuse alveolar inflammation. By contrast, inhaled fungal spores produce localized damage around pulmonary bronchioles. In the present study, we assessed lung injury in C57BL/6 mice after combined exposures to whole-body X radiation and inhaled fungal spores. Either animals were exposed to Aspergillus spores and immediately irradiated with 2 Gy, or the inoculation and irradiation were separated by 8 weeks. Pulmonary injury was assessed at 24 and 48 h and 1, 2, 4, 8, and 24 weeks later using standard H&E-stained sections and compared with sham-treated age-matched controls. Immunohistochemistry for invasive inflammatory cells (macrophages, neutrophils and B and T lymphocytes) was performed. A semi-quantitative assessment of pulmonary injury was made using three distinct parameters: local infiltration of inflammatory cells, diffuse inflammation, and thickening and distortion of alveolar architecture. Radiation-induced changes in lung architecture were most evident during the first 2 weeks postexposure. Fungal changes were seen over the first 4 weeks. Simultaneous combined exposures significantly increased the duration of acute pulmonary damage up to 24 weeks (P < 0.01). In contrast, administration of the fungus 8 weeks after irradiation did not produce enhanced levels of acute pulmonary damage. These data imply that the inhalation of fungal spores at the time of a radiation exposure alters the susceptibility of the lungs to radiation-induced injury. PMID:21275606

  15. NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury

    PubMed Central

    Li, Yang; Liu, Yong; Peng, XiangPing; Liu, Wei; Zhao, FeiYan; Feng, DanDan; Han, JianZhong; Huang, YanHong; Luo, SiWei; Li, Lian; Yue, Shao Jie; Cheng, QingMei; Huang, XiaoTing; Luo, ZiQiang

    2015-01-01

    Background Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. Methods C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. Results BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. Conclusions Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice. PMID:25942563

  16. Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.

    PubMed

    Jiang, Lei; Wang, Yixin; Su, Chenglei; Sun, Hao; Zhang, Huazhong; Zhu, Baoli; Zhang, Hengdong; Xiao, Hang; Wang, Jun; Zhang, Jinsong

    2015-01-01

    Acute pulmonary edema is one of the major outcomes of exposure to high levels of hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute pulmonary edema are still poorly understood. Therefore, the present study is designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal concentrations of inhaled H2S, then the pulmonary histological and lung epithelial cell injury were evaluated by hematoxylin-eosin staining and electron microscopy, respectively. In addition to morphological investigation, our results also revealed that H2S exposure significantly decreased the alveolar fluid clearance and increased the lung tissue wet-dry ratio. These changes were demonstrated to be associated with decreased ENaC expression. Furthermore, the extracellular-regulated protein kinases 1/2 pathway was demonstrated to be implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2 antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore, our results show that ENaC might represent a novel pharmacological target for the treatment of acute pulmonary edema induced by H2S and other hazardous gases.

  17. [A rare form of acute pulmonary edema: case report].

    PubMed

    Ricardo, José; Anaya, Maria José; Barbosa, Mário; André, Nelson; Magno, Pedro; Morais, José; Proença, Gonçalo; Rabaçal, Carlos; Gil, Victor

    2011-10-01

    We report the case of a 21-year-old man who underwent appendectomy under general anesthesia and developed acute pulmonary edema immediately after extubation. We then review the literature, focusing on the pathophysiology and the most important aspects of diagnosis and treatment of post-extubation pulmonary edema.

  18. Critical care in the ED: potentially fatal asthma and acute lung injury syndrome

    PubMed Central

    Hodder, Rick

    2012-01-01

    Emergency department clinicians are frequently called upon to assess, diagnose, and stabilize patients who present with acute respiratory failure. This review describes a rapid initial approach to acute respiratory failure in adults, illustrated by two common examples: (1) an airway disease – acute potentially fatal asthma, and (2) a pulmonary parenchymal disease – acute lung injury/acute respiratory distress syndrome. As such patients are usually admitted to hospital, discussion will be focused on those initial management aspects most relevant to the emergency department clinician. PMID:27147862

  19. Acute epididymitis: a work-related injury?

    PubMed Central

    Sawyer, E. K.; Anderson, J. R.

    1996-01-01

    Occupational medicine physicians frequently are presented with requests by employers to determine the work-relatedness of medical illnesses or injuries. Occasionally, this involves a sudden onset of acute epididymitis in the male employee after strenuous activity in the workplace. Because the vast majority of acute epididymitis cases have an underlying sexually transmitted disease component, this poses a real dilemma for the consulting physician. This article discusses the etiology and pathogenesis of acute epididymitis along with its epidemiologic significance and reviews workers' compensation and its possible legal interpretation when acute epididymitis occurs at the worksite. PMID:8691501

  20. Pulmonary oedema during treatment of acute water intoxication.

    PubMed Central

    Maclean, D.; Champion, M.; Trash, D. B.

    1976-01-01

    Acute water intoxication with deepening coma and uncontrolled epileptiform seizures in a 25-year-old previously fit male schizophrenic was treated with hypertonic (2 N) saline and a 20% mannitol solution. This improved his neurological state but precipitated severe pulmonary oedema. Intravenous frusemide increased his urinary output sufficiently to clear the pulmonary oedema. In acute water intoxication the use of hypertonic solutions may thus precipitate left heart failure by expanding the intra-pulmonary blood volume beyond the capacity of even a healthy left ventricle to compensate. Simple water restriction will produce a slower but perhaps safer improvement. Images Fig. 1 PMID:981097

  1. The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model.

    PubMed

    Garofalo, Michael; Bennett, Alexander; Farese, Ann M; Harper, Jamie; Ward, Amanda; Taylor-Howell, Cheryl; Cui, Wanchang; Gibbs, Allison; Lasio, Giovanni; Jackson, William; MacVittie, Thomas J

    2014-01-01

    Several radiation dose- and time-dependent tissue sequelae develop following acute high-dose radiation exposure. One of the recognized delayed effects of such exposures is lung injury, characterized by respiratory failure as a result of pneumonitis that may subsequently develop into lung fibrosis. Since this pulmonary subsyndrome may be associated with high morbidity and mortality, comprehensive treatment following high-dose irradiation will ideally include treatments that mitigate both the acute hematologic and gastrointestinal subsyndromes as well as the delayed pulmonary syndrome. Currently, there are no drugs approved by the Food and Drug Administration to counteract the effects of acute radiation exposure. Moreover, there are no relevant large animal models of radiation-induced lung injury that permit efficacy testing of new generation medical countermeasures in combination with medical management protocols under the FDA animal rule criteria. Herein is described a nonhuman primate model of delayed lung injury resulting from whole thorax lung irradiation. Rhesus macaques were exposed to 6 MV photon radiation over a dose range of 9.0-12.0 Gy and medical management administered according to a standardized treatment protocol. The primary endpoint was all-cause mortality at 180 d. A comparative multiparameter analysis is provided, focusing on the lethal dose response relationship characterized by a lethal dose50/180 of 10.27 Gy [9.88, 10.66] and slope of 1.112 probits per linear dose. Latency, incidence, and severity of lung injury were evaluated through clinical and radiographic parameters including respiratory rate, saturation of peripheral oxygen, corticosteroid requirements, and serial computed tomography. Gross anatomical and histological analyses were performed to assess radiation-induced injury. The model defines the dose response relationship and time course of the delayed pulmonary sequelae and consequent morbidity and mortality. Therefore, it may provide

  2. Soluble transition metals mediate residual oil fly ash induced acute lung injury.

    PubMed

    Dreher, K L; Jaskot, R H; Lehmann, J R; Richards, J H; McGee, J K; Ghio, A J; Costa, D L

    1997-02-21

    Identification of constituents responsible for the pulmonary toxicity of fugitive combustion emission source particles may provide insight into the adverse health effects associated with exposure to these particles as well as ambient air particulate pollution. Herein, we describe results of studies conducted to identify constituents responsible for the acute lung injury induced by residual oil fly ash (ROFA) and to assess physical-chemical factors that influence the pulmonary toxicity of these constituents. Biochemical and cellular analyses performed on bronchoalveolar lavage fluid obtained from rats following intratracheal instillation of ROFA suspension demonstrated the presence of severe inflammation, an indicator of pulmonary injury, which included recruitment of neutrophils, eosinophils, and monocytes into the airway. A leachate prepared from ROFA, containing predominantly Fe, Ni, V, Ca, Mg, and sulfate, produced similar lung injury to that induced by ROFA suspension. Depletion of Fe, Ni, and V from the ROFA leachate abrogated its pulmonary toxicity. Correspondingly, minimal lung injury was observed in animals exposed to saline-washed ROFA particles. A surrogate transition metal sulfate solution containing Fe, V, and Ni largely reproduced the lung injury induced by ROFA. Metal interactions and pH were found to influence the severity and kinetics of lung injury induced by ROFA and soluble transition metals. These findings provide direct evidence for the role of soluble transition metals in the pulmonary injury induced by the combustion emission source particulate, ROFA.

  3. Bioinforrnatics of Gene Expression Profiling Data Provide Mechanistic Understanding of Acute Ozone-Induced Lung injury

    EPA Science Inventory

    Acute ozone-induced pulmonary injury and inflammation are well characterized. A few studies have used gene expression profiling to determine the types of changes induced by ozone; however the mechanisms or the pathways involved are less well understood. We presumed that robust bi...

  4. ROLE OF CELL SIGNALING IN PROTECTION FROM DIESEL AND LPS INDUCED ACUTE LUNG INJURY

    EPA Science Inventory

    We have previously demonstrated in CD-1 mice that pre-administration of N-acetyl cysteine (NAC) or the p38 MAP kinase inhibitor (SB203580) reduces acute lung injury and inflammation following pulmonary exposures to diesel exhaust particles (DEP) or lipopolysaccharide (LPS). Here ...

  5. Pulmonary thromboembolic disease. Clinical management of acute and chronic disease.

    PubMed

    Torbicki, Adam

    2010-07-01

    Pulmonary thromboembolism falls between the areas of pulmonology and cardiology, internal medicine and intensive care, radiology and nuclear medicine, and hematology and cardiothoracic surgery. Depending on their clinical background, physicians faced with a patient with a pulmonary thromboembolism may speak different languages and adopt different treatment approaches. Now, however, there is an opportunity to end the Tower of Babel surrounding pulmonary thromboembolism. There is a growing acknowledgement that the key clinical problems in both acute pulmonary embolism and chronic thromboembolic pulmonary hypertension are linked to right ventricular pressure overload and right ventricular failure. As a result, cardiologists and cardiac intensive care specialists are taking an increasing interest in understanding and combating these conditions. The European Society of Cardiology was the first to elaborate comprehensive clinical practice guidelines for pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension. The task forces involved in producing these guidelines included radiologists, pulmonologists, hematologists, intensive care physicians and surgeons, which ensured that the final document was universally acceptable. The aim of this article was to provide an overview of the epidemiology, risk factors, diagnosis, treatment, prognosis and prevention of acute pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension, while taking into account European Society of Cardiology guidelines and incorporating new evidence where necessary.

  6. Acute injuries from mountain biking.

    PubMed Central

    Chow, T K; Bracker, M D; Patrick, K

    1993-01-01

    We questioned members of 2 southern California off-road bicycling organizations about injuries associated with the use of all-terrain bicycles. Cyclists were asked about riding and safety habits, the kind(s) of injury sustained with their most recent accident and whether they sought medical treatment, and the circumstances of the accident. Of 459 mailed surveys, 268 (58.4%) were returned. Respondents (82.8% of whom were male) ranged in age from 14 to 68 years. Of these, 225 (84%) had been injured while riding all-terrain bicycles, 51% in the past year. Although most injuries were characterized as minor, 26% required professional medical care, and 4.4% of those injured were admitted to hospital. Extremity injuries--abrasions, lacerations, contusions--occurred in 201 (90%) cyclists with 27 (12%) sustaining a fracture or dislocation. High levels of helmet use (88%) may explain the low occurrence of head and neck trauma (12%). Frequent riding and riding on paved terrain were associated with increased severity of injury, although most accidents--197 (87.6%)--occurred off paved roads. These results suggest that, compared with regular bicyclists, all-terrain cyclists have more, but not necessarily more severe, injuries. Clinicians and emergency medical personnel should be aware that the increasing popularity of off-road cycling may change the frequency and nature of bicycling injuries. PMID:8212679

  7. Transfusion-related acute lung injury: a review.

    PubMed

    Looney, Mark R; Gropper, Michael A; Matthay, Michael A

    2004-07-01

    Transfusion-related acute lung injury (TRALI) is an underreported complication of transfusion therapy, and it is the third most common cause of transfusion-associated death. TRALI is defined as noncardiogenic pulmonary edema temporally related to transfusion therapy. The diagnosis of TRALI relies on excluding other diagnoses such as sepsis, volume overload, and cardiogenic pulmonary edema. Supportive diagnostic evidence includes identifying neutrophil or human leukocyte antigen (HLA) antibodies in the donor or recipient plasma. All plasma-containing blood products have been implicated in TRALI, with the majority of cases linked to whole blood, packed RBCs, platelets, and fresh-frozen plasma. The pathogenesis of TRALI may be explained by a "two-hit" hypothesis, with the first "hit" being a predisposing inflammatory condition commonly present in the operating room or ICU. The second hit may involve the passive transfer of neutrophil or HLA antibodies from the donor or the transfusion of biologically active lipids from older, cellular blood products. Treatment is supportive, with a prognosis substantially better than most causes of clinical acute lung injury.

  8. [The acute knee injury - practical considerations].

    PubMed

    Bouaicha, Samy

    2014-04-09

    The acute knee injury represents one of the most common reasons to visit a general practitioner or an emergency department in a hospital. The initial assessment of an acute knee injury usually is affected by severe swelling, pain and a significant lack of motion. Conventional radiographs in three planes may provide additional information to limit the differential diagnosis. A clinical re-evaluation after five to ten days usually allows proper functional testing and therefore correct diagnosis in the majority of cases can be made. With suspicious clinical findings, MRI may be helpful to evaluate ligamentous, meniscal and cartilaginous structures. Femoro-tibial knee dislocation represents the most harmful acute knee injury and needs to be further evaluated and treated in an adequate medical institution in every suspicious case. Rapid vascular diagnostic with (CT)-angiography is crucial. Behind a multi-ligament injury of the knee a spontaneously reduced dislocation may hide and proper neuro-vascular exam therefore is mandatory in every patient. When fracture, blocking and major instability can be excluded at initial assessment, there is usually no need for any acute surgical intervention and initial conservative treatment may be conducted on an out-patient basis for most of the patients. Priority of surgical treatment depends on the injury pattern and delayed intervention with a pre-habilitative phase may be beneficial for certain pathologies.

  9. [Pregnancy-related acute kidney injury].

    PubMed

    Filipowicz, Ewa; Staszków, Monika

    Acute kidney injury (AKI) in obstetrics may be caused by the same disorders that are observed in the general population or may be specific for a pregnancy such as: preeclampsia, HELLP syndrome or acute fatty liver of pregnancy. The renal changes may be only temporary, and resolve within a few weeks postpartum, or may become irreversible leading to a progression of chronic kidney disease (CKD). In the article the most important pregnancy related syndromes associated with AKI have been shortly reviewed.

  10. Polymer-surfactant treatment of meconium-induced acute lung injury.

    PubMed

    Lu, K W; William Taeusch, H; Robertson, B; Goerke, J; Clements, J A

    2000-08-01

    Substances (for example, serum proteins or meconium) that interfere with the activity of pulmonary surfactant in vitro may also be important in the pathogenesis or progression of acute lung injury. Addition of polymers such as dextran or polyethylene glycol (PEG) to surfactants prevents and reverses surfactant inactivation. The purpose of this study was to find out whether surfactant/polymer mixtures are more effective for treating one form of acute lung injury than is surfactant alone. Acute lung injury in adult rats was created by tracheal instillation of human meconium. Injured animals, which were anesthetized, paralyzed, and ventilated with 100% oxygen and not treated with surfactant mixtures, remained hypoxic and required high ventilator pressures to maintain Pa(CO(2)) in the normal range over the 3 h of the experiment. Uninjured animals maintained normal values for oxygen and compliance of the respiratory system. The greatest improvement in both oxygenation (178%) and compliance (42%) occurred in animals with lung injury that were treated with Survanta and PEG (versus untreated control animals; p < 0.01), whereas little improvement was found after treatment with Survanta alone. Similar results were found when postmortem pulmonary pressure-volume curves and histology were examined. We conclude that adding PEG to Survanta improves gas exchange, pulmonary mechanics, and histologic appearance of the lungs in a rat model of acute lung injury caused by meconium.

  11. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood.

    PubMed Central

    Nysom, K.; Holm, K.; Olsen, J. H.; Hertz, H.; Hesse, B.

    1998-01-01

    The aim of this study was to examine pulmonary function after acute lymphoblastic leukaemia in childhood and identify risk factors for reduced pulmonary function. We studied a population-based cohort of 94 survivors of acute lymphoblastic leukaemia in childhood who were in first remission after treatment without spinal irradiation or bone marrow transplantation. Pulmonary function test results were compared with reference values for our laboratory, based on 348 healthy subjects who had never smoked from a local population study. A median of 8 years after cessation of therapy (range 1-18 years) the participants had a slight, subclinical, restrictive ventilatory insufficiency and reduced transfer factor and transfer coefficient. The changes in lung function were related to younger age at treatment and to more dose-intensive treatment protocols that specified more use of cranial irradiation and higher cumulative doses of anthracyclines, cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We conclude that, 8 years after treatment without bone marrow transplantation or spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first remission were without pulmonary symptoms but had signs of slight restrictive pulmonary disease including reduced transfer factor. The increased dose intensity of many recent protocols for childhood acute lymphoblastic leukaemia may lead to increased late pulmonary toxicity. PMID:9662245

  12. Pulmonary embolism: treatment of the acute episode.

    PubMed

    Casazza, Franco; Roncon, Loris; Greco, Francesco

    2005-10-01

    The prognosis of acute pulmonary embolism (PE) is mainly related to the clinical presentation and circulatory state of the patient: the therapeutic strategy is consequently different, ranging from an aggressive treatment in patients in life-threatening clinical conditions to a "stabilization" treatment in those hemodynamically stable. Since the majority of PE patients are clinically stable, a well conducted anticoagulant therapy, either with unfractionated or low-molecular-weight heparins together with a vitamin K antagonist, is sufficient to stop thrombus extension, to minimize the risk of recurrent embolism and prevent mortality. In about 15-20% of cases presenting with clinical instability of variable severity, prompt intravenous thrombolysis with a short-acting compound often represents a life-saving treatment and should be the first-line approach. In normotensive patients with right ventricular dysfunction at echocardiography, who represent about 30% of PE patients, the debate regarding the optimal therapy is still open and further studies are required to document a clinically relevant improvement in the benefit-risk ratio of thrombolytic agents over heparin alone: young people, with a very low risk of bleeding and a concomitant reduction of cardiopulmonary reserve might be the best candidates to systemic thrombolysis. In any case such patients should be admitted to an intensive care unit to monitor the clinical status for at least 48-72 hours and detect signs of possible hemodynamic worsening. Mechanical thrombectomy, either percutaneous or surgical, are ancillary procedures and should be reserved to a minority of highly compromised patients who are unable to receive thrombolysis.

  13. Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin

    PubMed Central

    Tejera, Paula; Meyer, Nuala; Chen, Feng; Feng, Rui; Zhao, Yang; O’Mahony, D. Shane; Li, Lin; Sheu, Chau-Chyun; Zhai, Rihong; Wang, Zhaoxi; Su, Li; Bajwa, Ed; Ahasic, Amy M.; Clardy, Peter; Gong, Michelle N.; Frank, Angela J.; Lanken, Paul N.; Thompson, B. Taylor; Christie, Jason D.; Wurfel, Mark; O’Keefe, Grant; Christiani, David C.

    2013-01-01

    Background The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been investigated specifically. The aim of this study was to identify genetic variants contributing to ARDS from pulmonary or extrapulmonary causes. Methods We conducted a multi-stage genetic association study. We first performed a large-scale genotyping (50K IBC Chip) in 1,717 Caucasian critically ill patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p ≤ 0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n = 765) and pneumonia/pulmonary sepsis (Population II; n = 838), as causes for ARDS/ALI. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second trauma-associated ALI population (n = 224, Stage III). Results In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p < 0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p < 0.007, Stage II; p < 0.05, Stage III). Meta-analysis confirmed these associations. Conclusions Different genetic variants may influence ARDS susceptibility depending on direct vs indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI, respectively. PMID:23048207

  14. Suppression of pulmonary injury in experimental 'Goodpasture's syndrome' by deoxyspergualin (DSP).

    PubMed Central

    Lan, H Y; Nikolic-Paterson, D J; Zarama, M; Kerr, P G; Atkins, R C

    1994-01-01

    DSP is a potent immunosuppressive drug which can prevent allograft rejection and suppress acute rejection episodes. In this study, the ability of DSP to suppress pulmonary injury in experimental Goodpasture's syndrome was investigated. Passive accelerated anti-glomerular basement membrane (GBM) disease was induced in rats by priming with rabbit IgG, followed 5 days later by injection of rabbit anti-GBM serum (day 0). Groups of five animals were treated with DSP (5 mg/kg intraperitoneally per day) or saline (untreated) from day 0 until being killed on days 1, 7, 14 or 21. At day 1, both DSP-treated and untreated animals exhibited similar pulmonary haemorrhage, oedema, and prominent perivascular leucocyte infiltration. Untreated animals subsequently developed severe widespread pulmonary damage including granulomatous lesions and extensive fibrosis, which correlated with infiltration of macrophages and immune-activated (IL-2R+) mononuclear cells (P < 0.01). Tumour necrosis factor-alpha (TNF-alpha), a known mediator of acute lung damage, was produced by pulmonary mononuclear cells throughout the experimental course. In contrast, DSP treatment resolved pulmonary haemorrhage, prevented the appearance of granulomatous lesions, and resulted in a histologically normal lung structure by day 21. This improvement was associated with a marked suppression of macrophage infiltration (P < 0.001 versus untreated), accumulation of immune activated (IL-2R+) mononuclear cells (P < 0.01 versus untreated), and TNF-alpha production (P < 0.05 versus untreated). DSP treatment also suppressed the deposition of rat anti-rabbit IgG immunoglobulin and C3 along the alveolar basement membrane (P < 0.05 versus untreated). In conclusion, DSP suppressed pulmonary injury in accelerated anti-GBM disease by acting on the local cellular immune response and the systemic humoral immune response. Further studies are warranted to determine whether this could be a useful drug for the treatment of

  15. DNA repair in ischemic acute kidney injury.

    PubMed

    Pressly, Jeffrey D; Park, Frank

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury leading to an induction of oxidative stress, cellular dysfunction, and loss of renal function. DNA damage, including oxidative base modifications and physical DNA strand breaks, is a consequence of renal IRI. Like many other organs in the body, a redundant and highly conserved set of endogenous repair pathways have evolved to selectively recognize the various types of cellular DNA damage and combat its negative effects on cell viability. Severe damage to the DNA, however, can trigger cell death and elimination of the injured tubular epithelial cells. In this minireview, we summarize the state of the current field of DNA damage and repair in the kidney and provide some expected and, in some cases, unexpected effects of IRI on DNA damage and repair in the kidney. These findings may be applicable to other forms of acute kidney injury and could provide new opportunities for renal research.

  16. [Acute lung injury as a consequence of blood transfusion].

    PubMed

    Rodríguez-Moyado, Héctor

    2011-01-01

    Acute lung injury (ALI) has been recognized as a consequence of blood transfusion (BT) since 1978; the Food and Drug Administration, has classified it as the third BT mortality issue, in 2004, and in first place related with ALI. It can be mainly detected as: Acute respiratory distress syndrome (ARDS), transfusion associated circulatory overload (TACO) and transfusion related acute lung injury (TRALI). The clinical onset is: severe dyspnea, bilateral lung infiltration and low oxygen saturation. In USA, ARDS has an incidence of three to 22.4 cases/100 000 inhabitants, with 58.3 % mortality. TACO and TRALI are less frequent; they have been reported according to the number of transfusions: one in 1275 to 6000 for TRALI and one in 356 transfusions for TACO. Mortality is reported from two to 20 % in TRALI and 20 % in TACO. Antileukocyte antibodies in blood donors plasma, caused TRALI in 89 % of cases; also it has been found antigen specificity against leukocyte blood receptor in 59 %. The UCI patients who received a BT have ALI as a complication in 40 % of cases. The capillary pulmonary endothelia is the target of leukocyte antibodies and also plasma biologic modifiers of the stored plasma, most probable like a Sanarelli-Shwar-tzman phenomenon.

  17. Asialoerythropoietin ameliorates bleomycin-induced acute lung injury in rabbits by reducing inflammation

    PubMed Central

    SONODA, AKINAGA; NITTA, NORIHISA; TSUCHIYA, KEIKO; OTANI, HIDEJI; WATANABE, SHOBU; MUKAISHO, KENICHI; TOMOZAWA, YUKI; NAGATANI, YUKIHIRO; OHTA, SHINICHI; TAKAHASHI, MASASHI; MURATA, KIYOSHI

    2014-01-01

    Acute lung injury, a critical illness characterized by acute respiratory failure with bilateral pulmonary infiltrates, remains unresponsive to current treatments. The condition involves injury to the alveolar capillary barrier, neutrophil accumulation and the induction of proinflammatory cytokines followed by lung fibrosis. In the present study, a rabbit model of bleomycin-induced acute lung injury was established to examine the effects of asialoerythropoietin (AEP), an agent with tissue-protective activities, on pulmonary inflammation. Six Japanese white rabbits were randomly divided into two equal groups. Acute lung injury was induced in all rabbits by intratracheally injecting bleomycin. The control group was injected with bleomycin only; the experimental (AEP) group was injected intravenously with AEP (80 μg/kg) prior to the bleomycin injection. Computed tomography (CT) studies were performed seven days later. The CT inflammatory scores of areas exhibiting abnormal density and the pathological inflammatory scores were recorded as a ratio on a 7×7 mm grid. The CT and pathological inflammatory scores were significantly different between the control and AEP groups [122±10 and 16.3±1.5 (controls) vs. 71±8.5 and 9.7±1.4 (AEP), respectively; P<0.01]. Thus, the present study revealed that AEP prevents bleomycin-induced acute lung injury in rabbits. PMID:25289037

  18. Cell proliferation contributes to PNEC hyperplasia after acute airway injury.

    PubMed

    Stevens, T P; McBride, J T; Peake, J L; Pinkerton, K E; Stripp, B R

    1997-03-01

    Pulmonary neuroendocrine cells (PNECs) are airway epithelial cells that are capable of secreting a variety of neuropeptides. PNECs are scattered throughout the bronchial tree either as individual cells or clusters of cells termed neuroepithelial bodies (NEBs). PNECs and their secretory peptides have been considered to play a role in fetal lung development. Although the normal physiological function of PNECs and neuropeptides in normal adult lungs and in repair from lung injury is not known, PNEC hyperplasia has been associated with chronic lung diseases, such as bronchopulmonary dysplasia, and with chronic exposures, such as hypoxia, tobacco smoke, nitrosamines, and ozone. To evaluate changes in PNEC number and distribution after acute airway injury, FVB/n mice were treated with either naphthalene or vehicle. Naphthalene is an aromatic hydrocarbon that, at the dose used in this study, selectively destroys nonciliated bronchial epithelial cells (Clara cells) through cytochrome P-450-mediated metabolic activation into cytotoxic epoxides. PNECs were identified by immunohistochemical analysis of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Proliferating cells were marked with [(3)H]thymidine incorporation. Acute naphthalene toxicity results in PNEC hyperplasia that is detectable after 5 days of recovery. PNEC hyperplasia is characterized by increased numbers of NEBs without significant changes in the number of isolated PNECs and by increased [(3)H]thymidine labeling of CGRP-IR cells. These data show that cell proliferation contributes to PNEC hyperplasia after acute airway injury and suggest that PNECs may be capable of more rapidly increasing their number in response to injury than previously recognized.

  19. Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis

    PubMed Central

    Hartman, Alan R.; Manetta, Frank; Lessen, Ronald; Kozikowski, Andrzej; Jahn, Lynda; Akerman, Meredith; Lesser, Martin L.; Glassman, Lawrence R.; Graver, Michael; Scheinerman, Jacob S.; Kalimi, Robert; Palazzo, Robert; Vatsia, Sheel; Pogo, Gustave; Hall, Michael; Yu, Pey-Jen; Singh, Vijay

    2015-01-01

    Acute pulmonary embolism is a substantial cause of morbidity and death. Although the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend surgical pulmonary embolectomy in patients with acute pulmonary embolism associated with hypotension, there are few reports of 30-day mortality rates. We performed a retrospective review of acute pulmonary embolectomy procedures performed in 96 consecutive patients who had severe, globally hypokinetic right ventricular dysfunction as determined by transthoracic echocardiography. Data on patients who were treated from January 2003 through December 2011 were derived from health system databases of the New York State Cardiac Surgery Reporting System and the Society of Thoracic Surgeons. The data represent procedures performed at 3 tertiary care facilities within a large health system operating in the New York City metropolitan area. The overall 30-day mortality rate was 4.2%. Most patients (68 [73.9%]) were discharged home or to rehabilitation facilities (23 [25%]). Hemodynamically stable patients with severe, globally hypokinetic right ventricular dysfunction had a 30-day mortality rate of 1.4%, with a postoperative mean length of stay of 9.1 days. Comparable findings for hemodynamically unstable patients were 12.5% and 13.4 days, respectively. Acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise; however, caution is warranted. Our outcomes might be dependent upon institutional capability, experience, surgical ability, and careful patient selection. PMID:25873794

  20. beta2 adrenergic agonists in acute lung injury? The heart of the matter.

    PubMed

    Lee, Jae W

    2009-01-01

    Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of beta2 adrenergic agonists as potential therapy has gained considerable interest due to their ability to increase the resolution of pulmonary edema. However, the results of clinical trials of beta agonist therapy for ALI/ARDS have been conflicting in terms of benefit. In the previous issue of Critical Care, Briot and colleagues present evidence that may help clarify the inconsistent results. The authors demonstrate that, in oleic acid lung injury in dogs, the inotropic effect of beta agonists may recruit damaged pulmonary capillaries, leading to increased lung endothelial permeability.

  1. Endovascular treatment for acute pulmonary embolism in neurological patient

    PubMed Central

    Paul, Gunchan; Paul, Birinder S; Gautam, Parshotam L; Mohan, Bishav; Sharma, Shruti

    2015-01-01

    Among the spectrum of venous thrombo-embolic disease, acute pulmonary embolism accounts for the most life threatening manifestations with mortality exceeding 50%. It can affect many patient populations across various disciplines, hence immediate attention and aggressive treatment is crucial. With the advancement of technologies, various catheter-based devices are available to treat massive or submassive PE. In this paper we report two patients of acute pulmonary embolism with neurological issues where the life threatening emergency was successfully managed by utilizing endovascular directed thrombolytic reperfusion therapy. PMID:26609298

  2. Visualizing the Propagation of Acute Lung Injury

    PubMed Central

    Cereda, Maurizio; Xin, Yi; Meeder, Natalie; Zeng, Johnathan; Jiang, YunQing; Hamedani, Hooman; Profka, Harrilla; Kadlecek, Stephen; Clapp, Justin; Deshpande, Charuhas G.; Wu, Jue; Gee, James C.; Kavanagh, Brian P.; Rizi, Rahim R.

    2015-01-01

    Background Mechanical ventilation worsens acute respiratory distress syndrome (ARDS), but this secondary ‘ventilator-associated’ injury is variable and difficult to predict. We aimed to visualize the propagation of such ventilator-induced injury, in the presence (and absence) of a primary underlying lung injury, and to determine the predictors of propagation. Methods Anesthetized rats (n=20) received acid aspiration (HCl) followed by ventilation with moderate tidal volume (VT). In animals surviving ventilation for at least two hours, propagation of injury was quantified using serial computed tomography (CT). Baseline lung status was assessed by oxygenation, lung weight, and lung strain (VT/expiratory lung volume). Separate groups of rats without HCl aspiration were ventilated with large (n=10) or moderate (n=6) VT. Results In 15 rats surviving longer than two hours, CT opacities spread outwards from the initial site of injury. Propagation was associated with higher baseline strain (propagation vs. no propagation, mean ± SD: 1.52 ± 0.13 vs. 1.16 ± 0.20, p<0.01), but similar oxygenation and lung weight. Propagation did not occur where baseline strain <1.29. In healthy animals, large VT caused injury that was propagated inwards from the lung periphery; in the absence of preexisting injury, propagation did not occur where strain was <2.0. Conclusions Compared with healthy lungs, underlying injury causes propagation to occur at a lower strain threshold and, it originates at the site of injury; this suggests that tissue around the primary lesion is more sensitive. Understanding how injury is propagated may ultimately facilitate a more individualized monitoring or management. PMID:26536308

  3. [Transfusion related acute lung injury (TRALI): an unrecognised pathology].

    PubMed

    Moalic, V; Vaillant, C; Ferec, C

    2005-03-01

    Transfusion related acute lung injury (TRALI) is a rare but potentially severe complication of blood transfusion, manifested by pulmonary oedema, fever and hypotension. The signs and symptoms are often attributed to other clinical aspects of a patient's condition, and therefore, TRALI may go unrecognised. It has been estimated to be the third cause of transfusion related mortality, so it should be better diagnosed. Cases are related to multiple blood units, such as white blood cells, red blood cells, fresh frozen plasma, platelets or intravenous immunoglobulins. Physiopathology of TRALI is poorly understood, and still controversial. It is often due to an immunological conflict between transfused plasma antibodies and recipients' blood cells. These antibodies are either HLA (class I or II) or granulocyte-specific. They appear to act as mediators, which result in granulocytes aggregation, activation and micro vascular pulmonary injury. Lipids or cytokines in blood units are also involved as TRALI priming agents. Diagnosis is based on antibody screening in blood components and on specific-antigen detection in the recipient. The screening of anti-HLA or anti-granulocytes is recommended as part of prevention for female donors who had been pregnant. Preventative measures should also include leucoreduction and measures to decrease the amount of priming agents in blood components. In this article, we summarise what is known about TRALI, and we focus attention on unanswered questions and controversial issues related to TRALI.

  4. Acute Lung Injury Accompanying Alveolar Hemorrhage Associated with Flu Vaccination in the Elderly.

    PubMed

    Satoh, Etsuko; Nei, Takahito; Kuzu, Shinichi; Chubachi, Kumi; Nojima, Daisuke; Taniuchi, Namiko; Yamano, Yoshimitsu; Gemma, Akihiko

    2015-01-01

    Flu vaccinations are administered worldwide every winter for prevention. We herein describe a case of acute lung injury resulting from a pathologically confirmed alveolar hemorrhage, which may have been closely related to a preceding vaccination for pandemic influenza A of 2009/10. The present patient had been hospitalized with an acute lung injury after flu vaccination one year prior to the present hospitalization, however, he received another flu vaccination. We should consider a vaccine-related adverse reaction as a potential cause of pulmonary disease if patients present with this illness during the winter season.

  5. Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis.

    PubMed

    Lin, Ze-Si; Ku, Chuen Fai; Guan, Yi-Fu; Xiao, Hai-Tao; Shi, Xiao-Ke; Wang, Hong-Qi; Bian, Zhao-Xiang; Tsang, Siu Wai; Zhang, Hong-Jie

    2016-04-01

    Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans-resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 µg/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-κB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro-inflammatory response, which was associated with a suppression of the NF-κB signaling pathway.

  6. Sodium hypochlorite-induced acute kidney injury.

    PubMed

    Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul

    2014-03-01

    Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis.

  7. Morphine in the treatment of acute pulmonary oedema--Why?

    PubMed

    Ellingsrud, C; Agewall, S

    2016-01-01

    Morphine has for a long time, been used in patients with acute pulmonary oedema due to its anticipated anxiolytic and vasodilatory properties, however a discussion about the benefits and risks has been raised recently. A literature search in Medline and Embase using the keywords "pulmonary oedema" OR "lung oedema" OR "acute heart failure" AND "morphine" was performed. A certain vasodilation has been described after morphine administration, but the evidence for this mechanism is relatively poor and morphine-induced anxiolysis may possibly be the most important factor of morphine in pulmonary oedema and therefore some authors have suggested benzodiazepines as an alternative treatment. Respiratory depression seems to be a less relevant clinical problem according to the literature, whereas vomiting is common, which may cause aspiration. In the largest outcome study, based on the ADHERE registry, morphine given in acute decompensated heart failure was an independent predictor of increased hospital mortality, with an odds ratio of 4.8 (95% CI: 4.52-5.18, p<0.001). Other, smaller studies have shown a significant association between morphine administration and mortality, which was lost after adjusting for confounding factors. Morphine is still used for pulmonary oedema in spite of poor scientific background data. A randomised, controlled study is necessary in order to determine the effect--and especially the risk--when using morphine for pulmonary oedema. Since the positive effects are not sufficiently documented, and since the risk for increased mortality cannot be ruled out, one can advocate that the use should be avoided.

  8. Dengue-associated acute kidney injury

    PubMed Central

    Oliveira, João Fernando Picollo; Burdmann, Emmanuel A.

    2015-01-01

    Dengue is presently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. Acute kidney injury (AKI) is a serious and potentially lethal complication of this disease, and the actual incidence is unknown. In this review, we will assess the most relevant epidemiological and clinical data regarding dengue and the available evidence on the frequency, etiopathogenesis, outcomes and treatment of dengue-associated AKI. PMID:26613023

  9. [Non-invasive ventilation and acute cardiogenic pulmonary oedema].

    PubMed

    Golmard, Céline

    2015-11-01

    Non-invasive ventilation is an integral part of therapies used in patients presenting acute cardiogenic pulmonary oedema. In cardiac intensive care, these patients are treated by teams trained and practised in this technique. The nurses play a central role in the support and monitoring of the patients.

  10. Pulmonary expression of nitric oxide synthase isoforms in sheep with smoke inhalation and burn injury.

    PubMed

    Cox, Robert A; Jacob, Sam; Oliveras, Gloria; Murakami, Kazunori; Enkhbaatar, Perenlei; Traber, Lillian; Schmalstieg, Frank C; Herndon, David N; Traber, Daniel L; Hawkins, Hal K

    2009-03-01

    Previous studies have indicated increased plasma levels of inducible nitric oxide synthase in lung. This study further examines the pulmonary expression of nitric oxide synthase (NOS) isoforms in an ovine model of acute lung injury induced by smoke inhalation and burn injury (S+B injury). Female range bred sheep (4 per group) were sacrificed at 4, 8, 12, 24, and 48 hours after injury and immunohistochemistry was performed in tissues for various NOS isoforms. The study indicates that in uninjured sheep lung, endothelial (eNOS) is constitutively expressed in the endothelial cells associated with the airways and parenchyma, and in macrophages. Similarly, neuronal (nNOS) is constitutively present in the mucous cells of the epithelium and in neurons of airway ganglia. In uninjured lung, inducible (iNOS) was present in bronchial secretory cells and macrophages. In tissue after S+B injury, new expression of iNOS was evident in bronchial ciliated cells, basal cells, and mucus gland cells. In the parenchyma, a slight increase in iNOS immunostaining was seen in type I cells at 12 and 24 hours after injury only. Virtually no change in eNOS or nNOS was seen after injury.

  11. Interleukin-1 and acute brain injury

    PubMed Central

    Murray, Katie N.; Parry-Jones, Adrian R.; Allan, Stuart M.

    2015-01-01

    Inflammation is the key host-defense response to infection and injury, yet also a major contributor to a diverse range of diseases, both peripheral and central in origin. Brain injury as a result of stroke or trauma is a leading cause of death and disability worldwide, yet there are no effective treatments, resulting in enormous social and economic costs. Increasing evidence, both preclinical and clinical, highlights inflammation as an important factor in stroke, both in determining outcome and as a contributor to risk. A number of inflammatory mediators have been proposed as key targets for intervention to reduce the burden of stroke, several reaching clinical trial, but as yet yielding no success. Many factors could explain these failures, including the lack of robust preclinical evidence and poorly designed clinical trials, in addition to the complex nature of the clinical condition. Lack of consideration in preclinical studies of associated co-morbidities prevalent in the clinical stroke population is now seen as an important omission in previous work. These co-morbidities (atherosclerosis, hypertension, diabetes, infection) have a strong inflammatory component, supporting the need for greater understanding of how inflammation contributes to acute brain injury. Interleukin (IL)-1 is the prototypical pro-inflammatory cytokine, first identified many years ago as the endogenous pyrogen. Research over the last 20 years or so reveals that IL-1 is an important mediator of neuronal injury and blocking the actions of IL-1 is beneficial in a number of experimental models of brain damage. Mechanisms underlying the actions of IL-1 in brain injury remain unclear, though increasing evidence indicates the cerebrovasculature as a key target. Recent literature supporting this and other aspects of how IL-1 and systemic inflammation in general contribute to acute brain injury are discussed in this review. PMID:25705177

  12. [Acute respiratory distress revealing severe pulmonary leptospirosis].

    PubMed

    Sekkach, Y; Qaçif, H; Jira, M; El Qatni, M; El omri, N; Ghafir, D

    2007-01-01

    We return a clinical case of leptospirose revelated by a complicated febrile harp pneumopathie of a sharp respiratory distress syndrome having required a transfer in resuscitation. The goal of our article is to recall that it is necessary to think systematically about a pulmonary shape of leptospirose facing an atypical pneumopahie.

  13. [Acute myocardial infarction complicated by acute pulmonary oedema and cardiogenic collapse during dobutamine stress echocardiography].

    PubMed

    Yameogo, Nobila Valentin; Mbaye, Alassane; Kagambega, Larissa Justine; Dioum, Momar; Diagne-Sow, Dior; Kane, Moussa; Diack, Bouna; Kane, Abdoul

    2013-06-23

    Acute myocardial infarction is a rare complication of dobutamine stress echocardiography. We describe the case of a diabetic patient who presented with an anterior myocardial infarction complicated by an acute pulmonary oedema and cardiogenic collapse during dobutamine stress echocardiography, requiring five days' hospitalisation. Coronarography could not be performed because of inadequate medical facilities.

  14. Acute respiratory failure and pulmonary thrombosis in leukemic children.

    PubMed

    Marraro, G; Uderzo, C; Marchi, P; Castagnini, G; Vaj, P L; Masera, G

    1991-02-01

    Acute respiratory failure (ARF) in an 11-year-old child with pre-T acute lymphoblastic leukemia (ALL) at the beginning of induction therapy was observed, connected with a pulmonary thrombosis and not with an infective origin. A systematic search for this pathology identified six other children with the same pulmonary complication, five of whom where in the early phase of acute nonlymphoblastic leukemia (ANLL) and one in induction therapy for ALL in marrow relapse. At the beginning of the symptomatology, all children presented severe hypoxia and hypercapnia, with no or minimal chest radiograph abnormalities and no clear hemodynamic involvement. In all patients the arteriography and nuclear imaging studies confirmed the diagnosis. The causes of the thrombi could be connected with neoplastic emboli after cell lysis and/or with the vascular damage resulting from antiblastic therapy. Intravenous urokinase treatment and respiratory assistance had been successfully carried out in six of seven children.

  15. Omeprazole Attenuates Pulmonary Aryl Hydrocarbon Receptor Activation and Potentiates Hyperoxia-Induced Developmental Lung Injury in Newborn Mice

    PubMed Central

    Shivanna, Binoy; Zhang, Shaojie; Patel, Ananddeep; Jiang, Weiwu; Wang, Lihua; Welty, Stephen E.; Moorthy, Bhagavatula

    2015-01-01

    Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in human preterm infants and a similar lung phenotype characterized by alveolar simplification in newborn mice. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury (HLI) in adult mice. Whether OM activates pulmonary AhR and protects C57BL/6J newborn mice against hyperoxia-induced developmental lung (alveolar and pulmonary vascular simplification, inflammation, and oxidative stress) injury (HDLI) is unknown. Therefore, we tested the hypothesis that OM will activate pulmonary AhR and mitigate HDLI in newborn mice. Newborn mice were treated daily with i.p. injections of OM at doses of 10 (OM10) or 25 (OM25) mg/kg while being exposed to air or hyperoxia (FiO2 of 85%) for 14 days, following which their lungs were harvested to determine alveolarization, pulmonary vascularization, inflammation, oxidative stress, vascular injury, and AhR activation. To our surprise, hyperoxia-induced alveolar and pulmonary vascular simplification, inflammation, oxidative stress, and vascular injury were augmented in OM25-treated animals. These findings were associated with attenuated pulmonary vascular endothelial growth factor receptor 2 expression and decreased pulmonary AhR activation in the OM25 group. We conclude that contrary to our hypothesis, OM decreases functional activation of pulmonary AhR and potentiates HDLI in newborn mice. These observations are consistent with our previous findings, which suggest that AhR activation plays a protective role in HDLI in newborn mice. PMID:26272953

  16. Airway pressure release ventilation in morbidly obese surgical patients with acute lung injury and acute respiratory distress syndrome.

    PubMed

    Testerman, George M; Breitman, Igal; Hensley, Sarah

    2013-03-01

    Morbidly obese patients with body mass index greater than 40 kg/m(2) and respiratory failure requiring critical care services are increasingly seen in trauma and acute care surgical centers. Baseline respiratory pathophysiology including decreased pulmonary compliance with dependent atelectasis and abnormal ventilation-perfusion relationships predisposes these patients to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) as well as prolonged stays in the intensive care unit. Airway pressure release ventilation (APRV) is an increasingly used alternative mode for salvage therapy in patients with hypoxemic respiratory failure that also provides lung protection from ventilator-induced lung injury. APRV provides the conceptual advantage of an "open lung" approach to ventilation that may be extended to the morbidly obese patient population with ALI and ARDS. We discuss the theoretical benefits and a recent clinical experience of APRV ventilation in the morbidly obese patient with respiratory failure at a Level I trauma, surgical critical care, and acute care surgery center.

  17. Pulmonary capillaritis: a possible histologic form of acute pulmonary allograft rejection.

    PubMed

    Badesch, D B; Zamora, M; Fullerton, D; Weill, D; Tuder, R; Grover, F; Schwarz, M I

    1998-04-01

    Acute rejection after lung transplantation occurs commonly and is usually characterized histologically by a perivascular mononuclear infiltrate. We report five cases of pulmonary capillaritis with a histologic appearance distinct from typical rejection, occurring in patients ranging in age from 18 to 45 years, with a variety of underlying diseases including alpha1 antitrypsin deficiency, pulmonary hypertension, cystic fibrosis, and rheumatoid arthritis. Four of the five patients had alveolar hemorrhage histologically, and two had frank hemoptysis. Time of onset ranged from 3 weeks to many months after transplantation. Three cases were fulminant, and there were two deaths. In only one case, with methicillin-resistant Staphylococcus aureus bronchitis, could infection be established. All were treated with intensification of immunosuppressive therapy. Plasmapheresis was carried out in two cases and coincided with temporary improvement, but its efficacy was questionable because of concurrent immunosuppressive therapy. Two had recurrent biopsy-proven acute rejection within 6 weeks of treatment, and one had recurrent severe pulmonary hemorrhage that abated with total lymphoid irradiation. Our experience suggests that pulmonary capillaritis in lung transplant recipients can be an acute, fatal illness with the potential for recurrence in the survivors. We speculate that it represents a form of acute vascular rejection. Early pathologic diagnosis and aggressive immunosuppressive therapy are recommended. Although a humoral component was not documented, the possible response to plasmapheresis requires continued evaluation.

  18. [Pulmonary edemas due to acute heroin poisoning].

    PubMed

    Francois, G; Faizende, J; Reboul, J

    1975-01-01

    Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics.

  19. Epidemiology of Overuse and Acute Injuries Among Competitive Collegiate Athletes

    PubMed Central

    Yang, Jingzhen; Tibbetts, Abigail S.; Covassin, Tracey; Cheng, Gang; Nayar, Saloni; Heiden, Erin

    2012-01-01

    Context: Although overuse injuries are gaining attention, epidemiologic studies on overuse injuries in male and female collegiate athletes are lacking. (70.7%) acute injuries were reported. The overall injury rate was Objective: To report the epidemiology of overuse injuries sustained by collegiate athletes and to compare the rates of overuse and acute injuries. Design: Descriptive epidemiology study. Setting: A National Collegiate Athletic Association Division I university. Patients or Other Participants: A total of 1317 reported injuries sustained by 573 male and female athletes in 16 collegiate sports teams during the 2005–2008 seasons. Main Outcome Measure(s): The injury and athlete-exposure (AE) data were obtained from the Sports Injury Monitoring System. An injury was coded as either overuse or acute based on the nature of injury. Injury rate was calculated as the total number of overuse (or acute) injuries during the study period divided by the total number of AEs during the same period. Results: A total of 386 (29.3%) overuse injuries and 931 63.1 per 10000 AEs. The rate ratio (RR) of acute versus overuse injuries was 2.34 (95% confidence interval [CI] = 2.05, 2.67). Football had the highest RR (RR = 8.35, 95% CI = 5.38, 12.97), and women's rowing had the lowest (RR = 0.75, 95% CI = 0.51, 1.10). Men had a higher acute injury rate than women (49.8 versus 38.6 per 10000 AEs). Female athletes had a higher rate of overuse injury than male athletes (24.6 versus 13.2 per 10000 AEs). More than half of the overuse injuries (50.8%) resulted in no time loss from sport. Conclusions: Additional studies are needed to examine why female athletes are at greater risk for overuse injuries and identify the best practices for prevention and rehabilitation of overuse injuries. PMID:22488286

  20. Management of acute traumatic spinal cord injuries.

    PubMed

    Shank, C D; Walters, B C; Hadley, M N

    2017-01-01

    Acute traumatic spinal cord injury (SCI) is a devastating disease process affecting tens of thousands of people across the USA each year. Despite the increase in primary prevention measures, such as educational programs, motor vehicle speed limits, automobile running lights, and safety technology that includes automobile passive restraint systems and airbags, SCIs continue to carry substantial permanent morbidity and mortality. Medical measures implemented following the initial injury are designed to limit secondary insult to the spinal cord and to stabilize the spinal column in an attempt to decrease devastating sequelae. This chapter is an overview of the contemporary management of an acute traumatic SCI patient from the time of injury through the stay in the intensive care unit. We discuss initial triage, immobilization, and transportation of the patient by emergency medical services personnel to a definitive treatment facility. Upon arrival at the emergency department, we review initial trauma protocols and the evidence-based recommendations for radiographic evaluation of the patient's vertebral column. Finally, we outline closed cervical spine reduction and various aggressive medical therapies aimed at improving neurologic outcome.

  1. Acute Kidney Injury in Patients with Cirrhosis

    PubMed Central

    Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.

    2015-01-01

    Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266

  2. A patient with possible TRALI who developed pulmonary hypertensive crisis and acute pulmonary edema during cardiac surgery.

