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Sample records for lung infections due

  1. [Lung cancer with bronchial stenosis due to foreign body and Entoameba gingivalis infection].

    PubMed

    Monaco, F; Mondello, B; Barone, M; Familiari, D; Sibilio, M; La Rocca, A; Lentini, S; Monaco, M

    2011-03-01

    Oral cavity infection by protozoarian agents may lead to pathologies such as stomatitis and gengivitis. An higher incidence has been reported in immunocompromised patients and in patients with dental disorders. Entoameba gingivalis localizes into oral cavity and in particular into interstitial and interdental spaces. Infection propagation to bronchial or lung parenchyma represents a complication. In this report the Authors, starting from a recently treated case, discuss on the incidence, complications and surgical management of lung infection by Entoameba gingivalis. PMID:21453594

  2. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

    PubMed Central

    Bahr, Nathan C.; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S.

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. PMID:26697244

  3. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient.

    PubMed

    Bahr, Nathan C; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. PMID:26697244

  4. Acute liver failure due to Varicella zoster virus infection after lung transplantation: a case report.

    PubMed

    Verleden, G M; Vos, R; Van Raemdonck, D E; Laleman, W; Vanaudenaerde, B M

    2012-06-01

    Most adults are Varicella zoster virus (VZV)-positive at the age of 20 years. Some, however, remain antibody-negative and may develop primary chicken pox during adulthood. We report a patient with Williams-Campbell syndrome who underwent double-lung transplantation while being VZV-negative. One year after the successful procedure, he was admitted with fulminant hepatic failure and some cutaneous vesicles in his face. Despite a rapid diagnosis of VZV infection and treatment with acyclovir, his situation deteriorated within 24 hours and while awaiting an urgent liver transplantation, he developed multiple organ failure and died. PMID:22664036

  5. Anaerobic lung infections.

    PubMed

    Vincent, M T; Goldman, B S

    1994-06-01

    Aspiration is the leading cause of anaerobic lung infections. Risk factors for these infections include a depressed level of consciousness, a history of seizure, general anesthesia, central nervous system or neuromuscular disease, cerebrovascular accident, impaired swallowing and use of a tracheal or nasogastric tube. Clinical presentation includes fever, weight loss, malaise and cough productive of foul-smelling sputum. Diagnosis is based on radiographic findings, clinical features and a characteristic morphology of mixed flora on Gram stain of uncontaminated pulmonary specimens. The diagnosis is confirmed by isolation of organisms, usually polymicrobial, on culture. Treatment includes proper drainage, debridement of necrotic tissue and an antibiotic regimen (often initially empiric) with an agent active against anaerobic and aerobic organisms. PMID:8203319

  6. Gallium scintigraphic pattern in lung CMV infections

    SciTech Connect

    Ganz, W.I.; Cohen, D.; Mallin, W.

    1994-05-01

    Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patients without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.

  7. Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa

    PubMed Central

    Pewzner-Jung, Yael; Tavakoli Tabazavareh, Shaghayegh; Grassmé, Heike; Becker, Katrin Anne; Japtok, Lukasz; Steinmann, Jörg; Joseph, Tammar; Lang, Stephan; Tuemmler, Burkhard; Schuchman, Edward H; Lentsch, Alex B; Kleuser, Burkhard; Edwards, Michael J; Futerman, Anthony H; Gulbins, Erich

    2014-01-01

    Cystic fibrosis patients and patients with chronic obstructive pulmonary disease, trauma, burn wound, or patients requiring ventilation are susceptible to severe pulmonary infection by Pseudomonas aeruginosa. Physiological innate defense mechanisms against this pathogen, and their alterations in lung diseases, are for the most part unknown. We now demonstrate a role for the sphingoid long chain base, sphingosine, in determining susceptibility to lung infection by P. aeruginosa. Tracheal and bronchial sphingosine levels were significantly reduced in tissues from cystic fibrosis patients and from cystic fibrosis mouse models due to reduced activity of acid ceramidase, which generates sphingosine from ceramide. Inhalation of mice with sphingosine, with a sphingosine analog, FTY720, or with acid ceramidase rescued susceptible mice from infection. Our data suggest that luminal sphingosine in tracheal and bronchial epithelial cells prevents pulmonary P. aeruginosa infection in normal individuals, paving the way for novel therapeutic paradigms based on inhalation of acid ceramidase or of sphingoid long chain bases in lung infection. PMID:25085879