    PubMed

    Kojima, Taiki; Nishisako, Ryo; Sato, Hideo

    2012-06-01

    There are very few case reports of transfusion-related acute lung injury (TRALI) under close hemodynamic monitoring. We encountered a case of possible TRALI during on-pump coronary artery bypass grafting (CABG). A 66-year-old man who had undergone on-pump CABG was administered fresh frozen plasma (FFP). One hour after FFP transfusion, pulmonary hypertensive crisis and subsequent hypoxic decompensation occurred. A second cardiopulmonary bypass (CPB) was needed for circulatory and respiratory deterioration. Extracorporeal life support (ECLS), intraaortic balloon pumping (IABP), and nitric oxide therapy were required after the surgery. Despite the severity of the initial state, his recovery was comparatively smooth. ECLS and IABP were removed on postoperative day (POD)1; the patient was extubated and discharged from the ICU on POD7 and POD12, respectively. The diagnosis of TRALI was confirmed by human leukocyte antigen antibody detection in the administered FFP. In addition, lymphocytic immunofluorescence test showed that a cross-match of the plasma from the pooled FFP against the recipient leukocytes was positive. The clinical course of the pulmonary artery hypertension was followed by a decrease in dynamic lung compliance. The mechanism of this phenomenon is unclear. However, it might suggest the possibility of vasoconstriction or obstruction of the peripheral pulmonary artery preceding lung damage, as in the case in animal models reported previously.

  3. Prognostic value of computed tomography in acute pulmonary thromboembolism.

    PubMed

    Plasencia-Martínez, J M; Carmona-Bayonas, A; Calvo-Temprano, D; Jiménez-Fonseca, P

    2016-01-01

    In addition to being the standard reference for the diagnosis of acute pulmonary thromboembolism, CT angiography of the pulmonary arteries can also provide valuable information about the patient's prognosis. Although which imaging findings are useful for prognosis remains controversial, signs of right ventricular dysfunction on CT are now included in clinical algorithms for the management of pulmonary thromboembolism. However, the optimal method for obtaining these measurements while maintaining a balance between the ease of use necessary to include their evaluation in our daily activity and the loss of precision in its predictive capacity remains to be determined. Moreover, other variables associated with pulmonary thromboembolism that often go unobserved can complement the prognostic information we can offer to clinicians. This review aims to clarify some of the more controversial aspects related to the prognostic value of CT in patients with pulmonary embolisms according to the available evidence. Knowing which variables are becoming more important in the prognosis, how to detect them, and why it is important to include them in our reports will help improve the management of patients with pulmonary embolism.

  4. Rhabdomyolysis and acute kidney injury after acupuncture sessions.

    PubMed

    Papasotiriou, Marios; Betsi, Grigoria; Tsironi, Maria; Assimakopoulos, Georgios

    2014-05-01

    Rhabdomyolysis is usually caused by muscle injury, drugs or alcohol and presents with muscle weakness and pain. It is characterized by rise in serum creatine kinase, aminotransferases and electrolytes as well as myoglobinuria. Myoglobinuria may cause acute kidney injury by direct proximal tubule cytotoxicity, renal vasoconstriction, intraluminal cast formation and distal tubule obstruction. Muscle pain and weakness as well as vascular injury have been reported after acupuncture. We report a case of severe rhabdomyolysis and acute kidney injury after acupuncture sessions.

  5. Human Recombinant Apyrase Therapy Protects Against Canine Pulmonary Ischemia-Reperfusion Injury

    PubMed Central

    Ibrahim, Mohsen; Wang, Xingan; Puyo, Carlos A.; Montecalvo, Alessandro; Huang, Howard J.; Hachem, Ramsey R.; Andreetti, Claudio; Menna, Cecilia; Chen, Ridong; Krupnick, Alexander S.; Kreisel, Daniel; Rendina, Erino A.; Gelman, Andrew E.

    2014-01-01

    INTRODUCTION There is accumulating evidence that extracellular adenosine triphosphate (eATP) promotes many of the underlying mechanisms that exacerbate acute lung injury. However, much of this data is from inbred rodent models indicating the need for further investigation in higher vertebrates to better establish clinical relevance. To this end we evaluated a human recombinant apyrase therapy in a canine warm pulmonary ischemia-reperfusion injury (IRI) model and measured eATP levels in human lung recipients with or without primary lung allograft dysfunction (PGD). METHODS Warm ischemia was induced for 90 minutes in the left lung of 14 mongrel dogs. Seven minutes after reperfusion, the apyrase APT102 (1 mg/kg, N=7) or saline vehicle (N=7) was injected into the pulmonary artery. Arterial blood gases were obtained every 30 minutes up to 180 minutes after reperfusion. Bronchioalveolar lavage fluid (BALF) was analyzed for eATP concentration, cellularity and inflammatory mediator accumulation. Thirty bilateral human lung transplant recipients were graded for immediate early PGD and assessed for BALF eATP levels. RESULTS APT102-treated dogs had progressively better lung function and less pulmonary edema over the 3-hour reperfusion period when compared to vehicle-treated controls. Protection from IRI was observed with lower BALF eATP levels, fewer airway leukocytes and blunted inflammatory mediator expression. Additionally, human lung recipients with moderate to severe PGD had significantly higher eATP levels when compared to recipients without this injury. CONCLUSIONS Extracellular ATP accumulates in acutely injured canine and human lungs. Strategies that target eATP reduction may help protect lung recipients from IRI. PMID:25455749

  6. SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

  7. Acute kidney injury in the cancer patient.

    PubMed

    Campbell, G Adam; Hu, Daniel; Okusa, Mark D

    2014-01-01

    Acute kidney injury (AKI) is a frequent and significant complication of cancer and cancer therapy. Cancer patients frequently encounter risk factors for AKI including older age, CKD, prerenal conditions, sepsis, exposure to nephrotoxins, and obstructive physiology. AKI can also be secondary to paraneoplastic conditions, including glomerulonephritis and microangiopathic processes. This complication can have significant consequences, including effects on patients' ability to continue to receive therapy for their malignancy. This review will serve to summarize potential etiologies of AKI that present in patients with cancer as well as to highlight specific patient populations, such as the critically ill cancer patient.

  8. Synthetic cannabinoids and acute kidney injury

    PubMed Central

    Jamal, Faisal; Prabhakar, Sharma

    2015-01-01

    Synthetic cannabinoids (SCB) are a family of chemicals that bind to cannabinoid receptors and cause psychoactive effects. Over the past few years, they have been increasingly used for recreational purposes, especially by young adults, and have been reported to have many adverse effects. Acute kidney injury (AKI) has been recently reported; the pathophysiology of SCB-induced AKI is unknown. We report three cases of AKI in the setting of SCB use. The peak serum creatinine levels ranged from 3.0 to 5.7 mg/dL; one patient required hemodialysis. SCB can induce AKI. PMID:26424946

  9. Acute kidney injury in the elderly.

    PubMed

    Rosner, Mitchell H

    2013-08-01

    Most patients who develop acute kidney injury (AKI) are older than 65 years. Specific structural and functional changes that occur in the aging kidney predispose the elderly patient to AKI. This risk is further compounded by comorbid conditions, polypharmacy, and the need for invasive procedures. When AKI does occur, it is associated with significant morbidity and mortality. Although morbidity and mortality increases with advancing age, many elderly patients can survive AKI and do well. Thus, decision making should be thoughtful and individualized, and not dependent on age. Whenever possible, preventive approaches should be pursued to lessen the burden of AKI.

  10. Acute Kidney Injury: Diagnostic Approaches and Controversies

    PubMed Central

    Makris, Konstantinos; Spanou, Loukia

    2016-01-01

    Acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality. In the last ten years a large number of publications have highlighted the limitations of traditional approaches and the inadequacies of conventional biomarkers to diagnose and monitor renal insufficiency in the acute setting. A great effort was directed not only to the discovery and validation of new biomarkers aimed to detect AKI more accurately but also to standardise the definition of AKI. Despite the advances in both areas, biomarkers have not yet entered into routine clinical practice and the definition of this syndrome has many areas of uncertainty. This review will discuss the controversies in diagnosis and the potential of novel biomarkers to improve the definition of the syndrome. PMID:28167845

  11. Acute kidney injury in the pregnant patient.

    PubMed

    Nwoko, Rosemary; Plecas, Darko; Garovic, Vesna D

    2012-12-01

    Acute kidney injury (AKI) is costly and is associated with increased mortality and morbidity. An understanding of the renal physiologic changes that occur during pregnancy is essential for proper evaluation, diagnosis, and management of AKI. As in the general population, AKI can occur from prerenal, intrinsic, and post-renal causes. Major causes of pre-renal azotemia include hyperemesis gravidarum and uterine hemorrhage in the setting of placental abruption. Intrinsic etiologies include infections from acute pyelonephritis and septic abortion, bilateral cortical necrosis, and acute tubular necrosis. Particular attention should be paid to specific conditions that lead to AKI during the second and third trimesters, such as preeclampsia, HELLP syndrome, acute fatty liver of pregnancy, and TTP-HUS. For each of these disorders, delivery of the fetus is the recommended therapeutic option, with additional therapies indicated for each specific disease entity. An understanding of the various etiologies of AKI in the pregnant patient is key to the appropriate clinical management, prevention of adverse maternal outcomes, and safe delivery of the fetus. In pregnant women with pre-existing kidney disease, the degree of renal dysfunction is the major determining factor of pregnancy outcomes, which may further be complicated by a prior history of hypertension.

  12. Pleural effusion: An uncommon manifestation of nitrofurantoin-induced pulmonary injury.

    PubMed

    Davis, Jared W; Jones, Lynn S

    2016-01-01

    Nitrofurantoin has been documented as a cause of acute, sub-acute, and chronic pulmonary injury. This is a case of an 82 year-old female who presented with multiple episodes of respiratory symptoms due to recurrent pleural effusions after beginning nitrofurantoin therapy for urinary tract infection prophylaxis. Due to the rarity of pleural effusion as an adverse reaction to nitrofurantoin, the diagnosis was overlooked at first. This led to the patient undergoing multiple invasive procedures and accruing unnecessary healthcare cost before the diagnosis was made. This case demonstrates the need for physicians to remain mindful of rare adverse reactions from medications and maintain a high index of clinical suspicion with any patient presenting with a respiratory complaint while taking nitrofurantoin.

  13. Acute pulmonary edema secondary to hyperbaric oxygen therapy

    PubMed Central

    Obiagwu, Chukwudi; Paul, Vishesh; Chadha, Sameer; Hollander, Gerald; Shani, Jacob

    2015-01-01

    Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of diabetic ulcers, air embolism, carbon monoxide poisoning and gas gangrene with minimal adverse effects. Very few cases of HBOT causing acute pulmonary edema (PE) has been described; with a study on dogs suggesting that a complication of this therapy could be PE. We describe the case of an 80-year-old man with a history of stable systolic heart failure and diabetes mellitus presenting with acute PE following treatment with HBOT for diabetic foot. PMID:25988073

  14. Massive Pulmonary Embolism at the Onset of Acute Promyelocytic Leukemia.

    PubMed

    Sorà, Federica; Chiusolo, Patrizia; Laurenti, Luca; Autore, Francesco; Giammarco, Sabrina; Sica, Simona

    2016-01-01

    Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission.

  15. Massive Pulmonary Embolism at the Onset of Acute Promyelocytic Leukemia

    PubMed Central

    Sorà, Federica; Chiusolo, Patrizia; Laurenti, Luca; Autore, Francesco; Giammarco, Sabrina; Sica, Simona

    2016-01-01

    Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission. PMID:27413520

  16. Adenosine and protection from acute kidney injury

    PubMed Central

    Yap, Steven C.; Lee, H. Thomas

    2012-01-01

    Purpose of Review Acute Kidney Injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality, and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor (AR) manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal AR biology and potential clinical therapies for AKI. Recent Findings The 4 AR subtypes (A1AR, A2AAR, A2BAR and A3AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific AR subtype activation needed to produce renal protection. The A1AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion (IR) injury by modulating metabolic demand, decreasing necrosis, apoptosis and inflammation. The A2AAR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation whereas the A2BAR activation protects by direct activation of renal parenchymal ARs. In contrast, the A1AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A3AR-activation exacerbates apoptosis and tissue damage due to renal IR, selective A3AR antagonism may hold promise to attenuate renal IR injury. Finally, renal A1AR activation also protects against renal endothelial dysfunction caused by hepatic IR injury. Summary Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal ARs holds promise in treating AKI and extrarenal injury. PMID:22080856

  17. Aerosolized alpha-tocopherol ameliorates acute lung injury following combined burn and smoke inhalation injury in sheep.

    PubMed

    Morita, Naoki; Traber, Maret G; Enkhbaatar, Perenlei; Westphal, Martin; Murakami, Kazunori; Leonard, Scott W; Cox, Robert A; Hawkins, Hal K; Herndon, David; Traber, Lillian D; Traber, Daniel L

    2006-03-01

    Victims of fire accidents who sustain both thermal injury to the skin and smoke inhalation have gross evidence of oxidant injury. Therefore, we hypothesized that delivery of vitamin E, an oxygen superoxide scavenger, directly into the airway would attenuate acute lung injury postburn and smoke inhalation. Sheep (N = 17 female, 35 +/- 5 kg) were divided into 3 groups: (1) injured, then nebulized with vitamin E (B&S, Vitamin E, n = 6); (2) injured, nebulized with saline (B&S, Saline, n = 6); and (3) not injured, not treated (Sham, n = 5). While under deep anesthesia with isoflurane, the sheep were subjected to a flame burn (40% total body surface area, 3rd degree) and inhalation injury (48 breaths of cotton smoke, <40 degrees C). All groups were resuscitated with Ringer lactate solution (4 mL/kg/%burn/24 h) and placed on a ventilator [positive end-expiratory pressure (PEEP) = 5 cm H2O, tidal volume = 15 mL/kg] for 48 h. B&S injury halved the lung alpha-tocopherol concentrations (0.9 +/- 0.1 nmol/g) compared with sham-injured animals (1.5 +/- 0.3), whereas vitamin E treatment elevated the lung alpha-tocopherol concentrations (7.40 +/- 2.61) in the injured animals. B&S injury decreased pulmonary gas exchange (PaO2/FiO2 ratios) from 517 +/- 15 at baseline to 329 +/- 49 at 24 h and to 149 +/- 32 at 48 h compared with sham ratios of 477 +/- 14, 536 +/- 48, and 609 +/- 49, respectively. Vitamin E treatment resulted in a significant improvement of pulmonary gas exchange; ratios were 415 +/- 34 and 283 +/- 42 at 24 and 48 h, respectively. Vitamin E nebulization therapy improved the clinical responses to burn and smoke inhalation-induced acute lung injury.

  18. Mononuclear Phagocyte-Derived Microparticulate Caspase-1 Induces Pulmonary Vascular Endothelial Cell Injury

    PubMed Central

    Mitra, Srabani

    2015-01-01

    Lung endothelial cell apoptosis and injury occurs throughout all stages of acute lung injury (ALI/ARDS) and impacts disease progression. Lung endothelial injury has traditionally been focused on the role of neutrophil trafficking to lung vascular integrin receptors induced by proinflammatory cytokine expression. Although much is known about the pathogenesis of cell injury and death in ALI/ARDS, gaps remain in our knowledge; as a result of which there is currently no effective pharmacologic therapy. Enzymes known as caspases are essential for completion of the apoptotic program and secretion of pro-inflammatory cytokines. We hypothesized that caspase-1 may serve as a key regulator of human pulmonary microvascular endothelial cell (HPMVEC) apoptosis in ALI/ARDS. Our recent experiments confirm that microparticles released from stimulated monocytic cells (THP1) induce lung endothelial cell apoptosis. Microparticles pretreated with the caspase-1 inhibitor, YVAD, or pan-caspase inhibitor, ZVAD, were unable to induce cell death of HPMVEC, suggesting the role of caspase-1 or its substrate in the induction of HPMVEC cell death. Neither un-induced microparticles (control) nor direct treatment with LPS induced apoptosis of HPMVEC. Further experiments showed that caspase-1 uptake into HPMVEC and the induction of HPMVEC apoptosis was facilitated by caspase-1 interactions with microparticulate vesicles. Altering vesicle integrity completely abrogated apoptosis of HPMVEC suggesting an encapsulation requirement for target cell uptake of active caspase-1. Taken together, we confirm that microparticle centered caspase-1 can play a regulator role in endothelial cell injury. PMID:26710067

  19. VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

    PubMed Central

    Carapau, Daniel; Pena, Ana C.; Ataíde, Ricardo; Monteiro, Carla A. A.; Félix, Nuno; Costa-Silva, Artur; Marinho, Claudio R. F.; Dias, Sérgio; Mota, Maria M.

    2010-01-01

    The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies. PMID:20502682

  20. Acute Kidney Injury Subsequent to Cardiac Surgery

    PubMed Central

    Kramer, Robert S.; Herron, Crystal R.; Groom, Robert C.; Brown, Jeremiah R.

    2015-01-01

    Abstract: Acute kidney injury (AKI) after cardiac surgery is a common and underappreciated syndrome that is associated with poor short- and long-term outcomes. AKI after cardiac surgery may be epiphenomenon, a signal for adverse outcomes by virtue of other affected organ systems, and a consequence of multiple factors. Subtle increases in serum creatinine (SCr) postoperatively, once considered inconsequential, have been shown to reflect a kidney injury that likely occurred in the operating room during cardiopulmonary bypass (CPB) and more often in susceptible individuals. The postoperative elevation in SCr is a delayed signal reflecting the intraoperative injury. Preoperative checklists and the conduct of CPB represent opportunities for prevention of AKI. Newer definitions of AKI provide us with an opportunity to scrutinize perioperative processes of care and determine strategies to decrease the incidence of AKI subsequent to cardiac surgery. Recognizing and mitigating risk factors preoperatively and optimizing intraoperative practices may, in the aggregate, decrease the incidence of AKI. This review explores the pathophysiology of AKI and addresses the features of patients who are the most vulnerable to AKI. Preoperative strategies are discussed with particular attention to a readiness for surgery checklist. Intraoperative strategies include minimizing hemodilution and maximizing oxygen delivery with specific suggestions regarding fluid management and plasma preservation. PMID:26390675

  1. Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and in acute cardiogenic pulmonary edema.

    PubMed

    Rialp Cervera, G; del Castillo Blanco, A; Pérez Aizcorreta, O; Parra Morais, L

    2014-03-01

    Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis.

  2. Hemorrhage and resuscitation induce alterations in cytokine expression and the development of acute lung injury.

    PubMed

    Shenkar, R; Coulson, W F; Abraham, E

    1994-03-01

    Acute pulmonary injury occurs frequently following hemorrhage and injury. In order to better examine the sequence of events leading to lung injury in this setting, we investigated lung histology as well as in vivo mRNA levels for cytokines with proinflammatory and immunoregulatory properties (IL-1 beta, IL-6, IL-10, TNF-alpha, TGF-beta, IFN-gamma) over the 3 days following hemorrhage and resuscitation. Significant increases in mRNA levels for IL-1 beta, IL-6, IL-10, and IFN-gamma, but not TNF-alpha, were present among intraparenchymal pulmonary mononuclear cells obtained 1 and 3 days after hemorrhage. Among alveolar macrophages, TNF-alpha and IL-1 beta mRNA levels were increased 3 days after hemorrhage. Few changes in cytokine mRNA levels, with the exception of TNF-alpha at 3 days after hemorrhage, were present among peripheral blood mononuclear cells. Histologic examination of lungs from hemorrhaged animals showed no alterations 1 day after hemorrhage, but neutrophil and mononuclear cell infiltrates, edema, intra-alveolar hemorrhage, and fibrin generation were present 3 days after hemorrhage. These results suggest that hemorrhage-induced enhancement of proinflammatory cytokine gene transcription may be an important mechanism contributing to the frequent development of acute lung injury following blood loss and injury.

  3. Obesity-induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-03-09

    Obesity is a significant risk factor for the acute respiratory distress syndrome (ARDS). The mechanisms underlying this association are unknown. We recently showed that diet-induced obese (DIO) mice exhibit pulmonary vascular endothelial dysfunction which is associated with enhanced susceptibility to lipopolysaccharide (LPS)-induced lung injury. Here, we demonstrate that lung endothelial dysfunction in DIO mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins including PERK, IREα and ATF6, in whole lung and in lung endothelial cells isolated from DIO mice. Further, we found that lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of DIO mice. Similar changes were observed in lung endothelial cells and in whole lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation; indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-PBA, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in DIO mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the endoplasmic reticulum of pulmonary endothelial cells might protect against ARDS in obese individuals.

  4. Lung transcriptional profiling: insights into the mechanisms of ozone-induced pulmonary injury in Wistar Kyoto rats.

    PubMed

    Ward, William O; Ledbetter, Allen D; Schladweiler, Mette C; Kodavanti, Urmila P

    2015-01-01

    Acute ozone-induced pulmonary injury and inflammation are well characterized in rats; however, mechanistic understanding of the pathways involved is limited. We hypothesized that acute exposure of healthy rats to ozone will cause transcriptional alterations, and comprehensive analysis of these changes will allow us to better understand the mechanism of pulmonary injury and inflammation. Male Wistar Kyoto rats (10-12 week) were exposed to air, or ozone (0.25, 0.5 or 1.0 ppm) for 4 h and pulmonary injury and inflammation were assessed at 0-h or 20-h (n = 8/group). Lung gene expression profiling was assessed at 0-h (air and 1.0 ppm ozone, n = 3-4/group). At 20-h bronchoalveolar lavage, fluid protein and neutrophils increased at 1 ppm ozone. Numerous genes involved in acute inflammatory response were up-regulated along with changes in genes involved in cell adhesion and migration, steroid metabolism, apoptosis, cell cycle control and cell growth. A number of NRF2 target genes were also induced after ozone exposure. Based on expression changes, Rela, SP1 and TP3-mediated signaling were identified to be mediating downstream changes. Remarkable changes in the processes of endocytosis provide the insight that ozone-induced lung injury and inflammation are likely initiated by changes in cell membrane components and receptors likely from oxidatively modified lung lining lipids and proteins. In conclusion, ozone-induced injury and inflammation are preceded by changes in gene targets for cell adhesion/migration, apoptosis, cell cycle control and growth regulated by Rela, SP1 and TP53, likely mediated by the process of endocytosis and altered steroid receptor signaling.

  5. Erythropoietin (EPO) in acute kidney injury.

    PubMed

    Moore, Elizabeth; Bellomo, Rinaldo

    2011-03-21

    Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is mostly well-known for its physiological function in regulating red blood cell production in the bone marrow. Accumulating evidence, however, suggests that EPO has additional organ protective effects, which may be useful in the prevention or treatment of acute kidney injury. These protective mechanisms are multifactorial in nature and include inhibition of apoptotic cell death, stimulation of cellular regeneration, inhibition of deleterious pathways, and promotion of recovery.In this article, we review the physiology of EPO, assess previous work that supports the role of EPO as a general tissue protective agent, and explain the mechanisms by which it may achieve this tissue protective effect. We then focus on experimental and clinical data that suggest that EPO has a kidney protective effect.

  6. Acute liver injury secondary to sertraline.

    PubMed

    Suen, Christopher F D Li Wai; Boyapati, Ray; Simpson, Ian; Dev, Anouk

    2013-09-26

    Sertraline is widely prescribed to treat depression and anxiety disorders. However, hepatitis secondary to its use is a rare entity. We report the case of a 26-year-old woman in her 20th week of pregnancy presented with nausea, vomiting, malaise and dark urine. This occurred 6 months after sertraline 50 mg daily was started for the treatment of depression. Three weeks prior to her presentation, the dose of sertraline was increased to 100 mg daily. The patient's liver biochemical profile demonstrated increased transaminases. The biopsy of the liver showed lobular hepatitis, with a mild prominence of eosinophils, suggestive of a drug-induced or toxin-induced aetiology. Extensive biochemical work-up failed to show any other pathology to account for her hepatitis. Liver function tests normalised after cessation of sertraline, indicating a probable association between sertraline use and acute hepatocellular injury in our patient.

  7. Fluid management in acute kidney injury.

    PubMed

    Goldstein, Stuart L

    2014-01-01

    Fluid management in critical illness has undergone extensive reevaluation in the past decade. Since a significant percentage of critically ill patients develop acute kidney injury (AKI), optimal fluid management is even more paramount to prevent the ill effects of either underhydration or overhydration. The concepts of early goal-directed fluid therapy (EGDT) and conservative late fluid management permeate current clinical research, and the independent association between fluid accumulation and mortality has been repeatedly demonstrated. A number of prospective randomized trials are planned to provide an adequately powered assessment of the effect of EGDT or earlier renal replacement therapy initiation in patients with, or at risk for AKI. The aim of this analytical review is to use existing clinical and physiological studies to support a 3-phase model of fluid management in the critically ill patient with AKI.

  8. Transfusion-related acute lung injury (TRALI).

    PubMed

    Roberts, George H

    2004-01-01

    Transfusion is an inevitable event in the life of many individuals. Transfusion medicine personnel attempt to provide blood products that will result in a safe and harmless transfusion. However, this is not always possible since no laboratory test gives totally accurate and reliable results all the time and testing in routine transfusion services is devoted primarily to the identification of red blood cell problems. Thus, when patients are transfused, several possible adverse effects may occur in the transfused patient even though quality testing indicates no potential problem. These adverse events include infectious complications, hemolytic reactions, anaphylaxis, urticaria, circulatory overload, transfusion-associated graft-versus-host disease, chills and fever, immunomodulation, and transfusion-related acute lung injury (TRALI).

  9. Autophagy in acute kidney injury and repair.

    PubMed

    He, Liyu; Livingston, Man J; Dong, Zheng

    2014-01-01

    Acute kidney injury (AKI) is a major kidney disease associated with a poor clinical outcome both in the short and long term. Autophagy is a cellular stress response that plays important roles in the pathogenesis of various diseases. Autophagy is induced in proximal tubules during AKI. A renoprotective role of autophagy in AKI has been demonstrated by pharmacological and genetic inhibition studies. The role of autophagy in kidney recovery and repair from AKI, however, remains largely unknown. A dynamic change in autophagy during the recovery phase of AKI seems to be important for tubular proliferation and repair. In renal fibrosis, autophagy may either promote this via the induction of tubular atrophy and decomposition, or prevent it via effects on the intracellular degradation of excessive collagen. Further research is expected to improve the understanding of the regulation of autophagy in kidney injury and repair, elucidate the pathological roles of autophagy in renal fibrosis, and discover therapeutic targets for treating AKI and preventing its progression to chronic kidney disease.

  10. Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure - demographics, etiologic and pulmonary histologic analysis

    PubMed Central

    de Matos Soeiro, Alexandre; Ruppert, Aline D; Canzian, Mauro; Capelozzi, Vera L; Serrano, Carlos V

    2012-01-01

    OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has

  11. TGF-β is a critical mediator of acute lung injury

    PubMed Central

    Pittet, Jean-Francois; Griffiths, Mark J.D.; Geiser, Tom; Kaminski, Naftali; Dalton, Stephen L.; Huang, Xiaozhu; Brown, Lou Anne S.; Gotwals, Phillip J.; Koteliansky, Victor E.; Matthay, Michael A.; Sheppard, Dean

    2001-01-01

    We have shown that the integrin αvβ6 activates latent TGF-β in the lungs and skin. We show here that mice lacking this integrin are completely protected from pulmonary edema in a model of bleomycin-induced acute lung injury (ALI). Pharmacologic inhibition of TGF-β also protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin. TGF-β directly increased alveolar epithelial permeability in vitro by a mechanism that involved depletion of intracellular glutathione. These data suggest that integrin-mediated local activation of TGF-β is critical to the development of pulmonary edema in ALI and that blocking TGF-β or its activation could be effective treatments for this currently untreatable disorder. PMID:11413161

  12. Delayed Pneumoperitoneum and Acute Pulmonary Edema Secondary to Acute Gastric Dilatation

    PubMed Central

    Ahn, Jae Yun; Kim, Jong Kun

    2015-01-01

    Pneumoperitoneum caused by acute gastric dilatation (AGD) is a very rare complication. We report a case of pneumoperitoneum and acute pulmonary edema caused by AGD in a patient with Parkinson’s disease. A 78-year-old woman presented with pneumonia and AGD. We inserted a nasogastric tube and administered empirical antibiotics. We performed an endoscopy, and perforation or necrosis of the stomach and pyloric stenosis were not observed. Thirty-six hours after admission, the patient suddenly developed dyspnea and shock, and eventually died. We suspected the cause of death was pneumoperitoneum and acute pulmonary edema caused by AGD during the conservative treatment period. Immunocompromised patients with chronic illness require close observation even if they do not show any symptoms suggestive of complications. Even if the initial endoscopic or abdominal radiologic findings do not show gastric necrosis or perforation, follow-up with endoscopy is essential to recognize complications of AGD early. PMID:26668807

  13. Involvement of Protein Kinase C-δ in Vascular Permeability in Acute Lung Injury.

    PubMed

    Ahn, Jong J; Jung, Jong P; Park, Soon E; Lee, Minhyun; Kwon, Byungsuk; Cho, Hong R

    2015-08-01

    Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-δ (PKC-δ) in ALI has been a controversial topic. Here we investigated PKC-δ function in ALI using PKC-δ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-δ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-δ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-δ-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-δ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-δ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.

  14. Acute kidney injury: global health alert.

    PubMed

    Li, Philip Kam Tao; Burdmann, Emmanuel A; Mehta, Ravindra L

    2013-05-01

    Acute kidney injury (AKI) is increasingly prevalent in developing and developed countries and is associated with severe morbidity and mortality. Most etiologies of AKI can be prevented by interventions at the individual, community, regional and in-hospital levels. Effective measures must include community-wide efforts to increase an awareness of the devastating effects of AKI and provide guidance on preventive strategies, as well as early recognition and management. Efforts should be focused on minimizing causes of AKI, increasing awareness of the importance of serial measurements of serum creatinine in high-risk patients, and documenting urine volume in acutely ill people to achieve early diagnosis; there is as yet no definitive role for alternative biomarkers. Protocols need to be developed to systematically manage prerenal conditions and specific infections. More accurate data about the true incidence and clinical impact of AKI will help to raise the importance of the disease in the community, and increase awareness of AKI by governments, the public, general and family physicians and other healthcare professionals to help prevent the disease. Prevention is the key to avoid the heavy burden of mortality and morbidity associated with AKI.

  15. Acute renal injury after partial hepatectomy

    PubMed Central

    Peres, Luis Alberto Batista; Bredt, Luis Cesar; Cipriani, Raphael Flavio Fachini

    2016-01-01

    Currently, partial hepatectomy is the treatment of choice for a wide variety of liver and biliary conditions. Among the possible complications of partial hepatectomy, acute kidney injury (AKI) should be considered as an important cause of increased morbidity and postoperative mortality. Difficulties in the data analysis related to postoperative AKI after liver resections are mainly due to the multiplicity of factors to be considered in the surgical patients, moreover, there is no consensus of the exact definition of AKI after liver resection in the literature, which hampers comparison and analysis of the scarce data published on the subject. Despite this multiplicity of risk factors for postoperative AKI after partial hepatectomy, there are main factors that clearly contribute to its occurrence. First factor relates to large blood losses with renal hypoperfusion during the operation, second factor relates to the occurrence of post-hepatectomy liver failure with consequent distributive circulatory changes and hepatorenal syndrome. Eventually, patients can have more than one factor contributing to post-operative AKI, and frequently these combinations of acute insults can be aggravated by sepsis or exposure to nephrotoxic drugs. PMID:27478539

  16. Acute kidney injury in the tropics

    PubMed Central

    Mathew, Ashish Jacob; George, Jacob

    2011-01-01

    Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus–related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation. PMID:21911980

  17. Acute kidney injury in the tropics.

    PubMed

    Mathew, Ashish Jacob; George, Jacob

    2011-01-01

    Acute kidney injury (AKI) is one of the most challenging problems faced by clinicians in the tropics owing to its fast-changing burden. AKI in the tropics is strikingly different from that in the developed world in terms of etiology and presentation. In addition, there is a stark contrast between well-developed and poor areas in the tropics. The true epidemiological picture of AKI in the tropics is not well understood due to the late presentation of patients to tertiary centers. Infections remain the major culprit in most cases of AKI, with high mortality rates in the tropics. Human immunodeficiency virus-related AKI, related to nephrotoxicity due to antiretroviral therapy, is on the rise. Acute tubular necrosis and thrombotic microangiopathy are the most common mechanisms of AKI. A notable problem in the tropics is the scarcity of resources in health centers to support patients who require critical care due to AKI. This article reviews the unique and contrasting nature of AKI in the tropics and describes its management in each situation.

  18. Influence of acute pancreatitis on the in vitro responsiveness of rat mesenteric and pulmonary arteries

    PubMed Central

    Camargo, Enilton A; Delbin, Maria Andréia; Ferreira, Tatiane; Landucci, Elen CT; Antunes, Edson; Zanesco, Angelina

    2008-01-01

    Background Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis. Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A2 (PLA2). Pancreatitis was induced by administration of TAU or PLA2 from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC50) and maximal responses (EMAX) were determined. Blood samples were collected for biochemical analysis. Results In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA2 (about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC50 nor EMAX values for Ach were altered in pulmonary rings in any group. Similarly, the pEC50 and the EMAX values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the EMAX for PHE. The nitrite/nitrate (NOx-) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA2 protocol, respectively. Conclusion Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NOx- levels as consequence of

  19. Acute Exacerbation of Idiopathic Pulmonary Fibrosis. An International Working Group Report.

    PubMed

    Collard, Harold R; Ryerson, Christopher J; Corte, Tamera J; Jenkins, Gisli; Kondoh, Yasuhiro; Lederer, David J; Lee, Joyce S; Maher, Toby M; Wells, Athol U; Antoniou, Katerina M; Behr, Juergen; Brown, Kevin K; Cottin, Vincent; Flaherty, Kevin R; Fukuoka, Junya; Hansell, David M; Johkoh, Takeshi; Kaminski, Naftali; Kim, Dong Soon; Kolb, Martin; Lynch, David A; Myers, Jeffrey L; Raghu, Ganesh; Richeldi, Luca; Taniguchi, Hiroyuki; Martinez, Fernando J

    2016-08-01

    Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. Finally, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.

  20. Acute Kidney Injury Predicts Mortality after Charcoal Burning Suicide

    PubMed Central

    Chen, Yu-Chin; Tseng, Yi-Chia; Huang, Wen-Hung; Hsu, Ching-Wei; Weng, Cheng-Hao; Liu, Shou-Hsuan; Yang, Huang-Yu; Chen, Kuan-Hsin; Chen, Hui-Ling; Fu, Jen-Fen; Lin, Wey-Ran; Wang, I-Kuan; Yen, Tzung-Hai

    2016-01-01

    A paucity of literature exists on risk factors for mortality in charcoal burning suicide. In this observational study, we analyzed the data of 126 patients with charcoal burning suicide that seen between 2002 and 2013. Patients were grouped according to status of renal damage as acute kidney injury (N = 49) or non-acute kidney injury (N = 77). It was found that patients with acute kidney injury suffered severer complications such as respiratory failure (P = 0.002), myocardial injury (P = 0.049), hepatic injury (P < 0.001), rhabdomyolysis (P = 0.045) and out-of-hospital cardiac arrest (P = 0.028) than patients without acute kidney injury. Moreover, patients with acute kidney injury suffered longer hospitalization duration (16.9 ± 18.3 versus 10.7 ± 10.9, P = 0.002) and had higher mortality rate (8.2% versus 0%, P = 0.011) than patients without injury. In a multivariate Cox regression model, it was demonstrated that serum creatinine level (P = 0.019) and heart rate (P = 0.022) were significant risk factors for mortality. Finally, Kaplan-Meier analysis revealed that patients with acute kidney injury suffered lower cumulative survival than without injury (P = 0.016). In summary, the overall mortality rate of charcoal burning suicide population was 3.2%, and acute kidney injury was a powerful predictor of mortality. Further studies are warranted. PMID:27430168

  1. [Anesthetic management of a patient with transfusion-related acute lung injury (TRALI)].

    PubMed

    Sakata, Yuko; Wada, Hiroki; Oshima, Takashi; Aramaki, Yoshihiko; Kikuta, Yoshinori; Iwasaki, Yasuji

    2008-08-01

    Transfusion-related acute lung injury (TRALI) is characterized by pulmonary edema and hypoxemia within 6 hours of transfusion in the absence of other causes of acute lung injury or circulatory overload and is now considered the leading cause of transfusion-related death. We report a female patient who showed hypoxemia after transfusion without any other causes of acute lung injury. The patient is a 43-year-old woman, who received emergency transurethral hemostasis for bladder hemorrhage with hematuria and low hemoglobin concentration (3.2 g x dl(-1)). General anesthesia was maintained with sevoflurane, remifentanil, and vecuronium. Two units of RBC were transfused during operation. Since she showed high blood pressure, tachycardia, and a painful expression after operation, we extubated her. Although we gave her O2 6 l x min(-1) after extubation, she showed low oxygen saturation (90%), thus we started bag-mask ventilation. However, she complained of dyspnea and the chest X-ray revealed bilateral diffuse pulmonary edema following hypoxemia (80%). Thus we inserted endotracheal tube and started positive pressure assist ventilation. The next day, hypoxemia was improved under PEEP therapy. The anti-HLA antibody in the transfused plasma was positive. We conclude that the early recognition and management of TRALI is essential during and after operation.

  2. Acute Pulmonary Edema Associated With Propofol: An Unusual Complication

    PubMed Central

    Waheed, Mian Adnan; Oud, Lavi

    2014-01-01

    Propofol is frequently used in the emergency department to provide procedural sedation for patients undergoing various procedures and is considered to be safe when administered by trained personnel. Pulmonary edema after administration of propofol has rarely been reported. We report a case of a 23-year-old healthy male who developed acute cough, hemoptysis and hypoxia following administration of propofol for splinting of a foot fracture. Chest radiography showed bilateral patchy infiltrates. The patient was treated successfully with supportive care. This report emphasizes the importance of this potentially fatal propofol-associated complication and discusses possible underlying mechanisms and related literature. PMID:25493132

  3. Amlodipine poisioning complicated with acute non-cardiogenic pulmonary oedema.

    PubMed

    Hasson, Ruairi; Mulcahy, Victoria; Tahir, Hasan

    2011-09-04

    Amlodipine poisoning is an uncommon presentation with potentially life threatening complications. As there are few cases of severe poisoning documented, management guidelines are limited. The authors present the case of a 22-year-old female who presented to hospital 6 h after ingesting 280 mg of amlodipine. She was treated with aggressive fluid resuscitation and calcium gluconate infusion. She went on to develop acute non-cardiogenic pulmonary odema for which she needed a frusemide infusion. She stayed in hospital for 5 days and was discharged after a psychiatric review with no long-term complications. The authors discuss the other management options available for patients presenting with amlodipine overdose.

  4. Amlodipine poisioning complicated with acute non-cardiogenic pulmonary oedema

    PubMed Central

    Hasson, Ruairi; Mulcahy, Victoria; Tahir, Hasan

    2011-01-01

    Amlodipine poisoning is an uncommon presentation with potentially life threatening complications. As there are few cases of severe poisoning documented, management guidelines are limited. The authors present the case of a 22-year-old female who presented to hospital 6 h after ingesting 280 mg of amlodipine. She was treated with aggressive fluid resuscitation and calcium gluconate infusion. She went on to develop acute non-cardiogenic pulmonary odema for which she needed a frusemide infusion. She stayed in hospital for 5 days and was discharged after a psychiatric review with no long-term complications. The authors discuss the other management options available for patients presenting with amlodipine overdose. PMID:22679190

  5. Acute liver injury induced by weight-loss herbal supplements

    PubMed Central

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-01-01

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss. PMID:21173910

  6. Acute liver injury induced by weight-loss herbal supplements.

    PubMed

    Chen, Gary C; Ramanathan, Vivek S; Law, David; Funchain, Pauline; Chen, George C; French, Samuel; Shlopov, Boris; Eysselein, Viktor; Chung, David; Reicher, Sonya; Pham, Binh V

    2010-11-27

    We report three cases of patients with acute liver injury induced by weight-loss herbal supplements. One patient took Hydroxycut while the other two took Herbalife supplements. Liver biopsies for all patients demonstrated findings consistent with drug-induced acute liver injury. To our knowledge, we are the first institute to report acute liver injury from both of these two types of weight-loss herbal supplements together as a case series. The series emphasizes the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss.

  7. [Acute pulmonary embolism: beware of the wolf in sheep's clothing].

    PubMed

    Klok, Frederikus A; Vahl, Jelmer E; Huisman, Menno V; van Dijkman, Paul R M

    2012-01-01

    Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoea. In one patient, the general practitioner had previously adopted an expectative policy because of a clean chest X-ray. At presentation after 4 weeks, the patient was diagnosed with and treated for acute coronary syndrome because of minor ECG abnormalities. Additional CT scanning showed a large saddle embolus. Despite adequate treatment, the patient suffered an electrical asystole and died. The other patient underwent ECG, bicycle ergometry, MRI adenosine, echocardiography and lung function tests over a period of 5 weeks before pulmonary embolism (PE) was diagnosed. As the signs and symptoms of PE are largely non-specific, diagnostic delay is common, with risk of poor clinical outcome. PE should at least be considered whenever a patient presents with acute or worsening breathlessness, chest pain, circulatory collapse or coughing, particularly in the presence of known thrombotic risk factors or when there is no clear alternative.

  8. Pathology consultation on transfusion-related acute lung injury (TRALI).

    PubMed

    Schmidt, Amy E; Adamski, Jill

    2012-10-01

    Transfusion-related acute lung injury (TRALI) is a serious condition characterized by respiratory distress, hypoxia, and bilateral pulmonary infiltrates, which occur within 6 hours of transfusion. Several theories have been proposed to explain the underlying pathologic mechanisms of TRALI. Immune-mediated TRALI accounts for over 80% of reported cases and is mediated by donor antibodies to HLAs and/or human neutrophil antigens (HNA). Immune-mediated TRALI is most commonly associated with donor plasma transfusion or other blood products from multiparous women, which has led many countries to reduce or exclude women from donating high-volume plasma products. This policy change has resulted in a decrease in the incidence of TRALI and highlighted the importance of nonimmune-mediated TRALI, which is thought to be caused by bioreactive lipids and other biologic response modifiers that accumulate during storage of blood products. When TRALI is suspected, clinical consultation with a transfusion medicine specialist helps differentiate it from other transfusion reactions with similar characteristics.

  9. Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.

    PubMed Central

    Simon, R H; DeHart, P D; Todd, R F

    1986-01-01

    The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a 51Cr-release assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neutrophils with an antibody (anti-Mo1) that reduced neutrophil adherence to epithelial cells limited killing. Although a variety of serine protease inhibitors partially inhibited cytotoxicity, we found that neutrophil cytoplasts, neutrophil lysates, neutrophil-conditioned medium, purified azurophilic or specific granule contents, and purified human neutrophil elastase did not duplicate the injury. We conclude that stimulated neutrophils can kill alveolar epithelial cells in an oxygen metabolite-independent manner. Tight adherence of stimulated neutrophils to epithelial cell monolayers appears to promote epithelial cell killing. Images PMID:3771800

  10. Key Molecular Mechanisms of Chaiqinchengqi Decoction in Alleviating the Pulmonary Albumin Leakage Caused by Endotoxemia in Severe Acute Pancreatitis Rats

    PubMed Central

    Wu, Wei; Luo, Ruijie; Lin, Ziqi; Xia, Qing

    2016-01-01

    To reveal the key molecular mechanisms of Chaiqinchengqi decoction (CQCQD) in alleviating the pulmonary albumin leakage caused by endotoxemia in severe acute pancreatitis (SAP) rats. Rats models of SAP endotoxemia-induced acute lung injury were established, the studies in vivo provided the important evidences that the therapy of CQCQD significantly ameliorated the increases in plasma levels of lipopolysaccharide (LPS), sCd14, and Lbp, the elevation of serum amylase level, the enhancements of systemic and pulmonary albumin leakage, and the depravation of airways indicators, thus improving respiratory dysfunction and also pancreatic and pulmonary histopathological changes. According to the analyses of rats pulmonary tissue microarray and protein-protein interaction network, c-Fos, c-Src, and p85α were predicted as the target proteins for CQCQD in alleviating pulmonary albumin leakage. To confirm these predictions, human umbilical vein endothelial cells were employed in in vitro studies, which provide the evidences that (1) LPS-induced paracellular leakage and proinflammatory cytokines release were suppressed by pretreatment with inhibitors of c-Src (PP1) or PI3K (LY294002) or by transfection with siRNAs of c-Fos; (2) fortunately, CQCQD imitated the actions of these selective inhibitions agents to inhibit LPS-induced high expressions of p-Src, p-p85α, and c-Fos, therefore attenuating paracellular leakage and proinflammatory cytokines release. PMID:27413385

  11. The throw: biomechanics and acute injury.

    PubMed

    Gainor, B J; Piotrowski, G; Puhl, J; Allen, W C; Hagen, R

    1980-01-01

    The throw and its modifications are integral components of many sports. This study correlates case histories of acute injuries in throwing with a biomechanical analysis of the throwing mechanism. Comparisons are made with a similar analysis of the kick analyzed by the same film technique and computer program. Just prior to ball release, the pitching arm extends through an arc of about 73 degress in 40 msec, beginning with the elbow flexed at 80 degrees. This produces an axial load on the humerus and coincides with a pulse of external torque at the shoulder. This acts as stress protection to the humerus which is developing an internal torque of 14,000 inch-lb prior to ball release. The change in angular velocity, or the angular acceleration, during the throw is acquired in a much shorter time than in the kick. Torque is directly proportional to angular acceleration. This necessitates the development of substantially higher torques in the humerus during the throw than about the knee during a kick. The kinetic energy in the arm is 27,000 inch-lb during the throw. This is much higher than the kinetic energy in the kicking leg because the kinetic energy varies proportionally with the square of the angular velocity of the extremity. The angular velocity of the arm is about twice that of the leg. Thus, the pitching arm contains about four times as much kinetic energy as the kicking leg. These severe overloading conditions predispose the upper extremity to injury in the throwing mechanism.

  12. Acute kidney injury and dialysis in children: illustrative cases.

    PubMed

    Symons, Jordan M; Picca, Stefano

    2008-09-01

    Pediatric nephrologists and critical care physicians are faced with a heterogeneous patient population with varied epidemiology caring for children with acute kidney injury or other diseases that may require renal replacement therapy provision. We have composed 4 detailed case scenarios to highlight the challenges and interdisciplinary approach required for optimal care provision to children, and that serve to direct the different articles contained in this special issue of Seminars of Nephrology devoted to acute kidney injury in children.

  13. Transfusion-related acute lung injury (TRALI): clinical presentation, treatment, and prognosis.

    PubMed

    Moore, S Breanndan

    2006-05-01

    The term transfusion-related acute lung injury (TRALI) was coined in 1983 to describe a constellation of clinical and laboratory features seen within 6 hrs of the transfusion of plasma-containing blood products. These products contain antibodies directed to human leukocyte antigens (and subsequently described to nonhuman leukocyte antigens) found on white blood cells. In the intervening 2 decades, other cases not associated with antibodies have been reported as TRALI and an association with passive infusion of lipids accumulated in stored cellular blood products has been made in those cases. This has led to confusion as to what should be considered to constitute TRALI. Therefore, the true incidence of this pulmonary reaction to blood products is currently conjectural at best. Recent consensus development conferences have been held to develop and standardize definitions of TRALI so that epidemiologic and research aspects of this condition can be explored in a scientific manner. These conferences have set out criteria by which TRALI is distinguished from other causes of acute lung injury. This review outlines the widely accepted clinical (mainly pulmonary) features of TRALI, the treatment options, and the excellent long-term prognosis for patients who survive the initial pulmonary insult.

  14. Prostatic surgery associated acute kidney injury

    PubMed Central

    Costalonga, Elerson Carlos; Costa e Silva, Verônica Torres; Caires, Renato; Hung, James; Yu, Luis; Burdmann, Emmanuel A

    2014-01-01

    Acute kidney injury (AKI) is associated with extended hospital stays, high risks of in-hospital and long-term mortality, and increased risk of incident and progressive chronic kidney disease. Patients with urological diseases are a high-risk group for AKI owing to the coexistence of obstructive uropathy, older age, and preexistent chronic kidney disease. Nonetheless, precise data on the incidence and outcomes of postoperative AKI in urological procedures are lacking. Benign prostatic hyperplasia and prostate cancer are common diagnoses in older men and are frequently treated with surgical procedures. Whereas severe AKI after prostate surgery in general appears to be unusual, AKI associated with transurethral resection of the prostate (TURP) syndrome and with rhabdomyolysis (RM) after radical prostatectomy have been frequently described. The purpose of this review is to discuss the current knowledge regarding the epidemiology, risk factors, outcomes, prevention, and treatment of AKI associated with prostatic surgery. The mechanisms of TURP syndrome and RM following prostatic surgeries will be emphasized. PMID:25374813

  15. Acute Kidney Injury in Diabetes Mellitus

    PubMed Central

    Müller, G. A.

    2016-01-01

    Diabetes mellitus (DM) significantly increases the overall morbidity and mortality, particularly by elevating the cardiovascular risk. The kidneys are severely affected as well, partly as a result of intrarenal athero- and arteriosclerosis but also due to noninflammatory glomerular damage (diabetic nephropathy). DM is the most frequent cause of end-stage renal disease in our society. Acute kidney injury (AKI) remains a clinical and prognostic problem of fundamental importance since incidences have been increased in recent years while mortality has not substantially been improved. As a matter of fact, not many studies particularly addressed the topic “AKI in diabetes mellitus.” Aim of this article is to summarize AKI epidemiology and outcomes in DM and current recommendations on blood glucose control in the intensive care unit with regard to the risk for acquiring AKI, and finally several aspects related to postischemic microvasculopathy in AKI of diabetic patients shall be discussed. We intend to deal with this relevant topic, last but not least with regard to increasing incidences and prevalences of both disorders, AKI and DM. PMID:27974972

  16. Cardiac surgery-associated acute kidney injury

    PubMed Central

    Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique

    2016-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701

  17. Post-partum acute kidney injury.

    PubMed

    Pahwa, Naresh; Bharani, Rajesh; Kumar, Ravindra

    2014-11-01

    To determine the risk factors, course of hospital stay and mortality rate among women with post-partum acute kidney injury (AKI), we studied (of 752 patients with AKI admitted to a tertiary care center during the study period between November 2009 and August 2012) 27 (3.59%) women with post-partum AKI. The data regarding age, parity, cause of renal failure, course of hospital stay and requirement of dialysis were recorded. Sepsis was the major cause (70.3%) of post-partum AKI. Other causes included disseminated intravascular coagulation (55.5%), pre-eclampsia/eclampsia (40.7%), ante- and post-partum hemorrhage (40.7% and 22.2%) and hemolytic anemia and elevated liver enzymes and low platelet count syndrome (29.6%); most patients had more than one cause of AKI. We found a very high prevalence (18.5%) of cortical necrosis in our study patients. A significant correlation was also found between the creatinine level on admission and the period of onset of disease after delivery. In conclusion, several factors are involved in causing post-partum AKI in our population, and sepsis was the most common of them.

  18. Update on traumatic acute spinal cord injury. Part 1.

    PubMed

    Galeiras Vázquez, R; Ferreiro Velasco, M E; Mourelo Fariña, M; Montoto Marqués, A; Salvador de la Barrera, S

    2017-02-01

    Traumatic spinal cord injury requires a multidisciplinary approach both for specialized treatment of the acute phase and for dealing with the secondary complications. A suspicion or diagnosis of spinal cord injury is the first step for a correct management. A review is made of the prehospital management and characteristics of the acute phase of spinal cord injury. Respiratory monitoring for early selective intubation, proper identification and treatment of neurogenic shock are essential for the prevention of secondary spinal cord injury. The use of corticosteroids is currently not a standard practice in neuroprotective treatment, and hemodynamic monitoring and early surgical decompression constitute the cornerstones of adequate management. Traumatic spinal cord injury usually occurs as part of multiple trauma, and this can make diagnosis difficult. Neurological examination and correct selection of radiological exams prevent delayed diagnosis of spinal cord injuries, and help to establish the prognosis.

  19. Targeting Neutrophils to Prevent Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome in Mice

    PubMed Central

    Soeiro-Pereira, Paulo V.; Gomes, Eliane; Neto, Antonio Condino; D' Império Lima, Maria R.; Alvarez, José M.; Portugal, Silvia; Epiphanio, Sabrina

    2016-01-01

    Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS. Mice developing ALI/ARDS showed greater neutrophil accumulation in the lungs compared with mice that did not develop pulmonary complications. In addition, mice with ALI/ARDS produced more neutrophil-attracting chemokines, myeloperoxidase and reactive oxygen species. We also observed that the parasites Plasmodium falciparum and PbA induced the formation of neutrophil extracellular traps (NETs) ex vivo, which were associated with inflammation and tissue injury. The depletion of neutrophils, treatment with AMD3100 (a CXCR4 antagonist), Pulmozyme (human recombinant DNase) or Sivelestat (inhibitor of neutrophil elastase) decreased the development of malaria-associated ALI/ARDS and significantly increased mouse survival. This study implicates neutrophils and NETs in the genesis of experimentally induced malaria-associated ALI/ARDS and proposes a new therapeutic approach to improve the prognosis of severe malaria. PMID:27926944

  20. Inductive and Deductive Approaches to Acute Cell Injury

    PubMed Central

    DeGracia, Donald J.; Tri Anggraini, Fika; Taha, Doaa Taha Metwally; Huang, Zhi-Feng

    2014-01-01

    Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems. PMID:27437490

  1. Acute and subacute pulmonary toxicity caused by a single intratracheal instillation of colloidal silver nanoparticles in mice: pathobiological changes and metallothionein responses.

    PubMed

    Kaewamatawong, Theerayuth; Banlunara, Wijit; Maneewattanapinyo, Pattwat; Thammachareon, Chuchaat; Ekgasit, Sanong

    2014-01-01

    To study the acute and subacute pulmonary toxicity of colloidal silver nanoparticles (Ag-NPs), 0 or 100 ppm of Ag-NPs were instilled intratracheally in mice. Cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and histological alterations were determined 1, 3, 7, 15, and 30 days after instillation. Ag-NPs induced moderate pulmonary inflammation and injury on BALF indices during the acute period; however, these changes gradually regressed in a time-dependent manner. Concomitant histopathological and laminin immunohistochemical findings generally correlated to BALF data. Superoxide dismutase and metallothionein expression occurred in particle-laden macrophages and alveolar epithelial cells, which correlated to lung lesions in mice treated with Ag-NPs. These findings suggest that instillation of Ag-NPs causes transient moderate acute lung inflammation and tissue damage. Oxidative stress may underlie the induction of injury to lung tissue. Moreover, the expression of metallothionein in tissues indicated the protective response to exposure to Ag-NPs.

  2. Glomerular haematuria, renal interstitial haemorrhage and acute kidney injury.

    PubMed

    Martín Cleary, Catalina; Moreno, Juan Antonio; Fernández, Beatriz; Ortiz, Alberto; Parra, Emilio G; Gracia, Carolina; Blanco-Colio, Luis M; Barat, Antonio; Egido, Jesús

    2010-12-01

    Macroscopic haematuria of glomerular origin has been associated with acute kidney injury. We report a patient with IgA nephropathy, macroscopic haematuria and acute kidney injury. Systemic anticoagulation may have aggravated haematuria. There was extensive interstitial and intratubular red blood cell extravasation, and interstitial haemosiderin deposits. The abundant presence of macrophages expressing the haemoglobin scavenger receptor CD163 and of cells stained for oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) in areas of interstitial haemorrhage and red blood cell cast-containing tubules provided evidence for a role for free haemoglobin in tubulointerstitial renal injury in human glomerular disease.

  3. Bath Salts: A Newly Recognized Cause of Acute Kidney Injury

    PubMed Central

    McNeely, Jonathan; Parikh, Samir; Valentine, Christopher; Haddad, Nabil; Shidham, Ganesh; Rovin, Brad; Hebert, Lee; Agarwal, Anil

    2012-01-01

    Bath salts are substance of abuse that are becoming more common and are difficult to recognize due to negative toxicology screening. Acute kidney injury due to bath salt use has not previously been described. We present the case of a previously healthy male who developed acute kidney injury and dialysis dependence after bath salt ingestion and insufflation. This was self-reported with negative toxicology screening. Clinical course was marked by severe hyperthermia, hyperkalemia, rhabdomyolysis, disseminated intravascular coagulation, oliguria, and sepsis. We discuss signs and symptoms, differential diagnoses, potential mechanisms of injury, management, and review of the literature related to bath salt toxicity. PMID:24555135

  4. Giant multinucleated macrophages occur in acute spinal cord injury.

    PubMed

    Leskovar, A; Turek, J; Borgens, R B

    2001-05-01

    Using a cell-isolation and -culture procedure specific for macrophages, we report the existence of giant (more than 50 microm diameter), multinucleated macrophages within an acute, 5-day-old adult rat spinal cord injury. The size and multinuclearity of these isolated giant cells was confirmed using transmission electron microscopy. Giant macrophages are markers for long-term infection, disease, and chronic injury in other soft tissues and are unexpected in the acute inflammatory stage of central nervous system injury. To our knowledge, this descriptive report is the first confirming the existence of giant macrophages in any injured nervous tissue, with additional data suggesting some of these cells to be multinucleated.

  5. Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats.

    PubMed

    Peng, Xinqi; Perkins, Michael W; Simons, Jannitt; Witriol, Alicia M; Rodriguez, Ashley M; Benjamin, Brittany M; Devorak, Jennifer; Sciuto, Alfred M

    2014-06-01

    This study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250-300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m³ or 0.2, 0.5 and 0.8 LCt₅₀, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m³ of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m³ VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

  6. Effect of pulmonary-generated reactive oxygen species on left-ventricular dysfunction associated with cardio-pulmonary ischemia-reperfusion injury.

    PubMed

    Khan, Mahmood; Brauner, Mark E; Plewa, Michael C; Kutala, Vijay K; Angelos, Mark; Kuppusamy, Periannan

    2013-11-01

    The purpose of the present study was to demonstrate the contribution of pulmonary-generated reactive oxygen species (ROS) on cardiac dysfunction using a rat model of ischemia-reperfusion (IR) injury. Three groups of rats were subjected to regional IR injury in (i) lung, (ii) heart, (iii) lung + heart. A fourth (control) group of rats were instrumented using the same methods but without induction IR. Hemodynamic data were recorded in real time. Blood from the proximal aorta was sampled during baseline, ischemia, and reperfusion, mixed with α-phenyl-N-tert-butylnitrone (PBN) for measuring ROS by electron paramagnetic resonance spectrometry. Data were analyzed by a two-way analysis of variance. The results showed that the lung IR generated an increased burst of ROS that resulted in significant cardiac dysfunction, including hypotension and ECG changes. The results indicated that generation of ROS as a result of acute IR lung injury may be sufficiently large enough to cause direct cardiac dysfunction that is independent of injury caused to the myocardium as a result of regional myocardial IR injury alone.

  7. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    NASA Astrophysics Data System (ADS)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  8. Non-cardiogenic pulmonary edema, rhabdomyolysis and myocardial injury following heroin inhalation: a case report

    PubMed Central

    Bazoukis, G; Spiliopoulou, A; Mourouzis, K; Grigoropoulou, P; Yalouris, A

    2016-01-01

    Background: Heroin use by non-injecting routes of administration (snorting, swallowing, “chasing the dragon”) is considered to be safer but is not risk-free for fatal overdose or serious side effects. We report the case of an adolescent who was transferred unconscious to the emergency department after heroin inhalation. Description of the case: A 17-year-old male was transferred to the emergency department unconscious (Glasgow coma scale: 6/15) after heroin inhalation. He was treated with non-rebreather mask and intravenous infusion of naloxone with gradual improvement of consciousness and arterial blood gasses. The chest computed tomography showed signs of acute respiratory distress syndrome. Laboratory exams on the second day of hospitalization showed elevated creatine kinase (CK) and troponin-I levels while his electrocardiography (ECG) showed J-point elevation in V1, V2, and V3 precordial leads. On the second day of hospitalization the pulmonary infiltrates were not present in his chest X-ray while on the eighth day, troponin-I and CK levels were normalized without dynamic ECG changes and the patient was discharged uneventfully. Conclusion: Heroin inhalation may cause severe complications, such as non-cardiogenic pulmonary edema, rhabdomyolysis or myocardial injury. Hippokratia 2016, 20(1): 84-87 PMID:27895451

  9. Laboratory Test Surveillance following Acute Kidney Injury

    PubMed Central

    Matheny, Michael E.; Peterson, Josh F.; Eden, Svetlana K.; Hung, Adriana M.; Speroff, Theodore; Abdel-Kader, Khaled; Parr, Sharidan K.; Ikizler, T. Alp; Siew, Edward D.

    2014-01-01

    Background Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort. Methods We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients. Results A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients. Conclusions Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. PMID:25117447

  10. Acute kidney injury in pregnancy: a clinical challenge.

    PubMed

    Machado, Susana; Figueiredo, Nuno; Borges, Andreia; São José Pais, Maria; Freitas, Luís; Moura, Paulo; Campos, Mário

    2012-01-01

    The incidence of acute kidney injury in pregnancy declined significantly over the second half of the 20th century; however, it is still associated with major maternal and perinatal morbidity and mortality. A set of systemic and renal physiological adaptive mechanisms occur during a normal gestation that will constrain several changes in laboratory parameters of renal function, electrolytes, fluid and acid-base balances. The diagnosis of acute kidney injury in pregnancy is based on the serum creatinine increase. The usual formulas for estimating glomerular filtration rate are not validated in this population. During the first trimester of gestation, acute kidney injury develops most often due to hyperemesis gravidarum or septic abortion. In the third trimester, the differential diagnosis is more challenging for the obstetrician and the nephrologist and comprises some pathologies that are reviewed in this article: preeclampsia/HELLP syndrome, acute fatty liver of pregnancy and thrombotic microangiopathies.

  11. The anatomy and biomechanics of acute and chronic whiplash injury.

    PubMed

    Siegmund, Gunter P; Winkelstein, Beth A; Ivancic, Paul C; Svensson, Mats Y; Vasavada, Anita

    2009-04-01

    Whiplash injury is the most common motor vehicle injury, yet it is also one of the most poorly understood. Here we examine the evidence supporting an organic basis for acute and chronic whiplash injuries and review the anatomical sites within the neck that are potentially injured during these collisions. For each proposed anatomical site--facet joints, spinal ligaments, intervertebral discs, vertebral arteries, dorsal root ganglia, and neck muscles--we present the clinical evidence supporting that injury site, its relevant anatomy, the mechanism of and tolerance to injury, and the future research needed to determine whether that site is responsible for some whiplash injuries. This article serves as a snapshot of the current state of whiplash biomechanics research and provides a roadmap for future research to better understand and ultimately prevent whiplash injuries.

  12. Update on traumatic acute spinal cord injury. Part 2.

    PubMed

    Mourelo Fariña, M; Salvador de la Barrera, S; Montoto Marqués, A; Ferreiro Velasco, M E; Galeiras Vázquez, R

    2017-02-01

    The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers).

  13. Severe Acute Pulmonary Toxicity Associated with Brentuximab in a Patient with Refractory Hodgkin's Lymphoma

    PubMed Central

    Sabet, Yasmin; Ramirez, Saul; Rosell Cespedes, Elizabeth; Rensoli Velasquez, Marimer; Porres-Muñoz, Mateo; Gaur, Sumit; Figueroa-Casas, Juan B.; Porres-Aguilar, Mateo

    2016-01-01

    Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin's lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique. PMID:27190667

  14. [The immunological conflict in the transfusion-related acute lung injury or TRALI].

    PubMed

    Drouet, C; Khoy, K; Masson, D; Bardy, B; Giannoli, C; Dubois, V

    2011-04-01

    Despite its underrated incidence, transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality worldwide. The pulmonary edema in TRALI occurs in the course of the transfusion of apheresis products or erythrocyte concentrates. Its pathogenesis is attributed to the infusion of donor antibodies that recognize leucocyte antigens in the transfused host, with subsequent sequestration of leucocytes in the pulmonary vessels. It is also associated with the passive transfer of lipids and other biological response modifiers that accumulate during the storage or processing of blood components. The innate immunity and inflammatory kinins are key components. The knowledge of its etiopathogenesis must come into play for improving prevention and diagnosis and for application of adapted care of the patient.

  15. Gas exchange and pulmonary hypertension following acute pulmonary thromboembolism: has the emperor got some new clothes yet?

    PubMed Central

    2014-01-01

    Abstract Patients present with a wide range of hypoxemia after acute pulmonary thromboembolism (APTE). Recent studies using fluorescent microspheres demonstrated that the scattering of regional blood flows after APTE, created by the embolic obstruction unique in each patient, significantly worsened regional ventilation/perfusion (V/Q) heterogeneity and explained the variability in gas exchange. Furthermore, earlier investigators suggested the roles of released vasoactive mediators in affecting pulmonary hypertension after APTE, but their quantification remained challenging. The latest study reported that mechanical obstruction by clots accounted for most of the increase in pulmonary vascular resistance, but that endothelin-mediated vasoconstriction also persisted at significant level during the early phase. PMID:25006441

  16. Gas exchange and pulmonary hypertension following acute pulmonary thromboembolism: has the emperor got some new clothes yet?

    PubMed

    Tsang, John Y C; Hogg, James C

    2014-06-01

    Patients present with a wide range of hypoxemia after acute pulmonary thromboembolism (APTE). Recent studies using fluorescent microspheres demonstrated that the scattering of regional blood flows after APTE, created by the embolic obstruction unique in each patient, significantly worsened regional ventilation/perfusion (V/Q) heterogeneity and explained the variability in gas exchange. Furthermore, earlier investigators suggested the roles of released vasoactive mediators in affecting pulmonary hypertension after APTE, but their quantification remained challenging. The latest study reported that mechanical obstruction by clots accounted for most of the increase in pulmonary vascular resistance, but that endothelin-mediated vasoconstriction also persisted at significant level during the early phase.

  17. Clinical and morphologic features of acute, subacute and chronic cor pulmonale (pulmonary heart disease).

    PubMed

    Roberts, William Clifford; Shafii, Alexis E; Grayburn, Paul A; Ko, Jong Mi; Weissenborn, Matthew R; Rosenblatt, Randall L; Guileyardo, Joseph M

    2015-03-01

    Described are certain clinical and morphologic features of one patient with acute, another with subacute, and one with chronic cor pulmonale. All 3 had evidence of severe pulmonary hypertension. The patient with acute cor pulmonale 4 days after coronary bypass for unstable angina pectoris suddenly developed severe breathlessness with cyanosis and had fatal cardiac arrest and necropsy disclosed massive pulmonary embolism. The patient with subacute cor pulmonale had severe right-sided heart failure for 5 weeks and necropsy disclosed microscopic-sized neoplastic pulmonary emboli from a gastric carcinoma without parenchymal pulmonary metastases. The patient with chronic cor pulmonale had evidence of right-sided heart failure for years, the result of primary or idiopathic pulmonary hypertension almost certainly present from birth because the pattern of elastic fibers in the pulmonary trunk was that seen in newborns where the pressure in the pulmonary trunk and ascending aorta are similar. The patient with chronic cor pulmonale had plexiform pulmonary lesions indicative of irreversible pulmonary hypertension. Neither the acute nor the subacute patient had chronic pulmonary vascular changes. All 3 patients had dilated right ventricular cavities and non-dilated left ventricular cavities and only the patient with chronic cor pulmonale had right ventricular hypertrophy.

  18. Biomarkers in acute kidney injury: Evidence or paradigm?

    PubMed

    Lombi, Fernando; Muryan, Alexis; Canzonieri, Romina; Trimarchi, Hernán

    2016-01-01

    Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant economic impacts in terms of public health costs. Currently its diagnosis is still based on the presence of oliguria and/or a gradual increase in serum creatinine, which make the diagnosis a delayed event and to detriment of the so-called 'therapeutic window'. The appearance of new biomarkers of acute kidney injury could potentially improve this situation, contributing to the detection of 'subclinical acute kidney injury', which could allow the precocious employment of multiple treatment strategies in order to preserve kidney function. However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, given the lack of specific validated treatments for acute kidney injury. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury.

  19. Endovascular Treatment of Acute and Chronic Thoracic Aortic Injury

    SciTech Connect

    Raupach, Jan Ferko, Alexander; Lojik, Miroslav; Krajina, Antonin; Harrer, Jan; Dominik, Jan

    2007-11-15

    Our aim is to present midterm results after endovascular repair of acute and chronic blunt aortic injury. Between December 1999 and December 2005, 13 patients were endovascularly treated for blunt aortic injury. Ten patients, 8 men and 2 women, mean age 38.7 years, were treated for acute traumatic injury in the isthmus region of thoracic aorta. Stent-graftings were performed between the fifth hour and the sixth day after injury. Three patients (all males; mean age, 66 years; range, 59-71 years) were treated due to the presence of symptoms of chronic posttraumatic pseudoaneurysm of the thoracic aorta (mean time after injury, 29.4 years, range, 28-32). Fifteen stent-grafts were implanted in 13 patients. In the group with acute aortic injury one patient died due to failure of endovascular technique. Lower leg paraparesis appeared in one patient; the other eight patients were regularly followed up (1-72 months; mean, 35.6 months), without complications. In the group with posttraumatic pseudoaneurysms all three patients are alive. One patient suffered postoperatively from upper arm claudication, which was treated by carotidosubclavian bypass. We conclude that the endoluminal technique can be used successfully in the acute repair of aortic trauma and its consequences. Midterm results are satisfactory, with a low incidence of neurologic complications.

  20. Diffuse Brain Injury Induces Acute Post-Traumatic Sleep

    PubMed Central

    Rowe, Rachel K.; Striz, Martin; Bachstetter, Adam D.; Van Eldik, Linda J.; Donohue, Kevin D.; O'Hara, Bruce F.; Lifshitz, Jonathan

    2014-01-01

    Objective Clinical observations report excessive sleepiness immediately following traumatic brain injury (TBI); however, there is a lack of experimental evidence to support or refute the benefit of sleep following a brain injury. The aim of this study is to investigate acute post-traumatic sleep. Methods Sham, mild or moderate diffuse TBI was induced by midline fluid percussion injury (mFPI) in male C57BL/6J mice at 9:00 or 21:00 to evaluate injury-induced sleep behavior at sleep and wake onset, respectively. Sleep profiles were measured post-injury using a non-invasive, piezoelectric cage system. In separate cohorts of mice, inflammatory cytokines in the neocortex were quantified by immunoassay, and microglial activation was visualized by immunohistochemistry. Results Immediately after diffuse TBI, quantitative measures of sleep were characterized by a significant increase in sleep (>50%) for the first 6 hours post-injury, resulting from increases in sleep bout length, compared to sham. Acute post-traumatic sleep increased significantly independent of injury severity and time of injury (9:00 vs 21:00). The pro-inflammatory cytokine IL-1β increased in brain-injured mice compared to sham over the first 9 hours post-injury. Iba-1 positive microglia were evident in brain-injured cortex at 6 hours post-injury. Conclusion Post-traumatic sleep occurs for up to 6 hours after diffuse brain injury in the mouse regardless of injury severity or time of day. The temporal profile of secondary injury cascades may be driving the significant increase in post-traumatic sleep and contribute to the natural course of recovery through cellular repair. PMID:24416145

  1. Nilotinib ameliorates lipopolysaccharide-induced acute lung injury in rats

    SciTech Connect

    El-Agamy, Dina S.

    2011-06-01

    The present study aimed to investigate the effect of the new tyrosine kinase inhibitor, nilotinib on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and explore its possible mechanisms. Male Sprague-Dawley rats were given nilotinib (10 mg/kg) by oral gavage twice daily for 1 week prior to exposure to aerosolized LPS. At 24 h after LPS exposure, bronchoalveolar lavage fluid (BALF) samples and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathological changes in lungs. Malondialdehyde (MDA) content, superoxidase dismutase (SOD) and reduced glutathione (GSH) activities as well as nitrite/nitrate (NO{sub 2}{sup -}/NO{sub 3}{sup -}) levels were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-{alpha} (TNF-{alpha}), transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) and inducible nitric oxide synthase (iNOS) were determined in lung tissues. Treatment with nilotinib prior to LPS exposure significantly attenuated the LPS-induced pulmonary edema, as it significantly decreased lung W/D ratio, protein concentration and the accumulation of the inflammatory cells in the BALF. This was supported by the histopathological examination which revealed marked attenuation of LPS-induced ALI in nilotinib treated rats. In addition, nilotinib significantly increased SOD and GSH activities with significant decrease in MDA content in the lung. Nilotinib also reduced LPS mediated overproduction of pulmonary NO{sub 2}{sup -}/NO{sub 3}{sup -} levels. Importantly, nilotinib caused down-regulation of the inflammatory cytokines TNF-{alpha}, TGF-{beta}{sub 1} and iNOS levels in the lung. Taken together, these results demonstrate the protective effects of nilotinib against the LPS-induced ALI. This effect can be attributed to nilotinib ability to counteract the inflammatory cells

  2. Ozone-induced injury and oxidative stress in bronchiolar epithelium are associated with altered pulmonary mechanics.

    PubMed

    Sunil, Vasanthi R; Vayas, Kinal N; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2013-06-01

    In these studies, we analyzed the effects of ozone on bronchiolar epithelium. Exposure of rats to ozone (2 ppm, 3 h) resulted in rapid (within 3 h) and persistent (up to 72 h) histological changes in the bronchiolar epithelium, including hypercellularity, loss of cilia, and necrotizing bronchiolitis. Perivascular edema and vascular congestion were also evident, along with a decrease in Clara cell secretory protein in bronchoalveolar lavage, which was maximal 24 h post-exposure. Ozone also induced the appearance of 8-hydroxy-2'-deoxyguanosine, Ym1, and heme oxygenase-1 in the bronchiolar epithelium. This was associated with increased expression of cleaved caspase-9 and beclin-1, indicating initiation of apoptosis and autophagy. A rapid and persistent increase in galectin-3, a regulator of epithelial cell apoptosis, was also observed. Following ozone exposure (3-24 h), increased expression of cyclooxygenase-2, inducible nitric oxide synthase, and arginase-1 was noted in bronchiolar epithelium. Ozone-induced injury and oxidative stress in bronchiolar epithelium were linked to methacholine-induced alterations in pulmonary mechanics. Thus, significant increases in lung resistance and elastance, along with decreases in lung compliance and end tidal volume, were observed at higher doses of methacholine. This indicates that ozone causes an increase in effective stiffness of the lung as a consequence of changes in the conducting airways. Collectively, these studies demonstrate that bronchiolar epithelium is highly susceptible to injury and oxidative stress induced by acute exposure to ozone; moreover, this is accompanied by altered lung functioning.

  3. The predictive value of echocardiography for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism in Korea

    PubMed Central

    Park, Jin Sup; Ahn, Jinhee; Choi, Jung Hyun; Lee, Hye Won; Oh, Jun-Hyok; Lee, Han Cheol; Cha, Kwang Soo; Hong, Taek Jong

    2017-01-01

    Background/Aims Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening complication after acute pulmonary embolism (APE) and is associated with substantial morbidity and mortality. This study aimed to investigate the incidence of CTEPH after APE in Korea and to determine echocardiographic predictors of CTEPH. Methods Among 381 patients with APE confirmed by chest computed tomography (CT) between January 2007 and July 2013, 246 consecutive patients with available echocardiographic data were enrolled in this study. CTEPH was defined as a persistent right ventricular systolic pressure (RVSP) greater than 35 mmHg on echocardiography during follow-up and persistent pulmonary embolism on the follow-up CT. Results Fifteen patients (6.1%) had CTEPH. The rate of right ventricular (RV) dilatation (66.7% vs. 28.1%, p = 0.002) and the RVSP (75.5 mmHg vs. 39.0 mmHg, p < 0.001) were significantly higher in the CTEPH group. D-dimers, RV dilatation, RV hypertrophy, RVSP, and intermediate-risk APE were associated with the risk of CTEPH after APE (odds ratio [OR] 0.59, 5.11, 7.82, 1.06, and 4.86, respectively) on univariate analysis. RVSP remained as a significant predictor of CTEPH on multivariate analysis (OR, 1.056; 95% confidence interval, 1.006 to 1.109; p = 0.029). Conclusions This study showed that the incidence of CTEPH after APE in Korea was 6.1% and that initial RVSP by echocardiography was a strong prognostic factor for CTEPH. PMID:27044855

  4. Adjunctive Inferior Vena Cava Filter Placement for Acute Pulmonary Embolism

    SciTech Connect

    Jha, V. M.; Lee-Llacer, J.; Williams, J.; Ubaissi, H.; Gutierrez, G.

    2010-08-15

    Inferior vena cava (IVC) filters are sometimes placed as an adjunct to full anticoagulation in patients with significant pulmonary embolism (PE). We aimed to determine the prevalence of adjunctive IVC filter placement in individuals diagnosed with PE, as well as the effect of adjunctive filter placement on mortality in patients with right heart strain associated with PE. This was a retrospective study of patients with acute PE treated with full anticoagulation admitted to a single academic medical center. Information abstracted from patient charts included presence or absence of right heart strain and of deep-vein thrombosis, and whether or not an IVC filter was placed. The endpoint was in-hospital mortality. Over 2.75 years, we found that 248 patients were diagnosed with acute PE, with an in-hospital mortality rate of 4.4%. The prevalence of adjunctive IVC filter placement was 13.3% (33 of 248), and the prevalence of documented right heart strain was 27.0% (67 of 248). In-hospital mortality was 10.2% in the non-filter-treated group (5 of 49), whereas there were no deaths in the filter-treated group (0 of 18); however, the difference was not statistically significant (P = 0.37). Both the presence of deep-vein thrombosis and of right heart strain increased the likelihood that an adjunctive IVC filter was placed (P < 0.0001 and P < 0.001, respectively). At our institution, patients were treated with IVC filters in addition to anticoagulation in 13.3% of cases of acute PE. Prospective studies or large clinical registries should be conducted to clarify whether this practice improves outcomes.

  5. Acute ECG ST-segment elevation mimicking myocardial infarction in a patient with pulmonary embolism

    PubMed Central

    2010-01-01

    Pulmonary embolism is a common cardiovascular emergency, but it is still often misdiagnosed due to its unspecific clinical symptoms. Elevated troponin concentrations are associated with greater morbidity and mortality in patients with pulmonary embolism. Right ventricular ischemia due to increased right ventricular afterload is believed to be underlying mechanism of elevated troponin values in acute pulmonary embolism, but a paradoxical coronary artery embolism through opened intra-artrial communication is another possible explanation as shown in our case report. PMID:21106090

  6. Attenuation of acute nitrogen mustard-induced lung injury, inflammation and fibrogenesis by a nitric oxide synthase inhibitor

    SciTech Connect

    Malaviya, Rama; Venosa, Alessandro; Hall, LeRoy; Gow, Andrew J.; Sinko, Patrick J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-12-15

    Nitrogen mustard (NM) is a toxic vesicant known to cause damage to the respiratory tract. Injury is associated with increased expression of inducible nitric oxide synthase (iNOS). In these studies we analyzed the effects of transient inhibition of iNOS using aminoguanidine (AG) on NM-induced pulmonary toxicity. Rats were treated intratracheally with 0.125 mg/kg NM or control. Bronchoalveolar lavage fluid (BAL) and lung tissue were collected 1 d–28 d later and lung injury, oxidative stress and fibrosis assessed. NM exposure resulted in progressive histopathological changes in the lung including multifocal lesions, perivascular and peribronchial edema, inflammatory cell accumulation, alveolar fibrin deposition, bronchiolization of alveolar septal walls, and fibrosis. This was correlated with trichrome staining and expression of proliferating cell nuclear antigen (PCNA). Expression of heme oxygenase (HO)-1 and manganese superoxide dismutase (Mn-SOD) was also increased in the lung following NM exposure, along with levels of protein and inflammatory cells in BAL, consistent with oxidative stress and alveolar-epithelial injury. Both classically activated proinflammatory (iNOS{sup +} and cyclooxygenase-2{sup +}) and alternatively activated profibrotic (YM-1{sup +} and galectin-3{sup +}) macrophages appeared in the lung following NM administration; this was evident within 1 d, and persisted for 28 d. AG administration (50 mg/kg, 2 ×/day, 1 d–3 d) abrogated NM-induced injury, oxidative stress and inflammation at 1 d and 3 d post exposure, with no effects at 7 d or 28 d. These findings indicate that nitric oxide generated via iNOS contributes to acute NM-induced lung toxicity, however, transient inhibition of iNOS is not sufficient to protect against pulmonary fibrosis. -- Highlights: ► Nitrogen mustard (NM) induces acute lung injury and fibrosis. ► Pulmonary toxicity is associated with increased expression of iNOS. ► Transient inhibition of iNOS attenuates acute

  7. Acute gastroduodenal injury after ingestion of diluted herbicide pendimethalin.

    PubMed

    Tsukada, K; Azuhata, H; Katoh, H; Kuwano, H

    2009-03-01

    The herbicide, pendimethalin, is used worldwide, but its acute toxicity is not yet widely known. There have been some reported acute pendimethalin poisoning cases in humans and most of them intentionally ingested the concentrated formulation. We describe a 73-year-old man who developed corrosive gastroduodenal injury after accidental ingestion of the diluted (300 times with water) pendimethalin formulation. He had a history of reflux oesophagitis and had been taking omeprazol (10 mg/day) for a year. He consumed alcohol two hours after the accidental ingestion and then had nausea and epigastric pain. Endoscopy performed three days post-exposure revealed gastroduodenal injury. As he had consumed alcohol every day for years and had no history of gastroduodenal ulcer, the accidental ingestion may be associated with this injury. He was successfully treated by increasing his dosage of omeprazol (20 mg/day) for two weeks. This case indicates that ingestion of a small quantity of pendimethalin can provoke gastroduodenal injury.

  8. [Acute and overuse injuries in elite paracycling - an epidemiological study].

    PubMed

    Kromer, P; Röcker, K; Sommer, A; Baur, H; Konstantinidis, L; Gollhofer, A; Südkamp, N P; Hirschmüller, A

    2011-09-01

    Although paracycling is a growing discipline in high level competitive sports as well as in posttraumatic rehabilitation, epidemiological data of resulting injuries is still missing. Therefore, 19 athletes of the German national paracycling team were asked about their injuries during the 2008 season using a standardized questionnaire. Overall, 18 (94.7 %) of 19 athletes reported overuse injuries; most commonly localized at the back (83.3 %), neck/shoulder (77.8 %), knee (50 %), groin/buttock (50 %) and hands/wrists (38.9 %). Altogether, 18 accidents were registered, corresponding to an injury rate of 0,95 acute injuries per athlete per year (0,07 / 1000 km). The most common acute injuries were abrasions (69.2 %) and contusions (61.5 %), whereas fractures were stated only twice (11.8 %). The anatomical distribution of overuse injuries in disabled cyclists confirms the results of studies in able-bodied cycling, although the incidences in low-back pain and neck/shoulder pain is clearly higher in disabled cycling, as well as the rate of traumatic injuries.

  9. Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Itoh, Takefumi; Obata, Hiroaki; Murakami, Shinsuke; Hamada, Kaoru; Kangawa, Kenji; Kimura, Hiroshi; Nagaya, Noritoshi

    2007-08-01

    Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 microg x kg(-1) x min(-1)) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-alpha and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-alpha and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.

  10. Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model.

    PubMed

    Liu, Hao; Xue, Jian-Xing; Li, Xing; Ao, Rui; Lu, You

    2013-08-01

    In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-β1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-β1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage.

  11. Quercetin liposomes protect against radiation-induced pulmonary injury in a murine model

    PubMed Central

    LIU, HAO; XUE, JIAN-XING; LI, XING; AO, RUI; LU, YOU

    2013-01-01

    In the present study, the hypothesis that quercetin liposomes are able to effectively protect against radiation-induced pulmonary injury in a murine model was tested. C57BL/6J mice receiving whole-thorax radiotherapy (16 Gy) were randomly divided into three groups: control, radiation therapy plus saline (RT+NS) and RT plus quercetin (RT+QU). At 1, 4, 8 and 24 weeks post-irradiation, lung injury was assessed by measuring oxidative damage and the extent of acute pneumonitis and late fibrosis. In the lung tissues from the RT+NS group, the malondialdehyde (MDA) levels were significantly elevated and superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities were significantly reduced; the total cell counts and inflammatory cell proportions in the bronchoalveolar lavage fluid (BALF), plasma tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 concentrations and the hydroxyproline (HP) content were significantly increased. Quercetin liposome administration significantly reduced the MDA content and increased SOD and GSH-PX activities in the lung tissues, and reduced the total cell counts and inflammatory cell proportions in the BALF, plasma TNF-α and TGF-β1 concentrations and the HP content in the lung tissues. A histological examination revealed suppression of the inflammatory response and reduced TGF-β1 expression and fibrosis scores. Radiation-induced oxidative damage ranged from pneumonitis to lung fibrosis. Quercetin liposomes were shown to protect against radiation-induced acute pneumonitis and late fibrosis, potentially by reducing oxidative damage. PMID:24137346

  12. Ammonium dichromate poisoning: A rare cause of acute kidney injury.

    PubMed

    Radhakrishnan, H; Gopi, M; Arumugam, A

    2014-11-01

    Ammonium dichromate is an inorganic compound frequently used in screen and color printing. Being a strong oxidizing agent, it causes oxygen free radical injury resulting in organ failure. We report a 25-year-old female who presented with acute kidney injury after consumption of ammonium dichromate. She was managed successfully with hemodialysis and supportive measures. This case is reported to highlight the toxicity of ammonium dichromate.

  13. Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

    PubMed

    Fujita, Yoshiro; Hasegawa, Midori; Nabeshima, Kuihiro; Tomita, Makoto; Murakami, Kazutaka; Nakai, Shigeru; Yamakita, Takashi; Matsunaga, Kayoko

    2010-01-01

    Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

  14. Peripheral blood monocyte-derived chemokine blockade prevents murine transfusion-related acute lung injury (TRALI).

    PubMed

    McKenzie, Christopher G J; Kim, Michael; Singh, Tarandeep K; Milev, Youli; Freedman, John; Semple, John W

    2014-05-29

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and can occur with any type of transfusion. TRALI is thought to be primarily mediated by donor antibodies activating recipient neutrophils resulting in pulmonary endothelial damage. Nonetheless, details regarding the interactions between donor antibodies and recipient factors are unknown. A murine antibody-mediated TRALI model was used to elucidate the roles of the F(ab')2 and Fc regions of a TRALI-inducing immunoglobulin G anti-major histocompatibility complex (MHC) class I antibody (34.1.2s). Compared with intact antibody, F(ab')2 fragments significantly increased serum levels of the neutrophil chemoattractant macrophage inflammatory protein 2 (MIP-2); however, pulmonary neutrophil levels were only moderately increased, and no pulmonary edema or mortality occurred. Fc fragments did not modulate any of these parameters. TRALI induction by intact antibody was completely abrogated by in vivo peripheral blood monocyte depletion by gadolinium chloride (GdCl3) or chemokine blockade with a MIP-2 receptor antagonist but was restored upon repletion with purified monocytes. The results suggest a two-step process for antibody-mediated TRALI induction: the first step involves antibody binding its cognate antigen on blood monocytes, which generates MIP-2 chemokine production that is correlated with pulmonary neutrophil recruitment; the second step occurs when antibody-coated monocytes increase Fc-dependent lung damage.

  15. Bench-to-bedside review: Adenosine receptors – promising targets in acute lung injury?

    PubMed Central

    Schepp, Carsten P; Reutershan, Jörg

    2008-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening disorders that have substantial adverse effects on outcomes in critically ill patients. ALI/ARDS develops in response to pulmonary or extrapulmonary injury and is characterized by increased leakage from the pulmonary microvasculature and excessive infiltration of polymorphonuclear cells into the lung. Currently, no therapeutic strategies are available to control these fundamental pathophysiological processes in human ALI/ARDS. In a variety of animal models and experimental settings, the purine nucleoside adenosine has been demonstrated to regulate both endothelial barrier integrity and polymorphonuclear cell trafficking in the lung. Adenosine exerts its effects through four G-protein-coupled receptors (A1, A2A, A2B, and A3) that are expressed on leukocytes and nonhematopoietic cells, including endothelial and epithelial cells. Each type of adenosine receptor (AR) is characterized by a unique pharmacological and physiological profile. The development of selective AR agonists and antagonists, as well as the generation of gene-deficient mice, has contributed to a growing understanding of the cellular and molecular processes that are critically involved in the development of ALI/ARDS. Adenosine-dependent pathways are involved in both protective and proinflammatory effects, highlighting the need for a detailed characterization of the distinct pathways. This review summarizes current experimental observations on the role of adenosine signaling in the development of acute lung injury and illustrates that adenosine and ARs are promising targets that may be exploited in the development of innovative therapeutic strategies. PMID:18828873

  16. Oral penicillin-associated acute kidney injury in an infant with acute pyelonephritis.

    PubMed

    Zieg, Jakub; Hacek, Jaromir

    2015-04-01

    Beta-lactam-associated acute tubulointerstitial nephritis (ATIN) is a rare condition in childhood. We report the case of an infant with penicillin-associated ATIN and concomitant acute pyelonephritis resulting in the development of severe acute kidney injury (AKI). The treatment consisted of penicillin suspension and appropriate AKI management, which required a short period of dialysis. Finally, full recovery and normalization of laboratory parameters occurred. We present here the first case of oral penicillin-associated ATIN in childhood.

  17. Neonatal acute kidney injury - Severity and recovery prediction and the role of serum and urinary biomarkers.

    PubMed

    Sweetman, Deirdre U

    2017-02-01

    Neonatal acute kidney injury is common, in part due to incomplete renal maturation and also due to frequent exposure to risk factors for acute kidney injury such as perinatal asphyxia, extracorporeal-membrane-oxygenation, cardiac surgery, sepsis, prematurity and nephrotoxicity. However the current method by which acute kidney injury is diagnosed is sub-optimal and not universally accepted which impairs the accurate estimation of the true incidence of neonatal acute kidney injury. Serum Cystatin-C, urinary NGAL, KIM-1 and IL-18 are promising neonatal acute kidney injury biomarkers however the diagnosis of acute kidney injury remains serum creatinine/urine output-based in many studies. Emerging biomarkers which require further study in the neonatal population include netrin-1 and EGF. Increased awareness amongst clinicians of nephrotoxic medications being a modifiable risk factor for the development of neonatal acute kidney injury is imperative. The burden of chronic kidney failure following neonatal acute kidney injury is unclear and requires further study.

  18. Acute right ventricular failure caused by concomitant coronary and pulmonary embolism: successful treatment with endovascular coronary and pulmonary thrombectomy

    PubMed Central

    Koul, Sasha; Roijer, Anders; Holmqvist, Jasminka; Keussen, Inger; Cwikiel, Wojciech; Öhlin, Bertil; Erlinge, David

    2013-01-01

    Patent foramen ovale (PFO) is present in approximately 25% of the general population. PFO is characterized by intermittent shunting of blood from the right to the left atrium, especially in the context of increased right-sided filling pressures, with risk of paradoxical embolism. We describe a 69-year-old woman presenting with acute chest pain, severe dyspnoea, and acute inferolateral ST-segment elevation on the electrocardiogram. The patient was diagnosed with myocardial infarction and failure of the right cardiac ventricle, which was considered to be secondary to extensive pulmonary embolism leading to increased filling pressures and paradoxical coronary embolism. The patient underwent emergent percutaneous interventions with coronary thrombus extraction and pulmonary thrombus fragmentation and local thrombolysis. The patient was free of symptoms at follow up 6 months later and echocardiography showed substantially improved right ventricular function. We discuss issues related to the diagnosis, treatment, and secondary prevention for patients with concomitant pulmonary and coronary arterial thrombosis. PMID:24222822

  19. c-ANCA-induced neutrophil-mediated lung injury: a model of acute Wegener's granulomatosis.

    PubMed

    Hattar, K; Oppermann, S; Ankele, C; Weissmann, N; Schermuly, R T; Bohle, R M; Moritz, R; Krögel, B; Seeger, W; Grimminger, F; Sibelius, U; Grandel, U

    2010-07-01

    Anti-neutrophil cytoplasmic antibodies (c-ANCA) targeting proteinase 3 (PR3) are implicated in the pathogenesis of Wegener's granulomatosis (WG). Fulminant disease can present as acute lung injury (ALI). In this study, a model of ALI in WG was developed using isolated rat lungs. Isolated human polymorphonuclear leukocytes (PMNs) were primed with tumour necrosis factor (TNF) to induce surface expression of PR3. Co-perfusion of TNF-primed neutrophils and monoclonal anti-PR3 antibodies induced a massive weight gain in isolated lungs. This effect was not observed when control immunoglobulin G was co-perfused with TNF-primed PMNs. The c-ANCA-induced oedema formation was paralleled by an increase in the capillary filtration coefficient as a marker of increased pulmonary endothelial permeability. In contrast, pulmonary artery pressure was not affected. In the presence of the oxygen radical scavenger superoxide dismutase and a NADPH oxidase inhibitor, c-ANCA-induced lung oedema could be prevented. Inhibition of neutrophil elastase was equally effective in preventing c-ANCA-induced lung injury. In conclusion, anti-PR3 antibodies induced neutrophil mediated, elastase- and oxygen radical-dependent ALI in the isolated lung. This experimental model supports the hypothesis of a pathogenic role for c-ANCA in WG and offers the possibility of the development of therapeutic strategies for the treatment of lung injury in fulminant WG.

  20. VE-cadherin involved in the pulmonary microvascular endothelial cell barrier injury induced by angiotensin II through modulating the cellular apoptosis and skeletal rearrangement

    PubMed Central

    Wu, Zhiyong; Liu, Huagang; Ren, Wei; Dai, Feifeng; Chang, Jinxing; Li, Bowen

    2016-01-01

    Objective: Angiotensin II (AngII) involved in the pathogenesis of pulmonary injury through impairing the integrity of pulmonary microvascular endothelial barrier, but the mechanism is still not clear. We aim to determine the roles of VE-cadherin, playing crucial roles in the adhesion of the vascular endothelial barrier and the barrier function, in the pulmonary microvascular endothelial cell (PMVEC) barrier injury mediated by AngII. Methods: Mice acute lung injury (ALI) model was induced through pumping of AngII. The infiltration of macrophages and neutrophils as well as the PMVEC permeability were determined in order to determine the barrier injury in vivo and in vitro. Knockdown of VE-cadherin was established using siRNA technique, and its roles in the apoptosis and skeletal rearrangement in the PMVECs were evaluated. Results: After AngII interference, the expression of VE-cadherin in the PMVECs and pulmonary tissues in mice was down-regulated. Upon VE-cadherin knockdown through siRNA technique, AngII induced susceptibility of PMVECs to apoptosis. Knockdown of VE-cadherin contributed to the skeletal rearrangement in the endothelial cells, together with increase of permeability. Conclusions: VE-cadherin expression is closely related to the apoptosis and skeletal rearrangement of PMVECs induced by AngII. PMID:27830014

  1. Transfusion-related acute lung injury (TRALI) during remission induction course of acute myeloid leukemia: a possible role for all-transretinoic-acid (ATRA)?

    PubMed

    Jeddi, R; Mansouri, R; Kacem, K; Gouider, E; Abid, H B; Belhadjali, Z; Meddeb, B

    2009-09-01

    Transfusion-related acute lung injury (TRALI) is a clinical syndrome characterized by sudden onset of respiratory distress due to pulmonary edema during or following transfusion. Two proposed pathophysiologic mechanisms for TRALI were proposed: the antibody hypothesis and the two-event hypothesis. The two-event hypothesis postulates that a pathway to neutrophil activation and aggregation can occur without leukocyte antibodies. We report a case of TRALI occurring during remission induction course of acute myeloid leukemia in a 27-year-old woman who received All-transretinoic-acid (ATRA). We postulate that ATRA may have played a role in this life-threatening complication by priming neutrophil and enhancing their adherence and their activation in the pulmonary endothelium. TRALI improved with non-invasive ventilation support and use of high dose corticosteroids.

  2. Severe but reversible acute kidney injury resulting from Amanita punctata poisoning

    PubMed Central

    Kang, Eunjung; Cheong, Ka-Young; Lee, Min-Jeong; Kim, Seirhan; Shin, Gyu-Tae; Kim, Heungsoo; Park, In-Whee

    2015-01-01

    Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury. PMID:26779427

  3. Pulmonary Epithelial TLR4 Activation Leads to Lung Injury in Neonatal Necrotizing Enterocolitis.

    PubMed

    Jia, Hongpeng; Sodhi, Chhinder P; Yamaguchi, Yukihiro; Lu, Peng; Martin, Laura Y; Good, Misty; Zhou, Qinjie; Sung, Jungeun; Fulton, William B; Nino, Diego F; Prindle, Thomas; Ozolek, John A; Hackam, David J

    2016-08-01

    We seek to define the mechanisms leading to the development of lung disease in the setting of neonatal necrotizing enterocolitis (NEC), a life-threatening gastrointestinal disease of premature infants characterized by the sudden onset of intestinal necrosis. NEC development in mice requires activation of the LPS receptor TLR4 on the intestinal epithelium, through its effects on modulating epithelial injury and repair. Although NEC-associated lung injury is more severe than the lung injury that occurs in premature infants without NEC, the mechanisms leading to its development remain unknown. In this study, we now show that TLR4 expression in the lung gradually increases during postnatal development, and that mice and humans with NEC-associated lung inflammation express higher levels of pulmonary TLR4 than do age-matched controls. NEC in wild-type newborn mice resulted in significant pulmonary injury that was prevented by deletion of TLR4 from the pulmonary epithelium, indicating a role for pulmonary TLR4 in lung injury development. Mechanistically, intestinal epithelial TLR4 activation induced high-mobility group box 1 release from the intestine, which activated pulmonary epithelial TLR4, leading to the induction of the neutrophil recruiting CXCL5 and the influx of proinflammatory neutrophils to the lung. Strikingly, the aerosolized administration of a novel carbohydrate TLR4 inhibitor prevented CXCL5 upregulation and blocked NEC-induced lung injury in mice. These findings illustrate the critical role of pulmonary TLR4 in the development of NEC-associated lung injury, and they suggest that inhibition of this innate immune receptor in the neonatal lung may prevent this devastating complication of NEC.

  4. Management of acute cardiogenic pulmonary edema: a literature review.

    PubMed

    Johnson, Jeremy M

    2009-01-01

    Acute cardiogenic pulmonary edema (CPE) is a pathology frequently seen in patients presenting to emergency departments (EDs) and can usually be attributed to preexisting cardiovascular disease. Heart failure alone accounts for more than 1 million hospital admissions annually and has one of the highest ED morbidity and mortality to date (). Historically, CPE has been managed by the treating clinician in a manner that is based largely on anecdotal evidence. Furosemide (Lasix), morphine, and nitroglycerin have historically been the baseline standard for drug therapy in CPE management. A lack of drastic improvement in the patient's condition over the course of the ED visit may reflect a management style that results in higher morbidity and mortality for CPE patients. Several recent articles provide evidence-based outcomes that suggest changing standard therapy along with the adjunctive use of other medications. These articles also describe treatment modalities that result in a marked improvement in the management of patients with CPE along with decreases in adverse outcomes and hospital length of stay. The goal of this article is to present a summary of the evidence regarding the management of CPE and discuss the implications for current practice.

  5. Syncope as a presentation of acute pulmonary embolism

    PubMed Central

    Altınsoy, Bülent; Erboy, Fatma; Tanrıverdi, Hakan; Uygur, Fırat; Örnek, Tacettin; Atalay, Figen; Tor, Meltem

    2016-01-01

    Purpose Syncope is an atypical presentation for acute pulmonary embolism (APE). There are conflicting data concerning syncope and prognosis of APE. Patients and methods One hundred and seventy-nine consecutive patients aged 22–96 years (median, 68 years) with APE were retrospectively enrolled in the study. Results Prevalence of syncope was 13% (n=23) at the time of presentation. Compared to patients without syncope, those with syncope had a higher rate of central embolism (83% vs 43%, respectively, P=0.002), right ventricular dysfunction (91% vs 68%, P=0.021), and troponin positivity (80% vs 39%, P=0.001) but not 30-day mortality (13% vs 10%, P=0.716). Multivariate analysis showed that central localization (odds ratio: 9.08) and cardiac troponin positivity (odds ratio: 4.67) were the independent correlates of the presence of syncope in the patients with APE. Frequency of cardiopulmonary disease was lower, and duration from symptom onset to hospital admission was shorter in patients with syncope (P=0.138 and 0.118, respectively), although not significant. Conclusion Syncope most likely represents an intermediate condition between massive APE and hypotension. In APE patients with syncope, the prognosis seems to depend on the underlying pathology, the patient’s age, comorbidities and duration from symptom onset to hospital admission, and the use of thrombolytic therapy. PMID:27390523

  6. Efficiency and Safety of Pulmonary Rehabilitation in Acute Exacerbation of Chronic Obstructive Pulmonary Disease

    PubMed Central

    He, Mei; Yu, Sue; Wang, Lemin; Lv, Hanjing; Qiu, Zhongmin

    2015-01-01

    Background Pulmonary rehabilitation (PR) is able to improve dyspnea, endurance capacity, and health-related quality of life in chronic obstructive pulmonary disease (COPD) patients, but it is rarely used in China. This study aimed to assess the effectiveness and safety of PR after exacerbation of COPD. Material/Methods Patients admitted to hospital due to an exacerbation of COPD were randomized to receive either PR or routine care (control group). The PR program was performed from the second day of admission until discharge. The pre-post changes in 6-minute walk distance (6MWD), self-reported quality of life (QOL) assessed by CAT score and CRQ-SAS score, and activity of daily life assessed by ADL-D score were determined. The perceived end-effort dyspnea (Borg scale) was measured throughout the study. Results A total of 101 patients were enrolled, of whom 7 withdrew after randomization, and 94 completed this study. There were 66 patients in the PR group and 28 in the control group. The 6MWD, resting SpO2, and exercise Borg dyspnea score were significantly improved in the PR group. In addition, the PR group had greater improvement in the total CRQ-SAS score and had a lower CAT score. Significant improvements were also found in the ADL-D and BODE index in the PR group. No adverse events were recorded during exercise. Conclusions Our study provides evidence that it is safe and feasible to apply an early PR in patients with acute exacerbation of COPD. PMID:25783889

  7. Thromboembolism in the Sub-Acute Phase of Spinal Cord Injury: A Systematic Review of the Literature

    PubMed Central

    Belci, Maurizio; Van Middendorp, Joost J; Al Halabi, Ahmed; Meagher, Tom M

    2016-01-01

    To review the evidence of thromboembolism incidence and prophylaxis in the sub-acute phase of spinal cord injury (SCI) 3–6 months post injury. All observational and experimental studies with any length of follow-up and no limitations on language or publication status published up to March 2015 were included. Two review authors independently selected trials for inclusion and extracted data. Outcomes studied were incidence of pulmonary embolism (PE) and deep vein thrombosis (DVT) in the sub-acute phase of SCI. The secondary outcome was type of thromboprophylaxis. Our search identified 4305 references and seven articles that met the inclusion criteria. Five papers reported PE events and three papers reported DVT events in the sub-acute phase of SCI. Studies were heterogeneous in populations, design and outcome reporting, therefore a meta-analysis was not performed. The included studies report a PE incidence of 0.5%–6.0% and DVT incidence of 2.0%–8.0% in the sub-acute phase of SCI. Thromboprophylaxis was poorly reported. Spinal patients continue to have a significant risk of PE and DVT after the acute period of their injury. Clinicians are advised to have a low threshold for suspecting venous thromboembolism in the sub-acute phase of SCI and to continue prophylactic anticoagulation therapy for a longer period of time. PMID:27790330

  8. Growth and development alter susceptibility to acute renal injury.

    PubMed

    Zager, Richard A; Johnson, Ali C M; Naito, Masayo; Lund, Steve R; Kim, Nayeon; Bomsztyk, Karol

    2008-09-01

    Many of the studies of acute renal injury have been conducted in young mice usually during their rapid growth phase; yet, the impact of age or growth stage on the degree of injury is unknown. To address this issue, we studied three forms of injury (endotoxemic-, glycerol-, and maleate-induced) in mice ranging in age from adolescence (3 weeks) to maturity (16 weeks). The severity of injury within each model significantly correlated with weight and age. We also noticed a progressive age-dependent reduction in renal cholesterol content, a potential injury modifier. As the animals grew and aged they also exhibited stepwise decrements in the mRNAs of HMG CoA reductase and the low density lipoprotein receptor, two key cholesterol homeostatic genes. This was paralleled by decreased amounts of RNA polymerase II and the transcription factor SREBP1/2 at the reductase and lipoprotein receptor gene loci as measured by chromatin immunoprecipitation. Our study shows that the early phase of mouse growth can profoundly alter renal susceptibility to diverse forms of experimental acute renal injury.

  9. Neutrophils as early immunologic effectors in hemorrhage- or endotoxemia-induced acute lung injury.

    PubMed

    Abraham, E; Carmody, A; Shenkar, R; Arcaroli, J

    2000-12-01

    Acute lung injury is characterized by accumulation of neutrophils in the lungs, accompanied by the development of interstitial edema and an intense inflammatory response. To assess the role of neutrophils as early immune effectors in hemorrhage- or endotoxemia-induced lung injury, mice were made neutropenic with cyclophosphamide or anti-neutrophil antibodies. Endotoxemia- or hemorrhage-induced lung edema was significantly reduced in neutropenic animals. Activation of the transcriptional regulatory factor nuclear factor-kappaB after hemorrhage or endotoxemia was diminished in the lungs of neutropenic mice compared with nonneutropenic controls. Hemorrhage or endotoxemia was followed by increases in pulmonary mRNA and protein levels for interleukin-1beta (IL-1beta), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha). Endotoxin-induced increases in proinflammatory cytokine expression were greater than those found after hemorrhage. The amounts of mRNA or protein for IL-1beta, MIP-2, and TNF-alpha were significantly lower after hemorrhage in the lungs of neutropenic versus nonneutropenic mice. Neutropenia was associated with significant reductions in IL-1beta and MIP-2 but not in TNF-alpha expression in the lungs after endotoxemia. These experiments show that neutrophils play a central role in initiating acute inflammatory responses and causing injury in the lungs after hemorrhage or endotoxemia.

  10. Body temperature control in sepsis-induced acute lung injury.

    PubMed

    Wang, Giueng-Chueng; Chi, Wei-Ming; Perng, Wan-Cherng; Huang, Kun-Lun

    2003-12-31

    Body temperature is precisely regulated to maintain homeostasis in homeothermic animals. Although it remains unproved whether change of body temperature constitutes a beneficial or a detrimental component of the septic response, temperature control should be an important entity in septic experiments. We investigated the effect of body temperature control on the lipopolysaccharide (LPS)-induced lung injury. Acute lung injury in rats was induced by intratracheal spray of LPS and body temperature was either clamped at 37 degrees C for 5 hours or not controlled. The severity of lung injury was evaluated at the end of the experiment. Intratracheal administration of aerosolized LPS caused a persistent decline in body temperature and a significant lung injury as indicated by an elevation of protein-concentration and LDH activity in the bronchoalveolar lavage (BAL) fluid and wet/dry weight (W/D) ratio of lungs. Administration of LPS also caused neutrophil sequestration and lipid peroxidation in the lung tissue as indicated by increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) production, respectively. Control of body temperature at 37 degrees C after LPS (LPS/BT37, n = 11) significantly reduced acute lung injury as evidenced by decreases in BAL fluid protein concentration (983 +/- 189 vs. 1403 +/- 155 mg/L) and LDH activity (56 +/- 10 vs. 123 +/- 17 deltamAbs/min) compared with the LPS group (n = 11). Although the W/D ratio of lung and MDA level were lower in the rats received temperature control compared with those received LPS only, the differences were not statistically significant. Our results demonstrated that intratracheal administration of aerosolized LPS induced a hypothermic response and acute lung injury in rats and controlling body temperature at a normal range may alleviate the LPS-induced lung injury.

  11. Understanding acute ankle ligamentous sprain injury in sports.

    PubMed

    Fong, Daniel Tp; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick Sh; Chan, Kai-Ming

    2009-07-30

    This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing - a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60-90 ms). The failure supination or inversion torque is about 41-45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not be

  12. Understanding acute ankle ligamentous sprain injury in sports

    PubMed Central

    Fong, Daniel TP; Chan, Yue-Yan; Mok, Kam-Ming; Yung, Patrick SH; Chan, Kai-Ming

    2009-01-01

    This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing – a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60–90 ms). The failure supination or inversion torque is about 41–45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not

  13. State of the art management of transfusion-related acute lung injury (TRALI).

    PubMed

    Goldberg, Andrew D; Kor, Daryl J

    2012-01-01

    Transfusion-Related Acute Lung Injury (TRALI) is the leading cause of transfusion-related mortality in most developed countries. Despite this fact, well-designed investigations on specific management strategies for TRALI are lacking. Indeed, current recommendations are primarily based on data extrapolated from trials of the histo-pathologically similar Acute Lung Injury and Acute Respiratory Distress Syndromes. The cornerstone of TRALI management is supportive care with oxygen supplementation and ventilatory assistance when needed. When mechanical ventilation is required, attenuating additional ventilator-induced lung injury through the avoidance of high tidal volumes and elevated airway pressures, with additional measures such as positive end-expiratory pressure to prevent low-volume shear stress injury, are recommended. The literature is not currently sufficient to support either corticosteroids or statins as effective therapies in TRALI. Conservative fluid practices are desirable, provided care is taken to avoid hypotension. Preventative strategies have shown the most promise in mitigating this transfusion-related pulmonary complication. Specifically, conservative transfusion practices and deferral of high-plasma component donors who have, or at high risk of having, anti-human leukocyte antigen and/or anti-human neutrophil antigen antibodies have meaningfully impacted the incidence of TRALI. Future considerations for patients who are at increased risk for developing TRALI may include therapies such as anti-platelet agents and alternatives to traditional blood components such as prothrombin complex concentrates (PCC). However, these potential TRALI prevention strategies are insufficiently studied, have unclear risk/benefit profiles and cannot be currently recommended.

  14. Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model.

    PubMed Central

    Silliman, C C; Voelkel, N F; Allard, J D; Elzi, D J; Tuder, R M; Johnson, J L; Ambruso, D R

    1998-01-01

    Transfusion-related acute lung injury (TRALI) is a serious complication of hemotherapy. During blood storage, lipids are generated and released into the plasma. In this study, the role of these lipids in TRALI was investigated using an isolated, perfused rat lung model. Rats were pretreated with endotoxin (LPS) or saline in vivo and the lungs were isolated, ventilated, and perfused with saline, or (a) 5% (vol/ vol) fresh human plasma, (b) plasma from stored blood from the day of isolation (D.0) or from the day of outdate (D.42), (c) lipid extracts from D.42 plasma, or (d) purified lysophosphatidylcholines. Lungs from saline or LPS-pretreated rats perfused with fresh (D.0) plasma showed no pulmonary damage as compared with saline perfused controls. LPS pretreatment/D.42 plasma perfusion caused acute lung injury (ALI) manifested by dramatic changes in both pulmonary artery pressure and edema. Incubation of LPS pre-tx rats with mibefradil, a Ca2+ channel blocker, or WEB 2170, a platelet-activating factor (PAF) receptor antagonist, inhibited ALI caused by D.42 plasma. Lung histology showed neutrophil sequestration without ALI with LPS pretreatment/saline or D.0 plasma perfusion, but ALI with LPS pretreatment/D.42 plasma perfusion, and inhibition of D.42 plasma induced ALI with WEB 2170 or mibefradil. A significant increase in leukotriene E4 was present in LPS-pretreated/D.42 plasma-perfused lungs that was inhibited by WEB 2170. Lastly, significant pulmonary edema was produced when lipid extracts of D.42 plasma or lysophosphatidylcholines were perfused into LPS-pretreated lungs. Lipids caused ALI without vasoconstriction, except at the highest dose employed. In conclusion, both plasma and lipids from stored blood produced pulmonary damage in a model of acute lung injury. TRALI, like the adult respiratory distress syndrome, may be the result of two insults: one derived from stored blood and the other from the clinical condition of the patient. PMID:9525989

  15. Protection by N-acetylcysteine against pulmonary endothelial cell damage induced by oxidant injury.

    PubMed

    Sala, R; Moriggi, E; Corvasce, G; Morelli, D

    1993-03-01

    The protective effect of N-acetylcysteine (NAC) against oxidant lung injury was investigated in a model of acute immunological alveolitis in the rat. Intrapulmonary immune complex deposition into rat lungs, induced by intratracheal infusion of immunoglobulin G (IgG) anti-bovine serum albumin (BSA) antibodies and intravenous injection of the antigen, caused lung damage associated with a marked decrease in [14C]5-hydroxytryptamine ([14C]5HT) uptake capacity, taken as a biochemical marker of endothelial cell function. The oral administration of a single dose of NAC (2 mmol.kg-1) 60 min before antigen/antibody (Ag/Ab) treatment was effective in preventing pulmonary endothelial cell [14C]5HT uptake loss induced by immune complex deposition. The mechanisms involved in this lung protective action of NAC were investigated by studying the antioxidant activity of NAC on hypoxanthine/xanthine oxidase-induced lung damage in vitro, and the effectiveness of the drug as lung glutathione (reduced form) (GSH) precursor in diethylmaleate-depleted rats. The results obtained provide further evidence on the ability of NAC to reduce the susceptibility of lung tissue to free radical-induced damage, by potentiating the antioxidant defence systems.

  16. [Evidence for treatment of acute syndesmosis injuries in sports].

    PubMed

    Best, R; Mauch, F; Bauer, G

    2013-06-01

    Injuries of the distal syndesmosis often accompany acute ankle sprains especially in professional team sports. While small partial syndesmosis lesions can often be missed as a consequence of impressive symptoms due to ventrolateral capsuloligamentous injuries, higher grade injuries of the syndesmosis can mostly be diagnosed without any problem. Furthermore, there is a consensus concerning the necessity of operative treatment in significantly unstable situations as well concerning conservative treatment of incomplete partial lesions. Consequently, the greatest challenge regarding diagnostic tools, quantification and optimal therapy arises in the most common form of sport-associated, complete or partial lesions of the distal syndesmosis. This review article summarizes sports-associated injuries of the distal tibiofibular syndesmosis considering the current literature and placing the emphasis on the anatomy, pathobiomechanics, diagnostics and therapy of syndesmosis lesions from an evidence-based viewpoint.

  17. Anti-oxidative aspect of inhaled anesthetic gases against acute brain injury

    PubMed Central

    Yang, Tuo; Sun, Yang; Zhang, Feng

    2016-01-01

    Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury. PMID:28217295

  18. Spironolactone Attenuates Bleomycin-Induced Pulmonary Injury Partially via Modulating Mononuclear Phagocyte Phenotype Switching in Circulating and Alveolar Compartments

    PubMed Central

    Zhou, Xin; Zhang, Yi-Dan; Lu, Rui-Yi; Guo, Zhao-Zeng; Sun, Hai-Ying; Hu, Dao-Chuan; Yang, Guo-Hong; Li, Yu-Ming; Wei, Lu-Qing

    2013-01-01

    Background Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR) has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. Methodology/Principal Findings We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF) from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20mg/kg/day by oral gavage) revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels) and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson’ trichrome staining) in bleomycin treated (2.5mg/kg, via oropharyngeal instillation) male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6Chi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+) of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c-) remained unaffected by spironolactone during investigation. Conclusions/Significance The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching. PMID:24260540

  19. Factors Affecting Recovery Time of Pulmonary Function in Hospitalized Patients With Acute Asthma Exacerbations

    PubMed Central

    Kim, Hyo-Jung; Lee, Jaemoon; Kim, Jung-Hyun; Park, So-Young; Kwon, Hyouk-Soo; Kim, Tae-Bum; Moon, Hee-Bom

    2016-01-01

    Purpose Prolonged recovery time of pulmonary function after an asthma exacerbation is a significant burden on asthmatics, and management of these patients needs to be improved. The aim of this study was to evaluate factors associated with a longer recovery time of pulmonary function among asthmatic patients hospitalized due to a severe asthma exacerbation. Methods We retrospectively reviewed the medical records of 89 patients who were admitted for the management of acute asthma exacerbations. The recovery time of pulmonary function was defined as the time from the date each patient initially received treatment for asthma exacerbations to the date the patient reached his or her previous best FEV1% value. We investigated the influence of various clinical and laboratory factors on the recovery time. Results The median recovery time of the patients was 1.7 weeks. Multiple linear regression analysis revealed that using regular inhaled corticosteroids (ICS) before an acute exacerbation of asthma and concurrent with viral infection at admission were associated with the prolonged recovery time of pulmonary function. Conclusions The prolonged recovery time of pulmonary function after a severe asthma exacerbation was not shown to be directly associated with poor adherence to ICS. Therefore the results indicate that an unknown subtype of asthma may be associated with the prolonged recovery of pulmonary function time after an acute exacerbation of asthma despite regular ICS use. Further prospective studies to investigate factors affecting the recovery time of pulmonary function after an asthma exacerbation are warranted. PMID:27582400

  20. Early Acute Kidney Injury in Military Casualties

    DTIC Science & Technology

    2015-05-01

    J. A.; Kwan, H. K.; Glass, K. R.; Morrow, B . D.; Latack, W.; Henderson, A. T.; Saenz, K. K.; Siew, E. D.; Ikizler, T. A.; Chung, K. K.; 5d. PROJECT...19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b . ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98...among trauma patients. Ann Surg. 2010;252:158Y165. 12. Skinner DL, Hardcastle TC, Rodseth RN, Muckart DJ. The incidence and outcomes of acute kidney

  1. Respiratory viruses in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Koul, Parvaiz A; Mir, Hyder; Akram, Shabir; Potdar, Varsha; Chadha, Mandeep S

    2017-01-01

    Objective: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) cause significant morbidity, mortality, and an inexorable decline of lung function. Data from developed countries have shown viruses to be important causes of AECOPD, but data from developing countries like India are scant. We set out to determine the contribution of viruses in the causation of hospitalized patients with AECOPD. Methods: Twin nasopharyngeal/oropharyngeal swabs collected from 233 patients admitted with an acute AECOPD and tested for respiratory viruses including respiratory syncytial virus A and B, parainfluenza were (PIV) 1, 2, 3, and 4, human metapneumovirus (hMPV) A and B, influenza A and B, enterovirus, corona NL65, OC43, and 229E viruses, adenovirus 2 and 4, rhinovirus, and bocavirus, by duplex real time reverse-transcription polymerase chain reaction (qRT-PCR) using CDC approved primers and probes. Samples positive for influenza A were subtyped for A/H1N1pdm09 and A/H3N2 whereas influenza B samples were subtyped into B/Yamagata and B/Victoria subtypes, using primers and probes recommended by CDC, USA. Results: Respiratory viruses were detected in 46 (19.7%) cases, influenza A/H3N2 and rhinoviruses being the most common viruses detected. More than one virus was isolated in four cases consisting of hMPV-B + adeno-2 + Inf-B; rhino + H3N2, PIV-1 + rhino; and PIV-1+ hMPV-B in one case each. Ancillary supportive therapeutic measures included bronchodilators, antibiotics, steroids, and ventilation (noninvasive in 42 and invasive in 4). Antiviral therapy was instituted in influenza-positive patients. Three patients with A/H3N2 infection died during hospitalization. Conclusions: We conclude that respiratory viruses are important contributors to AECOPD in India. Our data calls for prompt investigation during an exacerbation for viruses to obviate inappropriate antibiotic use and institute antiviral therapy in viral disease amenable to antiviral therapy. Appropriate

  2. Hypothyroidism causing paralytic ileus and acute kidney injury - case report

    PubMed Central

    2011-01-01

    We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit. Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far. It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications. PMID:21303532

  3. Hypothyroidism causing paralytic ileus and acute kidney injury - case report.

    PubMed

    Rodrigo, Chaturaka; Gamakaranage, Champika Sssk; Epa, Dhanesha S; Gnanathasan, Ariaranee; Rajapakse, Senaka

    2011-02-08

    We present a patient with severe hypothyroidism complicated by paralytic ileus and acute kidney injury. A 65 year old male patient, diagnosed with hypothyroidism one year ago was transferred to our unit in a state of drowsiness and confusion. He was severely hypothyroid and had paralytic ileus and impaired renal function at the time of transfer. Hypokalaemia was present, and was likely to have contributed to the paralytic ileus and this together with dehydration was likely to have contributed to renal injury. Nonetheless, hypothyroidism is very likely to have been the principal precipitant of both these complications, and both paralytic ileus and acute kidney injury improved with thyroxine replacement. Unfortunately, the patient died unexpectedly eight days after admission to the unit.Hypothyroidism may induce de novo acute kidney injury or it may exacerbate ongoing chronic kidney disease. This rare complication is assumed to be due to the hypodynamic circulatory state created by thyroid hormone deficiency. Paralytic ileus is an even rarer fatal manifestation of hypothyroidism and is thought to be due to an autonomic neuropathy affecting the intestines that is reversible with thyroxine replacement. To our knowledge, both these complications have not been observed in a single patient so far.It is important that clinicians are aware of these rare manifestations of hypothyroidism as in most occasions, thyroxine deficiency may be missed, and treatment can reverse the complications.

  4. Lethal acute lung injury and hypoglycemia after subcutaneous administration of monochloroacetic acid.

    PubMed

    Kato, Junko; Dote, Tomotaro; Shimizu, Hiroyasu; Shimbo, Yukari; Fujihara, Michiko; Kono, Koichi

    2006-06-01

    Hypoglycemia is suspected in the acute lethal toxicity induced by cutaneous exposure to monochloroacetic acid (MCA). Although it has been shown that hepato-renal dysfunction is involved, the mechanism and the target organs that directly affect mortality remain to be determined. We suspected respiratory failure as a main cause of death in some reported cases. We investigated dose-response effects, hypoglycemia, and lung injury in rats exposed to MCA. Serum glucose, blood gases, and parameters of alveolar injury in bronchoalveolar lavage fluid (BALF) were analysed 2 and 4 h after subcutaneous administration of MCA (108, 135 or 163 mg/kg). Apparent pulmonary injury and hypoglycemia were not identified 2 h after administration, but lactate dehydrogenase (LDH) and total cells in BALF were dose-dependently increased; and severe hypoglycemia was identified 4 h after administration. Blood gas analysis showed remarkable alveolar gas dysfunction as exchange in the 163 mg/kg group. Thus, hypoglycemia and lung injury appear to cause death in response to MCA exposure.

  5. Pulmonary circulatory parameters as indices for the early detection of acute rejection after single lung transplantation.

    PubMed

    Yamamoto, H; Okada, M; Tobe, S; Tsuji, F; Ohbo, H; Nakamura, H; Yamashita, C

    1998-01-01

    We investigated the relationship between the changes in the pulmonary blood flow and histology during acute rejection following single lung transplantation. In single lung transplantation using adult mongrel dogs, immunosuppression with cyclosporine and azathioprine was discontinued after postoperative day 14 to induce rejection. Doppler flow probes were placed adjacent to the ascending aorta and the left pulmonary artery to measure the blood flow on a daily basis. In addition, chest roentgenograms were also examined daily. The pulmonary pressure was measured using a Swan-Ganz catheter prior to and following the induction of rejection. Open lung biopsies were performed when the left pulmonary artery flow decreased to half of the prerejection value. The pulmonary artery flow decreased to 14.3% of the aortic flow 5 days after the discontinuation of immunosuppression. The graft pulmonary vascular resistance increased significantly compared to the prerejection values (P < 0.001). This was not accompanied by any abnormalities on chest roentgenography. The histology was consistent, with marked perivascular lymphocytic infiltration with little alveolar or interstitial changes. During rejection, the increased pulmonary vascular resistance in the graft was probably the result of perivascular inflammatory cell infiltration, which was seen prior to changes on chest roentgenography. Changes in the left pulmonary artery flow and histology thus appear to be closely correlated in the early stages of acute rejection.

  6. Acute Ozone-Induced Pulmonary and Systemic Metabolic ...

    EPA Pesticide Factsheets

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats underwent adrenal demedullation (DEMED), total bilateral adrenalectomy (ADREX), or sham surgery (SHAM). After a 4 day recovery, rats were exposed to air or ozone (1ppm), 4h/day for 1 or 2 days. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to air-exposed SHAM. Corticosterone levels tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED rats with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids (p=0.15) and branched-chain amino acids increased after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX>DMED). Ozone-mediated decreases in circulating white blood cells in SHAM were not obser

  7. Acute Ozone-Induced Pulmonary and Systemic Metabolic ...

    EPA Pesticide Factsheets

    Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wistar-Kyoto rats (12 week-old) underwent total bilateral adrenalectomy (ADREX), adrenal demedullation (DEMED) or sham surgery (SHEM). After 4 day recovery, rats were exposed to air or ozone (1ppm), 4h/day for 1 or 2 days. Circulating adrenaline levels dropped to nearly zero in DEMED and ADREX rats relative to air-exposed SHAM. Corticosterone levels tended to be low in DEMED rats and dropped to nearly zero in ADREX rats. Adrenalectomy in air-exposed rats caused modest changes in metabolites and lung toxicity parameters. Ozone-induced hyperglycemia and glucose intolerance were markedly attenuated in DEMED with nearly complete reversal in ADREX rats. Ozone increased circulating epinephrine and corticosterone in SHAM but not in DEMED or ADREX rats. Free fatty acids and branched-chain amino acids tended to increase after ozone exposure in SHAM but not in DEMED or ADREX rats. Lung minute volume was not affected by surgery or ozone but ozone-induced labored breathing was less pronounced in ADREX rats. Ozone-induced increases in lung protein leakage and neutrophilic inflammation were markedly reduced in DEMED and ADREX rats (ADREX>DMED). Ozone-mediated decrease in circulating WBC in SHAM was not

  8. Endothelial Semaphorin 7A Promotes Inflammation in Seawater Aspiration-Induced Acute Lung Injury

    PubMed Central

    Zhang, Minlong; Wang, Li; Dong, Mingqing; Li, Zhichao; Jin, Faguang

    2014-01-01

    Inflammation is involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have shown that Semaphorin 7A (SEMA7A) promotes inflammation, there are limited reports regarding immunological function of SEMA7A in seawater aspiration-induced ALI. Therefore, we investigated the role of SEMA7A during seawater aspiration-induced ALI. Male Sprague–Dawley rats were underwent seawater instillation. Then, lung samples were collected at an indicated time for analysis. In addition, rat pulmonary microvascular endothelial cells (RPMVECs) were cultured and then stimulated with 25% seawater for indicated time point. After these treatments, cells samples were collected for analysis. In vivo, seawater instillation induced lung histopathologic changes, pro-inflammation cytokines release and increased expression of SEMA7A. In vitro, seawater stimulation led to pro-inflammation cytokine release, cytoskeleton remodeling and increased monolayer permeability in pulmonary microvascular endothelial cells. In addition, knockdown of hypoxia-inducible factor (HIF)-1α inhibited the seawater induced increase expression of SEMA7A. Meanwhile, knockdown of SEMA7A by specific siRNA inhibited the seawater induced aberrant inflammation, endothelial cytoskeleton remodeling and endothelial permeability. These results suggest that SEMA7A is critical in the development of lung inflammation and pulmonary edema in seawater aspiration-induced ALI, and may be a therapeutic target for this disease. PMID:25353180

  9. Paeoniflorin ameliorates acute necrotizing pancreatitis and pancreatitis‑induced acute renal injury.

    PubMed

    Wang, Peng; Wang, Weixing; Shi, Qiao; Zhao, Liang; Mei, Fangchao; Li, Chen; Zuo, Teng; He, Xiaobo

    2016-08-01

    Acute renal injury caused by acute necrotizing pancreatitis (ANP) is a common complication that is associated with a high rate of mortality. Paeoniflorin is the active ingredient of paeonia radix and exhibits a number of pharmacological effects, such as anti‑inflammatory, anticancer, analgesic and immunomodulatory effects. The present study detected the potential treatment effects of paeoniflorin on acute renal injury induced by ANP in a rat model. The optimal dose of paeoniflorin for preventing acute renal injury induced by ANP was determined. Then, the possible protective mechanism of paeoniflorin was investigated. The serum levels of tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β and IL‑6 were measured with enzyme‑linked immunosorbent assay kits. Renal inflammation and apoptosis were measured by immunohistochemistry and terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling assay. The expression of nitric oxide in kidney tissues was also evaluated. The p38 mitogen‑activated protein kinases (MAPKs) were measured by western blotting. The results shown that paeoniflorin may ameliorate acute renal injury following ANP in rats by inhibiting inflammatory responses and renal cell apoptosis. These effects may be associated with the p38MAPK and nuclear factor‑κB signal pathway.

  10. Aminophylline treatment in meconium-induced acute lung injury in a rabbit model.

    PubMed

    Mokra, D; Mokry, J; Tatarkova, Z; Redfors, B; Petraskova, M; Calkovska, A

    2007-11-01

    Administration of methylxanthines may diminish meconium-induced acute lung injury. Meconium-instilled rabbits intravenously received aminophylline (2.0 mg/kg) at two doses 0.5 h and 2.5 h after meconium instillation or were left without treatment, and were oxygen-ventilated for additional 5 h. At the end of experiment, lungs and trachea were excised. Within 5 h after the first dose of treatment, aminophylline significantly improved gas exchange and decreased right-to-left pulmonary shunts, central venous pressure, and ventilatory pressures. Moreover, aminophylline reduced meconium-induced lung edema formation, airway hyperreactivity to histamine, count of neutrophils in bronchoalveolar lavage fluid associated with higher total white blood cells and neutrophils in the blood, and diminished oxidative modifications of proteins and lipids in lung tissue compared with the non-treated meconium-instilled group. In a rabbit model of the meconium aspiration syndrome, aminophylline treatment enhanced pulmonary functions and alleviated oxidative injury and changes in airway reactivity related to lung inflammation.

  11. Acute Pharmacological DVT Prophylaxis after Spinal Cord Injury

    PubMed Central

    Thibault-Halman, Ginette; Casha, Steven

    2011-01-01

    Abstract A systematic review of the literature was performed to address pertinent clinical questions regarding deep vein thrombosis (DVT) prophylaxis in the setting of acute spinal cord injury (SCI). Deep vein thromboses are a common occurrence following SCI. Administration of low-molecular-weight heparin (LMWH) within 72 h of injury is recommended to minimize the occurrence of DVT. Furthermore, when surgical intervention is required, LMWH should be held the morning of surgery, and resumed within 24 h post-operatively. PMID:20795870

  12. Diagnostic Delay and Antibiotic Overuse in Acute Pulmonary Blastomycosis

    PubMed Central

    Alpern, Jonathan D.; Bahr, Nathan C.; Vazquez-Benitez, Gabriela; Boulware, David R.; Sellman, Jonathan S.; Sarosi, George A.

    2016-01-01

    The diagnosis of blastomycosis is often delayed. We identified 28 cases of pulmonary blastomycosis in a retrospective chart review. Most patients received multiple antibiotic courses before being diagnosed, and the sputum KOH smear was rarely used. Diagnostic delay can be decreased with higher suspicion for pulmonary blastomycosis and early use of the sputum KOH smear. PMID:27419155

  13. Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation

    PubMed Central

    Tyurin, Vladimir A.; Kaynar, A. Murat; Kapralova, Valentyna I.; Wasserloos, Karla; Li, Jin; Mosher, Mackenzie; Wright, Lindsay; Wipf, Peter; Watkins, Simon; Pitt, Bruce R.; Kagan, Valerian E.

    2010-01-01

    Reactive oxygen species have been shown to play a significant role in hyperoxia-induced acute lung injury, in part, by inducing apoptosis of pulmonary endothelium. However, the signaling roles of phospholipid oxidation products in pulmonary endothelial apoptosis have not been studied. Using an oxidative lipidomics approach, we identified individual molecular species of phospholipids involved in the apoptosis-associated peroxidation process in a hyperoxic lung. C57BL/6 mice were killed 72 h after exposure to hyperoxia (100% oxygen). We found that hyperoxia-induced apoptosis (documented by activation of caspase-3 and -7 and histochemical terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of pulmonary endothelium) was accompanied by nonrandom oxidation of pulmonary lipids. Two anionic phospholipids, mitochondria-specific cardiolipin (CL) and extramitochondrial phosphatidylserine (PS), were the two major oxidized phospholipids in hyperoxic lung. Using electrospray ionization mass spectrometry, we identified several oxygenation products in CL and PS. Quantitative assessments revealed a significant decrease of CL and PS molecular species containing C18:2, C20:4, C22:5, and C22:6 fatty acids. Similarly, exposure of mouse pulmonary endothelial cells (MLEC) to hyperoxia (95% oxygen; 72 h) resulted in activation of caspase-3 and -7 and significantly decreased the content of CL molecular species containing C18:2 and C20:4 as well as PS molecular species containing C22:5 and C22:6. Oxygenated molecular species were found in the same two anionic phospholipids, CL and PS, in MLEC exposed to hyperoxia. Treatment of MLEC with a mitochondria-targeted radical scavenger, a conjugate of hemi-gramicidin S with nitroxide, XJB-5-131, resulted in significantly lower oxidation of both CL and PS and a decrease in hyperoxia-induced changes in caspase-3 and -7 activation. We speculate that cytochrome c driven oxidation of CL and PS is associated with the signaling

  14. Mitochondrial biogenesis in the pulmonary vasculature during inhalation lung injury and fibrosis

    EPA Science Inventory

    Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammatio...

  15. Acute myocardial infarction with concomitant pulmonary embolism as a result of patent foramen ovale.

    PubMed

    Hayıroğlu, Mert İlker; Bozbeyoğlu, Emrah; Akyüz, Şükrü; Yıldırımtürk, Özlem; Bozbay, Mehmet; Bakhshaliyev, Nijad; Renda, Emir; Gök, Gülay; Eren, Mehmet; Pehlivanoğlu, Seçkin

    2015-07-01

    Acute myocardial infarction (MI) and pulmonary embolism canal one lead to life-threatening conditions such as sudden cardiac death and congestive heart failure. We discuss a case of a 74-year-old man presented to the emergency department with acute dyspnea and chest pain. Acute anterior MI and pulmonary embolism concomitantly were diagnosed. Primary percutaneous coronary intervention performed because of preliminary acute anterior MI diagnosis. Transthoracic echocardiography was performed to determine further complications caused by acute MI because patient had a continuous tachycardia and dyspnea although hemodynamically stable. Transthoracic echocardiography revealed a thrombus that was stuck into the patent foramen ovale with parts in right and left atria. Anticoagulation therapy was started; neither fibrinolytic therapy nor operation was performed because of low survey expectations of the patient's recently diagnosed primary disease stage IV lung cancer. Patient was discharged on his 20th day with oral anticoagulation and antiagregant therapy.

  16. METAL-INDUCED LATE PULMONARY INJURY IS REDUCED BY OZONE (O3) COEXPOSURE

    EPA Science Inventory

    METAL-INDUCED LATE PULMONARY INJURY IS REDUCED BY OZONE (O3) COEXPOSURE. UP Kodavanti, MCJ Schladweiler, WP Watkinson, JP Nolan, PA Evansky, ER Lappi, G Ross, JH Richards, and DL Costa. NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC USA.
    Ambient ...

  17. EFFECTS OF METAL COMPONENTS IN CONCENTRATED AMBIENT AIR PARTICLES ON PULMONARY INJURY

    EPA Science Inventory

    EFFECTS OF METAL COMPONENTS IN CONCENTRATED AMBIENT AIR PARTICLES ON PULMONARY INJURY. Yuh-Chin Huang, Jackie Stonehuerner, Jackie Carter, Andrew J. Ghio, Robert B. Devlin. NHEERL, US EPA, RTP, NC.
    The mechanisms for cardiopulmonary morbidity associated with exposure to air po...

  18. Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injury

    EPA Science Inventory

    Evaluation of autophagy as a mechanism involved in air pollutant-induced pulmonary injuryHenriquez, A.1, Snow, S.2, Miller, D1.,Schladweiler, M.2 and Kodavanti, U2.1 Curriculum in Toxicology, UNC, Chapel Hill, NC. 2 EPHD/NHEERL, US EPA, RTP, Durham, NC. ...

  19. ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON?

    EPA Science Inventory

    ARE MACROPHAGES ACTIVATED AND INDUCE PULMONARY INJURY BY INTRACELLULARLY BIOAVAILABLE IRON? UP Kodavanti1, MCJ Schladweiler1, S Becker2, DL Costa1, P Mayer3, A Ziesenis3, WG Kreyling3, 1ETD, 2HSDivision, NHEERL, USEPA, Research Triangle Park, NC, USA, and 3GSF, Inhalation Biology...

  20. Acute kidney injury and ESRD management in austere environments.

    PubMed

    Raman, Gaurav; Perkins, Robert M; Jaar, Bernard G

    2012-05-01

    Current knowledge about managing acute kidney injury in disaster situations stems mostly from lessons learned while taking care of crush syndrome patients during major earthquakes. More recently, there has been a greater focus on emergency preparedness for ESRD management. Natural or man-made disasters create an "austere environment," wherein resources to administer standard of care are limited. Advance planning and timely coordinated intervention during disasters are paramount to administer effective therapies and save lives. This article reviews the presentation and management of disaster victims with acute kidney injury and those requiring renal replacement therapies. Major contributions of some key national and international organizations in the field of disaster nephrology are highlighted. The article intends to increase awareness about nephrology care of disaster victims, among nephrology and non-nephrology providers alike.

  1. Experimental Models of Transfusion-Related Acute Lung Injury (TRALI)

    PubMed Central

    Gilliss, Brian M.; Looney, Mark R.

    2010-01-01

    Transfusion-related acute lung injury (TRALI) is defined clinically as acute lung injury occurring within six hours of the transfusion of any blood product. It is the leading cause of transfusion-related death in the United States, but under-recognition and diagnostic uncertainty have limited clinical research to smaller case control studies. In this review we will discuss the contribution of experimental models to the understanding of TRALI pathophysiology and potential therapeutic approaches. Experimental models suggest that TRALI occurs when a host, with a primed immune system, is exposed to an activating agent such as anti-leukocyte antibody or a biologic response modifier such as lysophosphatidylcholines. Recent work has suggested a critical role for platelets in antibody-based experimental models and identified potential therapeutic strategies for TRALI. PMID:21134622

  2. [Current concept of TRALI (transfusion-related acute lung injury)].

    PubMed

    Iijima, Takehiko; Okazai, Hitoshi

    2007-11-01

    It is only 20 years since TRALI was clinically recognized. As it is gradually recognized among Japanese medical community, the number of cases reported is increasing gradually. In the past nine years (1997-2005), Japanese Red Cross confirmed 118 TRALI cases and 38 possible TRALI cases in Japan. Twelve TRALI cases among them occurred during or after anesthesia on the day of operation. Since acute lung injury is caused by multiple pathological factors, it is difficult to identify its main cause as transfusion. Therefore, TRALI has been underdiagnosed and underreported. Several mechanisms have been proposed. Although anti-HLA antibody, anti-HNA antibody, or other immunoreactive substances appear to be involved in developing TRALI, underlying conditions like systemic inflammation may be required for igniting TRALI Although TRALI developed in the operating theater seems to be a small fraction of whole TRALI cases, anesthesiologists should be aware of TRALI, and remember it as one of the causes of acute lung injury.

  3. Diagnostic Criteria for Acute Kidney Injury: Present and Future

    PubMed Central

    Kellum, John A.

    2015-01-01

    Synopsis Acute kidney injury in a clinical diagnosis guided by standard criteria based on changes in serum creatinine, urine output or both. Severity of acute kidney injury is determined by the magnitude of increase in serum creatinine or decrease in urine output. Patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease and worse outcomes. Both short- and long-term outcomes are worse when patients have some stage of AKI by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. New biomarkers for AKI may substantially aid in the risk assessment and evaluation of patients at risk for AKI. PMID:26410133

  4. Protective effect of magnolol-loaded polyketal microparticles on lipopolysaccharide-induced acute lung injury in rats.

    PubMed

    Tsai, Tsuimin; Kao, Chen-Yu; Chou, Chun-Liang; Liu, Lu-Chun; Chou, Tz-Chong

    2016-08-01

    Magnolol has shown inhibitory effects on NO production and TNF-alpha production in lipopolysaccharide (LPS)-activated macrophages and LPS-induced acute lung injury; however, the poor solubility of magnolol has hindered its clinical success. In this study, magnolol-loaded microparticles were prepared via single emulsion method from a polyketal polymer, termed PK3. The particle sizes of magnolol-loaded PK3 microparticle is 3.73 ± 0.41 μm, and was suitable for phagocytosis by macrophages and pulmonary drug delivery. PK3 microparticles exhibited excellent biocompatibility both in vitro and in vivo. More importantly, intratracheal delivery of these magnolol-loaded microparticles significantly reduced the lung inflammatory responses at low dosage of magnolol (0.5 mg/kg), and have great clinical potential in treating acute lung injury.

  5. Acute Pulmonary Edema in an Eclamptic Pregnant Patient: A Rare Case of Takotsubo Syndrome.

    PubMed

    Karamchandani, Kunal; Bortz, Brandon; Vaida, Sonia

    2016-09-23

    BACKGROUND Acute pulmonary edema in a pregnant patient is associated with significant morbidity and mortality. Takotsubo syndrome, or stress-induced cardiomyopathy, is a rare cause of acute pulmonary edema in a pregnant patient, especially prior to delivery of the fetus. CASE REPORT We describe a case of a pregnant patient who presented with acute pulmonary edema and eclampsia and was found to have Takotsubo syndrome. To the best of our knowledge, eclampsia as a precipitating factor for Takotsubo syndrome has not been described in literature. CONCLUSIONS Clinicians taking care of pregnant patients should be aware of the potential link between eclampsia and Takotsubo cardiomyopathy. Prompt correction of the precipitating cause along with supportive management as described is the key to a successful outcome.

  6. Acute Pulmonary Edema in an Eclamptic Pregnant Patient: A Rare Case of Takotsubo Syndrome

    PubMed Central

    Karamchandani, Kunal; Bortz, Brandon; Vaida, Sonia

    2016-01-01

    Patient: Female, 35 Final Diagnosis: Takotsubo cardiomyopathy Symptoms: Seizures Medication: — Clinical Procedure: Cesarean section Specialty: Critical Care Medicine Objective: Rare co-existance of disease or pathology Background: Acute pulmonary edema in a pregnant patient is associated with significant morbidity and mortality. Takotsubo syndrome, or stress-induced cardiomyopathy, is a rare cause of acute pulmonary edema in a pregnant patient, especially prior to delivery of the fetus. Case Report: We describe a case of a pregnant patient who presented with acute pulmonary edema and eclampsia and was found to have Takotsubo syndrome. To the best of our knowledge, eclampsia as a precipitating factor for Takotsubo syndrome has not been described in literature. Conclusions: Clinicians taking care of pregnant patients should be aware of the potential link between eclampsia and Takotsubo cardiomyopathy. Prompt correction of the precipitating cause along with supportive management as described is the key to a successful outcome. PMID:27658947

  7. Subclavian steal syndrome presenting as recurrent pulmonary oedema associated with acute left ventricular diastolic dysfunction.

    PubMed

    Mangialavori, Giuseppe; Ballo, Piercarlo; Michelagnoli, Stefano; Ercolini, Leonardo; Barbanti, Enrico; Passuello, Franco; Abbondanti, Alessandro; Consoli, Lorenzo; Chechi, Tania; Fibbi, Veronica; Nannini, Marco; Chiodi, Leandro; Zuppiroli, Alfredo

    2013-01-01

    Subclavian steal syndrome typically presents as angina in patients with internal mammary artery grafts. Atypical clinical presentations have been rarely described. We report an unusual case of subclavian steal syndrome presenting as pulmonary oedema with acute left ventricular diastolic dysfunction and preserved ejection fraction in a patient with internal mammary artery graft and severe stenosis of the proximal left subclavian artery. After successful angioplasty and stenting of subclavian artery, the patient remained asymptomatic for six months, but then experienced acute diastolic dysfunction and recurrent pulmonary oedema associated with critical subclavian in-stent restenosis with stent deformation. This report points out that, in patients with internal mammary-to-LAD grafts, subclavian steal syndrome may present as acute left ventricular diastolic dysfunction and pulmonary oedema even in the presence of normal ejection fraction.

  8. Acute vasoreactivity test results in severe pulmonary hypertension patients with chronic obstructive pulmonary disease: our experience with 29 cases

    PubMed Central

    Asker, Selvi; Asker, Muntecep

    2015-01-01

    Aim The aim of the current study is to evaluate acute vasoreactivity test (AVT) results in severe pulmonary hypertension patients with chronic obstructive pulmonary disease and to compare the demographical, clinical, and laboratory variables in positive and negative cases. Methods This retrospective, clinical study was performed on 29 cases in the departments of cardiology and chest diseases of our tertiary care center. AVT was positive in 12 (41.4%) cases and negative in 17 (58.6%) cases. Demographical variables, cardiopulmonary indicators, and laboratory findings were compared in these two subgroups. Results The mean age was 62.3±7.8 years for AVT negative group, while it was 64.8±7.3 years in AVT positive group (P=0.38). Except for the changes in systolic, diastolic, and mean pulmonary arterial pressures before and after iloprost administration, there were no statistically significant differences regarding any of the parameters under investigation in both groups. Conclusion Despite the high rate of positivity for AVT in severe pulmonary hypertension patients with chronic obstructive pulmonary disease, none of the variables under investigation displayed a noteworthy difference between AVT negative and positive groups. Identification of factors likely to influence AVT results is important for establishment of appropriate treatment protocols especially for AVT negative cases. PMID:26064044

  9. Suramin protects from cisplatin-induced acute kidney injury.

    PubMed

    Dupre, Tess V; Doll, Mark A; Shah, Parag P; Sharp, Cierra N; Kiefer, Alex; Scherzer, Michael T; Saurabh, Kumar; Saforo, Doug; Siow, Deanna; Casson, Lavona; Arteel, Gavin E; Jenson, Alfred Bennett; Megyesi, Judit; Schnellmann, Rick G; Beverly, Levi J; Siskind, Leah J

    2016-02-01

    Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatin-induced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer.

  10. Acute kidney injury requiring haemodialysis following ingestion of mephedrone

    PubMed Central

    Rhidian, Rhys; Babu, Adarsh

    2013-01-01

    A 25-year-old man was found to have acute kidney injury (AKI) following ingestion of mephedrone. He presented to this local emergency department with worsening bilateral loin pain. He became oligoanuric, serum creatine peaked at 1214 µmol/l and he required several sessions of haemodialysis before kidney function began to improve. The mechanism of AKI and legal aspects of the use of mephedrone are discussed. PMID:23456157

  11. Transfusion related acute lung injury (TRALI): a review.

    PubMed

    Menitove, Jay E

    2007-01-01

    Transfusion Related Acute Lung Injury, or TRALI, denotes the most frequently reported fatal complication of blood transfusion. TRALI accounted for 34% of transfusion associated mortalities reported to the Food and Drug Administration (FDA) in 2005. TRALI caused more deaths than those attributed to hemolytic reactions following incorrect blood administration or sepsis resulting from bacterial contamination of platelet and red cell components. (Holness, Leslie. Food and Drug Administration. Personal Communication, 2006) This paper reviews TRALI for the clinical physician.

  12. Presumptive acute lung injury following multiple surgeries in a cat.

    PubMed

    Katayama, Masaaki; Okamura, Yasuhiko; Katayama, Rieko; Sasaki, Jun; Shimamura, Shunsuke; Uzuka, Yuji; Kamishina, Hiroaki; Nezu, Yoshinori

    2013-04-01

    A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass identified as malignant B-cell lymphoma. The cat had tracheal resection and subsequently developed laryngeal paralysis. Due to multiple episodes of respiratory distress the cat subsequently had tracheal surgeries. Finally, the cat had a sudden onset of severe respiratory distress and collapsed. Computed tomography imaging and arterial blood gas analysis supported a diagnosis of acute lung injury.

  13. Acetaminophen-induced acute liver injury in HCV transgenic mice

    SciTech Connect

    Uehara, Takeki; Kosyk, Oksana; Jeannot, Emmanuelle; Bradford, Blair U.; Tech, Katherine; Macdonald, Jeffrey M.; Boorman, Gary A.; Chatterjee, Saurabh; Mason, Ronald P.; Melnyk, Stepan B.; Tryndyak, Volodymyr P.; Pogribny, Igor P.; Rusyn, Ivan

    2013-01-15

    The exact etiology of clinical cases of acute liver failure is difficult to ascertain and it is likely that various co-morbidity factors play a role. For example, epidemiological evidence suggests that coexistent hepatitis C virus (HCV) infection increased the risk of acetaminophen-induced acute liver injury, and was associated with an increased risk of progression to acute liver failure. However, little is known about possible mechanisms of enhanced acetaminophen hepatotoxicity in HCV-infected subjects. In this study, we tested a hypothesis that HCV-Tg mice may be more susceptible to acetaminophen hepatotoxicity, and also evaluated the mechanisms of acetaminophen-induced liver damage in wild type and HCV-Tg mice expressing core, E1 and E2 proteins. Male mice were treated with a single dose of acetaminophen (300 or 500 mg/kg in fed animals; or 200 mg/kg in fasted animals; i.g.) and liver and serum endpoints were evaluated at 4 and 24 h after dosing. Our results suggest that in fed mice, liver toxicity in HCV-Tg mice is not markedly exaggerated as compared to the wild-type mice. In fasted mice, greater liver injury was observed in HCV-Tg mice. In fed mice dosed with 300 mg/kg acetaminophen, we observed that liver mitochondria in HCV-Tg mice exhibited signs of dysfunction showing the potential mechanism for increased susceptibility. -- Highlights: ► Acetaminophen-induced liver injury is a significant clinical challenge. ► HCV-infected subjects may be at higher risk for acetaminophen-induced liver injury. ► We used HCV transgenics to test if liver injury due to acetaminophen is exacerbated.

  14. Assessment of heat shock proteins and endothelial dysfunction in acute pulmonary embolism.

    PubMed

    İn, Erdal; Deveci, Figen; Kaman, Dilara

    2016-06-01

    We determined the levels of some heat shock proteins (HSP27, HSP70, and HSP90), L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) levels in patients with acute pulmonary embolism. The present case-control study comprised a healthy control group (n = 57) and patients with acute pulmonary embolism (n = 84). HSPs, L-arginine, ADMA, and SDMA levels were measured in all of the cases. The mean age of the control group was 56.72 ± 8.44 years, and the mean age of the patients with acute pulmonary embolism was 60.20 ± 16.56 years (P = 0.104). Compared with controls, patients with acute pulmonary embolism had significantly higher mean serum HSP27, HSP90, and ADMA levels, whereas the mean serum L-arginine and SDMA levels were lower (P < 0.001, for all parameters). In patients with acute pulmonary embolism serum HSP27, HSP70, and ADMA levels were negatively correlated with partial pressures of arterial oxygen levels (r = -0.281, P = 0.01; r = -0.263, P = 0.016; and r = -0.275, P = 0.011, respectively) and arterial oxygen saturation (r = -0.225, P = 0.039; r = -0.400, P < 0.001; r = -0.299, P = 0.006, respectively). The findings of the present study demonstrated that oxidative stress and endothelial damage increase in acute pulmonary embolism.

  15. Recurrent acute pulmonary oedema after aortic and mitral valve surgery due to trachea malacia and obstructive sleep apnoea syndrome

    PubMed Central

    Sankatsing, S.U.C.; Hanselaar, W.E.J.J.; van Steenwijk, R.P.; van der Sloot, J.A.P.; Broekhuis, E.; Kok, W.E.M.

    2008-01-01

    In this report we describe a patient with recurrent episodes of acute pulmonary oedema after aortic and mitral valve surgery. The first episode of pulmonary oedema was caused by mitral valve dysfunction. The second episode of pulmonary oedema was not clearly associated with a mitral valve problem, but reoperation was performed in the absence of another explanation. After the third episode of acute pulmonary oedema occurred, the diagnosis of obstructive sleep apnoea syndrome (OSAS) was considered and confirmed. After starting treatment with continuous positive airway pressure (CPAP) during his sleep the patient had no further episodes of acute respiratory failure. Our case demonstrates that acute pulmonary oedema after cardiothoracic surgery can be caused or at least be precipitated by OSAS and should be suspected in patients with unexplained episodes of (recurrent) pulmonary oedema. (Neth Heart J 2008;16:310-2.) PMID:18827875

  16. Limiting the use of routine radiography for acute ankle injuries.

    PubMed Central

    Cockshott, W. P.; Jenkin, J. K.; Pui, M.

    1983-01-01

    In the diagnosis of ankle injuries routine radiography is often productive. An international survey of the average number of radiographs made of injured ankles suggested that two projections are adequate to detect fractures. This was confirmed in a prospective study of 242 patients coming to a hospital emergency department with recent ankle injuries. All the fractures could be identified on an anteroposterior or a lateral projection, although some were more obvious on an oblique view. As well, all the fractures were associated with malleolar soft-tissue swelling. Thus, radiography for acute ankle injuries could safely be restricted to patients with soft-tissue swelling, and fractures could be diagnosed using only two routine projections, though for management purposes additional projections might be needed. With a policy of limiting the use of radiography substantial cost reductions are possible. Images FIG. 1 PMID:6407744

  17. Autophagy in Acute Brain Injury: Feast, Famine, or Folly?

    PubMed Central

    Smith, Craig M.; Chen, Yaming; Sullivan, Mara L.; Kochanek, Patrick M.; Clark, Robert S. B.

    2010-01-01

    In the central nervous system, increased autophagy has now been reported after traumatic brain and spinal cord injury, cerebral ischemia, intracerebral hemorrhage, and seizures. This increase in autophagy could be physiologic, converting damaged or dysfunctional proteins, lipids and/or organelles to their amino acid and fatty acid components for recycling. On the other hand, this increase in autophagy could be supraphysiologic, perhaps consuming and eliminating functional proteins, lipids and/or organelles as well. Whether an increase in autophagy is beneficial (feast) or detrimental (famine) in brain likely depends on both the burden of intracellular substrate targeted for autophagy and the capacity of the cell’s autophagic machinery. Of course, increased autophagy observed after brain injury could also simply be an epiphenomenon (folly). These divergent possibilities have clear ramifications for designing therapeutic strategies targeting autophagy after acute brain injury, and are the subject of this review. PMID:20883784

  18. Intrafacility transportation of patients with acute brain injury.

    PubMed

    Tu, Hsinfen

    2014-06-01

    Patients with acute brain injury (ABI) frequently require diagnostic and therapeutic procedures in the areas located outside of the intensive care unit. Transports can be risky for critically ill patients with ABI. Secondary brain injury can occur during the transport from causes such as ischemia, hypotension, hypoxia, hypercapnia, and cerebral edema. Preparation and implementation of preventive procedures including pretransport assessment, monitoring during transport, and posttransport examination and documentation for transports of patients with ABI deem to be necessary. The purpose of this article is to review the typical risks associated with the transports of the patients with ABI out of the intensive care unit and to propose the strategies that can be used to minimize the risks of secondary brain injury.

  19. Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury

    PubMed Central

    Long, Yanjun; Zhen, Xin; Zhu, Fengxin; Hu, Zheng; Lei, Wenjing; Li, Shuang; Zha, Yan; Nie, Jing

    2017-01-01

    Hyperhomocysteinemia (HHcy) has been linked to several clinical manifestations including chronic kidney disease. However, it is not known whether HHcy has a role in the development of acute kidney injury (AKI). In the present study, we reported that HHcy mice developed more severe renal injury after cisplatin injection and ischemia-reperfusion injury shown as more severe renal tubular damage and higher serum creatinine. In response to cisplatin, HHcy mice showed more prevalent tubular cell apoptosis and decreased tubular cell proliferation. Mechanistically, a heightened ER stress and a reduced Akt activity were observed in kidney tissues of HHcy mice after cisplatin injection. Stimulating cultured NRK-52E cells with Hcy significantly increased the fraction of cells in G2/M phase and cell apoptosis together with decreased Akt kinase activity. Akt agonist IGF-1 rescued HHcy-induced cell cycle arrest and cell apoptosis. In conclusion, the present study provides evidence that HHcy increases the sensitivity and severity of AKI. PMID:28255274

  20. Transfusion Related Acute Lung Injury after Cesarean Section in a Patient with HELLP Syndrome

    PubMed Central

    Moon, Kyoung Min; Rim, Ch'ang Bum; Kim, So Ri; Shin, Sang Ho; Kang, Min Seok; Lee, Jun Ho; Kim, Jihye; Kim, Sang Il

    2016-01-01

    Transfusion-related acute lung injury (TRALI) is a serious adverse reaction of transfusion, and presents as hypoxemia and non-cardiogenic pulmonary edema within 6 hours of transfusion. A 14-year-old primigravida woman at 34 weeks of gestation presented with upper abdominal pain without dyspnea. Because she showed the syndrome of HELLP (hemolysis, elevated liver enzymes, and low platelet count), an emergency cesarean section delivery was performed, and blood was transfused. In the case of such patients, clinicians should closely observe the patient's condition at least during the 6 hours while the patient receives blood transfusion, and should suspect TRALI if the patient complains of respiratory symptoms such as dyspnea. Furthermore, echocardiography should be performed to distinguish between the different types of transfusion-related adverse reactions. PMID:26885326

  1. Mesenteric lymph duct drainage attenuates acute lung injury in rats with severe intraperitoneal infection.

    PubMed

    Zhang, Yanmin; Zhang, Shukun; Tsui, Naiqiang

    2015-01-01

    The purpose of this study is to investigate the hypothesis that the mesenteric lymphatic system plays an important role in acute lung injury in a rat model induced by severe intraperitoneal infection. Male Wistar rats weighing 250∼300 g were randomly divided into 3 groups and subjected to sham operation, intraperitoneal infection, or mesenteric lymphatic drainage. The activity of diamine oxidase (DAO) and myeloperoxidase (MPO) were measured by enzymatic assay. The endotoxin levels in plasma, lymph, and bronchoalveolar lavage fluid (BALF) were evaluated using the limulus amoebocyte lysate reagent. The cytokines, adhesion factors, chemokines, and inflammatory factors were detected by ELISA. TLR-4, NF-kB, and IRAK-4 were analyzed by Western blotting. Compared with sham-operated rats, rats with intraperitoneal infection had increased MPO and decreased DAO activity in intestinal tissues. Mesenteric lymph drainage reduced the alterations in MPO and DAO activity induced by intraperitoneal infection. The MPO activity in pulmonary tissue and the permeability of pulmonary blood vessels were also increased, which were partially reversed by mesenteric lymph drainage. The endotoxin levels in lymphatic fluid and alveolar perfusion fluid were elevated after intraperitoneal infection but decreased to control levels after lymph drainage. No alterations in the levels of plasma endotoxin were observed. The number of neutrophils was increased in BALF and lymph in the infected rats, and was also reduced after drainage. Lymph drainage also decreased the levels of inflammatory cytokines, chemokines, and adhesion factors in the plasma, lymph, and BALF, as well as the levels of TLR-4, NF-kB, and IRAK-4 in pulmonary and intestinal tissues. The mesenteric lymphatic system is the main pathway involved in early lung injury caused by severe intraperitoneal infection, in which activation of the TLR-4 signal pathway may play a role.

  2. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  3. Free fat interpositional graft in acute physeal injuries: the anticipatory Langenskiöld procedure.

    PubMed

    Foster, B K; John, B; Hasler, C

    2000-01-01

    Free fat graft interposition has been used extensively in management of physeal injuries with established growth disturbances. The use of this technique as part of the management of acute physeal injuries has not been reported. Here we report on its application in acute physeal injuries, where it has prevented the formation of an anticipated physeal arrest.

  4. Therapeutic Dilemmas Regarding Anticoagulation: An Experience in a Patient with Nephrotic Syndrome, Pulmonary Embolism, and Traumatic Brain Injury

    PubMed Central

    Akimoto, Tetsu; Yamazaki, Tomoyuki; Kusano, Eiji; Nagata, Daisuke

    2016-01-01

    Patients with active bleeding complications who concomitantly develop overt pulmonary embolism (PE) present distinct therapeutic dilemmas, since they are perceived to be at substantial risk for the progression of the embolism in the absence of treatment and for aggravation of the hemorrhagic lesions if treated with anticoagulants. A 76-year-old patient with nephrotic syndrome, which is associated with an increased risk of thromboembolism, concurrently developed acute PE and intracranial bleeding because of traumatic brain injury. In this case, we prioritized the treatment for PE with the intravenous unfractionated heparin followed by warfarinization. Despite the transient hemorrhagic progression of the brain contusion after the institution of anticoagulation, our patient recovered favorably from the disease without any signs of neurological compromise. Several conundrums regarding anticoagulation that emerged in this case are also discussed. PMID:27840582

  5. Melatonin alleviates acute lung injury through inhibiting the NLRP3 inflammasome.

    PubMed

    Zhang, Yong; Li, Xiru; Grailer, Jamison J; Wang, Na; Wang, Mingming; Yao, Jianfei; Zhong, Rui; Gao, George F; Ward, Peter A; Tan, Dun-Xian; Li, Xiangdong

    2016-05-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are clinically severe respiratory disorders, and there are currently no Food and Drug Administration-approved drug therapies. Melatonin is a well-known anti-inflammatory molecule, which has proven to be effective in ALI induced by many conditions. Emerging studies suggest that the NLRP3 inflammasome plays a critical role during ALI. How melatonin directly blocks activation of the NLRP3 inflammasome in ALI remains unclear. In this study, using an LPS-induced ALI mouse model, we found intratracheal (i.t.) administration of melatonin markedly reduced the pulmonary injury and decreased the infiltration of macrophages and neutrophils into lung. During ALI, the NLRP3 inflammasome is significantly activated with a large amount of IL-1β and the activated caspase-1 occurring in the lung. Melatonin inhibits the activation of the NLRP3 inflammasome by both suppressing the release of extracellular histones and directly blocking histone-induced NLRP3 inflammasome activation. Notably, i.t. route of melatonin administration opens a more efficient therapeutic approach for treating ALI.

  6. In vivo microscopy in a porcine model of acute lung injury.

    PubMed

    Bickenbach, Johannes; Czaplik, Michael; Dembinski, Rolf; Pelosi, Paolo; Schroeder, Wolfgang; Marx, Gernot; Rossaint, Rolf

    2010-07-31

    Regional inhomogeneity and alveolar mechanics in a porcine model of acute lung injury (ALI) was evaluated using confocal laser scanning microscopy (CLSM). CLSM was performed through thoracic windows of the upper and lower lobes. Image quantification was conducted by use of a volume air index (VAI). Twelve anesthetized, mechanically ventilated pigs were randomized to non-injury (control group, n = 6) or ALI induced by surfactant depletion (ALI group, n = 6). CLSM was performed at baseline, after 1 h at 5 mbar and after 2 h at 15 mbar positive end-expiratory pressure (PEEP). Haemodynamics, respiratory mechanics and calculation of pulmonary ventilation-perfusion distribution by MIGET were determined. At baseline, VAI was not different. In the upper lobes, VAI significantly decreased in ALI compared to control group, with no changes after PEEP application. In the lower lobes, VAI significantly decreased in ALI compared to control group. Incremental PEEP significantly increased VAI in ALI, but not in control group. Haemodynamics were significantly compromised in the ALI group. A significant deterioration in oxygenation and ventilation-perfusion distribution could be seen being restored after PEEP adjustment. The VAI may help to assess regional inhomogeneity of the acutely injured lung.

  7. Transfusion-related acute lung injury (TRALI) in graft by blood donor antibodies against host leukocytes.

    PubMed

    Goodwin, Jodi; Tinckam, Kathryn; denHollander, Neal; Haroon, Ayesha; Keshavjee, Shaf; Cserti-Gazdewich, Christine M

    2010-09-01

    It is unknown the extent to which transfusion-related acute lung injury (TRALI) contributes to primary graft dysfunction (PGD), the leading cause of death after lung transplantation. In this case of suspected transfusion-associated acute bilateral graft injury in a 61-year-old idiopathic pulmonary fibrosis patient, recipient sera from before and after transplantation/transfusion, as well as the sera of 22 of the 24 implicated blood donors, were individually screened by Luminex bead assay for the presence of human leukocyte antigen (HLA) antibodies, with recipient and lung donor HLA typing to explore for cognate relationships. A red-cell-unit donor-source anti-Cw6 antibody, cognate with the HLA type of the recipient, was identified. This is the second reported case of TRALI in the setting of lung transplantation, and the first to show an associated interaction between donor antibodies (in a low-plasma volume product) with recipient leukocytes (rather than graft antigens); therefore, it should be considered in the differential diagnosis of PGD.

  8. Impact of fish oils on the outcomes of a mouse model of acute Pseudomonas aeruginosa pulmonary infection.

    PubMed

    Caron, Emilie; Desseyn, Jean-Luc; Sergent, Luce; Bartke, Nana; Husson, Marie-Odile; Duhamel, Alain; Gottrand, Frédéric

    2015-01-28

    Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that causes pneumonia in immunocompromised humans and severe pulmonary damage in patients with cystic fibrosis. Imbalanced fatty acid incorporation in membranes, including increased arachidonic acid and decreased DHA concentrations, is known to play a critical role in chronic inflammation associated with bacterial infection. Other lipids, such as EPA and alkylglycerols, are also known to play a role in inflammation, particularly by stimulating the immune system, decreasing inflammation and inhibiting bacterial growth. In this context, the goal of the present study was to assess the effect of dietary DHA/EPA, in a 2:1 ratio, and alkylglycerols, as natural compounds extracted from oils of rays and chimeras, respectively, on the inflammatory reaction induced by P. aeruginosa pulmonary infection in mice. To this end, mice were fed with a control diet or isolipidic, isoenergetic diets prepared with oils enriched in DHA/EPA (2:1) or alkylglycerols for 5 weeks before the induction of acute P. aeruginosa lung infection by endotracheal instillation. In our model, DHA/EPA (2:1) significantly improved the survival of mice after infection, which was associated with the acceleration of bacterial clearance and the resolution of inflammation leading to the improvement of pulmonary injuries. By contrast, alkylglycerols did not affect the outcomes of P. aeruginosa infection. Our findings suggest that supplementation with ray oil enriched in DHA/EPA (2:1) can be considered as a preventive treatment for patients at risk for P. aeruginosa infection.

  9. Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

    PubMed Central

    Jang, Tae Young; Jung, Ah-Yeoun; Kim, Young Hyo

    2016-01-01

    Objectives Antiorthostatic suspension (AOS) is ground-based model of simulated microgravity. There is still no study about the effect of long-term microgravity on the clinical course of acute lung injury. We evaluated the effect of simulated microgravity using AOS in a murine model of acute lung injury by lipopolysaccharide (LPS). Methods Thirty BALB/c mice were used. During 4 weeks, mice were equally allocated to control (free movement), restraint (tail suspended, but hindlimbs not unloaded), and AOS group (hindlimb unloaded). After then, mice got intranasal challenge with LPS (20 mg/kg, 50 μL). We measured: weight gain before and after AOS, the number of inflammatory cells and titers of cytokines (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) in bronchoalveolar lavage (BAL) fluid, titer of myeloperoxidase (MPO) in serum and lung homogenate, and histopathologic examination of lung tissue. Results AOS group had significant weight loss compared to control and restraint group (P<0.001). AOS group also showed significantly decreased lymphocytes (P=0.023) compared to control group. In AOS group, titer for IL-1β in BAL fluid was significantly lower than restraint group (P=0.049). Titer for serum MPO was significantly decreased in AOS group compared to restraint group (P=0.004). However, there was no significant difference of MPO titers in lung tissue between groups. Histopathologic examination of lung tissue revealed no significant difference in the degree of pulmonary infiltration between restraint and AOS group. Conclusion In spite of modest anti-inflammatory effect, prolonged AOS caused no significant change in LPS-induced pulmonary inflammation. PMID:27334509

  10. Acute Inhalation Exposure to Vaporized Methamphetamine Causes Lung Injury in Mice

    PubMed Central

    Wells, Sandra M.; Buford, Mary C.; Braseth, Sarah N.; Hutchison, James D.; Holian, Andrij

    2009-01-01

    Methamphetamine (MA) is currently the most widespread illegally used stimulant in the United States. Use of MA by smoking is the fastest growing mode of administration, which increases concerns about potential pulmonary and other medical complications. A murine exposure system was developed to study the pulmonary affects of inhaled MA. Mice were exposed to 25–100 mg vaporized MA and assessments were made 3 h following initiation of exposure to model acute lung injury. Inhalation of MA vapor resulted in dose-dependent increases in MA plasma levels that were in the range of those experienced by MA users. At the highest MA dose, histological changes were observed in the lung and small but significant increases in lung wet weight to body weight ratios (5.656 ± 0.176 mg/g for the controls vs. 6.706± 0.135 mg/g for the 100 mg MA-exposed mice) were found. In addition, there was 53% increase in total protein in bronchoalveolar lavage (BAL) fluid, greater than 20% increase in albumin levels in the BAL fluid, greater than 2.5-fold increase in lactate dehydrogenase levels in the BAL fluid, and reduced total BAL cell numbers (approximately 77% of controls). Levels of the early response cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 were dose-dependently increased in BAL fluid of MA-exposed mice. Exposure to 100 mg MA significantly increased free radical generation in the BAL cells to 107–146% of controls and to approximately 135% of the controls in lung tissue in situ. Together, these data show that acute inhalation exposure to relevant doses of volatilized MA is associated with elevated free radical formation and significant lung injury. PMID:18645723

  11. The role of leukocytes in the pathogenesis of fibrin deposition in bovine acute lung injury.

    PubMed Central

    Car, B. D.; Suyemoto, M. M.; Neilsen, N. R.; Slauson, D. O.

    1991-01-01

    The peculiarly fibrinous nature of bovine acute lung injury due to infection with Pasteurella haemolytica A1 suggests an imbalance between leukocyte-directed procoagulant and profibrinolytic influences in the inflamed bovine lung. Calves with experimental pneumonia produced by intratracheal inoculation with P. haemolytica A1 developed acute locally extensive cranioventral fibrinopurulent bronchopneumonia. Pulmonary alveolar macrophages (PAM) recovered by segmental lavage from affected lung lobes were 30 times more procoagulant than PAM obtained from unaffected lung lobes and 37-fold more procoagulant than PAM from control calf lungs. Unlike the enhancement of procoagulant activity, profibrinolytic activity (plasminogen activator amidolysis) of total lung leukocytes (PAM and plasminogen activator neutrophils [PMN]) was decreased 23 times in cells obtained from affected lung lobes and also was decreased four times in cells obtained from unaffected lobes of infected animals. This marked imbalance in cellular procoagulant and fibrinolytic activity probably contributes significantly to enhanced fibrin deposition and retarded fibrin removal. In addition, PAM from inflamed lungs were strongly positive for bovine tissue factor antigen as demonstrated by immunocytochemistry. Intensely tissue factor-positive PAM enmeshed in fibrinocellular exudates and positive alveolar walls were situated such that they were likely to have, in concert, initiated extrinsic activation of coagulation in the acutely inflamed lung. These data collectively suggest that enhanced PAM-directed procoagulant activity and diminished PAM- and PMN-directed profibrinolytic activity represent important modifications of local leukocyte function in bovine acute lung injury that are central to the pathogenesis of lesion development with extensive fibrin deposition and retarded fibrin removal. Images Figure 2 Figure 3 PMID:2024707

  12. Review article: lack of effect of opiates in the treatment of acute cardiogenic pulmonary oedema.

    PubMed

    Sosnowski, Marcin A

    2008-10-01

    Opiates have traditionally been used as one of the main treatments of acute heart failure and are still recognized as such. Most current textbooks and official guidelines advise the use of morphine as one of the first-line treatments for patients in acute cardiogenic pulmonary oedema and a majority of physicians accept it to be the case. The author performed an extensive literature search in order to validate the evidence for the use of opiates in this condition. A total of seven papers, six in English and one in Polish, were found that directly investigated or reported the clinically important outcomes of treatment of acute pulmonary oedema. Only five of these dealt specifically with the effects of administration of opiates in acute cardiogenic pulmonary oedema. None of the above publications suggested a clinically significant improvement in outcomes of patients treated with morphine, although early research did suggest reduced anxiety, blood pressure and pulse rate as well as a reduction in arterial oxygen contents. The more recent studies suggest a strong association between increased mortality and morbidity (e.g. intensive care unit admissions or intubation rates), although causality is difficult to establish because of research methodologies. The current evidence does not support the routine use of opiates in the treatment of acute pulmonary oedema.

  13. Acute ozone-induced lung injury in rats: Structural-functional relationships of developing alveolar edema

    SciTech Connect

    Paterson, J.F.; Hammond, M.D.; Montgomery, M.R.; Sharp, J.T.; Farrier, S.E.; Balis, J.U. )

    1992-11-01

    As part of a study on the effects of acute ozone stress on the lung surfactant system, we correlated morphometric, biochemical, and functional indices of lung injury using male rats exposed to 3 ppm ozone for 1, 2, 4, and 8 hr. Evaluation of lung mechanics, using the Pulmonary Evaluation and Diagnostic Laboratory System, revealed a significant decrease in dynamic lung compliance (ml/cmH[sub 2]O/kg) from a control value of 0.84 [plus minus] 0.02 (SEM) to 0.72 [plus minus] 0.04 and 0.57 [plus minus] 0.06 at 4 and 8 hr, respectively. At 2 hr there was a transient increase in PaO[sub 2] to 116 torr (control = 92 torr) followed by a decrease at 4 hr (65 torr) and 8 hr (55 torr). Morphometry of lung tissue, fixed by perfusion of fixative via the pulmonary artery at 12 cm H[sub 2]O airway distending pressure, demonstrated an increase in the area of the intravascular compartment at 8 hr, in association with a 65 and 39% replacement of the alveolar area by fluid in ventral and dorsal lung regions, respectively. There was a positive correlation (r = 0.966) between alveolar edema and transudated proteins in lavage fluid. A stepwise multiple regression model, with edema as the dependent variable, suggested that pulmonary vasodilatation, hypoxemia, and depletion of surfactant tubular myelin in lavage fluid were indices for predicting alveolar edema. In a second model, with lavage protein concentration as the dependent variable, decreasing dynamic compliance and hypoxemia were predictors of progressive, intraalveolar transudation of plasma proteins. The above structural-functional relationships support the concept that ozone-induced high-protein alveolar edema is pathogenetically linked to pulmonary hyperemia, deficiency of surfactant tubular myelin, and associated lung dysfunctions.

  14. Pioglitazone-induced Pulmonary Injury in a Very Elderly Patient.

    PubMed

    Katayama, Kohta; Kumagai, Ryo; Isono, Momoko; Fujihara, Kazuya; Yagyu, Hiroaki; Ohara, Gen; Kagohashi, Katsunori; Satoh, Hiroaki

    2016-01-01

    An 85-year-old woman with diabetes mellitus was admitted to our hospital due to progressive dyspnea. Two months previously, pioglitazone had been newly prescribed for diabetes management. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a drug-induced lung injury. With discontinuation of pioglitazone and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in some areas of the lungs. Results of drug-induced lymphocyte stimulation tests were positive for pioglitazone. Resumption of other drugs did not reinduce the lung injury. Therefore, a diagnosis of pioglitazone-induced lung injury was made. Although pioglitazone-induced lung injury is very rare, clinicians should keep it in mind when pioglitazone is used.

  15. Inflammation-associated repression of vasodilator-stimulated phosphoprotein (VASP) reduces alveolar-capillary barrier function during acute lung injury

    PubMed Central

    Henes, Janek; Schmit, Marthe A.; Morote-Garcia, Julio C.; Mirakaj, Valbona; Köhler, David; Glover, Louise; Eldh, Therese; Walter, Ulrich; Karhausen, Jörn; Colgan, Sean P.; Rosenberger, Peter

    2009-01-01

    Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function, increased pulmonary vascular permeability, and infiltration of leukocytes into the alveolar space. Pulmonary function might be compromised, its most severe form being the acute respiratory distress syndrome. A protein central to physiological barrier properties is vasodilator-stimulated phosphoprotein (VASP). Given the fact that VASP expression is reduced during periods of cellular hypoxia, we investigated the role of VASP during ALI. Initial studies revealed reduced VASP expressional levels through cytokines in vitro. Studies in the putative human VASP promoter identified NF-κB as a key regulator of VASP transcription. This VASP repression results in increased paracellular permeability and migration of neutrophils in vitro. In a model of LPS-induced ALI, VASP−/− mice demonstrated increased pulmonary damage compared with wild-type animals. These findings were confirmed in a second model of ventilator-induced lung injury. Studies employing bone marrow chimeric animals identified tissue-specific repression of VASP as the underlying cause of decreased barrier properties of the alveolar-capillary barrier during ALI. Taken together these studies identify tissue-specific VASP as a central protein in the control of the alveolar-capillary barrier properties during ALI.—Henes, J., Schmit, M. A., Morote-Garcia, J. C., Mirakaj, V., Köhler, D., Glover, L., Eldh, T., Walter, U., Karhausen, J., Colgan, S. P., Rosenberger, P. Inflammation-associated repression of vasodilator-stimulated phosphoprotein (VASP) reduces alveolar-capillary barrier function during acute lung injury. PMID:19690214

  16. Cytochrome b5 and cytokeratin 17 are biomarkers in bronchoalveolar fluid signifying onset of acute lung injury.

    PubMed

    Ménoret, Antoine; Kumar, Sanjeev; Vella, Anthony T

    2012-01-01

    Acute lung injury (ALI) is characterized by pulmonary edema and acute inflammation leading to pulmonary dysfunction and potentially death. Early medical intervention may ameliorate the severity of ALI, but unfortunately, there are no reliable biomarkers for early diagnosis. We screened for biomarkers in a mouse model of ALI. In this model, inhalation of S. aureus enterotoxin A causes increased capillary permeability, cell damage, and increase protein and cytokine concentration in the lungs. We set out to find predictive biomarkers of ALI in bronchoalveolar lavage (BAL) fluid before the onset of clinical manifestations. A cutting edge proteomic approach was used to compare BAL fluid harvested 16 h post S. aureus enterotoxin A inhalation versus BAL fluid from vehicle alone treated mice. The proteomic PF 2D platform permitted comparative analysis of proteomic maps and mass spectrometry identified cytochrome b5 and cytokeratin 17 in BAL fluid of mice challenged with S. aureus enterotoxin A. Validation of cytochrome b5 showed tropic expression in epithelial cells of the bronchioles. Importantly, S. aureus enterotoxin A inhalation significantly decreased cytochrome b5 during the onset of lung injury. Validation of cytokeratin 17 showed ubiquitous expression in lung tissue and increased presence in BAL fluid after S. aureus enterotoxin A inhalation. Therefore, these new biomarkers may be predictive of ALI onset in patients and could provide insight regarding the basis of lung injury and inflammation.

  17. The role of iron in Libby amphibole-induced acute lung injury and inflammation.

    PubMed

    Shannahan, Jonathan H; Ghio, Andrew J; Schladweiler, Mette C; McGee, John K; Richards, Judy H; Gavett, Stephen H; Kodavanti, Urmila P

    2011-05-01

    Complexation of host iron (Fe) on the surface of inhaled asbestos fibers has been postulated to cause oxidative stress contributing to in vivo pulmonary injury and inflammation. We examined the role of Fe in Libby amphibole (LA; mean length 4.99 µm ± 4.53 and width 0.28 µm ± 0.19) asbestos-induced inflammogenic effects in vitro and in vivo. LA contained acid-leachable Fe and silicon. In a cell-free media containing FeCl(3), LA bound #17 µg of Fe/mg of fiber and increased reactive oxygen species generation #3.5 fold, which was reduced by deferoxamine (DEF) treatment. In BEAS-2B cells exposure to LA, LA loaded with Fe (FeLA), or LA with DEF did not increase HO-1 or ferritin mRNA expression. LA increased IL-8 expression, which was reduced by Fe loading but increased by DEF. To determine the role of Fe in LA-induced lung injury in vivo, spontaneously hypertensive rats were exposed intratracheally to either saline (300 µL), DEF (1 mg), FeCl(3) (21 µg), LA (0.5 mg), FeLA (0.5 mg), or LA + DEF (0.5 mg). LA caused BALF neutrophils to increase 24 h post-exposure. Loading of Fe on LA but not chelation slightly decreased neutrophilic influx (LA + DEF > LA > FeLA). At 4 h post-exposure, LA-induced lung expression of MIP-2 was reduced in rats exposed to FeLA but increased by LA + DEF (LA + DEF > LA > FeLA). Ferritin mRNA was elevated in rats exposed to FeLA compared to LA. In conclusion, the acute inflammatory response to respirable fibers and particles may be inhibited in the presence of surface-complexed or cellular bioavailable Fe. Cell and tissue Fe-overload conditions may influence the pulmonary injury and inflammation caused by fibers.

  18. Variability in ozone-induced pulmonary injury and inflammation in healthy and cardiovascular-compromised rat models.

    PubMed

    Kodavanti, Urmila P; Ledbetter, Allen D; Thomas, Ronald F; Richards, Judy E; Ward, William O; Schladweiler, Mette C; Costa, Daniel L

    2015-01-01

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure dependent on the type and severity of disease. Healthy male 12-14-week-old Wistar Kyoto (WKY), Wistar (WS) and Sprague Dawley (SD); and CVD-compromised spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), stroke-prone spontaneously hypertensive (SHSP), obese spontaneously hypertensive heart failure (SHHF) and obese JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h; pulmonary injury and inflammation were analyzed immediately following (0-h) or 20-h later. Baseline bronchoalveolar lavage fluid (BALF) protein was higher in CVD strains except for FHH when compared to healthy. Ozone-induced increases in protein and inflammation were concentration-dependent within each strain but the degree of response varied from strain to strain and with time. Among healthy rats, SD were least affected. Among CVD strains, lean rats were more susceptible to protein leakage from ozone than obese rats. Ozone caused least neutrophilic inflammation in SH and SHHF while SHSP and FHH were most affected. BALF neutrophils and protein were poorly correlated when considering the entire dataset (r = 0.55). The baseline and ozone-induced increases in cytokine mRNA varied markedly between strains and did not correlate with inflammation. These data illustrate that the degree of ozone-induced lung injury/inflammation response is likely influenced by both genetic and physiological factors that govern the nature of cardiovascular compromise in CVD models.

  19. Inhalation Exposure Systems for the Development of Rodent Models of Sulfur Mustard-Induced Pulmonary Injury

    PubMed Central

    Weber, Waylon M.; Kracko, Dean A.; Lehman, Mericka R.; Irvin, Clinton M.; Blair, Lee F.; White, Richard K.; Benson, Janet M.; Grotendorst, Gary R.; Cheng, Yung-Sung; McDonald, Jacob D.

    2011-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg · min/m3 resulted in homogeneous lung injury with no nasal degeneration. PMID:20025432

  20. Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Irvin, Clinton M; Blair, Lee F; White, Richard K; Benson, Janet M; Grotendorst, Gary R; Cheng, Yung-Sung; McDonald, Jacob D

    2010-01-01

    Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.

  1. Pentoxifylline attenuates nitrogen mustard-induced acute lung injury, oxidative stress and inflammation.

    PubMed

    Sunil, Vasanthi R; Vayas, Kinal N; Cervelli, Jessica A; Malaviya, Rama; Hall, LeRoy; Massa, Christopher B; Gow, Andrew J; Laskin, Jeffrey D; Laskin, Debra L

    2014-08-01

    Nitrogen mustard (NM) is a toxic alkylating agent that causes damage to the respiratory tract. Evidence suggests that macrophages and inflammatory mediators including tumor necrosis factor (TNF)α contribute to pulmonary injury. Pentoxifylline is a TNFα inhibitor known to suppress inflammation. In these studies, we analyzed the ability of pentoxifylline to mitigate NM-induced lung injury and inflammation. Exposure of male Wistar rats (150-174 g; 8-10 weeks) to NM (0.125 mg/kg, i.t.) resulted in severe histopathological changes in the lung within 3d of exposure, along with increases in bronchoalveolar lavage (BAL) cell number and protein, indicating inflammation and alveolar-epithelial barrier dysfunction. This was associated with increases in oxidative stress proteins including lipocalin (Lcn)2 and heme oxygenase (HO)-1 in the lung, along with pro-inflammatory/cytotoxic (COX-2(+) and MMP-9(+)), and anti-inflammatory/wound repair (CD163+ and Gal-3(+)) macrophages. Treatment of rats with pentoxifylline (46.7 mg/kg, i.p.) daily for 3d beginning 15 min after NM significantly reduced NM-induced lung injury, inflammation, and oxidative stress, as measured histologically and by decreases in BAL cell and protein content, and levels of HO-1 and Lcn2. Macrophages expressing COX-2 and MMP-9 also decreased after pentoxifylline, while CD163+ and Gal-3(+) macrophages increased. This was correlated with persistent upregulation of markers of wound repair including pro-surfactant protein-C and proliferating nuclear cell antigen by Type II cells. NM-induced lung injury and inflammation were associated with alterations in the elastic properties of the lung, however these were largely unaltered by pentoxifylline. These data suggest that pentoxifylline may be useful in treating acute lung injury, inflammation and oxidative stress induced by vesicants.

  2. Protection against chemical-induced lung injury by inhibition of pulmonary cytochrome P-450

    SciTech Connect

    Verschoyle, R.D.; Dinsdale, D. )

    1990-04-01

    Protection afforded by trialkyl phosphorothionates against the lung injury caused by trialkyl phosphorothiolates probably results from the inhibition by the P{double bond}S moiety of the thionates, of one or more pulmonary cytochrome P-450 isozymes. The aromatic hydrocarbons p-xylene and pseudocumene also protect against this injury and inhibit some P-450 isozymes, but by a different mechanism. OOS-Trimethylphosphorothionate and p-xylene were compared as protective agents against the effect of OOS-trimethylphosphorothiolate and two other lung toxins ipomeanol and 1-nitronaphthalene that are known to be activated by cytochrome P-450. The effects of these protective compounds, in vivo, on pulmonary cytochrome P-450 activity were also determined. Both compounds inhibited pentoxyresorufin O-deethylase activity, but not ethoxyresorufin O-deethylase. The phosphorothionate was most effective against lung injury caused by the phosphorothiolates and 1-nitronaphthalene, whereas p-xylene was much more effective against ipomeanol. {beta}-Naphthoflavone, which induces pulmonary ethoxyresorufin O-deethylase activity, did not protect against phosphorothiolate or 1-nitronaphthalene injury, and it was only marginally effective in decreasing the toxicity or ipomeanol.

  3. An interesting cause of pulmonary emboli: Acute carbon monoxide poisoning

    SciTech Connect

    Sevinc, A.; Savli, H.; Atmaca, H.

    2005-07-01

    Carbon monoxide poisoning, a public health problem of considerable significance, is a relatively frequent event today, resulting in thousands of hospitalizations annually. A 70-year-old lady was seen in the emergency department with a provisional diagnosis of carbon monoxide poisoning. The previous night, she slept in a tightly closed room heated with coal ember. She was found unconscious in the morning with poor ventilation. She had a rare presentation of popliteal vein thrombosis, pulmonary emboli, and possible tissue necrosis with carbon monoxide poisoning. Oxygen treatment with low-molecular-weight heparin (nadroparine) and warfarin therapy resulted in an improvement in both popliteal and pulmonary circulations. In conclusion, the presence of pulmonary emboli should be sought in patients with carbon monoxide poisoning.

  4. Acute pulmonary edema after diazepam-ketamine in a dog.

    PubMed

    Boutureira, Joseph; Trim, Cynthia M; Cornell, Karen K

    2007-09-01

    An 8-year-old mixed-breed dog was anesthetized for colonoscopy. Moderate sedation was produced by premedication with glycopyrrolate, acepromazine, and hydromorphone, and anesthesia was induced by IV injection of diazepam and ketamine. Frothy, reddish-colored fluid flowed from the endotracheal tube immediately after endotracheal intubation but ceased after several minutes. Furosemide was injected IV. Anesthesia was maintained by sevoflurane in oxygen. Ventilation and arterial blood pressure were satisfactory, however, after oxygen was administered to maintain normal hemoglobin saturation. Radiography revealed changes consistent with a diagnosis of pulmonary edema. The following day, ventricular premature contractions developed and atrial dissociation, valvular regurgitation, and pulmonary hypertension were diagnosed on echocardiography. The proposed etiology is either profound transient hypotension and/or pulmonary hypertension induced by ketamine. The cardiac abnormalities that were present the following day suggest that myocardial dysfunction after induction of anesthesia was more severe than was apparent as assessed by routine physical examination and monitoring methods.

  5. Biomarkers of acute kidney injury and associations with short- and long-term outcomes

    PubMed Central

    Schaub, Jennifer A.; Parikh, Chirag R.

    2016-01-01

    Acute kidney injury is strongly associated with increased mortality and other adverse outcomes. Medical researchers have intensively investigated novel biomarkers to predict short- and long-term outcomes of acute kidney injury in many patient care settings, such as cardiac surgery, intensive care units, heart failure, and transplant. Future research should focus on leveraging this relationship to improve enrollment for clinical trials of acute kidney injury. PMID:27239295

  6. Alpinetin inhibits lipopolysaccharide-induced acute kidney injury in mice.

    PubMed

    Huang, Yi; Zhou, Li-shan; Yan, Li; Ren, Juan; Zhou, Dai-xing; Li, Shu-Sheng

    2015-10-01

    Alpinetin, a novel plant flavonoid isolated from Alpinia katsumadai Hayata, has been demonstrated to have anti-inflammatory and antioxidant effects. However, the effects of alpinetin on lipopolysaccharide (LPS)-induced acute kidney injury have not been reported. In the present study, we investigated the protective effects and the underlying mechanism of alpinetin against LPS-induced acute kidney injury in mice. The results showed that alpinetin inhibited LPS-induced kidney histopathologic changes, blood urea nitrogen (BUN) and creatinine levels. Alpinetin also inhibited LPS-induced ROS, MDA, and inflammatory cytokines TNF-α, IL-6 and IL-1β production in kidney tissues. Meanwhile, Western blot analysis showed that alpinetin suppressed LPS-induced TLR4 expression and NF-κB activation in kidney tissues. In addition, alpinetin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, alpinetin protected LPS-induced kidney injury through activating Nrf2 and inhibiting TLR4 expression.

  7. [From acute pulmonary embolism to chronic thromboembolic pulmonary hypertension: Pathobiology and pathophysiology].

    PubMed

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    Chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subtype of pulmonary hypertension characterized by the presence of mechanical obstruction of the major pulmonary vessels caused by venous thromboembolism. CTEPH is a progressive and devastating disease if not treated, and is the only subset of PH potentially curable by a surgical procedure known as pulmonary endarterectomy. The clot burden and pulmonary embolism recurrence may contribute to the development of CTEPH however only few thrombophilic factors have been found to be associated. A current hypothesis is that CTEPH results from the incomplete resolution and organization of thrombus modified by inflammatory, immunologic and genetic mechanisms, leading to the development of fibrotic stenosis and adaptive vascular remodeling of resistance vessels. The causes of thrombus non-resolution have yet to be fully clarified. CTEPH patients often display severe PH that cannot be fully explained by the degree of pulmonary vascular obstruction apparent on imaging studies. In such cases, the small vessel disease and distal obstructive thrombotic lesions beyond the sub-segmental level may contribute for out of proportion elevated PVR. The processes implicated in the development of arteriopathy and micro-vascular changes might explain the progressive nature of PH and gradual clinical deterioration with poor prognosis, as well as lack of correlation between measurable hemodynamic parameters and vascular obstruction even in the absence of recurrent venous thromboembolism. This review summarizes the most relevant up-to-date aspects on pathobiology and pathophysiology of CTEPH.

  8. Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury.

    PubMed

    Heilman, R L; Smith, M L; Kurian, S M; Huskey, J; Batra, R K; Chakkera, H A; Katariya, N N; Khamash, H; Moss, A; Salomon, D R; Reddy, K S

    2015-08-01

    Our aim was to determine outcomes with transplanting kidneys from deceased donors with acute kidney injury, defined as a donor with terminal serum creatinine ≥2.0 mg/dL, or a donor requiring acute renal replacement therapy. We included all patients who received deceased donor kidney transplant from June 2004 to October 2013. There were 162 AKI donor transplant recipients (21% of deceased donor transplants): 139 in the standard criteria donor (SCD) and 23 in the expanded criteria donor (ECD) cohort. 71% of the AKI donors had stage 3 (severe AKI), based on acute kidney injury network (AKIN) staging. Protocol biopsies were done at 1, 4, and 12 months posttransplant. One and four month formalin-fixed paraffin embedded (FFPE) biopsies from 48 patients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). DGF was more common in the AKI group but eGFR, graft survival at 1 year and proportion with IF/TA>2 at 1 year were similar for the two groups. At 1 month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4 months there were no differences. Transplanting selected kidneys from deceased donors with AKI is safe and has excellent outcomes.

  9. Sporadic Multicentric Right Atrial and Right Ventricular Myxoma Presenting as Acute Pulmonary Thromboembolism.

    PubMed

    Singh, Satyajit; Tripathy, Mahendra Prasad; Mohanty, Bipin Bihari; Biswas, Sutapa

    2016-01-01

    Multicentric cardiac myxoma is a rare syndrome; usually it is familial. We report a rare case of sporadic right atrium (RA) and right ventricle (RV) myxoma in a 26-year-old female presenting to our hospital for the evaluation of sudden onset of dyspnea and left precordial pain attributed to the embolization of degenerating tumor fragments to the pulmonary artery (PA). The exact incidence of sporadic multicentric RA and RV myxoma presenting as acute pulmonary embolism is unknown as multicentric RA and RV myxoma are very rare. Myxomas presenting as pulmonary embolism is <10%. Majority of cardiac myxomas present as exertional dyspnea, chest pain, positional syncope, fever, weight loss and other constitutional symptoms. Any young patient presenting with acute onset dyspnea with multiple cardiac masses may have tumor embolization to the PA diagnosis with transthoracic echocardiography and high-resolution computed tomography of thorax, fast-tracks patient transfer for urgent cardiac surgery to prevent further embolization.

  10. [Cardiogenic pulmonary edema following β2 agonist infusion for acute, severe asthma].

    PubMed

    Bahloul, M; Chaari, A; Dammak, H; Medhioub, F; Abid, L; Chtourou, K; Rekik, N; Chelly, H; Kallel, H; Bouaziz, M

    2015-09-01

    We report the case of a severe acute pulmonary edema secondary to the administration of salbutamol to a patient admitted for severe asthma. The diagnosis of acute pulmonary edema was suspected on the clinical examination, chest radiography, biological (plasmatic Pro-BNP rate) and echocardiographic findings. Rapid improvement under dobutamine and mechanical ventilation argue in favour of cardiogenic pulmonary edema. The young age of our patient, the absence of history of cardiovascular disease and the chronology of this complication onset regarded to salbutamol infusion could suggest β2 agonist involvement in this event. The improvement of cardiac function on echocardiography and the normal results obtained with myocardial perfusion scintigraphy performed 35 days later show the left ventricular reversible dysfunction.

  11. [Acute pulmonary edema from inhalation of the bite-block after anesthesia with a laryngeal mask].

    PubMed

    Banchereau, F; Marié, S; Pez, H; Boully-Balihaut, A; Tueux, O

    2001-12-01

    We report a case of acute pulmonary oedema, consecutive to upper airway obstruction due to the inhalation of the laryngeal mask airway (LMA) bite block during recovery. The LMA was used for general anaesthesia with the bite-block provided in France. No trouble occurred during LMA insertion and anaesthesia. Symptomatic treatment provided complete resolution within a few days.

  12. Improved Diagnosis of Acute Pulmonary Histoplasmosis by Combining Antigen and Antibody Detection

    PubMed Central

    Richer, Sarah M.; Smedema, Melinda L.; Durkin, Michelle M.; Herman, Katie M.; Hage, Chadi A.; Fuller, Deanna; Wheat, L. Joseph

    2016-01-01

    Background. Acute pulmonary histoplasmosis can be severe, especially following heavy inoculum exposure. Rapid diagnosis is critical and often possible by detection of antigen, but this test may be falsely negative in 17% of such cases. Antibody detection by enzyme immunoassay (EIA) may increase sensitivity and permit the measurement of immunoglobulin M (IgM) and immunoglobulin G (IgG) classes of antibodies separately. Methods. Microplates coated with Histoplasma antigen were used for testing of serum from patients with acute pulmonary histoplasmosis and controls in the MVista Histoplasma antibody EIA. Results for IgG and IgM were reported independently. Results. IgG antibodies were detected in 87.5%, IgM antibodies in 67.5%, and IgG and/or IgM antibodies in 88.8% of patients with acute pulmonary histoplasmosis in this assay, while immunodiffusion, complement fixation, and antigen testing showed sensitivities of 55.0%, 73.1%, and 67.5%, respectively (n = 80). Combining antigen and antibody detection increased the sensitivity to 96.3%. Conclusions. The MVista Histoplasma antibody EIA offers increased sensitivity over current antibody tests while also allowing separate detection of IgG and IgM antibodies and complementing antigen detection. Combining antigen and EIA antibody testing provides an optimal method for diagnosis of acute pulmonary histoplasmosis. PMID:26797210

  13. Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension.

    PubMed

    Saito, Yukihiro; Nakamura, Kazufumi; Miyaji, Katsumasa; Akagi, Satoshi; Mizoguchi, Hiroki; Ogawa, Aiko; Fuke, Soichiro; Fujio, Hideki; Kiyooka, Takahiko; Nagase, Satoshi; Kohno, Kunihisa; Morita, Hiroshi; Kusano, Kengo F; Matsubara, Hiromi; Ohe, Tohru; Ito, Hiroshi

    2012-01-01

    Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg⁻¹·min⁻¹ for 5 min and 2 μg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

  14. Pulmonary mucormycosis with embolism: two autopsied cases of acute myeloid leukemia.

    PubMed

    Kogure, Yasunori; Nakamura, Fumihiko; Shinozaki-Ushiku, Aya; Watanabe, Akira; Kamei, Katsuhiko; Yoshizato, Tetsuichi; Nannya, Yasuhito; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Mucormycosis is an increasingly important cause of morbidity and mortality for patients with hematological malignancies. The diagnosis of mucormycosis usually requires mycological evidence through tissue biopsy or autopsy because the signs and symptoms are nonspecific and there are currently no biomarkers to identify the disease. We herein present two autopsied cases of acute myeloid leukemia with prolonged neutropenia who developed invasive mucormycosis accompanied by pulmonary artery embolism. Our cases were featured by unexplained fever and rapidly progressive dyspnea. Computed tomography scan detected nodular lesions or nonspecific consolidations in the lungs. Cultures, cytological study, and serum fungal markers consistently gave negative results. Autopsy revealed embolism of the pulmonary artery which consisted of fibrin clots by filamentous fungi. Genomic DNA was extracted from the paraffin-embedded clots and was applied to polymerase chain reaction amplification, leading to the diagnosis of infection by Rhizopus microsporus. We should carefully search for life-threatening pulmonary embolism when patients with hematological malignancies develop pulmonary mucormycosis.

  15. A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.

    PubMed

    Kang, Kyung-Sik; Heo, Sang Taek

    2015-01-01

    Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.

  16. Pathophysiology of acute kidney injury: a new perspective.

    PubMed

    Wen, Xiaoyan; Murugan, Raghavan; Peng, Zhiyong; Kellum, John A

    2010-01-01

    Acute kidney injury (AKI) in critically ill patients is a devastating illness associated with prolonged hospital stay and high mortality. Limited progress has been made in the field of AKI, and its treatment using renal replacement therapy, at best, only provides partial renal support. Ischemia-reperfusion rodent AKI models do not resemble human renal injury and the absence of renal biopsy data limits our understanding of the pathophysiology of human AKI. However, laboratory and clinical evidence suggests that the inflammatory milieu leads to dysfunction of renal cells and this may be the key factor leading to AKI. Cells in injured tissues release immunological danger signals or danger-associated molecular pattern molecules which communicate with remote organs including the kidney, where they activate dendritic cells and T cells and thus initiate inflammation. Once the initial insult has passed, tubular epithelial cells undergo dedifferentiation, reacquire progenitorial ability to proliferate, migrate, and redifferentiate into mature intrinsic cells. Dissonance of mediator secretion and cell responses may lead to persistent injury and de novo chronic kidney disease. A number of soluble mediators including transforming growth factor-beta (TGF-beta) initiate a variety of pathophysiological processes at the beginning of kidney injury. TGF-beta also plays a fundamental role in cell proliferation and interstitial fibrosis in later phases. The renin-angiotensin-aldosterone system, especially angiotensin II, contributes to kidney injury through the angiotensin II type 1 receptor, TGF-beta receptor Smad and epidermal growth factor receptor by affecting general angiostasis and vascular remodeling, indirectly modulating inflammation and cell reactions. We review the pathophysiology of AKI in light of new information regarding renal injury and repair.

  17. Combined blood purification for treating acute fatty liver of pregnancy complicated by acute kidney injury: a case series.

    PubMed

    Tang, Wan Xin; Huang, Zhong Ying; Chen, Ze Jun; Cui, Tian Lei; Zhang, Ling; Fu, Ping

    2012-06-01

    Acute fatty liver of pregnancy (AFLP) complicated by acute kidney injury (AKI) is serious and life-threatening for the mother. The present study aimed to determine the clinical efficacy of combined blood purification treatment (CBPT) in patients with AFLP complicated by AKI. The CBPT involves plasma exchange (PE) combined with continuous venovenous hemofiltration (CVVH). The subjects were 17 patients with AFLP complicated by AKI. The CBPT was implemented based on the timely termination of pregnancy and general treatment. Changes in clinical manifestations, laboratory tests, liver ultrasounds, as well as Sequential Organ Failure Assessment (SOFA) and Glasgow scores were evaluated. The efficacy and adverse reactions of the CBPT were also assessed. The CBPT was smoothly performed without any obvious adverse reaction. After treatment, the clinical manifestations, laboratory examinations, and liver ultrasonography significantly improved. Therefore, the SOFA scores correspondingly decreased 1 week after treatment [9 (range 5-11) vs. 3 (range 0-10), P = 0.002], and the median was close to normal by the second week. The clearance rate of the total bilirubin in PE was significantly higher than that in CVVH (37.2 vs. 7.9%, P = 0.000). The incidence of acute pulmonary edema in CVVH was less than that in PE (0 vs. 41.2%, P = 0.007). Finally, the maternal mortality was 5.88% (95% CI: 0-29%). Overall, we think that CBPT aids in the recovery of liver and kidney function. Different blood purification methods may be combined to integrate and maximize their advantages to improve the prognoses of patients with serious AFLP.

  18. Acute cervical cord injuries in patients with epilepsy.

    PubMed Central

    Allen, J W; Kendall, B E; Kocen, R S; Milligan, N M

    1982-01-01

    Seven cases with acute cervical cord lesions associated with a fit and fall, were found in approximately 500 patients with epilepsy over a period of 7 years. In all patients the epilepsy was refractory to drug therapy and six suffered tonic fits which resulted in falls and frequent head injuries. Notable radiological changes were found in the cervical spine; there was ankylosis in five, hyperostosis in four and the minimum sagittal diameter of the bony canal was less than 11mm in three cases. The findings indicate that repetitive trauma may be a factor in producing bony changes in the cervical spine which put the patient at risk of cervical cord injury, especially when the spinal canal is developmentally narrow. Images PMID:7143009

  19. Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis.

    PubMed

    Shives, Katherine D; Tyler, Kenneth L; Beckham, J David

    2017-03-11

    Viral infections in the central nervous system are a major cause of encephalitis. West Nile virus (WNV) and Herpes simplex virus (HSV) are the most common causes of viral encephalitis in the United States. We review the role of neuroinflammation in the pathogenesis of WNV and HSV infections in the central nervous system (CNS). We discuss the role of the innate and cell-mediated immune responses in peripheral control of viral infection, viral invasion of the CNS, and in inflammatory-mediated neuronal injury. By understanding the role of specific inflammatory responses to viral infections in the CNS, targeted therapeutic approaches can be developed to maximize control of acute viral infection while minimizing neuronal injury in the CNS.

  20. Dapagliflozin-Induced Acute-on-Chronic Liver Injury

    PubMed Central

    Levine, Joshua A.; Ann Lo, Amy; Wallia, Amisha; Rogers, Melinda

    2016-01-01

    Sodium-glucose cotransporter 2 inhibitors are a new class of oral hypoglycemic agents, and thus safety data are limited. We present a 48-year-old woman with type 2 diabetes mellitus and Child’s Class A cirrhosis secondary to nonalcoholic steatohepatitis presenting with jaundice and acute cholestatic liver injury. Other than starting dapagliflozin, she reported no medication changes or supplement use. Before treatment, her total bilirubin was 1.2 mg/dL. On admission, her liver values were elevated and liver biopsy was consistent with drug-induced liver injury. This report raises awareness about the potential hepatotoxic effects of dapagliflozin, particularly in patients with chronic liver disease. PMID:28008402

  1. Protein methionine oxidation augments reperfusion injury in acute ischemic stroke

    PubMed Central

    Gu, Sean X.; Blokhin, Ilya O.; Wilson, Katina M.; Dhanesha, Nirav; Doddapattar, Prakash; Grumbach, Isabella M.; Chauhan, Anil K.; Lentz, Steven R.

    2016-01-01

    Reperfusion injury can exacerbate tissue damage in ischemic stroke, but little is known about the mechanisms linking ROS to stroke severity. Here, we tested the hypothesis that protein methionine oxidation potentiates NF-κB activation and contributes to cerebral ischemia/reperfusion injury. We found that overexpression of methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that reverses protein methionine oxidation, attenuated ROS-augmented NF-κB activation in endothelial cells, in part, by protecting against the oxidation of methionine residues in the regulatory domain of calcium/calmodulin-dependent protein kinase II (CaMKII). In a murine model, MsrA deficiency resulted in increased NF-κB activation and neutrophil infiltration, larger infarct volumes, and more severe neurological impairment after transient cerebral ischemia/reperfusion injury. This phenotype was prevented by inhibition of NF-κB or CaMKII. MsrA-deficient mice also exhibited enhanced leukocyte rolling and upregulation of E-selectin, an endothelial NF-κB–dependent adhesion molecule known to contribute to neurovascular inflammation in ischemic stroke. Finally, bone marrow transplantation experiments demonstrated that the neuroprotective effect was mediated by MsrA expressed in nonhematopoietic cells. These findings suggest that protein methionine oxidation in nonmyeloid cells is a key mechanism of postischemic oxidative injury mediated by NF-κB activation, leading to neutrophil recruitment and neurovascular inflammation in acute ischemic stroke. PMID:27294204

  2. Acute kidney injury: changing lexicography, definitions, and epidemiology.

    PubMed

    Himmelfarb, J; Ikizler, T A

    2007-05-01

    In recent years, there have been numerous advances in understanding the molecular determinants of functional kidney injury after ischemic and/or toxic exposure. However, translation of successful novel therapies designed to attenuate kidney functional injury from animal models to the clinical sphere has had modest results. This lack of translatability is at least in part due to lack of sufficient standardization in definitions and classification of cases of acute kidney injury (AKI), an incomplete understanding of the natural history of human AKI, and a limited understanding of how kidney injury interacts with other organ system failure in the context of systemic metabolic abnormalities. A concerted effort is now being made by nephrologists and intensivists to arrive at standardized terminology and classification of AKI. There have also been dramatic advances in our understanding of the epidemiology and natural history of AKI, particularly in the hospital and intensive care unit setting. Promising strategies are now being developed which may ultimately lead to improved outcomes for patients at risk for or who have developed AKI, which should be readily testable in the coming decade.

  3. Defining the acute kidney injury and repair transcriptome.

    PubMed

    Kumar, Sanjeev; Liu, Jing; McMahon, Andrew P

    2014-07-01

    The mammalian kidney has an intrinsic ability to repair after significant injury. However, this process is inefficient: patients are at high risk for the loss of kidney function in later life. No therapy exists to treat established acute kidney injury (AKI) per se: strategies to promote endogenous repair processes and retard associated fibrosis are a high priority. Whole-organ gene expression profiling has been used to identify repair responses initiated with AKI, and factors that may promote the transition from AKI to chronic kidney disease. Transcriptional profiling has shown molecular markers and potential regulatory pathways of renal repair. Activation of a few key developmental pathways has been reported during repair. Whether these are comparable networks with similar target genes with those in earlier nephrogenesis remains unclear. Altered microRNA profiles, persistent tubular injury responses, and distinct late inflammatory responses highlight continuing kidney pathology. Additional insights into injury and repair processes will be gained by study of the repair transcriptome and cell-specific translatome using high-resolution technologies such as RNA sequencing and translational profiling tailored to specific cellular compartments within the kidney. An enhanced understanding holds promise for both the identification of novel therapeutic targets and biomarker-based evaluation of the damage-repair process.

  4. Manipulating the air-filled zebrafish swim bladder as a neutrophilic inflammation model for acute lung injury

    PubMed Central

    Zhang, Yuefei; Liu, Hongcui; Yao, Junlin; Huang, Yanfeng; Qin, Shenlu; Sun, Zheng; Xu, Yingchun; Wan, Shu; Cheng, Hongqiang; Li, Chunqi; Zhang, Xue; Ke, Yuehai

    2016-01-01

    Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening diseases that are associated with high mortality rates due to treatment limitations. Neutrophils play key roles in the pathogenesis of ALI/ARDS by promoting the inflammation and injury of the alveolar microenvironment. To date, in vivo functional approaches have been limited by the inaccessibility to the alveolar sacs, which are located at the anatomical terminal of the respiratory duct in mammals. We are the first to characterize the swim bladder of the zebrafish larva, which is similar to the mammalian lung, as a real-time in vivo model for examining pulmonary neutrophil infiltration during ALI. We observed that the delivery of exogenous materials, including lipopolysaccharide (LPS), Poly IC and silica nanoparticles, by microinjection triggered significant time- and dose-dependent neutrophil recruitment into the swim bladder. Neutrophils infiltrated the LPS-injected swim bladder through the blood capillaries around the pneumatic duct or a site near the pronephric duct. An increase in the post-LPS inflammatory cytokine mRNA levels coincided with the in vivo neutrophil aggregation in the swim bladder. Microscopic examinations of the LPS-injected swim bladders further revealed in situ injuries, including epithelial distortion, endoplasmic reticulum swelling and mitochondrial injuries. Inhibitor screening assays with this model showed a reduction in neutrophil migration into the LPS-injected swim bladder in response to Shp2 inhibition. Moreover, the pharmacological suppression and targeted disruption of Shp2 in myeloid cells alleviated pulmonary inflammation in the LPS-induced ALI mouse model. Additionally, we used this model to assess pneumonia-induced neutrophil recruitment by microinjecting bronchoalveolar lavage fluid from patients into swim bladders; this injection enhanced neutrophil aggregation relative to the control. In conclusion, our findings

  5. Suspected acute exacerbation of idiopathic pulmonary fibrosis as an outcome measure in clinical trials

    PubMed Central

    2013-01-01

    Background Acute exacerbation of idiopathic pulmonary fibrosis has become an important outcome measure in clinical trials. This study aimed to explore the concept of suspected acute exacerbation as an outcome measure. Methods Three investigators retrospectively reviewed subjects enrolled in the Sildenafil Trial of Exercise Performance in IPF who experienced a respiratory serious adverse event during the course of the study. Events were classified as definite acute exacerbation, suspected acute exacerbation, or other, according to established criteria. Results Thirty-five events were identified. Four were classified as definite acute exacerbation, fourteen as suspected acute exacerbation, and seventeen as other. Definite and suspected acute exacerbations were clinically indistinguishable. Both were most common in the winter and spring months and were associated with a high risk of disease progression and short-term mortality. Conclusions In this study one half of respiratory serious adverse events were attributed to definite or suspected acute exacerbations. Suspected acute exacerbations are clinically indistinguishable from definite acute exacerbations and represent clinically meaningful events. Clinical trialists should consider capturing both definite and suspected acute exacerbations as outcome measures. PMID:23848435

  6. Matrix metalloproteinases and protein tyrosine kinases: potential novel targets in acute lung injury and ARDS.

    PubMed

    Aschner, Yael; Zemans, Rachel L; Yamashita, Cory M; Downey, Gregory P

    2014-10-01

    Acute lung injury (ALI) and ARDS fall within a spectrum of pulmonary disease that is characterized by hypoxemia, noncardiogenic pulmonary edema, and dysregulated and excessive inflammation. While mortality rates have improved with the advent of specialized ICUs and lung protective mechanical ventilation strategies, few other therapies have proven effective in the management of ARDS, which remains a significant clinical problem. Further development of biomarkers of disease severity, response to therapy, and prognosis is urgently needed. Several novel pathways have been identified and studied with respect to the pathogenesis of ALI and ARDS that show promise in bridging some of these gaps. This review will focus on the roles of matrix metalloproteinases and protein tyrosine kinases in the pathobiology of ALI in humans, and in animal models and in vitro studies. These molecules can act independently, as well as coordinately, in a feed-forward manner via activation of tyrosine kinase-regulated pathways that are pivotal in the development of ARDS. Specific signaling events involving proteolytic processing by matrix metalloproteinases that contribute to ALI, including cytokine and chemokine activation and release, neutrophil recruitment, transmigration and activation, and disruption of the intact alveolar-capillary barrier, will be explored in the context of these novel molecular pathways.

  7. Cannabidiol improves lung function and inflammation in mice submitted to LPS-induced acute lung injury.

    PubMed

    Ribeiro, A; Almeida, V I; Costola-de-Souza, C; Ferraz-de-Paula, V; Pinheiro, M L; Vitoretti, L B; Gimenes-Junior, J A; Akamine, A T; Crippa, J A; Tavares-de-Lima, W; Palermo-Neto, J

    2015-02-01

    We have previously shown that the prophylactic treatment with cannabidiol (CBD) reduces inflammation in a model of acute lung injury (ALI). In this work we analyzed the effects of the therapeutic treatment with CBD in mice subjected to the model of lipopolysaccharide (LPS)-induced ALI on pulmonary mechanics and inflammation. CBD (20 and 80 mg/kg) was administered (i.p.) to mice 6 h after LPS-induced lung inflammation. One day (24 h) after the induction of inflammation the assessment of pulmonary mechanics and inflammation were analyzed. The results show that CBD decreased total lung resistance and elastance, leukocyte migration into the lungs, myeloperoxidase activity in the lung tissue, protein concentration and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) in the bronchoalveolar lavage supernatant. Thus, we conclude that CBD administered therapeutically, i.e. during an ongoing inflammatory process, has a potent anti-inflammatory effect and also improves the lung function in mice submitted to LPS-induced ALI. Therefore the present and previous data suggest that in the future cannabidiol might become a useful therapeutic tool for the attenuation and treatment of inflammatory lung diseases.

  8. [Echocardiography in acute pulmonary embolism. Not a routine method but useful in the diagnosis of simultaneous hemodynamic disorders].

    PubMed

    Kierkegaard, A

    1998-08-19

    Echocardiographic diagnosis of acute pulmonary embolism as illustrated by three case reports is discussed in the article. Acute pulmonary embolism was diagnosed by demonstration of right heart strain in one case, of long vermiform thrombi floating in the right atrium in another, and in the third case by demonstration of a long thrombus lodged in the foramen ovale, astride the atrial septum, and with its ends floating in either atrium. Thus, as echocardiography enables pulmonary embolism to be diagnosed by demonstration either of right heart strain or of intracardial thrombi, it is a useful diagnostic tool in cases of haemodynamic compromise, though it does not detect minor pulmonary embolism.

  9. When to correct coagulopathy in acute kidney injury?

    PubMed Central

    Kaur, Manpreet; Gupta, Babita; D’souza, Nita; Shende, Seema

    2012-01-01

    Incidence of acute kidney injury (AKI) in adult trauma patients is 18% with 70% requiring renal replacement therapy. It is a challenge to treat AKI with coagulopathy since there are no defined transfusion triggers for these patients. We report a case wherein a polytrauma patient developed AKI for which he/she was dialysed and subsequently had an intracerebral bleed. There is a need to develop guidelines to transfusion triggers in AKI patients keeping vigilance on fluid overload, hyperkalemia and uraemia-induced platelet dysfunction. PMID:25885629

  10. Management of Acute Kidney Injury in Pregnancy for the Obstetrician.

    PubMed

    Acharya, Anjali

    2016-12-01

    Acute kidney injury (AKI) is a complex disorder that occurs in several clinical settings. During pregnancy, there are additional unique conditions that contribute to AKI. The clinical manifestations of AKI during pregnancy range from a minimal elevation in serum creatinine to renal failure requiring renal replacement therapy, similar to AKI in the general population. Recent epidemiologic studies in the general population show an increase in mortality associated with AKI, particularly when dialysis is required. The incidence of AKI in pregnancy remains a cause of significant morbidity and mortality.

  11. Acute spinal cord injury: tetraplegia and paraplegia in small animals.

    PubMed

    Granger, Nicolas; Carwardine, Darren

    2014-11-01

    Spinal cord injury (SCI) is a common problem in animals for which definitive treatment is lacking, and information gained from its study has benefit for both companion animals and humans in developing new therapeutic approaches. This review provides an overview of the main concepts that are useful for clinicians in assessing companion animals with severe acute SCI. Current available advanced ancillary tests and those in development are reviewed. In addition, the current standard of care for companion animals following SCI and recent advances in the development of new therapies are presented, and new predictors of recovery discussed.

  12. Acute cardiac injury after subarachnoid haemorrhage: two case reports.

    PubMed

    Marcì, Marcello; Savatteri, Paolino; Pizzuto, Antonino; Giammona, Giuseppe; Renda, Baldassare; Lojacono, Francesca; Sanfilippo, Nicola

    2009-12-09

    It is well known that cardiopulmonary complications are often associated to subarachnoid haemorrhage. For appropriate therapeutic managing it is very important to distinguish acute coronary syndrome from neurogenic myocardial injury, which is a reversible condition. Furthermore, because the hearts of brain dead patients may be utilized for therapeutic purpose, it has became of importance to rule out erroneous diagnosis of cardiac ischemia in order to avoid rejection of hearts potential suitable for transplantation.We present a report of two female patients affected by cardiac complications caused by aneurismal subarachnoid haemorrhage admitted to our neurosurgical intensive care department.

  13. Acute kidney injury in pregnancy: the thrombotic microangiopathies.

    PubMed

    Ganesan, Chitra; Maynard, Sharon E

    2011-01-01

    Acute kidney injury (AKI) is a rare but serious complication of pregnancy. Although prerenal and ischemic causes of AKI are most common, renal insufficiency can complicate several other pregnancy-specific conditions. In particular, severe preeclampsia/HELLP syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several clinical features which pose diagnostic challenges to the clinician. In this article, we discuss the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, with particular attention to renal manifestations. It is imperative to distinguish these conditions to make appropriate therapeutic decisions which can be lifesaving for the mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for TTP.

  14. Acute renal injury induced by valacyclovir hydrochloride: A case report

    PubMed Central

    Zhang, Yanning; Cong, Yuxi; Teng, Yan

    2016-01-01

    Acyclovir has been a frequently used antiviral agent in the clinical treatment of leukemia, acute encephalitis, malignant tumor and herpes simplex. The adverse effects of this drug have been widely described in clinical practice. In the present study, a case of a 35-year-old female patient diagnosed with herpes simplex, who developed acute renal injury following treatment with valacyclovir hydrochloride, is described. Kidney biopsy, light microscopy and laboratory examination were performed, and all findings revealed the signs of evident vacuolar degeneration of capillary endothelial and renal tubular epithelial cells, erythrocyte aggregation in partial renal tubule and microvilli exfoliation from epithelial cells. Renal interstitial edema was clearly identified. The clinical evidence observed from this female patient indicated that renal functions should be closely monitored during valacyclovir hydrochloride administration. A variety of effective measures, such as hydration, alkalizing urine, promoting the discharge of medication and the use of antagonists are recommended following the administration of antiviral agents. PMID:28101180

  15. Successful Interventional Management for Pulmonary Arterial Injury Secondary to Pacemaker Implantation

    PubMed Central

    Tokue, Azusa; Morita, Hideo; Tsushima, Yoshito

    2016-01-01

    Subclavian vein puncture is a relatively fast and safe technique to access the right heart for placement of pacemaker leads. Hemothorax related to injury of the pulmonary artery (PA) is a rare complication of subclavian vein access but can be life-threatening. We report a case of hemothorax occurring after subclavian vein puncture for pacemaker implantation. No cases of transcatheter arterial embolization for PA injury secondary to pacemaker implantation have been reported. Understanding of this rare complication after pacemaker implantation along with its specific clinical presentation may lead to early diagnosis and intervention. PMID:27882248

  16. Mesenchymal stem cells improves survival in LPS-induced acute lung injury acting through inhibition of NETs formation.

    PubMed

    Pedrazza, Leonardo; Cunha, Aline Andrea; Luft, Carolina; Nunes, Nailê Karine; Schimitz, Felipe; Gassen, Rodrigo Benedetti; Breda, Ricardo Vaz; Donadio, Marcio Vinícius Fagundes; de Souza Wyse, Angela Terezinha; Pitrez, Paulo Marcio Condessa; Rosa, Jose Luis; de Oliveira, Jarbas Rodrigues

    2017-01-23

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute hypoxemic respiratory failure resulting from a variety of direct and indirect injuries to the gas exchange parenchyma of the lungs. During the ALI, we have an increase release of proinflammatory cytokines and high reactive oxygen species (ROS) formation. These factors are responsible for the release and activation of neutrophil-derived proteases and the formation of neutrophil extracellular traps (NETs). The excessive increase in the release of NETs cause damage to lung tissue. Recent studies have studies involving the administration of mesenchymal stem cells (MSCs) for the treatment of experimental ALI has shown promising results. In this way, the objective of our study is to evaluate the ability of MSCs, in a lipopolysaccharide (LPS)-induced ALI model, to reduce inflammation, oxidative damage, and consequently decrease the release of NETs. Mice were submitted lung injury induced by intratracheal instillation of LPS and subsequently treated or not with MSCs. Treatment with MSCs was able to modulate pulmonary inflammation, decrease oxidative damage, and reduce the release of NETs. These benefits from treatment are evident when we observe a significant increase in the survival curve in the treated animals. Our results demonstrate that MSCs treatment is effective for the treatment of ALI. For the first time, it is described that MSCs can reduce the formation of NETs and an experimental model of ALI. This finding is directly related to these cells modulate the inflammatory response and oxidative damage in the course of the pathology.

  17. Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults.

    PubMed

    Kaddourah, Ahmad; Basu, Rajit K; Bagshaw, Sean M; Goldstein, Stuart L

    2017-01-05

    Background The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single-center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. Methods We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28-day mortality. Results A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal-replacement therapy. A stepwise increase in 28-day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log-rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. Conclusions Acute kidney injury is common and is associated with poor outcomes, including increased

  18. [Non-cardiogenic pulmonary edema, acute respiratory distress syndrome].

    PubMed

    Skalická, Hana; Bělohlávek, Jan

    2015-01-01

    Non-cardiogenic pulmonary edema is a clinical syndrome manifested by rapidly progressive respiratory distress leading, without therapy, to severe respiratory insufficiency and subsequent multiorgan failure. The pathophysiological causes are: the change in the pressure gradients in the pulmonary capillaries, the impaired membrane permeability of the alveolocapillary in the lungs, and impaired lymphatic drainage. Unlike in cardiogenic pulmonary edema, cardiac disease is not a cause, and there is no increase in wedge pressure (< 18 mm Hg). The aetiological base is diverse and includes more clinical pathological factors. The diagnosis and evaluation are usually very difficult due to the rapidly deteriorating clinical condition of the patients. A decisive, quick and comprehensive approach, using all available invasive and non-invasive methods is necessary. The basic steps of treatment are: the use of different types of ventilatory support in order to achieve adequate oxygenation, dealing with possible hemodynamic instability, and, when needed, other specific procedures. It is always important to keep in mind that this is a very serious condition with a high mortality rate. And there is a need for fast and efficient access to the best specialized clinic.

  19. Acute Cortical Transhemispheric Diaschisis after Unilateral Traumatic Brain Injury.

    PubMed

    Le Prieult, Florie; Thal, Serge C; Engelhard, Kristin; Imbrosci, Barbara; Mittmann, Thomas

    2017-03-01

    Focal neocortical brain injuries lead to functional alterations, which can spread beyond lesion-neighboring brain areas. The undamaged hemisphere and its associated disturbances after a unilateral lesion, so-called transhemispheric diaschisis, have been progressively disclosed over the last decades; they are strongly involved in the pathophysiology and, potentially, recovery of brain injuries. Understanding the temporal dynamics of these transhemispheric functional changes is crucial to decipher the role of the undamaged cortex in the processes of functional reorganization at different stages post-lesion. In this regard, little is known about the acute-subacute processes after 24-48 h in the brain hemisphere contralateral to injury. In the present study, we performed a controlled cortical impact to produce a unilateral traumatic brain injury (TBI) in the motor and somatosensory cortex of mice. In vitro extracellular multi-unit recordings from large neuronal populations, together with single-cell patch-clamp recordings in the cortical network contralateral to the lesion, revealed a strong, but transient, neuronal hyperactivity as early as 24-48 h post-TBI. This abnormal excitable state in the intact hemisphere was not accompanied by alterations in neuronal intrinsic properties, but it was associated with an impairment of the phasic gamma aminobutyric acid (GABA)ergic transmission and an increased expression of GABAA receptor subunits related to tonic inhibition exclusively in the contralateral hemisphere. These data unravel a series of early transhemispheric functional alterations after diffuse unilateral cortical injury, which may compensate and stabilize the disrupted brain functions. Therefore, our findings support the hypothesis that the undamaged hemisphere could play a significant role in early functional reorganization processes after a TBI.

  20. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury.

    PubMed

    Wu, Deqing; Zeng, Yue; Fan, Yuting; Wu, Jianghong; Mulatibieke, Tunike; Ni, Jianbo; Yu, Ge; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

    2016-02-04

    Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM.

  1. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury

    PubMed Central

    Wu, Deqing; Zeng, Yue; Fan, Yuting; Wu, Jianghong; Mulatibieke, Tunike; Ni, Jianbo; Yu, Ge; Wan, Rong; Wang, Xingpeng; Hu, Guoyong

    2016-01-01

    Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM. PMID:26841848

  2. Adrenal insufficiency presenting as hypercalcemia and acute kidney injury

    PubMed Central

    Ahn, Seung Won; Kim, Tong Yoon; Lee, Sangmin; Jeong, Jeong Yeon; Shim, Hojoon; Han, Yu min; Choi, Kyu Eun; Shin, Seok Joon; Yoon, Hye Eun

    2016-01-01

    Adrenal insufficiency is an uncommon cause of hypercalcemia and not easily considered as an etiology of adrenal insufficiency in clinical practice, as not all cases of adrenal insufficiency manifest as hypercalcemia. We report a case of secondary adrenal insufficiency presenting as hypercalcemia and acute kidney injury in a 66-year-old female. The patient was admitted to the emergency department with general weakness and poor oral intake. Hypercalcemia (11.5 mg/dL) and moderate renal dysfunction (serum creatinine 4.9 mg/dL) were shown in her initial laboratory findings. Studies for malignancy and hyperparathyroidism showed negative results. Basal cortisol and adrenocorticotropic hormone levels and adrenocorticotropic hormone stimulation test confirmed the diagnosis of adrenal insufficiency. With the administration of oral hydrocortisone, hypercalcemia was dramatically resolved within 3 days. This case shows that adrenal insufficiency may manifest as hypercalcemia and acute kidney injury, which implicates that adrenal insufficiency should be considered a cause of hypercalcemia in clinical practice. PMID:27536162

  3. Electrolyte disturbances and acute kidney injury in patients with cancer.

    PubMed

    Lameire, Norbert; Van Biesen, Wim; Vanholder, Raymond

    2010-11-01

    The interrelation between kidney disease and cancer is complex and reciprocal. Among the most frequent cancer-associated kidney diseases are the electrolyte and acid-base disturbances, which occur frequently and often are associated with an ominous prognosis, and acute kidney injury. Tumor lysis syndrome is a potentially life-threatening condition that frequently occurs in patients with a high tumor burden and high cellular turnover after cytotoxic therapy (including steroids in steroid-sensitive hematologic malignancies). Electrolyte and acid-base disturbances are the consequence of neoplastic spread, anticancer treatment, or, more rarely, paraneoplastic phenomena of all types of tumors. This article reviews hyponatremia and hypernatremia, hypokalemia and hyperkalemia, hypomagnesemia, hypercalcemia and hypocalcemia, hypophosphatemia, and the most important disturbances in acid-base balance in cancer patients. Acute kidney injury (AKI) is a frequent occurrence in cancer patients and has the potential to substantially alter the outcome of patients with cancer and jeopardize their chances of receiving optimal cancer treatment and a potential cure. As in many other circumstances, the etiology of AKI in cancer patients is multifactorial. Initiation and/or continuation of dialysis in the AKI cancer patient should be based on the general clinical condition and overall life expectancy and the personal patient expectations on quality of life after eventual recovery.

  4. Acute kidney injury by radiographic contrast media: pathogenesis and prevention.

    PubMed

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Michael, Ashour

    2014-01-01

    It is well known that iodinated radiographic contrast media may cause kidney dysfunction, particularly in patients with preexisting renal impairment associated with diabetes. This dysfunction, when severe, will cause acute renal failure (ARF). We may define contrast-induced Acute Kidney Injury (AKI) as ARF occurring within 24-72 hrs after the intravascular injection of iodinated radiographic contrast media that cannot be attributed to other causes. The mechanisms underlying contrast media nephrotoxicity have not been fully elucidated and may be due to several factors, including renal ischaemia, particularly in the renal medulla, the formation of reactive oxygen species (ROS), reduction of nitric oxide (NO) production, and tubular epithelial and vascular endothelial injury. However, contrast-induced AKI can be prevented, but in order to do so, we need to know the risk factors. We have reviewed the risk factors for contrast-induced AKI and measures for its prevention, providing a long list of references enabling readers to deeply evaluate them both.

  5. Microbiota protects mice against acute alcohol-induced liver injury

    PubMed Central

    Chen, Peng; Miyamoto, Yukiko; Mazagova, Magdalena; Lee, Kuei-Chuan; Eckmann, Lars; Schnabl, Bernd

    2015-01-01

    Background Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. Aim To investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. Methods We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. Results Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and upregulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute ethanol administration. The absence of microbiota was also associated with increased hepatic expression of ethanol metabolizing enzymes, which led to faster ethanol elimination from the blood and lower plasma ethanol concentrations. Intestinal levels of ethanol metabolizing genes showed regional expression differences, and were overall higher in germ-free relative to conventional mice. Conclusion Our findings indicate that absence of the intestinal microbiota increases hepatic ethanol metabolism and the susceptibility to binge-like alcohol drinking. PMID:26556636

  6. Acute kidney injury in patients with chronic liver disease

    PubMed Central

    Rognant, Nicolas

    2015-01-01

    Acute kidney injury (AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages: (1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndrome for which earlier intervention could improve patients’ survival; and (2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients. PMID:25954481

  7. Collective epithelial migration drives kidney repair after acute injury.

    PubMed

    Palmyre, Aurélien; Lee, Jeongeun; Ryklin, Gennadiy; Camarata, Troy; Selig, Martin K; Duchemin, Anne-Laure; Nowak, Paul; Arnaout, M Amin; Drummond, Iain A; Vasilyev, Aleksandr

    2014-01-01

    Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney's remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI.

  8. Acute kidney injury in pregnancy-current status.

    PubMed

    Acharya, Anjali; Santos, Jolina; Linde, Brian; Anis, Kisra

    2013-05-01

    Pregnancy-related acute kidney injury (PR-AKI) causes significant maternal and fetal morbidity and mortality. Management of PR-AKI warrants a thorough understanding of the physiologic adaptations in the kidney and the urinary tract. Categorization of etiologies of PR-AKI is similar to that of acute kidney injury (AKI) in the nonpregnant population. The causes differ between developed and developing countries, with thrombotic microangiopathies (TMAs) being common in the former and septic abortion and puerperal sepsis in the latter. The incidence of PR-AKI is reported to be on a decline, but there is no consensus on the exact definition of the condition. The physiologic changes in pregnancy make diagnosis of PR-AKI difficult. Newer biomarkers are being studied extensively but are not yet available for clinical use. Early and accurate diagnosis is necessary to improve maternal and fetal outcomes. Timely identification of "at-risk" individuals and treatment of underlying conditions such as sepsis, preeclampsia, and TMAs remain the cornerstone of management. Questions regarding renal replacement therapy such as modality, optimal prescription, and timing of initiation in PR-AKI remain unclear. There is a need to systematically explore these variables to improve care of women with PR-AKI.

  9. Endovascular Management of Acute Pulmonary Embolism Using the Ultrasound-Enhanced EkoSonic System.

    PubMed

    Garcia, Mark J

    2015-12-01

    Acute, symptomatic pulmonary embolism (PE) in the massive and submassive categories continues to be a healthcare concern with significant risk for increased morbidity and mortality. Despite increased awareness and venous thromboembolism prophylaxis, endovascular treatment is still an important option for many of these patients. There are a variety of techniques and devices used for treating PE, but none have been evaluated as extensively as the EkoSonic endovascular system that is also currently the only FDA-approved device for the treatment of pulmonary embolism. This article describes the use of the EkoSonic device for this patient population.

  10. Algorithm for the diagnosis and follow-up of acute pulmonary embolisms.

    PubMed

    Calvillo Batllés, P

    The urgent diagnosis of acute pulmonary thromboembolism benefits from the use of evidence-based clinical guidelines that improve patients' prognoses and reduce the unnecessary use of imaging tests. This article explains the diagnostic algorithms for pulmonary thromboembolism most recently published by the relevant scientific societies both for the general population and for special situations, trying to clear up common doubts and analyzing persistent controversies. It also discusses the need to follow up the thromboembolism after anticoagulation treatment, which is not currently recommended in the guidelines.

  11. Effects of methylene blue in acute lung injury induced by oleic acid in rats

    PubMed Central

    Cassiano Silveira, Ana Paula; Vento, Daniella Alves; Albuquerque, Agnes Afrodite Sumarelli; Celotto, Andrea Carla; Tefé-Silva, Cristiane; Ramos, Simone Gusmão; Rubens de Nadai, Tales; Rodrigues, Alfredo José; Poli-Neto, Omero Benedicto

    2016-01-01

    Background In acute lung injury (ALI), rupture of the alveolar-capillary barrier determines the protein-rich fluid influx into alveolar spaces. Previous studies have reported that methylene blue (MB) attenuates such injuries. This investigation was carried out to study the MB effects in pulmonary capillary permeability. Methods Wistar rats were divided into five groups: (I) Sham: saline bolus; (II) MB, MB infusion for 2 h; (III) oleic acid (OA), OA bolus; (IV) MB/OA, MB infusion for 2 h, and at 5 min after from the beginning, concurrently with an OA bolus; and (V) OA/MB, OA bolus, and after 2 h, MB infusion for 2 h. After 4 h, blood, bronchoalveolar lavage (BAL), and lung tissue were collected from all groups for analysis of plasma and tissue nitric oxide, calculation of the wet weight to dry weight ratio (WW/DW), and histological examination of lung tissue. Statistical analysis was performed using nonparametric test. Results Although favourable trends have been observed for permeability improvement parameters (WW/WD and protein), the results were not statistically significant. However, histological analysis of lung tissue showed reduced lesion areas in both pre- and post-treatment groups. Conclusions The data collected using this experimental model was favourable only through macroscopic and histological analysis. These observations are valid for both MB infusions before or after induction of ALI. PMID:26855944

  12. Pathophysiological Approaches of Acute Respiratory Distress syndrome: Novel Bases for Study of Lung Injury

    PubMed Central

    Castillo, R.L; Carrasco Loza, R; Romero-Dapueto, C

    2015-01-01

    Experimental approaches have been implemented to research the lung damage related-mechanism. These models show in animals pathophysiological events for acute respiratory distress syndrome (ARDS), such as neutrophil activation, reactive oxygen species burst, pulmonary vascular hypertension, exudative edema, and other events associated with organ dysfunction. Moreover, these approaches have not reproduced the clinical features of lung damage. Lung inflammation is a relevant event in the develop of ARDS as component of the host immune response to various stimuli, such as cytokines, antigens and endotoxins. In patients surviving at the local inflammatory states, transition from injury to resolution is an active mechanism regulated by the immuno-inflammatory signaling pathways. Indeed, inflammatory process is regulated by the dynamics of cell populations that migrate to the lung, such as neutrophils and on the other hand, the role of the modulation of transcription factors and reactive oxygen species (ROS) sources, such as nuclear factor kappaB and NADPH oxidase. These experimental animal models reproduce key components of the injury and resolution phases of human ALI/ARDS and provide a methodology to explore mechanisms and potential new therapies. PMID:26312099

  13. Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury

    PubMed Central

    Liu, Shuai; Su, Xiaoli; Pan, Pinhua; Zhang, Lemeng; Hu, Yongbin; Tan, Hongyi; Wu, Dongdong; Liu, Ben; Li, Haitao; Li, Haosi; Li, Yi; Dai, Minhui; Li, Yuanyuan; Hu, Chengping; Tsung, Allan

    2016-01-01

    Neutrophil extracellular traps (NETs) facilitate the extracellular killing of pathogens. However, excessive NETs formation and poor degradation are associated with exacerbated immune responses and tissue injury. In this study, we investigated the role of NETs in lipopolysaccharide (LPS)-mediated acute lung injury (ALI) and assessed the use of DNase I, for the treatment of ALI. Additionally, we focused on the controversial issue of whether LPS directly induces NETs release in vitro. NETs formation was detected in murine ALI tissue in vivo and was associated with increased NETs markers, citrullinated-histone H3 tissue levels and NET-DNA levels in BALF. Treatment with DNase I significantly degraded NETs and reduced citrullinated-histone H3 levels, which protected against ALI and ameliorated pulmonary oedema and total protein in BALF. In addition, DNase I significantly reduced IL-6 and TNF-α levels in plasma and BALF. In vitro, LPS-activated platelets rather than LPS alone efficiently induced NETs release. In conclusion, NETs formed during LPS-induced ALI, caused organ damage and initiated the inflammatory response. NETs degradation by DNase I promoted NET-protein clearance and protected against ALI in mice; thus, DNase I may be a new potential adjuvant for ALI therapy. Specifically, LPS induced NETs formation in an indirect manner via platelets activation. PMID:27849031

  14. Transfusion Related Acute Lung Injury (TRALI): A Single Institution Experience of 15 Years.

    PubMed

    Kumar, Ramesh; Sedky, Mohammed Jaber; Varghese, Sunny Joseph; Sharawy, Osama Ebrahim

    2016-09-01

    Transfusion related acute Lung injury (TRALI) though a serious blood transfusion reaction with a fatality rate of 5-25 % presents with acute respiratory distress with hypoxaemia and noncardiac pulmonary oedema within 6 h of transfusion. In non fatal cases, it may resolve within 72 h or earlier. Although reported with an incidence of 1:5000, its true occurrence is rather unknown. Pathogenesis is believed to be related to sequestration and adhesion of neutrophils to the pulmonary capillary endothelium and its activation leading to its destruction and leaks. The patient's underlying condition, anti-neutrophil antibody in the transfused donor plasma and certain lipids that accumulate in routinely stores blood and components are important in its aetiopathogenesis. Patient's predisposing conditions include haematological malignancy, major surgery (especially cardiac), trauma and infections. The more commonly incriminated products include fresh frozen plasma (FFP), platelets (whole blood derived and apheresis), whole blood and Packed RBC. Occasional cases involving cryoprecipitate and Intravenous immunoglobulin (IVig) have also been reported. We present a 15 year single institution experience of TRALI, during which we observed 9 cases among 170,871 transfusions, giving an incidence of 1:19,000. We did not encounter cases of haematological malignancy or cardiac surgery in our TRALI patients. Among the blood products, that could be related to TRALI in our patients included solitary cases receiving cryoprecipitate, IVIg, and recombinant Factor VII apart from platelets and FFP. All patients were treated with oxygen support. Six patients required mechanical ventilation. Off label hydrocortisone was given to all patients. There were no cases of fatality among our patients.

  15. Readmission to Acute Care Hospital during Inpatient Rehabilitation for Traumatic Brain Injury

    PubMed Central

    Hammond, Flora M.; Horn, Susan D.; Smout, Randall J.; Beaulieu, Cynthia L.; Barrett, Ryan S.; Ryser, David K.; Sommerfeld, Teri

    2015-01-01

    Objective To investigate frequency, reasons, and factors associated with readmission to acute care (RTAC) during inpatient rehabilitation for traumatic brain injury (TBI). Design Prospective observational cohort. Setting Inpatient rehabilitation. Participants 2,130 consecutive admissions for TBI rehabilitation. Interventions Not applicable. Main Outcome Measure(s) RTAC incidence, RTAC causes, rehabilitation length of stay (RLOS), and rehabilitation discharge location. Results 183 participants (9%) experienced RTAC for a total 210 episodes. 161 patients experienced 1 RTAC episode, 17 had 2, and 5 had 3. Mean days from rehabilitation admission to first RTAC was 22 days (SD 22). Mean duration in acute care during RTAC was 7 days (SD 8). 84 participants (46%) had >1 RTAC episode for medical reasons, 102 (56%) had >1 RTAC for surgical reasons, and RTAC reason was unknown for 6 (3%) participants. Most common surgical RTAC reasons were: neurosurgical (65%), pulmonary (9%), infection (5%), and orthopedic (5%); most common medical reasons were infection (26%), neurologic (23%), and cardiac (12%). Older age, history of coronary artery disease, history of congestive heart failure, acute care diagnosis of depression, craniotomy or craniectomy during acute care, and presence of dysphagia at rehabilitation admission predicted patients with RTAC. RTAC was less likely for patients with higher admission Functional Independence Measure Motor scores and education less than high school diploma. RTAC occurrence during rehabilitation was significantly associated with longer RLOS and smaller likelihood of discharge home. Conclusion(s) Approximately 9% of patients with TBI experience RTAC during inpatient rehabilitation for various medical and surgical reasons. This information may help inform interventions aimed at reducing interruptions in rehabilitation due to RTAC. RTACs were associated with longer RLOS and discharge to an institutional setting. PMID:26212405

  16. Prevalence of pulmonary edema among the deceased cases with acute Methadone poisoning: A report from Iran

    PubMed Central

    Eizadi-Mood, Nastaran; Naeini, Seyed Amir Hossein Madani; Hedaiaty, Mahrang; Sabzghabaee, Ali Mohammad; Moudi, Maryam

    2016-01-01

    Objective: Methadone poisoning is common in our society, mainly in drug addicts. One of its lethal complications is pulmonary edema. Therefore, we evaluated the prevalence of pulmonary edema in the deceased cases with methadone poisoning and its possible relationship with some medical variables. Methods: In this cross-sectional study which was done in 2014, we have investigated the deceased patients with methadone toxicity who underwent autopsy at Isfahan Forensic Medicine Department (Iran). All variables including age, gender, and autopsy findings were recorded and analyzed. Demographic characteristics and medical complications of the patients were compared between the patients with or without pulmonary edema in the autopsy findings. Findings: There were 64 cases who died with methadone poisoning during the 1-year study period. The average age of cases (±standard deviation) was 32.1 ± 10.29 years, among which 92.2% were male. Based on the autopsy findings, 64.1% were diagnosed with pulmonary edema. There was no statistically significant relationship between pulmonary edema and age, gender, history of addiction, and hepatic or cardiovascular complications. Conclusion: Pulmonary edema is a common finding in deceased methadone poisoning cases and must be considered and ruled out in patients with acute methadone toxicity. PMID:27843967

  17. Transfusion-related acute lung injury (TRALI): a case report and literature review.

    PubMed

    Donelan, Kent J; Anderson, Keith A

    2011-03-01

    Transfusion-related acute lung injury (TRALI), a previously ill-defined transfusion reaction, has emerged as the leading cause of transfusion-related morbidity and mortality reported to the Food and Drug Administration (FDA). A 3-year-old male with a history of acute lymphoblastic leukemia (ALL) developed TRALI after receiving three units of platelets and a partial unit of packed red cells. He recovered after 24 hours in the pediatric intensive care unit. Laboratory investigation revealed that two of the four blood donors, from which the platelets and packed red cells had derived, had positive human leukocyte antigen (HLA) antibody screens. Further testing of these two donors revealed that one had a specific HLA antibody matching an antigen of the patient. This donor was implicated in the TRALI reaction. TRALI is often mistaken for other transfusion reactions, most notably pulmonary edema caused by circulatory overload or congestive heart failure. It is difficult to gauge which transfusion recipients are at risk for TRALI. Good judgment and transfusion practices when ordering blood products and recognition of the clinical manifestations, diagnosis and treatment of TRALI is critical.

  18. Adenosine 2A receptors in acute kidney injury.

    PubMed

    Vincent, I S; Okusa, M D

    2015-07-01

    Acute kidney injury (AKI) is an important clinical problem that may lead to death and for those who survive, the sequelae of AKI include loss of quality of life, chronic kidney disease and end-stage renal disease. The incidence of AKI continues to rise without clear successes in humans for the pharmacological prevention of AKI or treatment of established AKI. Dendritic cells and macrophages are critical early initiators of innate immunity in the kidney and orchestrate inflammation subsequent to ischaemia-reperfusion injury. These innate cells are the most abundant leucocytes present in the kidney, and they represent a heterogeneous population of cells that are capable of responding to cues from the microenvironment derived from pathogens or endogenous inflammatory mediators such as cytokines or anti-inflammatory mediators such as adenosine. Lymphocyte subsets such as natural killer T cells and Tregs also play roles in regulating ischaemic injury by promoting and suppressing inflammation respectively. Adenosine, produced in response to IR, is generally considered as a protective signalling molecule and elicits its physiological responses through four distinct adenosine receptors. However, its short half-life, lack of specificity and rapid metabolism limit the use of adenosine as a therapeutic agent. These adenosine receptors play various roles in regulating the activity of the aforementioned hematopoietic cells in elevated levels of adenosine such as during hypoxia. This review focuses on the importance of one receptor, the adenosine 2A subtype, in blocking inflammation associated with AKI.

  19. Vitamin D deficiency aggravates ischemic acute kidney injury in rats

    PubMed Central

    de Bragança, Ana Carolina; Volpini, Rildo A; Canale, Daniele; Gonçalves, Janaína G; Shimizu, Maria Heloisa M; Sanches, Talita R; Seguro, Antonio C; Andrade, Lúcia

    2015-01-01

    Vitamin D deficiency (VDD) increases the risk of death in hospitalized patients. Renal ischemia/reperfusion injury (IRI) induces acute kidney injury (AKI), which activates cell cycle inhibitors, including p21, a cyclin-dependent kinase inhibitor and genomic target of 25-hydroxyvitamin D, which is in turn a potent immunomodulator with antiproliferative effects. In this study, we assess the impact of VDD in renal IRI. Wistar rats were divided into groups, each evaluated for 30 days: control (receiving a standard diet); VDD (receiving a vitamin D-free diet); IRI (receiving a standard diet and subjected to 45-min bilateral renal ischemia on day 28); and VDD + IRI (receiving a vitamin D-free diet and subjected to 45-min bilateral renal ischemia on day 28). At 48 h after IRI, animals were euthanized; blood, urine, and kidney tissue samples were collected. Compared with IRI rats, VDD + IRI rats showed a more severe decrease in glomerular filtration rate, greater urinary protein excretion, a higher kidney/body weight ratio and lower renal aquaporin 2 expression, as well as greater morphological damage, characterized by increased interstitial area and tubular necrosis. Our results suggest that the severity of tubular damage in IRI may be associated with downregulation of vitamin D receptors and p21. VDD increases renal inflammation, cell proliferation and cell injury in ischemic AKI. PMID:25780095

  20. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance.

    PubMed

    Schrezenmeier, E V; Barasch, J; Budde, K; Westhoff, T; Schmidt-Ott, K M

    2017-03-01

    Various biomarkers of acute kidney injury (AKI) have been discovered and characterized in the recent past. These molecules can be detected in urine or blood and signify structural damage to the kidney. Clinically, they are proposed as adjunct diagnostics to serum creatinine and urinary output to improve the early detection, differential diagnosis and prognostic assessment of AKI. The most obvious requirements for a biomarker include its reflection of the underlying pathophysiology of the disease. Hence, a biomarker of AKI should derive from the injured kidney and reflect a molecular process intimately connected with tissue injury. Here, we provide an overview of the basic pathophysiology, the cellular sources and the clinical performance of the most important currently proposed biomarkers of AKI: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinase 2 (TIMP-2) and calprotectin (S100A8/9). We also acknowledge each biomarker's advantages and disadvantages as well as important knowledge gaps and perspectives for future studies.

  1. Traumatic forequarter amputation associated acute lung injury (ALI): report of one case.

    PubMed

    Liang, K; Gan, X; Deng, Z

    2012-07-01

    One case of traumatic forequarter amputation associated acute lung injury (ALI) was presented. A discussion reviewing the treatment guidelines for this devastating injury, and pointing out the importance of supporting the lung and preventing the development of acute respiratory distress syndrome (ARDS) was included.

  2. Pulmonary Resection for Non–Small Cell Lung Cancer in Patients With Prior Spinal Cord Injury

    PubMed Central

    Brunworth, Louis S; Dharmasena, Dharson; Virgo, Katherine S; Johnson, Frank E

    2006-01-01

    Background/Objective: We sought to determine the clinical course of patients with spinal cord injury (SCI) who subsequently developed bronchogenic carcinoma and underwent pulmonary resection. Methods: A nationwide retrospective study was conducted of all veterans at Department of Veterans Affairs Medical Centers for fiscal years 1993–2002 who were diagnosed with SCI, subsequently developed non–small cell lung cancer, and were surgically treated with curative intent. Inclusion criteria included American Spinal Injury Association type A injury (complete loss of neural function distal to the injury site) and traumatic etiology. Data were compiled from national Department of Veterans Affairs data sets and supplemented by operative reports, pathology reports, progress notes, and discharge summaries. Results: Seven patients met the inclusion/exclusion criteria and were considered evaluable. Five (71%) had one or more comorbid conditions in addition to their SCIs. All 7 underwent pulmonary lobectomy. Postoperative complications occurred in 4 patients (57%). Two patients died postoperatively on days 29 and 499, yielding a 30-day mortality rate of 14% and an in-hospital mortality rate of 29%. Conclusions: This seems to be the only case study in the English language literature on this topic. Patients with SCI who had resectable lung cancer had a high incidence of comorbid conditions. Those who underwent curative-intent surgery had high morbidity and mortality rates. Available evidence suggests that SCI should be considered a risk factor for adverse outcomes in major surgery of all types, including operations for primary lung cancer. PMID:16739556

  3. Intravenous Immunoglobulin Prevents Murine Antibody-Mediated Acute Lung Injury at the Level of Neutrophil Reactive Oxygen Species (ROS) Production

    PubMed Central

    Semple, John W.; Kim, Michael; Hou, Jing; McVey, Mark; Lee, Young Jin; Tabuchi, Arata; Kuebler, Wolfgang M.; Chai, Zhong-Wei; Lazarus, Alan H.

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg) may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature) and respiratory distress (dyspnea) were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios) and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage. PMID:22363629

  4. Negative-pressure pulmonary edema complicated by acute respiratory distress syndrome in an orangutan (Pongo pygmaeus abelii).

    PubMed

    Kenny, David E; Knightly, Felicia; Haas, Bradley; Hergott, Lawrence; Kutinsky, Ilana; Eller, Jimmie L

    2003-12-01

    A 22-yr-old, 86-kg, morbidly obese female orangutan (Pongo pygmaeus abelii) was immobilized and transported to the Denver Zoological Gardens hospital for a routine physical examination. Immediately after arriving at the hospital, cyanosis and apparent inadequate ventilatory efforts were noted. Clinically significant hypoxia occurred despite attempts to ventilate the orangutan through face mask, and attempts to place an endotracheal tube began. A large volume of pink-tinged frothy fluid flowed from the trachea when the laryngoscope was inserted into the oropharynx. Severe pulmonary edema due to negative-pressure pulmonary edema, precipitating life-threatening hypoxia was suspected. The orangutan was maintained on a mechanical ventilator using the neuromuscular blocking agent cisatracurium besylate and sedation with periodic doses of isoflurane and midazolam for 48 hr. Positive end-expiratory pressure was used while the orangutan was ventilated mechanically to improve respiratory function. The edema and hypoxia improved, but respiratory arrest ensued 30 min after extubation, when the orangutan was removed from mechanical ventilation. Necropsy and histopathology demonstrated that serious lung injury had led to acute respiratory distress syndrome.

  5. Acute kidney injury requiring hemodialysis in the tropics.

    PubMed

    Okunola, Oluyomi O; Ayodele, Olugbenga E; Adekanle, Adebode D

    2012-11-01

    The morbidity and mortality from acute kidney injury (AKI) have remained relatively high over the last six decades. The triad of infections, nephrotoxins and obstetric complications are still major causes of acute kidney injury in the tropics. This retrospective study is a five-year audit of acute renal failure (ARF) (or stage 3 AKI) in patients requiring hemodialysis at the renal unit of the Department of Medicine of the Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Osogbo, Nigeria. A total of 80 patients with AKI were treated over a five-year period at our center, of which 45 (56.2%) were in ARF, i.e. stage 3 AKI requiring hemodialysis. There were 24 males and 21 females. The most common cause of ARF among the patients was sepsis syndrome 16 (35.5%), while pregnancy-related cases accounted for 15 (33.3%) and nephrotoxins for 6 (13.3%). Five (33%) of the 15 pregnancy-related patients survived, and all were cases of septic abortion. Of the other 10 patients that did not survive, three (30%) had post-partum hemorrhage and seven (70%) post-partum eclampsia. In all, the mortality rate among our AKI presenting for hemodialysis at our center over a given year period was 28.8%. Majority of these were eclampsia related. The causes of ARF still remain the same in the tropics, eclampsia portends poor prognosis. Concerted efforts should be made at limiting this trend by active preventive services and early recognition of high-risk obstetrics cases.

  6. Acute pulmonary edema following inflation of arterial tourniquet.

    PubMed

    Santhosh, M C B; Pai, R B; Rao, R P

    2014-10-01

    Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described.

  7. VASCULAR AND THROMBOGENIC EFFECTS OF PULMONARY EXPOSURE TO LIBBY AMPHIBOLE

    EPA Science Inventory

    Acute pulmonary injury and chronic disease can impact the systemic vasculature through the release of inflammogenic and vasoactive mediators from the lung into the circulation. Exposure to Libby amphibole (LA) asbestos is associated with increased human cardiovascular mortality a...

  8. The intensive care medicine agenda on acute kidney injury.

    PubMed

    Pickkers, Peter; Ostermann, Marlies; Joannidis, Michael; Zarbock, Alexander; Hoste, Eric; Bellomo, Rinaldo; Prowle, John; Darmon, Michael; Bonventre, Joseph V; Forni, Lui; Bagshaw, Sean M; Schetz, Miet

    2017-01-30

    Acute kidney injury (AKI) is a common complication in the critically ill. Current standard of care mainly relies on identification of patients at risk, haemodynamic optimization, avoidance of nephrotoxicity and the use of renal replacement therapy (RRT) in established AKI. The detection of early biomarkers of renal tissue damage is a recent development that allows amending the late and insensitive diagnosis with current AKI criteria. Increasing evidence suggests that the consequences of an episode of AKI extend long beyond the acute hospitalization. Citrate has been established as the anticoagulant of choice for continuous RRT. Conflicting results have been published on the optimal timing of RRT and on the renoprotective effect of remote ischaemic preconditioning. Recent research has contradicted that acute tubular necrosis is the common pathology in AKI, that septic AKI is due to global kidney hypoperfusion, that aggressive fluid therapy benefits the kidney, that vasopressor therapy harms the kidney and that high doses of RRT improve outcome. Remaining uncertainties include the impact of aetiology and clinical context on pathophysiology, therapy and prognosis, the clinical benefit of biomarker-driven interventions, the optimal mode of RRT to improve short- and long-term patient and kidney outcomes, the contribution of AKI to failure of other organs and the optimal approach for assessing and promoting renal recovery. Based on the established gaps in current knowledge the trials that must have priority in the coming 10 years are proposed together with the definition of appropriate clinical endpoints.

  9. Assessment and prevalence of pulmonary oedema in contemporary acute heart failure trials: a systematic review

    PubMed Central

    Platz, Elke; Jhund, Pardeep S.; Campbell, Ross T.; McMurray, John J.

    2015-01-01

    Aims Pulmonary oedema is a common and important finding in acute heart failure (AHF). We conducted a systematic review to describe the methods used to assess pulmonary oedema in recent randomized AHF trials and report its prevalence in these trials. Methods and results Of 23 AHF trials published between 2002 and 2013, six were excluded because they were very small or not randomized, or missing full-length publications. Of the remaining 17 (n = 200–7141) trials, six enrolled patients with HF and reduced ejection fraction (HF-REF) and 11, patients with both HF-REF and HF with preserved ejection fraction (HF-PEF). Pulmonary oedema was an essential inclusion criterion, in most trials, based upon findings on physical examination (‘rales’), radiographic criteria (‘signs of congestion’), or both. The prevalence of pulmonary oedema in HF-REF trials ranged from 75% to 83% and in combined HF-REF and HF-PEF trials from 51% to 100%. Five trials did not report the prevalence or extent of pulmonary oedema assessed by either clinical examination or chest x-ray. Improvement of pulmonary congestion with treatment was inconsistently reported and commonly grouped with other signs of congestion into a score. One trial suggested that patients with rales over >2/3 of the lung fields on admission were at higher risk of adverse outcomes than those without. Conclusion Although pulmonary oedema is a common finding in AHF, represents a therapeutic target, and may be of prognostic importance, recent trials used inconsistent criteria to define it, and did not consistently report its severity at baseline or its response to treatment. Consistent and ideally quantitative, methods for the assessment of pulmonary oedema in AHF trials are needed. PMID:26230356

  10. Evaluation of Pulmonary and Systemic Toxicity of Oil Dispersant (COREXIT EC9500A®) Following Acute Repeated Inhalation Exposure

    PubMed Central

    Roberts, Jenny R; Anderson, Stacey E; Kan, Hong; Krajnak, Kristine; Thompson, Janet A; Kenyon, Allison; Goldsmith, William T; McKinney, Walter; Frazer, David G; Jackson, Mark; Fedan, Jeffrey S

    2014-01-01

    INTRODUCTION Oil spill cleanup workers come into contact with numerous potentially hazardous chemicals derived from the oil spills, as well as chemicals applied for mitigation of the spill, including oil dispersants. In response to the Deepwater Horizon Macondo well oil spill in the Gulf of Mexico in 2010, a record volume of the oil dispersant, COREXIT EC9500A, was delivered via aerial applications, raising concern regarding potential health effects that may result from pulmonary exposure to the dispersant. METHODS The current study examined the effects on pulmonary functions, cardiovascular functions, and systemic immune responses in rats to acute repeated inhalation exposure of COREXIT EC9500A at 25 mg/m3, five hours per day, over nine work days, or filtered air (control). At one and seven days following the last exposure, a battery of parameters was measured to evaluate lung function, injury, and inflammation; cardiovascular function; peripheral vascular responses; and systemic immune responses. RESULTS No significant alterations in airway reactivity were observed at one or seven days after exposure either in baseline values or following methacholine (MCh) inhalation challenge. Although there was a trend for an increase in lung neutrophils and phagocyte oxidant production at one-day post exposure, there were no significant differences in parameters of lung inflammation. In addition, increased blood monocytes and neutrophils, and decreased lymphocyte numbers at one-day post exposure also did not differ significantly from air controls, and no alterations in splenocyte populations, or serum or spleen immunoglobulin M (IgM) to antigen were observed. There were no significant differences in peripheral vascular responsiveness to vasoconstrictor and vasodilator agonists or in blood pressure (BP) responses to these agents; however, the baseline heart rate (HR) and HR responses to isoproterenol (ISO) were significantly elevated at one-day post exposure, with resolution

  11. An unusual cause of acute kidney injury due to oxalate nephropathy in systemic scleroderma.

    PubMed

    Mascio, Heather M; Joya, Christie A; Plasse, Richard A; Baker, Thomas P; Flessner, Michael F; Nee, Robert

    2015-08-01

    Oxalate nephropathy is an uncommon cause of acute kidney injury. Far rarer is its association with scleroderma, with only one other published case report in the literature. We report a case of a 75-year-old African-American female with a history of systemic scleroderma manifested by chronic pseudo-obstruction and small intestinal bacterial overgrowth (SIBO) treated with rifaximin, who presented with acute kidney injury with normal blood pressure. A renal biopsy demonstrated extensive acute tubular injury with numerous intratubular birefringent crystals, consistent with oxalate nephropathy. We hypothesize that her recent treatment with rifaximin for SIBO and decreased intestinal transit time in pseudo-obstruction may have significantly increased intestinal oxalate absorption, leading to acute kidney injury. Oxalate nephropathy should be considered in the differential diagnosis of acute kidney injury in scleroderma with normotension, and subsequent evaluation should be focused on bowel function to include alterations in gut flora due to antibiotic administration.

  12. Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

    PubMed Central

    Lee, Sang-Min; McLaughlin, Joseph N.; Frederick, Daniel R.; Zhu, Lin; Thambiayya, Kalidasan; Wasserloos, Karla J.; Kaminski, Iris; Pearce, Linda L.; Peterson, Jim; Li, Jin; Latoche, Joseph D.; Peck Palmer, Octavia M.; Stolz, Donna Beer; Fattman, Cheryl L.; Alcorn, John F.; Oury, Tim D.; Angus, Derek C.; Pitt, Bruce R.

    2013-01-01

    Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury. PMID:23275622

  13. Histone lysine crotonylation during acute kidney injury in mice

    PubMed Central

    Ruiz-Andres, Olga; Sanchez-Niño, Maria Dolores; Cannata-Ortiz, Pablo; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto; Sanz, Ana Belen

    2016-01-01

    ABSTRACT Acute kidney injury (AKI) is a potentially lethal condition for which no therapy is available beyond replacement of renal function. Post-translational histone modifications modulate gene expression and kidney injury. Histone crotonylation is a recently described post-translational modification. We hypothesized that histone crotonylation might modulate kidney injury. Histone crotonylation was studied in cultured murine proximal tubular cells and in kidneys from mice with AKI induced by folic acid or cisplatin. Histone lysine crotonylation was observed in tubular cells from healthy murine and human kidney tissue. Kidney tissue histone crotonylation increased during AKI. This was reproduced by exposure to the protein TWEAK in cultured tubular cells. Specifically, ChIP-seq revealed enrichment of histone crotonylation at the genes encoding the mitochondrial biogenesis regulator PGC-1α and the sirtuin-3 decrotonylase in both TWEAK-stimulated tubular cells and in AKI kidney tissue. To assess the role of crotonylation in kidney injury, crotonate was used to increase histone crotonylation in cultured tubular cells or in the kidneys in vivo. Crotonate increased the expression of PGC-1α and sirtuin-3, and decreased CCL2 expression in cultured tubular cells and healthy kidneys. Systemic crotonate administration protected from experimental AKI, preventing the decrease in renal function and in kidney PGC-1α and sirtuin-3 levels as well as the increase in CCL2 expression. For the first time, we have identified factors such as cell stress and crotonate availability that increase histone crotonylation in vivo. Overall, increasing histone crotonylation might have a beneficial effect on AKI. This is the first observation of the in vivo potential of the therapeutic manipulation of histone crotonylation in a disease state. PMID:27125278

  14. Partial Ventilatory Support Modalities in Acute Lung Injury and Acute Respiratory Distress Syndrome—A Systematic Review

    PubMed Central

    McMullen, Sarah M.; Meade, Maureen; Rose, Louise; Burns, Karen; Mehta, Sangeeta; Doyle, Robert; Henzler, Dietrich

    2012-01-01

    Purpose The efficacy of partial ventilatory support modes that allow spontaneous breathing in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is unclear. The objective of this scoping review was to assess the effects of partial ventilatory support on mortality, duration of mechanical ventilation, and both hospital and intensive care unit (ICU) lengths of stay (LOS) for patients with ALI and ARDS; the secondary objective was to describe physiologic effects on hemodynamics, respiratory system and other organ function. Methods MEDLINE (1966–2009), Cochrane, and EmBase (1980–2009) databases were searched using common ventilator modes as keywords and reference lists from retrieved manuscripts hand searched for additional studies. Two researchers independently reviewed and graded the studies using a modified Oxford Centre for Evidence-Based Medicine grading system. Studies in adult ALI/ARDS patients were included for primary objectives and pre-clinical studies for supporting evidence. Results Two randomized controlled trials (RCTs) were identified, in addition to six prospective cohort studies, one retrospective cohort study, one case control study, 41 clinical physiologic studies and 28 pre-clinical studies. No study was powered to assess mortality, one RCT showed shorter ICU length of stay, and the other demonstrated more ventilator free days. Beneficial effects of preserved spontaneous breathing were mainly physiological effects demonstrated as improvement of gas exchange, hemodynamics and non-pulmonary organ perfusion and function. Conclusions The use of partial ventilatory support modalities is often feasible in patients with ALI/ARDS, and may be associated with short-term physiological benefits without appreciable impact on clinically important outcomes. PMID:22916094

  15. Development of an Animal Model of Thoracolumbar Burst Fracture Induced Acute Spinal Cord Injury

    DTIC Science & Technology

    2015-05-01

    AWARD NUMBER: W81XWH-14-2-0013 TITLE: DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE - INDUCED ACUTE SPINAL CORD INJURY...2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER DEVELOPMENT OF AN ANIMAL MODEL OF THORACOLUMBAR BURST FRACTURE -INDUCED ACUTE SPINAL CORD INJURY 5b...leads to permanent disability following traumatic spine injury. A dramatic increase in blast related spinal burst fracture has been observed in

  16. Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

    PubMed Central

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative. PMID:25215245

  17. One Center’s Guide to Outpatient Management of Pediatric Cystic Fibrosis Acute Pulmonary Exacerbation

    PubMed Central

    Muirhead, Corinne A.; Sanford, Jillian N.; McCullar, Benjamin G.; Nolt, Dawn; MacDonald, Kelvin D.

    2016-01-01

    Cystic fibrosis (CF) is a chronic disorder characterized by acute pulmonary exacerbations that comprise increased cough, chest congestion, increased mucus production, shortness of breath, weight loss, and fatigue. Typically, severe episodes are treated in the inpatient setting and include intravenous antimicrobials, airway clearance therapy, and nutritional support. Children with less-severe findings can often be managed as outpatients with oral antimicrobials and increased airway clearance therapy at home without visiting the specialty CF center to begin treatment. Selection of specific antimicrobial agents is dependent on pathogens found in surveillance culture, activity of an agent in patients with CF, and the unique physiology of these patients. In this pediatric review, we present our practice for defining acute pulmonary exacerbation, deciding treatment location, initiating treatment either in-person or remotely, determining the frequency of airway clearance, selecting antimicrobial therapy, recommending timing for follow-up visit, and recognizing and managing treatment failures. PMID:27429564

  18. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    PubMed

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

  19. Acute promyelocytic leukemia presenting as pulmonary thromboembolism: Not all APLs bleed

    PubMed Central

    Vaid, Ashok K; Batra, Sandeep; Karanth, Suman S; Gupta, Sachin

    2015-01-01

    We present a rare case of acute promyelocytic leukemia (APL) presenting as pulmonary thromboembolism being misdiagnosed as community-acquired pneumonia. Thrombotic phenomenon in APL are poorly understood and grossly underreported. In our case, following no response to standard antibiotic treatment, the patient was further investigated and detected to have an acute pulmonary thromboembolism following right lower limb deep vein thrombosis (DVT). Though, complete blood picture revealed only mild hyperleukocytosis, bone marrow biopsy and aspiration revealed 60% blasts and a positive t (15,17)(q22,12) and PML retinoic acid receptor alpha (RARA) fusion protein on molecular cytogenetics. He was diagnosed as APL and received treatment with all-transretinoic acid (ATRA) and arsenic trioxide (ATO) and therapeutic anticoagulation PMID:26629469

  20. An unusual case of reversible acute kidney injury due to chlorine dioxide poisoning.

    PubMed

    Bathina, Gangadhar; Yadla, Manjusha; Burri, Srikanth; Enganti, Rama; Prasad Ch, Rajendra; Deshpande, Pradeep; Ch, Ramesh; Prayaga, Aruna; Uppin, Megha

    2013-09-01

    Chlorine dioxide is a commonly used water disinfectant. Toxicity of chlorine dioxide and its metabolites is rare. In experimental studies, it was shown that acute and chronic toxicity were associated with insignificant hematological changes. Acute kidney injury due to chlorine dioxide was not reported. Two cases of renal toxicity due to its metabolites, chlorate and chlorite were reported. Herein, we report a case of chlorine dioxide poisoning presenting with acute kidney injury.

  1. Injury to skeletal muscle of mice following acute and sub-acute pregabalin exposure

    PubMed Central

    Moshiri, Mohammad; Moallem, Seyed Adel; Attaranzadeh, Armin; Saberi, Zahra; Etemad, Leila

    2017-01-01

    Objective(s): Pregabalin (PGB) is a new antiepileptic drug that has received FDA approval for patient who suffers from central neuropathic pain, partial seizures, generalized anxiety disorder, fibromyalgia and sleep disorders. This study was undertaken to evaluate the possible adverse effects of PGB on the muscular system of mice. Materials and Methods: To evaluate the effect of PGB on skeletal muscle, the animals were exposed to a single dose of 1, 2 or 5 g /kg or daily doses of 20, 40 or 80 mg/kg for 21 days, intraperitoneally (IP). Twaenty-four hr after the last drug administration, all animals were sacrificed. The level of fast-twitch skeletal muscle troponin I and CK-MM activity were evaluated in blood as an indicator of muscle injury. Skeletal muscle pathological findings were also reported as scores ranging from 1 to 3 based on the observed lesion. Results: In the acute and sub-acute toxicity assay IP injection of PGB significantly increased the activity and levels of CK-MM and fsTnI compared to the control group. Sub-acute exposure to PGB caused damages that include muscle atrophy, infiltration of inflammatory cells and cell degeneration. Conclusion: PGB administration especially in long term care causes muscle atrophy with infiltration of inflammatory cells and cell degeneration. The fsTnI and CK-MM are reliable markers in PGB-related muscle injury. The exact mechanisms behind the muscular damage are unclear and necessitate further investigations. PMID:28392896

  2. [Effect of artificial ventilation on pulmonary capillary pressure in acute respiratory insufficiency].

    PubMed

    Labrousse, J; Tenaillon, A; Massabie, P; Simonneau, G; Lissac, J

    1977-05-07

    To determine the influence of intermittent positive pressure breathing (IPPB), the level of pulmonary capillary wedge pressure (PCWP) was compared during IPPB and after a short period off the respirator in 68 occasions on 42 patients with an acute respiratory failure (ARF) of various etiologies. During IPPB, the average PCWP was in the normal range in patients with toxic or neurologic comas and in cases of increased pulmonary capillary permeability edema (IPCPE), PCWP slightly increased within chronic obstructive pulmonary disease (COPD) complicated with ARF and in hemodynamic acute pulmonary edema (HAPE). During the weaning stage, PCWP decreased in the groups of coma, COPD, and IPCPE, but increased in HAPE. The weaning test demonstrates that IPPB influenced PCWP in all patients. Therefore, PCWP cannot be assumed to represent the left ventricle filling pressure. The weaning test allows differentiation of IPCPE from HAPE. In the event of over-infusion or hypovolemia, PCWP measured under IPPB can lead to misinterpretation if not followed up by a second measurement off the respirator.

  3. Assessment of right ventricular afterload by pressure waveform analysis in acute pulmonary hypertension

    PubMed Central

    Grignola, Juan C; Domingo, Enric; Devera, Lucía; Ginés, Fernando

    2011-01-01

    AIM: To characterize hydraulic right ventricle (RV) afterload by pulmonary arterial pressure waveform analysis in an acute pulmonary hypertension (PH) model. METHODS: Pulmonary artery (PA) flow and pressure were recorded in six anesthetized sheep. Acute isobaric PH was induced by phenylephrine (active) and PA mechanical constriction (passive). We estimated the amplitude of the forward and reflected pressure waves according to the inflection point. In most cases the inflection pressure was smooth, thus the inflection point was defined as the time at which the first derivative of pulmonary arterial pressure reached its first minimum. We calculated the input and characteristic (ZC, time-domain Li method) impedances, the capacitance index (stroke volume/pulse pressure), the augmentation index (AI) (reflected pressure/pulse pressure), the fractional pulse pressure (pulse pressure/mean pressure) and the wasted energy generated by the RV due to wave reflection during ejection (EW). RESULTS: Pulse pressure, fractional pulse pressure, AI and ZC increased and capacitance index decreased during passive PH with respect to control (P < 0.05). In contrast, ZC and the capacitance index did not change and EW and the AI decreased during active PH. Pulse pressure correlated with EW and ZC and the AI was correlated with EW (r > 0.6, P < 0.05). CONCLUSION: PA pressure waveform analysis allows the quantification of the dynamic RV afterload. Prospective clinical studies will be necessary to validate this time-domain approach to evaluate the dynamic RV afterload in chronic PH. PMID:22053220

  4. Non-invasive ventilation in acute cardiogenic pulmonary oedema

    PubMed Central

    Agarwal, R; Aggarwal, A; Gupta, D; Jindal, S

    2005-01-01

    Non-invasive ventilation (NIV) is the delivery of assisted mechanical ventilation to the lungs, without the use of an invasive endotracheal airway. NIV has revolutionised the management of patients with various forms of respiratory failure. It has decreased the need for invasive mechanical ventilation and its attendant complications. Cardiogenic pulmonary oedema (CPO) is a common medical emergency, and NIV has been shown to improve both physiological and clinical outcomes. From the data presented herein, it is clear that there is sufficiently high level evidence to favour the use of continuous positive airway pressure (CPAP), and that the use of CPAP in patients with CPO decreases intubation rate and improves survival (number needed to treat seven and eight respectively). However, there is insufficient evidence to recommend the use of bilevel positive airway pressure (BiPAP), probably the exception being patients with hypercapnic CPO. More trials are required to conclusively define the role of BiPAP in CPO. PMID:16210459

  5. Does acute exposure to aldehydes impair pulmonary function and structure?

    PubMed

    Abreu, Mariana de; Neto, Alcendino Cândido; Carvalho, Giovanna; Casquillo, Natalia Vasconcelos; Carvalho, Niedja; Okuro, Renata; Ribeiro, Gabriel C Motta; Machado, Mariana; Cardozo, Aléxia; Silva, Aline Santos E; Barboza, Thiago; Vasconcellos, Luiz Ricardo; Rodrigues, Danielle Araujo; Camilo, Luciana; Carneiro, Leticia de A M; Jandre, Frederico; Pino, Alexandre V; Giannella-Neto, Antonio; Zin, Walter A; Corrêa, Leonardo Holanda Travassos; Souza, Marcio Nogueira de; Carvalho, Alysson R

    2016-07-15

    Mixtures of anhydrous ethyl alcohol and gasoline substituted for pure gasoline as a fuel in many Brazilian vehicles. Consequently, the concentrations of volatile organic compounds (VOCs) such as ketones, other organic compounds, and particularly aldehydes increased in many Brazilian cities. The current study aims to investigate whether formaldehyde, acetaldehyde, or mixtures of both impair lung function, morphology, inflammatory and redox responses at environmentally relevant concentrations. For such purpose, C57BL/6 mice were exposed to either medical compressed air or to 4 different mixtures of formaldehyde and acetaldehyde. Eight hours later animals were anesthetized, paralyzed and lung mechanics and morphology, inflammatory cells and IL-1β, KC, TNF-α, IL-6, CCL2, MCP-1 contents, superoxide dismutase and catalalase activities were determined. The extra pulmonary respiratory tract was also analyzed. No differences could be detected between any exposed and control groups. In conclusion, no morpho-functional alterations were detected in exposed mice in relation to the control group.

  6. Risk factors for treatment failure in patients with severe acute cardiogenic pulmonary oedema.

    PubMed

    Di Marco, F; Tresoldi, S; Maggiolini, S; Bozzano, A; Bellani, G; Pesenti, A; Fumagalli, R

    2008-05-01

    Intubation is necessary in 7 to 20% of patients with severe acute cardiogenic pulmonary oedema despite optimal treatment. This study evaluated the usefulness of parameters largely available in clinical practice to predict the need for intubation in a population of acute cardiogenic pulmonary oedema patients treated with medical therapy and continuous positive airway pressure. The present retrospective cohort study involved 142 patients with severe acute cardiogenic pulmonary oedema who were admitted to coronary care or the intensive care unit of a university hospital and were treated by an in-hospital protocol. Physiological measurements and blood gas samples were evaluated at 'baseline' (just after admission), 'early' (one to three hours after beginning treatment) and 'late' (eight to 10 hours after beginning treatment). Twenty-two patients (15.5%) required intubation. A systolic blood pressure at admission lower than 140 mmHg was significantly associated with a higher risk for intubation, while hypercapnic patients or those with a reduced left ventricular ejection fraction at admission did not show a worse prognosis. A simple score based on largely available parameters (1 point for each: age >78 years, systolic blood pressure <140 mmHg at admission, arterial blood gas acidosis and heart rate >95 bpm at early time) is proposed. The rate of intubation according to this score ranged from 0% (score of 0) to 90% (score of 3). Our study found that simple parameters available in clinical practice are significantly associated with the need for intubation in acute cardiogenic pulmonary oedema patients treated with continuous positive airway pressure and medical therapy. A simple score to evaluate the need for endotracheal intubation is proposed.

  7. Performance of magnetic resonance angiography in suspected acute pulmonary embolism.

    PubMed

    Blum, Alain; Bellou, Abdelouahab; Guillemin, Francis; Douek, Philippe; Laprévote-Heully, Marie-Claude; Wahl, Denis

    2005-03-01

    Pulmonary embolism (PE) is a common and potentially fatal disorder. Non-specific findings make the clinical diagnosis of PE difficult. To assess the diagnostic value and inter-observer agreement of magnetic resonance angiography (MRA) in a cohort of patients with suspected PE, we conducted a prospective clinical study. MRA was compared for sensitivity and specificity to a diagnostic strategy including clinical probability, D-dimer testing, spiral CT, ultrasound leg compression and pulmonary angiography. A total of 89 patients with clinically suspected PE were included: the clinical probability of PE was intermediate or high in 78, and low in the remaining 11. All patients underwent monoor multi-slice spiral CT and MRA with gadolinium injection (both within 24 hours of entry to the study). Anticoagulation was withheld in patients concerned about the strategy. All subjects were followed up for 3 months. MRA was read independently by two experienced teams of radiologists: one local and one from another university centre. Spiral CT was positive in 62 of 63 cases of confirmed PE. No patient with negative CT findings was positive ultrasonographically. Only one patient with a negative CT (and negative ultrasound) had a recurrent thromboembolic event. The first team diagnosed PE with MRA in 47 cases, with a sensitivity of 71% and a specificity of 92%; the second team obtained the diagnosis in 23 cases, with a sensitivity of 31% and a specificity of 85%. Inter-observer agreement between MRA reading was low: Kappa = 0.16 (-0.01 to 0.33); p = 0.07. In conclusion, compared with a non-invasive strategy based on spiral CT, the diagnostic value of MRA is limited by poor inter-observer agreement.

  8. Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice

    SciTech Connect

    Lee, Ye-Ji; Lee, Seung-Hae; Youn, Young-So; Choi, Ji-Yeon; Song, Keung-Sub; Cho, Min-Sun; Kang, Jihee Lee

    2012-08-15

    Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ►Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ►Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ►TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

  9. Acute Kidney Injury Associated With Vancomycin When Laxity Leads to Injury and Findings on Kidney Biopsy.

    PubMed

    Katikaneni, Madhavi; Lwin, Lin; Villanueva, Hugo; Yoo, Jinil

    2016-01-01

    The issue of vancomycin-induced acute kidney injury (AKI) has resurged with the use of intravenous vancomycin as a first-line antibiotic, often for prolonged periods of time for the management of serious methicillin-resistant Staphylococcus aureus infections, and with a higher recommended trough level (15-20 μg/mL). We have observed 3 patients on intravenous vancomycin who developed very high trough levels (>40 μg/mL) and severe (stage 3) AKI. Those 3 patients underwent kidney biopsy for unresolving AKI, which revealed findings compatible with acute tubular necrosis. The first patient initially developed asymptomatic acute interstitial nephritis because of a concomitant antibiotic that caused worsening of kidney function, and the dose of vancomycin was not properly adjusted while staying at the nursing home. The second was an emaciated patient (BMI, 14) whose serum creatinine level was a deceptive marker of kidney function for the proper dosing of vancomycin, resulting in a toxic level. The third patient developed vancomycin-related AKI on an initially high therapeutic level, which then contributed to further rising in vancomycin level and subsequently causing severe AKI. One patient required hemodialysis, but all 3 patients ultimately recovered their kidney function significantly. A regular monitoring (preferably twice weekly) of serum creatinine and vancomycin trough level is advisable to minimize vancomycin-associated AKI, primarily acute tubular necrosis, for patients requiring prolonged administration of vancomycin (>2 weeks) on the currently recommended higher therapeutic trough levels (>15 μg/mL).

  10. The HMGB1-RAGE Inflammatory Pathway: Implications for Brain Injury-Induced Pulmonary Dysfunction

    PubMed Central

    Weber, Daniel J.; Allette, Yohance M.; Wilkes, David S.

    2015-01-01

    Abstract Significance: Deceased patients who have suffered severe traumatic brain injury (TBI) are the largest source of organs for lung transplantation. However, due to severely compromised pulmonary lung function, only one-third of these patients are eligible organ donors, with far fewer capable of donating lungs (∼20%). As a result of this organ scarcity, understanding and controlling the pulmonary pathophysiology of potential donors are key to improving the health and long-term success of transplanted lungs. Recent Advances: Although the exact mechanism by which TBI produces pulmonary pathophysiology remains unclear, it may be related to the release of damage-associated molecular patterns (DAMPs) from the injured tissue. These heterogeneous, endogenous host molecules can be rapidly released from damaged or dying cells and mediate sterile inflammation following trauma. In this review, we highlight the interaction of the DAMP, high-mobility group box protein 1 (HMGB1) with the receptor for advanced glycation end-products (RAGE), and toll-like receptor 4 (TLR4). Critical Issues: Recently published studies are reviewed, implicating the release of HMGB1 as producing marked changes in pulmonary inflammation and physiology following trauma, followed by an overview of the experimental evidence demonstrating the benefits of blocking the HMGB1-RAGE axis. Future Directions: Targeting the HMGB1 signaling axis may increase the number of lungs available for transplantation and improve long-term benefits for organ recipient patient outcomes. Antioxid. Redox Signal. 23, 1316–1328. PMID:25751601

  11. Necroptosis in acute kidney injury: a shedding light

    PubMed Central

    Wang, S; Zhang, C; Hu, L; Yang, C

    2016-01-01

    Acute kidney injury (AKI) is a common and severe clinical condition with a heavy healthy burden around the world. In spite of supportive therapies, the mortality associated with AKI remains high. Our limited understanding of the complex cell death mechanism in the process of AKI impedes the development of desirable therapeutics. Necroptosis is a recently identified novel form of cell death contributing to numerable diseases and tissue damages. Increasing evidence has suggested that necroptosis has an important role in the pathogenesis of various types of AKI. Therefore, we present here the signaling pathways and main regulators of necroptosis that are potential candidate for therapeutic strategies. Moreover, we emphasize on the potential role and corresponding mechanisms of necroptosis in AKI based on recent advances, and also discuss the possible therapeutic regimens based on manipulating necroptosis. Taken together, the progress in this field sheds new light into the prevention and management of AKI in clinical practice. PMID:26938298

  12. Hypothermia-induced acute kidney injury in an elderly patient.

    PubMed

    Yoon, Hyun Ju; Kim, Mun Chul; Park, Jae Woo; Yang, Min A; Lee, Cheon Beom; Sun, In O; Lee, Kwang Young

    2014-01-01

    Hypothermia, defined as an unintentional decline in the core body temperature to below 35℃, is a life-threatening condition. Patients with malnutrition and diabetes mellitus as well as those of advanced age are at high risk for accidental hypothermia. Due to the high mortality rates of accidental hypothermia, proper management is critical for the wellbeing of patients. Accidental hypothermia was reported to be associated with acute kidney injury (AKI) in over 40% of cases. Although the pathogenesis remains to be elucidated, vasoconstriction and ischemia in the kidney were considered to be the main mechanisms involved. Cases of AKI associated with hypothermia have been reported worldwide, but there have been few reports of hypothermia-induced AKI in Korea. Here, we present a case of hypothermia-induced AKI that was treated successfully with rewarming and supportive care.

  13. Acute kidney injury after massive attack of Africanised bees

    PubMed Central

    Bridi, Ramaiane A; Balbi, Andre Luis; Neves, Precil M; Ponce, Daniela

    2014-01-01

    Acute kidney injury (AKI) is a well-documented complication of massive attack by Africanised bees and can be observed 48–72 h after the accident. We report a case of Africanised bees attack followed by severe and lethal AKI. A 56-year-old man was admitted to emergency department after a massive attack of Africanised bees (>1000 bee stings). He was unconscious, presenting with hypotension and tachycardia. Mechanical ventilation, volume expansion and care for anaphylaxis were instituted. The patient was transferred to the intensive care unit (ICU) and after 48 h he developed rhabdomyolysis, oliguria, increased creatinine levels, hyperkalaemia and refractory acidosis. A diagnosis of AKI secondary to rhabdomyolysis and shock was made. The patient was treated with a prolonged course of haemodialysis. However, he progressed to refractory shock and died 5 days after admission. PMID:24618864

  14. [Star fruit as a cause of acute kidney injury].

    PubMed

    Scaranello, Karilla Lany; Alvares, Valeria Regina de Cristo; Carneiro, Daniely Maria Queiroz; Barros, Flávio Henrique Soares; Gentil, Thais Marques Sanches; Thomaz, Myriam José; Pereira, Benedito Jorge; Pereira, Mariana Batista; Leme, Graziella Malzoni; Diz, Mary Carla Esteves; Laranja, Sandra Maria Rodrigues

    2014-01-01

    The star fruit belongs to the family Oxalidacea, species Averrhoa carambola. It is rich in minerals, vitamin A, C, B complex vitamins and oxalic acid. Recent studies show that the toxicity of the fruit differs between the patients and may be explained by single biological responses, age, and the intake quantity of the neurotoxin in each fruit in addition to glomerular filtration rate given by each patient. Additionally, the nephrotoxicity caused by the fruit is dose-dependent and may lead to the deposition of crystals of calcium oxalate intratubular, as well as by direct injury to the renal tubular epithelium, leading to apoptosis of the same. We report the case of a patient who after ingestion of the juice and fresh fruit, developed acute renal failure requiring dialysis, evolving with favourable outcome and recovery of renal function.

  15. Acute kidney injury in the fetus and neonate.

    PubMed

    Nada, Arwa; Bonachea, Elizabeth M; Askenazi, David J

    2017-04-01

    Acute kidney injury (AKI) is an under-recognized morbidity of neonates; the incidence remains unclear due to the absence of a unified definition of AKI in this population and because previous studies have varied greatly in screening for AKI with serum creatinine and urine output assessments. Premature infants may be born with less than half of the nephrons compared with term neonates, predisposing them to chronic kidney disease (CKD) early on in life and as they age. AKI can also lead to CKD, and premature infants with AKI may be at very high risk for long-term kidney problems. AKI in neonates is often multifactorial and may result from prenatal, perinatal, or postnatal insults as well as any combination thereof. This review focuses on the causes of AKI, the importance of early detection, the management of AKI in neonates, and long-term sequela of AKI in neonates.

  16. Galangin dampens mice lipopolysaccharide-induced acute lung injury.

    PubMed

    Shu, Yu-Sheng; Tao, Wei; Miao, Qian-Bing; Lu, Shi-Chun; Zhu, Ya-Bing

    2014-10-01

    Galangin, an active ingredient of Alpinia galangal, has been shown to possess anti-inflammatory and antioxidant activities. Inflammation and oxidative stress are known to play vital effect in the pathogenesis of acute lung injury (ALI). In this study, we determined whether galangin exerts lung protection in lipopolysaccharide (LPS)-induced ALI. Male BALB/c mice were randomized to receive galangin or vehicle intraperitoneal injection 3 h after LPS challenge. Samples were harvested 24 h post LPS administration. Galangin administration decreased biochemical parameters of oxidative stress and inflammation, and improved oxygenation and lung edema in a dose-dependent manner. These protective effects of galangin were associated with inhibition of nuclear factor (NF)-κB and upregulation of heme oxygenase (HO)-1. Galangin reduces LPS-induced ALI by inhibition of inflammation and oxidative stress.

  17. Warfarin related acute kidney injury: A case report

    PubMed Central

    Mendonca, S.; Gupta, D.; Valsan, A.; Tewari, R.

    2017-01-01

    Warfarin is an oral anticoagulant used extensively in clinical practice; However, its side-effect of causing renal damage has been recently detected. The mechanism leading to renal damage is glomerular hemorrhage and red blood cell tubular casts prothrombin time. Recently, it was found that warfarin causes renal damage in patients with chronic kidney disease and is also associated with progression of renal disease. Warfarin causing acute kidney injury in patients with normal renal function is a rare manifestation. It is important to be aware of this condition as its innocuous presence can lead to chronic kidney disease if not corrected in time. Further studies have also found that novel oral anticoagulants such as dabigatran also cause a similar syndrome and hence a new term called anticoagulant-related nephropathy is now in vogue. PMID:28182051

  18. Multiphoton imaging for assessing renal disposition in acute kidney injury

    NASA Astrophysics Data System (ADS)

    Liu, Xin; Liang, Xiaowen; Wang, Haolu; Roberts, Darren M.; Roberts, Michael S.

    2016-11-01

    Estimation of renal function and drug renal disposition in acute kidney injury (AKI), is important for appropriate dosing of drugs and adjustment of therapeutic strategies, but is challenging due to fluctuations in kidney function. Multiphoton microscopy has been shown to be a useful tool in studying drug disposition in liver and can reflect dynamic changes of liver function. We extend this imaging technique to investigate glomerular filtration rate (GFR) and tubular transporter functional change in various animal models of AKI, which mimic a broad range of causes of AKI such as hypoxia (renal ischemia- reperfusion), therapeutic drugs (e.g. cisplatin), rhabdomyolysis (e.g. glycerol-induced) and sepsis (e.g. LPSinduced). The MPM images revealed acute injury of tubular cells as indicated by reduced autofluorescence and cellular vacuolation in AKI groups compared to control group. In control animal, systemically injected FITC-labelled inulin was rapidly cleared from glomerulus, while the clearance of FITC-inulin was significantly delayed in most of animals in AKI group, which may reflect the reduced GFR in AKI. Following intravenous injection, rhodamine 123, a fluorescent substrate of p-glycoprotein (one of tubular transporter), was excreted into urine in proximal tubule via p-glycoprotein; in response to AKI, rhodamine 123 was retained in tubular cells as revealed by slower decay of fluorescence intensity, indicating P-gp transporter dysfunction in AKI. Thus, real-time changes in GFR and transporter function can be imaged in rodent kidney with AKI using multiphoton excitation of exogenously injected fluorescent markers.

  19. Segmental pulmonary vascular resistances during oleic acid lung injury in rabbits.

    PubMed

    Maarek, J M; Grimbert, F

    1994-10-01

    We studied in isolated rabbit lungs the effects of oleic acid (OA) injury on the segmental distribution of vascular resistance. Vascular occlusion pressures were measured in control and OA-injured preparations over 90 min. Capillary filtration coefficient KF,C increased from 0.61 (+/- 0.10) to 0.91 (+/- 0.14) g.min-1.mmHg-1.(100 g)-1 in OA-injured lungs whereas it remained constant in control lungs. Total pulmonary vascular resistance changed little in both control and OA-injured lungs. OA injury resulted in a 15% increase of the double occlusion capillary pressure. In addition, the contribution of the microvascular to the total vascular resistance rose from 8% to 22%. The increase in microvascular resistance was significant 15 min after OA on the arteriolar side and became significant 30 min later on the venular side. Oleic acid injury does not change the total pulmonary vascular resistance but alters the distribution of segmental resistances in the isolated rabbit lung, thereby contributing to the accumulation of lung water in this model of low pressure permeability edema.

  20. Transfusion-related acute lung injury: current concepts for the clinician.

    PubMed

    Triulzi, Darrell J

    2009-03-01

    The leading cause of transfusion-related morbidity and mortality in the United States is transfusion-related acute lung injury (TRALI). Diagnostic criteria for TRALI have recently been developed and primarily consist of hypoxia and bilateral pulmonary edema occurring during or within 6 h of a transfusion in the absence of cardiac failure or intravascular volume overload. The primary differential diagnosis is transfusion-associated circulatory overload and differentiation can be difficult. Treatment is supportive with oxygen and mechanical ventilation. Diuresis is not indicated and the role of steroids is unproven. Patients typically recover within a few days. All types of blood products have been associated with TRALI, however, the plasma-rich components, such as fresh frozen plasma and apheresis platelets, have been most frequently implicated. The pathogenesis of TRALI is not completely understood. Leukocyte antibodies in donor plasma have been implicated in most cases with antibodies directed at human leukocyte antigen (HLA) class I, HLA class II or neutrophil-specific antigens, particularly HNA-3a. Activation of pulmonary endothelium is important in the development of TRALI and may account for most cases being observed in surgical or intensive care unit patients. Transfused leukoagglutinating antibodies bind to recipients' neutrophils localized to pulmonary endothelium resulting in activation and release of oxidases and other damaging biologic response modifiers that cause capillary leak. In a minority of TRALI cases, no antibodies are identified and it is postulated that neutrophil priming factors in the transfused component can mediate TRALI in a patient with pulmonary endothelial activation, the so called "two hit" mechanism. Recognition of the role of anti-leukocyte antibodies has led to new strategies to reduce the risk of TRALI. Female blood donors with a previous pregnancy frequently have HLA antibodies with an overall prevalence of 24% and increasing

  1. Protective Effects of Cucurbitacin B on Acute Lung Injury Induced by Sepsis in Rats

    PubMed Central

    Hua, Shu; Liu, Xing; Lv, Shuguang; Wang, Zhifang

    2017-01-01

    Background The aim of this study was to investigate the protective effects of cucurbitacin B (CuB) on sepsis-induced acute lung injury (ALI) in rats. Material/Methods An ALI model was made by cecal ligation and puncture (CLP) in SD rats. Rats were randomly divided into 5 groups (n=15 per group): animals undergoing a sham CLP (sham group); animals undergoing CLP (CLP control group); animals undergoing CLP and treated with CuB at 1 mg/kg of body weight (bw) (low-dose CuB [L-CuB] group), animals undergoing CuB at 2 mg/kg of bw (mid-dose CuB [M-CuB] group); and animals undergoing CuB at 5 mg/kg of bw (high-dose CuB [H-CuB] group). Samples of blood and lung tissue were harvested at different time points (6, 12, and 24 hour post-CLP surgery) for the detection of indicators which represented ALI. Five rats were respectively sacrificed at each time point. Pathological changes of lung tissue were observed by H&E staining. Another 50 rats were distributed into the same five groups to record the 72 hour survival rates. Results Treatment with CuB significantly increased the blood gas PaO2 levels and decreased lung wet/dry (W/D) ratio (p<0.05). It significantly reduced protein concentration, accumulation of the inflammatory cells, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), (p<0.05), in the bronchoalveolar lavage fluid (BALF). Pulmonary pathological damage and survival rates at 72 hours were found to be effectively improved by CuB. In addition, CuB performed its pulmonary protection effects in a dose-depended manner. Conclusions CuB can effectively improve the pulmonary gas exchange function, reduce pulmonary edema, and inhibit the inflammatory response in the lung, revealing that CuB may serve as a potential therapeutic strategy for sepsis-induced ALI. PMID:28315572

  2. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats#

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for both ozone-induced metabolic effects and lung injury. Male Wistar-Kyoto rats ...

  3. Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects are Diminished in Adrenalectomized Rats

    EPA Science Inventory

    Acute ozone exposure increases circulating stress hormones and induces peripheral metabolic alterations in animals and humans. We hypothesized that the increase of adrenal-derived stress hormones is necessary for ozone-induced systemic metabolic effects and lung injury. Male Wis...

  4. Acute kidney injury associated with ingestion of star fruit: Acute oxalate nephropathy.

    PubMed

    Barman, A K; Goel, R; Sharma, M; Mahanta, P J

    2016-01-01

    Starfruit (Averrhoa carambola) and its juice are popular in the Indian subcontinent as an indigenous medicine. Oxalate concentration in this fruit and it's freshly prepared juice is very high. We present a report of patients presenting with acute kidney injury due to oxalate nephropathy admitted in a single center. All patients had history of ingesting star fruit. Patients became symptomatic after 10-12 h of eating and main symptoms were pain abdomen and decrease in urine output. Three patients needed hemodialysis. All improved with complete renal recovery. Taking star fruit in large amount on an empty stomach and in a dehydrated state is a risk factor for nephrotoxicity.

  5. Acute kidney injury associated with ingestion of star fruit: Acute oxalate nephropathy

    PubMed Central

    Barman, A. K.; Goel, R.; Sharma, M.; Mahanta, P. J.

    2016-01-01

    Starfruit (Averrhoa carambola) and its juice are popular in the Indian subcontinent as an indigenous medicine. Oxalate concentration in this fruit and it's freshly prepared juice is very high. We present a report of patients presenting with acute kidney injury due to oxalate nephropathy admitted in a single center. All patients had history of ingesting star fruit. Patients became symptomatic after 10–12 h of eating and main symptoms were pain abdomen and decrease in urine output. Three patients needed hemodialysis. All improved with complete renal recovery. Taking star fruit in large amount on an empty stomach and in a dehydrated state is a risk factor for nephrotoxicity. PMID:27942177

  6. Reversible anuric acute kidney injury secondary to acute renal autoregulatory dysfunction.

    PubMed

    Imbriano, Louis J; Maesaka, John K; Drakakis, James; Mattana, Joseph

    2014-02-01

    Autoregulation of glomerular capillary pressure via regulation of the resistances at the afferent and efferent arterioles plays a critical role in maintaining the glomerular filtration rate over a wide range of mean arterial pressure. Angiotensin II and prostaglandins are among the agents which contribute to autoregulation and drugs which interfere with these agents may have a substantial impact on afferent and efferent arteriolar resistance. We describe a patient who suffered an episode of anuric acute kidney injury following exposure to a nonsteroidal anti-inflammatory agent while on two diuretics, an angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker. The episode completely resolved and we review some of the mechanisms by which these events may have taken place and suggest the term "acute renal autoregulatory dysfunction" to describe this syndrome.

  7. Potential Application of Viral Empty Capsids for the Treatment of Acute Lung Injury/Acute Respiratory Distress Syndrome

    DTIC Science & Technology

    2016-07-01

    Acute Respiratory Distress Syndrome PRINCIPAL INVESTIGATOR: Prof. Ariella Oppenheim CONTRACTING ORGANIZATION: Hebrew University of Jerusalem...Lung / 5a. CONTRACT NUMBER Injury/Acute Respiratory Distress Syndrome 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Prof. Ariella...mechanism elicited by VLPs that attenuate 2CLP-induced sepsis, to be performed as the project continues. 15. SUBJECT TERMS Acute Respiratory Distress

  8. Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

    DTIC Science & Technology

    2007-05-01

    acute lung injury (ALI) and acute respiratory distress syndrome ( ARDS ). Criteria for diagnosing ALI and predicting...Rationale: Smoke inhalation victims are at high risk of developing acute respiratory distress syndrome ( ARDS ). Given the delay of 12 or more hours...Background: Although smoke inhalation injury victims frequently develop acute respiratory distress syndrome ( ARDS ), no early prognostic

  9. Acute Lung Injury Following Smoke Inhalation: Predictive Value of Sputum Biomarkers and Time Course of Lung Inflammation

    DTIC Science & Technology

    2006-04-01

    acute respiratory distress syndrome ( ARDS ). Given the delay of 12 or...Keywords: Inhalation Burns, Acute Respiratory Distress Syndrome , Interleukin-8, Interleukin- 1 beta. 4/14/2006 Markers of Smoke Inhalation Injury 2...Zimmerman 2005; Park et al., 2001), all hallmarks of acute lung injury (ALI) and acute respiratory distress syndrome ( ARDS ). The general

  10. Obesity, Acute Kidney Injury, and Mortality in Critical Illness

    PubMed Central

    Danziger, John; Chen, Ken; Lee, Joon; Feng, Mengling; Mark, Roger G.; Celi, Leo Anthony; Mukamal, Kenneth J.

    2015-01-01

    Background Although obesity is associated with risk for chronic kidney disease (CKD) and improved survival, less is known about the associations of obesity with risk of acute kidney injury (AKI) and post-AKI mortality. Methods In a single-center inception cohort of almost 15,000 critically ill patients, we evaluated the association of obesity with AKI and AKI severity, as well as in-hospital and one-year survival. AKI was defined using the Kidney Disease Outcome Quality Initiative criteria. Results The AKI incidence rates for normal, overweight, Class I, II, and III Obesity were 18.6, 20.6, 22.5, 24.3 and 24.0 percent respectively, and the adjusted odds ratios of AKI were 1.18 [95% CI 1.06–1.31], 1.35 [1.19–1.53], 1.47 [1.25–1.73], 1.59 [1.31–1.87], compared to normal weight, respectively. Each 5 kg/m2 increase in body mass index (BMI) was associated with a 10% risk [95% CI 1.06–1.24; p<0.001] of more severe AKI. Within-hospital and one-year survival rates associated with the AKI episodes were similar across BMI categories. In conclusion, obesity is a risk factor for AKI injury, which is associated with increased short- and long-term mortality. PMID:26496453

  11. Acute kidney injury: Renal disease in the ICU.

    PubMed

    Seller-Pérez, G; Más-Font, S; Pérez-Calvo, C; Villa-Díaz, P; Celaya-López, M; Herrera-Gutiérrez, M E

    2016-01-01

    Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine - the most common marker of AKI - should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a "static" disease to being a "dynamic process" that requires continuous evaluation of kidney function adapted to the reality of the ICU patient.

  12. A case study of bofutsushosan-induced pulmonary injury in a patient: Case report

    PubMed Central

    Miyazaki, Kunihiko; Satoh, Hiroaki; Watanabe, Hiroko; Shiozawa, Toshihiro; Tamura, Tomohiro; Kawaguchi, Mio; Hizawa, Nobuyuki

    2016-01-01

    Bofutsushosan, a herbal (traditional Kampo) medicine, is administered to obese patients in North-East Asia. Bofutsushosan has been reported to exert various anti-obesity effects by stimulating the adipose tissue. The present study describes the case of a patient who developed a severe pulmonary injury that was potentially associated with bofutsushosan therapy. A 52-year-old woman was admitted to Mito Medical Center, University of Tsukuba, Mito Kyodo General Hospital (Mito, Japan) due to progressive dyspnea. Two months previously, bofutsushosan had been newly prescribed for her obesity. Bilateral ground-glass opacities and progressive respiratory deterioration suggested respiratory failure due to a therapeutic agent-induced lung injury. With discontinuation of bofutsushosan and the administration of a corticosteroid, an improvement in her respiratory condition was achieved, although sequelae remained in certain areas of the lungs. Resumption of other therapeutic agents did not reinduce the lung injury. Therefore, a diagnosis of bofutsushosan-induced lung injury was made. Although bofutsushosan-induced lung injury is particularly rare, clinicians should consider it when bofutsushosan is used. PMID:28101346

  13. CFTR-regulated MAPK/NF-κB signaling in pulmonary inflammation in thermal inhalation injury

    PubMed Central

    Dong, Zhi Wei; Chen, Jing; Ruan, Ye Chun; Zhou, Tao; Chen, Yu; Chen, YaJie; Tsang, Lai Ling; Chan, Hsiao Chang; Peng, Yi Zhi

    2015-01-01

    The mechanism underlying pulmonary inflammation in thermal inhalation injury remains elusive. Cystic fibrosis, also hallmarked with pulmonary inflammation, is caused by mutations in CFTR, the expression of which is temperature-sensitive. We investigated whether CFTR is involved in heat-induced pulmonary inflammation. We applied heat-treatment in 16HBE14o- cells with CFTR knockdown or overexpression and heat-inhalation in rats in vivo. Heat-treatment caused significant reduction in CFTR and, reciprocally, increase in COX-2 at early stages both in vitro and in vivo. Activation of ERK/JNK, NF-κB and COX-2/PGE2 were detected in heat-treated cells, which were mimicked by knockdown, and reversed by overexpression of CFTR or VX-809, a reported CFTR mutation corrector. JNK/ERK inhibition reversed heat-/CFTR-knockdown-induced NF-κB activation, whereas NF-κB inhibitor showed no effect on JNK/ERK. IL-8 was augmented by heat-treatment or CFTR-knockdown, which was abolished by inhibition of NF-κB, JNK/ERK or COX-2. Moreover, in vitro or in vivo treatment with curcumin, a natural phenolic compound, significantly enhanced CFTR expression and reversed the heat-induced increases in COX-2/PGE2/IL-8, neutrophil infiltration and tissue damage in the airway. These results have revealed a CFTR-regulated MAPK/NF-κB pathway leading to COX-2/PGE2/IL-8 activation in thermal inhalation injury, and demonstrated therapeutic potential of curcumin for alleviating heat-induced pulmonary inflammation. PMID:26515683

  14. Postpartum acute kidney injury: a review of 99 cases.

    PubMed

    Eswarappa, Mahesh; Madhyastha, P Rakesh; Puri, Sonika; Varma, Vijay; Bhandari, Aneesh; Chennabassappa, Gurudev

    2016-07-01

    Postpartum acute kidney injury (PPAKI) constitutes an important cause of obstetric AKI. It is associated with high maternal and fetal mortality in developing nations. The aim of this study is to survey the etiology and outcomes of PPAKI in a tertiary care Indian hospital. Ninety-nine patients, without prior comorbidities, treated for PPAKI, between 2005-2014 at M.S. Ramaiah Medical College, were included for analysis in this retrospective, observational study. AKI was analyzed in terms of maximal stage of renal injury attained as per RIFLE criteria. Outcomes included requirement for renal replacement therapy (RRT), maternal and fetal outcomes. PPAKI constituted 60% of all obstetric AKI cases. Median maternal age was 23 years and 52% of patients were primigravidas. Mean serum creatinine was 4.1 mg/dL. Failure (33%) and injury (31%) were the major categories as per RIFLE criteria. Thirty-nine percent of cases required RRT. Sepsis, particularly puerperal sepsis, was the leading causes of PPAKI (75% of cases) and maternal mortality (94% of deaths). Maternal and fetal mortality were 19% and 22% respectively. The incidence of cortical necrosis was 10.3%. Three patients required long-term RRT. In conclusion, consistent with other Indian literature, we report a high incidence of PPAKI. We found incremental mortality on moving from "Risk" to "Failure" category of RIFLE. PPAKI was associated with high maternal and fetal mortality with sepsis being the leading cause. Our study highlights the need for provision of better quality of maternal care and fetal monitoring to decrease mortality associated with PPAKI in developing countries.

  15. Optimizing sedation in patients with acute brain injury.

    PubMed

    Oddo, Mauro; Crippa, Ilaria Alice; Mehta, Sangeeta; Menon, David; Payen, Jean-Francois; Taccone, Fabio Silvio; Citerio, Giuseppe

    2016-05-05

    Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has 'general' indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and 'neuro-specific' indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity.

  16. A crucial role of nitric oxide in acute lung injury secondary to the acute necrotizing pancreatitis.

    PubMed

    Cheng, Shi; Yan, Wen-Mao; Yang, Bin; Shi, Jing-dong; Song, Mao-min; Zhao, Yuqian

    2010-04-01

    To investigate the role of nitric oxide (NO) in acute lung inflammation and injury secondary to acute necrotizing pancreatitis (ANP), 5% sodium taurocholate was retrogradely injected into the biliopancreatic duct of rats to ANP model. These ANP rats were given L-Arginine (L-Arg, 100 mg/kg), L-NAME (10 mg/kg), or their combination by intraperitoneal injection 30 min prior to ANP induction. At 1, 3, 6, and 12 hours after ANP induction, lung NO production, and inducible NO synthase (iNOS) expression were measured. Lung histopathological changes, bronchoalveolar lavage (BAL) protein concentration, proinflammatory mediators tumor necrotic factor alpha (TNF-alpha), and lung tissue myeloperoxidase (MPO) activity were examined. Results showed that NO production and iNOS mRNA expression in alveolar macrophages (AMs) were significantly increased along with significant increases in lung histological abnormalities and BAL proteins in the ANP group, all of which were further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These markers were slightly attenuated by pretreatment with combination of L-Arg + L-NAME, suggesting that NO is required for initiating the acute lung damage in ANP rats, and also that L-Arg-enhanced lung injury is mediated by its NO generation rather than its direct effect. MPO activity and TNF-alpha expression in lung were upregulated in the ANP rats and further enhanced by pretreatment with L-Arg and attenuated by pretreatment with L-NAME, respectively. These results suggest that overproduction of NO mediated by iNOS in the lung is required for the acute lung inflammation and damage secondary to ANP.

  17. Acute kidney injury in liver cirrhosis: new definition and application

    PubMed Central

    Wong, Florence

    2016-01-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression. PMID:27987536

  18. Effect of Thoracentesis on Intubated Patients with Acute Lung Injury.

    PubMed

    Bloom, Matthew B; Serna-Gallegos, Derek; Ault, Mark; Khan, Ahsan; Chung, Rex; Ley, Eric J; Melo, Nicolas; Margulies, Daniel R

    2016-03-01

    Pleural effusions occur frequently in mechanically ventilated patients, but no consensus exists regarding the clinical benefit of effusion drainage. We sought to determine the impact of thoracentesis on gas exchange in patients with differing severities of acute lung injury (ALI). A retrospective analysis was conducted on therapeutic thoracenteses performed on intubated patients in an adult surgical intensive care unit of a tertiary center. Effusions judged by ultrasound to be 400 mL or larger were drained. Subjects were divided into groups based on their initial P:F ratios: normal >300, ALI 200 to 300, and acute respiratory distress syndrome (ARDS) <200. Baseline characteristics, physiologic variables, arterial blood gases, and ventilator settings before and after the intervention were analyzed. The primary end point was the change in measures of oxygenation. Significant improvements in P:F ratios (mean ± SD) were seen only in patients with ARDS (50.4 ± 38.5, P = 0.001) and ALI (90.6 ± 161.7, P = 0.022). Statistically significant improvement was observed in the pO2 (31.1, P = 0.005) and O2 saturation (4.1, P < 0.001) of the ARDS group. The volume of effusion removed did not correlate with changes in individual patient's oxygenation. These data support the role of therapeutic thoracentesis for intubated patients with abnormal P:F ratios.

  19. Renal oxygenation in acute renal ischemia-reperfusion injury.

    PubMed

    Abdelkader, Amany; Ho, Julie; Ow, Connie P C; Eppel, Gabriela A; Rajapakse, Niwanthi W; Schlaich, Markus P; Evans, Roger G

    2014-05-01

    Tissue hypoxia has been demonstrated, in both the renal cortex and medulla, during the acute phase of reperfusion after ischemia induced by occlusion of the aorta upstream from the kidney. However, there are also recent clinical observations indicating relatively well preserved oxygenation in the nonfunctional transplanted kidney. To test whether severe acute kidney injury can occur in the absence of widespread renal tissue hypoxia, we measured cortical and inner medullary tissue Po2 as well as total renal O2 delivery (Do2) and O2 consumption (Vo2) during the first 2 h of reperfusion after 60 min of occlusion of the renal artery in anesthetized rats. To perform this experiment, we used a new method for measuring kidney Do2 and Vo2 that relies on implantation of fluorescence optodes in the femoral artery and renal vein. We were unable to detect reductions in renal cortical or inner medullary tissue Po2 during reperfusion after ischemia localized to the kidney. This is likely explained by the observation that Vo2 (-57%) was reduced by at least as much as Do2 (-45%), due to a large reduction in glomerular filtration (-94%). However, localized tissue hypoxia, as evidence by pimonidazole adduct immunohistochemistry, was detected in kidneys subjected to ischemia and reperfusion, particularly in, but not exclusive to, the outer medulla. Thus, cellular hypoxia, particularly in the outer medulla, may still be present during reperfusion even when reductions in tissue Po2 are not detected in the cortex or inner medulla.

  20. Special nutrition challenges: current approach to acute kidney injury.

    PubMed

    McCarthy, Mary S; Phipps, Shauna C

    2014-02-01

    Acute kidney injury (AKI), previously known as acute renal failure, is defined as a sudden decline in glomerular filtration rate with accumulation of metabolic waste products, toxins, and drugs, as well as alteration in the intrinsic functions of the kidney. Reports of mortality are as high as 80%, with numerous contributing causes including infection, cardiorespiratory complications, and cardiovascular disease. Concurrent with the high prevalence of critical illness in this population is the protein energy wasting (PEW), seen in up to 42% of patients upon intensive care unit admission. The pathophysiologic derangements of critical illness, the low energy and protein stores, and uremic complications require early nutrition intervention to attenuate the inflammatory response and oxidative stress, improve endothelial function, stabilize blood sugar, and preserve lean body mass. This article addresses the unique challenges of nutrition support for the patient with AKI in the setting of critical illness and renal replacement therapy. Evidence-based recommendations are provided to meet the macronutrient and micronutrient requirements of this heterogeneous and complex patient population.

  1. Acute kidney injury in liver cirrhosis: new definition and application.

    PubMed

    Wong, Florence

    2016-12-01

    The traditional diagnostic criteria of renal dysfunction in cirrhosis are a 50% increase in serum creatinine (SCr) with a final value above 1.5 mg/dL. This means that patients with milder degrees of renal dysfunction are not being diagnosed, and therefore not offered timely treatment. The International Ascites Club in 2015 adapted the term acute kidney injury (AKI) to represent acute renal dysfunction in cirrhosis, and defined it by an increase in SCr of 0.3 mg/dL (26.4 µmoL/L) in <48 hours, or a 50% increase in SCr from a baseline within ≤3 months. The severity of AKI is described by stages, with stage 1 represented by these minimal changes, while stages 2 and 3 AKI by 2-fold and 3-fold increases in SCr respectively. Hepatorenal syndrome (HRS), renamed AKI-HRS, is defined by stage 2 or 3 AKI that fulfils all other diagnostic criteria of HRS. Various studies in the past few years have indicated that these new diagnostic criteria are valid in the prediction of prognosis for patients with cirrhosis and AKI. The future in AKI diagnosis may include further refinements such as inclusion of biomarkers that can identify susceptibility for AKI, differentiating the various prototypes of AKI, or track its progression.

  2. Malarial acute kidney injury in a paediatric intensive care unit.

    PubMed

    Kapoor, Kapil; Gupta, Shalu

    2012-10-01

    Acute kidney injury (AKI) is a serious complication of malaria which has a very high mortality rate. A retrospective analysis of medical record data of children treated for malarial AKI in a paediatric intensive care unit (PICU) was performed in order to evaluate the incidence, poor prognostic factors and outcome of AKI with malaria. Eighteen (48.6%) malarial patients had AKI (11 Plasmodium vivax positive, six P. falciparum positive and one mixed infection) with a male-to-female ratio of 1:2. The mean age was 75 ± 32 months (range, 1 month to 10 years). Oliguria was present in 61.1% and 55.5% required renal replacement therapy. Mortality was noted in 33.3% of patients and full recovery was achieved in 50% of patients. Oliguria, shock, central nervous system involvement, jaundice, disseminated intravascular coagulopathy and acute respiratory distress syndrome emerged as bad prognostic factors in simple univariate analysis. Malaria patients with and without AKI differ significantly in terms of shock, ventilator requirement, mortality and length of PICU stay.

  3. Peptide nanomedicines for treatment of acute lung injury.

    PubMed

    Sadikot, Ruxana T

    2012-01-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients. Despite the increased understanding of the molecular pathogenesis of ARDS, the mortality remains unacceptably high, ranging from 34% to 64%. Hence, ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Several promising targets that have been identified as potential therapies for ARDS have been limited because of difficulty with delivery. In particular, delivery of peptides and proteins to the lung is an ongoing challenge. Nanobiotechnology and nanoscience are the basis of innovative techniques to deliver drugs targeted to the site of inflamed organs, such as the lungs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and pharmakodynamics of agents allowing an increase in the biodistribution of therapeutic agents to target organs, resulting in improved efficacy with reduction in drug toxicity. These systems are exploited for therapeutic purpose to carry the drug in the body in a controlled manner from the site of administration to the therapeutic target. Hence, it is an attractive strategy to test potential targets for ALI/ARDS using nanotechnology. To this end, we have identified several potential targets and proposed the delivery of these agents using nanomicelles to improve the drug delivery.

  4. Acute Kidney Injury in Hematopoietic Stem Cell Transplantation: A Review

    PubMed Central

    Gupta, Mohit; Manu, Gurusidda; Kwatra, Shivani; Owusu, Osei-Tutu

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) is a highly effective treatment strategy for lymphoproliferative disorders and bone marrow failure states including aplastic anemia and thalassemia. However, its use has been limited by the increased treatment related complications, including acute kidney injury (AKI) with an incidence ranging from 20% to 73%. AKI after HSCT has been associated with an increased risk of mortality. The incidence of AKI reported in recipients of myeloablative allogeneic transplant is considerably higher in comparison to other subclasses mainly due to use of cyclosporine and development of graft-versus-host disease (GVHD) in allogeneic groups. Acute GVHD is by itself a major independent risk factor for the development of AKI in HSCT recipients. The other major risk factors are sepsis, nephrotoxic medications (amphotericin B, acyclovir, aminoglycosides, and cyclosporine), hepatic sinusoidal obstruction syndrome (SOS), thrombotic microangiopathy (TMA), marrow infusion toxicity, and tumor lysis syndrome. The mainstay of management of AKI in these patients is avoidance of risk factors contributing to AKI, including use of reduced intensity-conditioning regimen, close monitoring of nephrotoxic medications, and use of alternative antifungals for prophylaxis against infection. Also, early identification and effective management of sepsis, tumor lysis syndrome, marrow infusion toxicity, and hepatic SOS help in reducing the incidence of AKI in HSCT recipients. PMID:27885340

  5. [Acute kidney injury and septic shock: experiences in treatment].

    PubMed

    Pozzato, Marco; Ferrari, Fiorenza; Livigni, Sergio; Quarello, Francesco

    2012-01-01

    Acute kidney injury (AKI) occurs in 5-45% of critically ill patients, and renal replacement therapy (RRT) is required in 4-10% of patients with AKI. AKI has long been considered to be hemodynamic damage from low blood flow resulting in shock, and efforts have been made to prevent and cure it by increasing the renal blood flow and improving the cardiac output and perfusion pressure. In recent years, new experimental studies on patients with septic AKI have shown that the renal blood flow remains unaltered or even increases in septic shock. An important mechanism in the pathophysiology of sepsis and septic shock appears to be apoptosis rather than ischemic necrosis. The type of treatment as well as the dose and timing of initiation of RRT seem to have strategic importance in the recovery of AKI in patients admitted to the ICU. In critically ill (often postsurgical and septic) patients with acute renal failure the use of new anticoagulation strategies has permitted to perform treatments for a sufficient number of hours to achieve the correct level of purification by minimizing the downtime and the bleeding risk. In our center the use of protocols for different methods and different types of anticoagulants has simplified the treatment of all patients with AKI and septic shock admitted to the ICU.

  6. The pathogenesis of transfusion-related acute lung injury (TRALI).

    PubMed

    Bux, Jürgen; Sachs, Ulrich J H

    2007-03-01

    In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.

  7. Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila

    PubMed Central

    Katzenberger, Rebeccah J.; Ganetzky, Barry; Wassarman, David A.

    2016-01-01

    Outcomes of traumatic brain injury (TBI) vary because of differences in primary and secondary injuries. Primary injuries occur at the time of a traumatic event, whereas secondary injuries occur later as a result of cellular and molecular events activated in the brain and other tissues by primary injuries. We used a Drosophila melanogaster TBI model to investigate secondary injuries that cause acute mortality. By analyzing mortality percentage within 24 hr of primary injuries, we previously found that age at the time of primary injuries and diet afterward affect the severity of secondary injuries. Here, we show that secondary injuries peaked in activity 1–8 hr after primary injuries. Additionally, we demonstrate that age and diet activated distinct secondary injuries in a genotype-specific manner, and that concurrent activation of age- and diet-regulated secondary injuries synergistically increased mortality. To identify genes involved in secondary injuries that cause mortality, we compared genome-wide mRNA expression profiles of uninjured and injured flies under age and diet conditions that had different mortalities. During the peak period of secondary injuries, innate immune response genes were the predominant class of genes that changed expression. Furthermore, age and diet affected the magnitude of the change in expression of some innate immune response genes, suggesting roles for these genes in inhibiting secondary injuries that cause mortality. Our results indicate that the complexity of TBI outcomes is due in part to distinct, genetically controlled, age- and diet-regulated mechanisms that promote secondary injuries and that involve a subset of innate immune response genes. PMID:27754853

  8. Precision and improving outcomes in acute kidney injury: Personalizing the approach.

    PubMed

    Forni, Lui G; Chawla, Lakhmir; Ronco, Claudio

    2017-02-01

    It is now well over a decade since attempts at harmonization of acute renal failure into a definable entity termed acute kidney injury. This has led to several landmark studies outlining the epidemiology of acute kidney injury, particularly in the critically ill, as well as providing insights into the long-term effects of the syndrome. Despite the introduction of consensus definitions and improvement in recognition, this has not been translated into outcome benefits as yet. The introduction of novel biomarkers associated with renal damage was primarily aimed at aiding early recognition of acute kidney injury. We argue that, in the future, using biomarkers may not only alert to acute kidney injury but may direct therapy in a personalized fashion rather than a one-size-fits-all approach.

  9. Remote effects of acute kidney injury in a porcine model.

    PubMed

    Gardner, David S; De Brot, Simone; Dunford, Louise J; Grau-Roma, Llorenc; Welham, Simon J M; Fallman, Rebecca; O'Sullivan, Saoirse E; Oh, Weng; Devonald, Mark A J

    2016-02-15

    Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.

  10. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    PubMed Central

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-01-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries. PMID:27351915

  11. Acute Gastric Injury Caused by Undissolved Sodium Picosulfate/Magnesium Citrate Powder

    PubMed Central

    Ze, Eun Young; Choi, Chang Hwan; Kim, Jeong Wook

    2017-01-01

    Sodium picosulfate/magnesium citrate (SPMC) is a widely used oral bowel cleansing agent considered to be relatively safe. However, partially dissolved or undissolved SPMC powder may cause severe injuries of the esophagus and stomach. We report a very rare case of acute gastric injury without esophageal damage caused by the ingestion of undissolved SPMC powder. A 69-year-old man experienced epigastric pain after swallowing SPMC powder without dissolving it in water in preparation for a screening colonoscopy. He realized his mistake immediately and subsequently drank 2 L of water. The esophagogastroduodenoscopy conducted after 12 hours indicated an acute gastric ulceration without injury of the esophagus or duodenum. The endoscopy conducted after 6 weeks of oral proton pump inhibitor treatment showed healing of the gastric injury. This suggested that drinking large amounts of water after ingesting partially dissolved or undissolved SPMC powder can prevent serious esophageal injury, but offers no preventive benefit for acute gastric injury. PMID:27732774

  12. A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries

    NASA Astrophysics Data System (ADS)

    Mann, Aman P.; Scodeller, Pablo; Hussain, Sazid; Joo, Jinmyoung; Kwon, Ester; Braun, Gary B.; Mölder, Tarmo; She, Zhi-Gang; Kotamraju, Venkata Ramana; Ranscht, Barbara; Krajewski, Stan; Teesalu, Tambet; Bhatia, Sangeeta; Sailor, Michael J.; Ruoslahti, Erkki

    2016-06-01

    Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

  13. Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

    PubMed Central

    Gonçalves-de-Albuquerque, Cassiano Felippe; Silva, Adriana Ribeiro; Burth, Patrícia; Castro-Faria, Mauro Velho; Castro-Faria-Neto, Hugo Caire

    2015-01-01

    Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation. PMID:26640323

  14. Sequential Treatments with Tongsai and Bufei Yishen Granules Reduce Inflammation and Improve Pulmonary Function in Acute Exacerbation-Risk Window of Chronic Obstructive Pulmonary Disease in Rats

    PubMed Central

    Lu, Xiaofan; Li, Ya; Wang, Haifeng; Wu, Zhaohuan; Li, Hangjie; Wang, Yang

    2016-01-01

    Background. Sequential treatments of Chinese medicines for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) risk window (RW) have benefits for preventing reoccurrences of AEs; however, the effects on pulmonary function, pulmonary, and systemic inflammatory biomarkers remain unclear. Methods. Cigarette-smoke/bacterial infections induced rats were randomized into Control, COPD, AECOPD, Tongsai Granule/normal saline (TSG/NS), moxifloxacin + salbutamol/NS (MXF+STL/NS), TSG/Bufei Yishen Granule (BYG), MXF+STL/STL, and TSG+MXF+STL/BYG+STL groups and given corresponding medicine(s) in AE- and/or RW phase. Body temperature, pulmonary function, blood cytology, serum amyloid A (SAA) and C-reactive protein (CRP), pulmonary histomorphology and myeloperoxidase (MPO), polymorphonuclear (PMN) elastase, interleukins IL-1β, IL-6, and IL-10, and tumor necrosis factor- (TNF-) α expressions were determined. Results. Body temperature, inflammatory cells and cytokines, SAA, CRP, and pulmonary impairment were higher in AECOPD rats than stable COPD, while pulmonary function declined and recovered to COPD level in 14–18 days. All biomarkers were improved in treated groups with shorter recovery times of 4–10 days, especially in TSG+MXF+STL/BYG+STL group. Conclusion. Sequential treatments with Tongsai and Bufei Yishen Granules, during AECOPD-RW periods, can reduce inflammatory response and improve pulmonary function and shorten the recovery courses of AEs, especially the integrated Chinese and Western medicines. PMID:27563333

  15. Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

    PubMed Central

    de Matos Soeiro, Alexandre; Ruppert, Aline D; Canzian, Mauro; Parra, Edwin R; Farhat, Cecília; Capelozzi, Vera L

    2011-01-01

    INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7% (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure. PMID:21876973

  16. Acute pulmonary edema due to rosiglitazone use in a patient with diabetes mellitus.

    PubMed

    Cekmen, Nedim; Cesur, Mustafa; Cetinbas, Riza; Bedel, Pasa; Erdemli, Ozcan

    2006-01-01

    Rosiglitazone is a peroxisome proliferator active receptor. gamma agonist, which increases insulin sensitivity in adipose tissue, muscle, and liver. Rosiglitazone is a member of the thiazolidinedione group, and because of its significantly positive effect on glycemic control, it is especially preferred in type 2 diabetic patients with a high cardiovascular disease risk. This drug, because of its decreasing effect on insulin resistance, is used alone or combined with type 2 diabetic drugs. A 73-year-old female patient was admitted to the emergency department with dyspnea, pink frothing phlegm, cyanosis, and tiredness. She was lethargic, uncooperative, and had no orientation. In arterial blood gases, hypoxemia and hypercapnia were found. She was taken to the general intensive care unit, and oxygen was applied via mask. The patient had a history of 10 years of diabetes mellitus, hypertension, and atherosclerotic cardiac disease, and she was using rosiglitazone for the past 6 weeks. Her chest x-ray was taken, and acute pulmonary edema was diagnosed. In her last echocardiography, which was performed 1 year before, no signs indicating cardiac failure and pleural effusion could be found. Therefore, it was concluded that pulmonary edema occurred as a complication of rosiglitazone use. After stabilizing the patient's vital signs, blood glucose levels, and lactate levels, medical treatment of diabetes mellitus was rearranged, and she was discharged on the seventh day after her admittance. In a patient with diabetes mellitus who has been admitted to the intensive care unit because of acute pulmonary edema, for differential diagnosis, use of rosiglitazone should be kept in mind during the determination of treatment. Therefore, the authors aim to discuss the effect of rosiglitazone on creating acute pulmonary edema with a case report presentation.

  17. Preventing and Treating Acute Kidney Injury Among Hospitalized Patients with Cirrhosis and Ascites: A Narrative Review.

    PubMed

    Tapper, Elliot B; Bonder, Alan; Cardenas, Andres

    2016-05-01

    Acute kidney injury in the setting of ascites and cirrhosis is a medical emergency characterized by significant morbidity and mortality. Clinicians other than gastroenterologists are often the front line against acute kidney injury for patients with ascites. Owing to the specifics of cirrhotic physiology, the treatment and prevention of acute kidney injury in the setting of ascites has unique features, widespread knowledge of which will benefit our patients with cirrhosis. Early detection and treatment of infection, maximization of cardiac output, and avoidance of medications that limit cardiorenal adaptations to arterial underfilling are part of a multipronged strategy to protect the renal function of our patients with cirrhosis and ascites.

  18. Acute pulmonary toxicity of urban particulate matter and ozone.

    PubMed Central

    Vincent, R.; Bjarnason, S. G.; Adamson, I. Y.; Hedgecock, C.; Kumarathasan, P.; Guénette, J.; Potvin, M.; Goegan, P.; Bouthillier, L.

    1997-01-01

    We have investigated the acute lung toxicity of urban particulate matter in interaction with ozone. Rats were exposed for 4 hours to clean air, ozone (0.8 ppm), the urban dust EHC-93 (5 mg/m3 or 50 mg/m3), or ozone in combination with urban dust. The animals were returned to clean air for 32 hours and then injected (intraperitoneally) with [3H]thymidine to label proliferating cells and killed after 90 minutes. The lungs were fixed by inflation, embedded in glycol methacrylate, and processed for light microscopy autoradiography. Cell labeling was low in bronchioles (0.14 +/- 0.04%) and parenchyma (0.13 +/- 0.02%) of air control animals. Inhalation of EHC-93 alone did not induce cell labeling. Ozone alone increased (P < 0.05) cell labeling (bronchioles, 0.42 +/- 0.16%; parenchyma, 0.57 +/- 0.21%), in line with an acute reparative cell proliferation. The effects of ozone were clearly potentiated by co-exposure with either the low (3.31 +/- 0.31%; 0.99 +/- 0.18%) or the high (4.45 +/- 0.51%; 1.47 +/- 0.18%) concentrations of urban dust (ozone X EHC-93, P < 0.05). Cellular changes were most notable in the epithelia of terminal bronchioles and alveolar ducts and did not distribute to the distal parenchyma. Enhanced DNA synthesis indicates that particulate matter from ambient air can exacerbate epithelial lesions in the lungs. This may extend beyond air pollutant interactions, such as to effects of inhaled particles in the lungs of compromised individuals. Images Figure 1 PMID:9403707

  19. Acute alcohol intoxication suppresses the pulmonary ELR-negative CXC chemokine response to lipopolysaccharide.

    PubMed

    Happel, Kyle I; Rudner, Xiaowen; Quinton, Lee J; Movassaghi, Jennifer L; Clark, Charles; Odden, Anthony R; Zhang, Ping; Bagby, Gregory J; Nelson, Steve; Shellito, Judd E

    2007-08-01

    Alcohol abuse impairs the pulmonary immune response to infection and increases the morbidity and mortality of bacterial pneumonia. Acute alcohol intoxication suppresses lung expression of CXC chemokines bearing the Glu-Leu-Arg motif (ELR+) following lipopolysaccharide (LPS) challenge, but its effect on the structurally related ELR- CXC chemokines, which attract T cells, is unknown. We therefore investigated the effect of acute alcohol intoxication on the pulmonary response to intratracheal (i.t.) LPS challenge for the ELR- CXC chemokines monokine induced by gamma (MIG or CXCL9), interferon-inducible protein 10 (IP-10 or CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC or CXCL11). Male C57BL/6 or C3H/HeN mice were given an intraperitoneal injection of ethanol (3.0 g/kg) or phosphate buffered saline 30 min before i.t. LPS challenge. Chemokine mRNA transcripts were measured at 0, 2, 6, and 16 h. Acute alcohol intoxication inhibited the lung's expression of all three chemokine genes in response to LPS. Lung IFN-gamma mRNA was also inhibited by acute intoxication over the same time course. The in vitro effect of ethanol on chemokine secretion was further studied in the MH-S alveolar macrophage cell line. IP-10, MIG, and I-TAC in response to LPS were enhanced by exogenous interferon (IFN)-gamma, and these responses were blunted by exposure to ethanol. Alcohol exposure did not affect MH-S cell nuclear factor kappa beta p65 nuclear localization during challenge, despite dose-dependent inhibition of Erk 1/2 phosphorylation. In addition, phospho-signal transduction and activator of transcription 1 was not decreased in the presence of acute ethanol, thereby indicating that acute intoxication does not affect IFN-gamma signaling in MH-S cells. Recruitment of CD3+ T cells into the alveolar space 4 days after LPS challenge was moderately impaired by acute ethanol intoxication. These results implicate acute ethanol intoxication as a significant inhibitor of

  20. Characterization of a nose-only inhaled phosgene acute lung injury mouse model

    PubMed Central

    Plahovinsak, Jennifer L.; Perry, Mark R.; Knostman, Katherine A.; Segal, Robert; Babin, Michael C.

    2016-01-01

    Context Phosgene’s primary mode of action is as a pulmonary irritant characterized by its early latent phase where life-threatening, non-cardiogenic pulmonary edema is typically observed 6–24 h post-exposure. Objective To develop an inhaled phosgene acute lung injury (ALI) model in C57BL/6 mice that can be used to screen potential medical countermeasures. Methods A Cannon style nose-only inhalation exposure tower was used to expose mice to phosgene (8 ppm) or air (sham). An inhalation lethality study was conducted to determine the 8 ppm median lethal exposure (LCt50) at 24 and 48 h post-exposure. The model was then developed at 1.2 times the 24 h LCt50. At predetermined serial sacrifice time points, survivors were euthanized, body and lung weights collected, and lung tissues processed for histopathology. Additionally, post-exposure clinical observations were used to assess quality of life. Results and discussion The 24-hour LCt50 was 226ppm*min (8 ppm for 28.2 min) and the 48-hour LCt50 was 215ppm*min (8 ppm for 26.9 min). The phosgene exposed animals had a distinct progression of clinical signs, histopathological changes and increased lung/body weight ratios. Early indicators of a 1.2 times the 24-hour LCt50 phosgene exposure were significant changes in the lung-to-body weight ratios by 4 h post-exposure. The progression of clinical signs and histopathological changes were important endpoints for characterizing phosgene-induced ALI for future countermeasure studies. Conclusion An 8 ppm phosgene exposure for 34 min (1.2 × LCt50) is the minimum challenge recommended for evaluating therapeutic interventions. The predicted higher mortality in the phosgene-only controls will help demonstrate efficacy of candidate treatments and increase the probability that a change in survival rate is statistically significant PMID:26671199

  1. Dimethyl silicone dry nanoemulsion inhalations: Formulation study and anti-acute lung injury effect.

    PubMed

    Zhu, Lifei; Li, Miao; Dong, Junxing; Jin, Yiguang

    2015-08-01

    Acute lung injury (ALI) is a severe disease, leading to death if not treated quickly. An emergency medicine is necessary for ALI therapy. Dimethyl silicone (DMS) is an effective agent to defoam the bubbles in the lung induced by ALI. However, DMS aerosols, a marketed formulation of DMS, affect environments and will be limited in the future. Here we firstly report a dry nanoemulsion inhalation for pulmonary delivery. Novel DMS dry nanoemulsion inhalations (DSNIs) were developed in this study. The optimal formulation of stable and homogenous DMS nanoemulsions (DSNs) was composed of Cremophor RH40/PEG 400/DMS (4:4:2, w/w/w) and water. The DSNs showed the tiny size of 19.8 nm, the zeta potential of -9.66 mV, and the low polydispersity index (PDI) of 0.37. The type of DSNs was identified as oil-in-water. The DSNs were added with mannitol followed by freeze-drying to obtain the DSNIs that were loose white powders, showed good fluidity, and were capable of rapid reconstitution to DSNs. The DSNs could adhere on the surfaces of lyophilized mannitol crystals. The aerodynamic diameter of DSNIs was 4.82 μm, suitable for pulmonary inhalation. The in vitro defoaming rate of DSNIs was 1.25 ml/s, much faster than those of the blank DSNIs, DMS, and DMS aerosols. The DSNIs showed significantly higher anti-ALI effect on the ALI rat models than the blank DSNIs and the DMS aerosols according to lung appearances, histological sections, and lung wet weight/dry weight ratios. The DSNIs are effective anti-ALI nanomedicines. The novel DMS formulation is a promising replacement of DMS aerosols.

  2. Salidroside alleviates paraquat-induced rat acute lung injury by repressing TGF-β1 expression

    PubMed Central

    Zhang, Zhuoyi; Ding, Limin; Wu, Liqun; Xu, Liying; Zheng, Lanzhi; Huang, Xiaomin

    2014-01-01

    Objective: This study was designed to investigate the protective effects of salidroside (SDS) via suppressing the expression of transforming growth factor-β1 (TGF-β1) in rat acute lung injury (ALI) induced by paraquat (PQ) and to explore the potential molecular mechanisms. Methods: A total of 90 male rats (190-210 g) were randomly and evenly divided into 9 groups: control group, PQ groups (4 groups), and PQ + SDS groups (4 groups). The rats in control group were treated with equal volume of saline intraperitoneally. The rats in PQ groups were exposed to PQ solution (20 mg/kg) by gastric gavage for 1, 6, 24, and 72 hours, respectively. The rats in PQ + SDS groups were intraperitoneally injected once with SDS (10 mg/kg) every 12 hours after PQ perfusion. Pulmonary pathological changes were observed by hematoxylin and eosin (HE) staining. The expression of TGF-β1 and the mRNA were evaluated by immunohistochemical (IHC) scoring and real time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR), respectively. Results: SDS alleviated the symptoms of PQ induced ALI. Moreover, SDS reduced the expression of the inflammatory cytokine TGF-β1 including TGF-β1 IHC scores (at each time point from 6 to 72 hours after PQ perfusion) and mRNA level (at each time point from 1 to 72 hours after PQ perfusion) compared with PQ groups (P < 0.05). Conclusion: SDS alleviated the pulmonary symptoms of PQ-induced ALI, at least partially, by repressing inflammatory cell infiltration and the expression of TGF-β1 resulting in delayed lung fibrosis. PMID:25674253

  3. Mechanisms of transfusion-related acute lung injury (TRALI): anti-leukocyte antibodies.

    PubMed

    Curtis, Brian R; McFarland, Janice G

    2006-05-01

    There is abundant evidence that leukocyte antibodies in blood donor products are somehow involved in transfusion-related acute lung injury (TRALI). Human leukocyte antigen (HLA) class I, HLA class II, and neutrophil-specific antibodies in the plasma of both blood donors and recipients have been implicated in the pathogenesis of TRALI. The case for a relationship between leukocyte antibodies and TRALI is more compelling if concordance between the antigen specificity of the leukocyte antibodies in the donor plasma and the corresponding antigen on the cells of the affected recipient is demonstrated. Such antibody-antigen concordance can be investigated by typing the recipient for the cognate leukocyte antigens or by cross-matching the donor plasma against the recipient's leukocytes. Two proposed pathophysiologic mechanisms for TRALI have received the most attention: the antibody hypothesis and the two-event hypothesis. The final common pathway in all of the proposed pathogenic mechanisms of TRALI is increased pulmonary capillary permeability, which results in movement of plasma into the alveolar space causing pulmonary edema. A typical TRALI serologic workup consists of tests for HLA class I and II and neutrophil-specific antibodies. The use of flow cytometry and HLA-coated microbeads is recommended for detection of HLA antibodies in plasma of implicated blood donors and a combination of the granulocyte agglutination test and granulocyte immunofluorescence test for detection of neutrophil-specific antibodies. Genotyping for class I and II HLA and for a limited number of neutrophil antigens may also be helpful in establishing antibody-antigen concordance.

  4. Non-invasive ventilation in chronic obstructive pulmonary disease: management of acute type 2 respiratory failure.

    PubMed

    Roberts, C M; Brown, J L; Reinhardt, A K; Kaul, S; Scales, K; Mikelsons, C; Reid, K; Winter, R; Young, K; Restrick, L; Plant, P K

    2008-10-01

    Non-invasive ventilation (NIV) in the management of acute type 2 respiratory failure in patients with chronic obstructive pulmonary disease (COPD) represents one of the major technical advances in respiratory care over the last decade. This document updates the 2002 British Thoracic Society guidance and provides a specific focus on the use of NIV in COPD patients with acute type 2 respiratory failure. While there are a variety of ventilator units available most centres now use bi-level positive airways pressure units and this guideline refers specifically to this form of ventilatory support although many of the principles encompassed are applicable to other forms of NIV. The guideline has been produced for the clinician caring for COPD patients in the emergency and ward areas of acute hospitals.

  5. Successful retreatment with osimertinib after osimertinib-induced acute pulmonary embolism in a patient with lung adenocarcinoma: A case report.

    PubMed

    Shiroyama, Takayuki; Hayama, Manabu; Satoh, Shingo; Nasu, Shingo; Tanaka, Ayako; Morita, Satomu; Morishita, Naoko; Suzuki, Hidekazu; Okamoto, Norio; Hirashima, Tomonori

    2017-01-01

    Pulmonary embolism (PE) can be life-threatening, and it is challenging to diagnose because of its nonspecific signs and symptoms. PE is also an important potential risk of osimertinib treatment, however, clinical courses regarding retreatment after osimertinib-induced acute pulmonary embolism remain unclear. We described a 77-year-old woman with postoperative recurrent lung adenocarcinoma who developed osimertinib-induced acute PE. She received apixaban and was later successfully retreated with osimertinib. This case suggests that retreatment with osimertinib after osimertinib-induced acute PE may be a treatment option when alternative therapeutic options are limited.

  6. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  7. Temporal and spatial characterization of mononuclear phagocytes in circulating, lung alveolar and interstitial compartments in a mouse model of bleomycin-induced pulmonary injury.

    PubMed

    Ji, Wen-Jie; Ma, Yong-Qiang; Zhou, Xin; Zhang, Yi-Dan; Lu, Rui-Yi; Sun, Hai-Ying; Guo, Zhao-Zeng; Zhang, Zhuoli; Li, Yu-Ming; Wei, Lu-Qing

    2014-01-31

    The mononuclear phagocyte system, including circulating monocytes and tissue resident macrophages, plays an important role in acute lung injury and fibrosis. The detailed dynamic changes of mononuclear phagocytes in the circulating, lung alveolar and interstitial compartments in bleomycin-induced pulmonary injury model have not been fully characterized. The present study was designed to address this issue and analyzed their relationships with pulmonary pathological evolution after bleomycin challenge. A total of 100 male C57BL/6 mice were randomly divided to receive bleomycin (2.5mg/kg, n=50) or normal saline (n=50) via oropharyngeal approach, and were sacrificed on days 1, 3, 7, 14 and 21. Circulating monocyte subsets, polarization state of bronchoalveolar lavage fluid (BALF)-derived alveolar macrophages (AMφ) and lung interstitial macrophages (IMφ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. There was a rapid expansion of circulating Ly6C(hi) monocytes which peaked on day 3, and its magnitude was positively associated with pulmonary inflammatory response. Moreover, an expansion of M2-like AMφ (F4/80+CD11c+CD206+) peaked on day 14, and was positively correlated with the magnitude of lung fibrosis. The polarization state of IMφ remained relatively stable in the early- and mid-stage after bleomycin challenge, expect for an increase of M2-like (F4/80+CD11c-CD206+) IMφ on day 21. These results support the notion that there is a Ly6C(hi)-monocyte-directed pulmonary AMφ alternative activation. Our result provides a dynamic view of mononuclear phagocyte change in three compartments after bleomycin challenge, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

  8. Nutritional Status of Chronic Obstructive Pulmonary Disease Patients Admitted in Hospital With Acute Exacerbation

    PubMed Central

    Gupta, Barkha; Kant, Surya; Mishra, Rachna; Verma, Sanjay

    2010-01-01

    Background Patients with Chronic Obstructive Pulmonary Disease (COPD) are frequently hospitalized with an acute exacerbation. Patients with COPD often lose weight. Consequently, deterioration in nutritional status (loss of lean body mass) is a likely repercussion of acute exacerbation in hospitalized COPD patients. The study was carried out to assess the nutritional status of COPD patients with acute exacerbation, during the period of hospital admission, and to evaluate the relationships between the nutritional indices and the pulmonary function parameters. Methods A cross sectional observation study constituting 83 COPD patients consecutively hospitalized with acute exacerbation on accrual during a period of one year. Lung function was measured by routine spirometry. Nutritional status was assessed by the measurement of anthropometric parameters. Hospital outcome was also assessed. Statistical analysis was performed using SPSS version 16.0 Independent t-tests and Pearsons correlation coefficient was used. Results Mean body weight was 50.03 ± 9.23 kg. Subjects had approximately 5 kg weight loss in previous six months. All the subjects had low BMI (19.38 ± 3.10) and MUAC (21.18 ± 2.31) that was significantly below the predicted levels. The correlation between body weight and FEV1/FVC% was good (r = 0.648, p = 0.003). BMI was negatively correlated (r = - 0.0103, p= 0.03) with duration of hospital stay. Conclusions The high prevalence of malnutrition among hospitalized COPD patients with acute exacerbation is related to their lung function and hospital outcome such as duration of hospital stay. Keywords Nutritional status; COPD; Acute exacerbation; Hospitalization PMID:21811522

  9. Fas ligand-expressing lymphocytes enhance alveolar macrophage apoptosis in the resolution of acute pulmonary inflammation

    PubMed Central

    Barthel, Lea; Bednarek, Joseph M.; Yunt, Zulma X.; Henson, Peter M.; Janssen, William J.

    2014-01-01

    Apoptosis of alveolar macrophages and their subsequent clearance by neighboring phagocytes are necessary steps in the resolution of acute pulmonary inflammation. We have recently identified that activation of the Fas death receptor on the cell surface of macrophages drives macrophage apoptosis. However, the source of the cognate ligand for Fas (FasL) responsible for induction of alveolar macrophage apoptosis is not defined. Given their known role in the resolution of inflammation and ability to induce macrophage apoptosis ex vivo, we hypothesized that T lymphocytes represented a critical source of FasL. To address this hypothesis, C57BL/6J and lymphocyte-deficient (Rag-1−/−) mice were exposed to intratracheal lipopolysaccharide to induce pulmonary inflammation. Furthermore, utilizing mice expressing nonfunctional FasL, we adoptively transferred donor lymphocytes into inflamed lymphocyte-deficient mice to characterize the effect of lymphocyte-derived FasL on alveolar macrophage apoptosis in the resolution of inflammation. Herein, evidence is presented that lymphocytes expressing FasL enhance alveolar macrophage apoptosis during the resolution of LPS-induced inflammation. Moreover, lymphocyte induction of alveolar macrophage apoptosis results in contraction of the alveolar macrophage pool, which occurs in a FasL-dependent manner. Specifically, FasL-expressing CD8+ T lymphocytes potently induce alveolar macrophage apoptosis and contraction of the alveolar macrophage pool. Together, these studies identify a novel role for CD8+ T lymphocytes in the resolution of acute pulmonary inflammation. PMID:24838751

  10. Free Floating Right Heart Thrombus Associated with Acute Pulmonary Embolism: An Unsettled Therapeutic Difficulty

    PubMed Central

    Nkoke, Clovis; Faucher, Olivier; Camus, Lise; Flork, Laurence

    2015-01-01

    Free floating right heart thrombus is a rare phenomenon in the context of acute pulmonary embolism and it is associated with a poor outcome. The increased use of echocardiography has led to an increased detection of right heart thrombi. However, optimal management of free floating right heart thrombus remains controversial with no clear consensus. We present the case of a 74-year-old woman who presented to the emergency department with acute onset dyspnea on minimal exertion which had developed over a period of 1 day. A computed tomography of the chest demonstrated massive bilateral proximal pulmonary embolism. A bedside transthoracic echocardiography performed showed a moderately dilated, poorly functioning right ventricle with visible highly mobile serpiginous thrombus moving to and fro across the tricuspid valve. Thrombolytic therapy was immediately initiated with tenecteplase which resulted in excellent results. Although there is no clear consensus for the management of right heart thrombus associated with pulmonary embolism, thrombolysis is readily available and can be effective in carefully selected patients. PMID:26078887

  11. Split-Bolus Single-Pass Multidetector-Row CT Protocol for Diagnosis of Acute Pulmonary Embolism

    PubMed Central

    Scialpi, Michele; Rebonato, Alberto; Cagini, Lucio; Brunese, Luca; Piscioli, Irene; Pierotti, Luisa; Bellantonio, Lucio; D’Andrea, Alfredo; Rotondo, Antonio

    2016-01-01

    Background: Currently computed tomography pulmonary angiography (CTPA) has become a widely accepted clinical tool in the diagnosis of acute pulmonary embolism (PE). Objectives: To report split-bolus single-pass 64-multidetector-row CT (MDCT) protocol for diagnosis of PE. Patients and Methods: MDCT split-bolus results in 40 patients suspicious of PE were analyzed in terms of image quality of target pulmonary vessels (TPVs) and occurrence and severity of flow-related artifact, flow-related artifact, false filling defect of the pulmonary veins and beam hardening streak artifacts. Dose radiation to patients was calculated. Results: MDCT split-bolus protocol allowed diagnostic images of high quality in all cases. Diagnosis of PE was obtained in 22 of 40 patients. Mean attenuation for target vessels was higher than 250 HU all cases: 361 ± 98 HU in pulmonary artery trunk (PAT); 339 ± 93 HU in right pulmonary artery (RPA); 334 ± 100 HU in left pulmonary artery (LPA). Adequate enhancement was obtained in the right atrium (RA):292 ± 83 HU; right pulmonary vein (RPV): 302 ± 91 HU, and left pulmonary vein (LPV): 291 ± 83 HU. The flow related artifacts and the beam hardening streak artifacts have been detected respectively in 4 and 25 patients. No false filling defect of the pulmonary veins was revealed. Conclusion: MDCT split-bolus technique by simultaneous opacification of pulmonary arteries and veins represents an accurate technique for diagnosis of acute PE, removes the false filling defects of the pulmonary veins, and reduces flow related artifacts. PMID:27110334

  12. Inhibition of hepatic cells pyroptosis attenuates CLP-induced acute liver injury

    PubMed Central

    Chen, Yuan-Li; Xu, Guo; Liang, Xiao; Wei, Juan; Luo, Jing; Chen, Guan-Nan; Yan, Xiao-Di; Wen, Xue-Ping; Zhong, Ming; Lv, Xin

    2016-01-01

    Pyroptosis is a programmed cell death associated with caspase-1 and accompanied by the secretion of a large number of pro-inflammatory cytokines. In the acute stage of sepsis, the release of several pro-inflammatory cytokines aggravates hepatic cell death, and acute liver injury is aggravated with the progress of the disease, resulting in acute liver failure with a very high mortality rate. The present study investigated the effect of inhibiting hepatic cell pyroptosis on the septic acute liver injury. Septic acute liver injury mice model was established by cecal ligation and puncture (CLP model). The liver tissues were assessed for inflammatory infiltration by HE, serum concentrations of ALT, AST, IL-1β, and IL-18 were examined by ELISA, hepatic cell pyroptosis was determined by flow cytometry, and expressions of caspase-1 and NLRP3 were assessed by Western blot. CLP-induced acute liver injury was distinct at 24 h post-operation, with the highest hepatic cell pyroptosis rate. The pyroptosis rate and liver injury indexes were positively correlated. Western blot showed that the expressions of pyroptosis-related proteins, caspase-1, and NLRP3, were increased. Normal mouse hepatic cells were cultured in vitro and LPS+ATP introduced to establish the cell model of septic acute liver injury. The expressions of caspase-1, NLRP3, IL-1β, and IL-18 in LPS+ATP group were significantly higher than the control group by Western blot and ELISA. The inhibitors of NLRP3 (Glyburide) and caspase-1 (AC-YVAD-CMK) alone or in combination were used to pre-treat the hepatic cells, which revealed that the pyroptosis rate was decreased and the cell damage alleviated. The in vivo assay in rats showed that post inhibitor treatment, the 10-days survival was significantly improved and the liver damage reduced. Therefore, inhibiting the hepatic cell pyroptosis could alleviate CLP-induced acute liver injury, providing a novel treatment target for septic acute liver injury. PMID:28078039

  13. Dose-Dependent Effects of Glucocorticoids on Pulmonary Vascular Development in a Murine Model of Hyperoxic Lung Injury

    PubMed Central

    Perez, Marta; Wisniewska, Kamila; Lee, Keng Jin; Cardona, Herminio J.; Taylor, Joann M.; Farrow, Kathryn N.

    2015-01-01

    BACKGROUND Exposure of neonatal mice to hyperoxia results in pulmonary vascular remodeling and aberrant phosphodiesterase-5 (PDE5) signaling. Although glucocorticoids are frequently utilized in the NICU, little is known about their effects on the developing pulmonary vasculature and on PDE5. We sought to determine the effects of hydrocortisone (HC) on pulmonary vascular development and on PDE5 in a neonatal mouse model of hyperoxic lung injury. METHODS C57BL/6 mice were placed in 21% O2 or 75% O2 within 24h of birth and received HC (1, 5, or 10 mg/kg subcutaneously every other day) or vehicle. At 14d, right ventricular hypertrophy (RVH), medial wall thickness (MWT), lung morphometry, and pulmonary artery (PA) PDE5 activity were assessed. PDE5 activity was measured in isolated pulmonary artery smooth muscle cells (PASMC) exposed to 21% or 95% O2 ± 100nM HC for 24h. RESULTS Hyperoxia resulted in alveolar simplification, RVH, increased MWT, and increased PA PDE5 activity. HC decreased hyperoxia-induced RVH and attenuated MWT. HC had dose-dependent effects on alveolar simplification. HC decreased hyperoxia-induced PDE5 activity in vivo and in vitro. CONCLUSIONS HC decreases hyperoxia-induced pulmonary vascular remodeling and attenuates PDE5 activity. These findings suggest that HC may protect against hyperoxic injury in the developing pulmonary vasculature. PMID:26756781