  8. Lung adenocarcinoma and human papillomavirus infection.

    PubMed

    Chen, Yen-Ching; Chen, Jen-Hau; Richard, Kradin; Chen, Pao-Yang; Christiani, David C

    2004-09-15

    Over the past three decades, the incidence of lung adenocarcinoma has increased worldwide. Most individuals with lung adenocarcinoma (especially women) are nonsmokers. Reported risk factors for the development of lung adenocarcinoma include cigarette smoking; exposure to cooking fumes, air pollution, second-hand smoke, asbestos, and radon; nutritional status; genetic susceptibility; immunologic dysfunction; tuberculosis infection; and asthma. Human papillomavirus (HPV) infection is a known risk factor for the development of squamous cell carcinoma (SCC), but it has not been thoroughly assessed as a potential risk factor for the development of pulmonary adenocarcinoma. More than 50% of people are infected with HPV during their lifetimes, either via intrauterine or postnatal infection. Recent studies involving Taiwanese patients have demonstrated a possible association between HPV infection and the risk of developing pulmonary adenocarcinoma. HPV transmission pathways have not yet been conclusively identified. The observation of certain types of HPV in association with cervical and oral SCC raises the possibility of sexual transmission of HPV from the cervix to the oral cavity, with subsequent transmission to the larynx and then to the lung. HPV infection and metaplasia in lung tissue may increase an individual's susceptibility to the tumorigenesis of pulmonary adenocarcinoma. Further epidemiologic and pathologic investigations will be necessary to establish a causal relation. PMID:15368331

  9. Invasive lung infection by Scedosporium apiospermum in an immunocompetent individual.

    PubMed

    Agatha, David; Krishnan, Krishnan Usha; Dillirani, Ved-achalam; Selvi, Rangam

    2014-01-01

    Scedosporium apiospermum previously known as Monospermum apiospermum is a ubiquitous fungus found in soil, polluted water and sewage. It causes broad spectrum of diseases, including soft tissue infections, septic arthritis, osteomyelitis, ophthalmic infections, sinusitis, pneumonia, meningitis, brain abscesses, endocarditis and disseminated infection. In recent years, it has been shown to be pathogenic for both immunocompetent and immunosuppressed patients. It is a significant opportunist with very high levels of antifungal resistance. We report here a case of invasive lung infection due to S. apiospermum in an immunocompetent patient who responded to antifungal therapy and surgical treatment. PMID:25308027

  10. [Nontuberculous mycobacterial infections of the lung].

    PubMed

    Latshang, Tsogyal D; Lo Cascio, Christian M; Russi, Erich W

    2011-07-01

    Nontuberculous mycobacterium (NTM) species are mycobacterial species other than those belonging to the Mycobacterium tuberculosis complex and M. leprae. NTM are generally free-living organisms that are ubiquitous in the environment. Pulmonary disease, especially in older persons with and without underlying lung disease, is caused primarily by M. avium complex (MAC) and M. kansasii. The symptoms and signs of MAC lung disease are variable and not specific, but include cough, malaise, weakness, dyspnoea, chest discomfort and occasionally hemoptoe. Two major clinical presentations include disease in those with underlying lung disease, primarily white, middle-aged or elderly men - often alcoholics and/or smokers with underlying chronic obstructive lung disease, patients in whom MAC develops in areas of prior bronchiectasis, and patients with cystic fibrosis; and those without known underlying lung disease, including non-smoking women over age 50 who have interstitial patterns on chest radiography. M. kansasii infections are endemic in cities with infected tap water. Symptoms of the M. kansasii lung disease resemble to tuberculosis. M. abszessus is the most pathogenic rapid growing Mycobacterium which causes pulmonary infection. The American Thoracic Society and Infectious Disease Society of America's diagnostic criteria for nontuberculous mycobacterial pulmonary infections include both imaging studies consistent with pulmonary disease and recurrent isolation of mycobacteria from sputum or isolated from at least one bronchial wash in a symptomatic patient. For treatment of MAC lung disease we recommend depending on severity and susceptibility testing a three to four drug treatment with a macrolide, rifampicin and ethambutol and for M. kansasii a treatment with Isoniazid, rifampicin and ethambutol. Surgical management only plays a role in rare and special cases. Treatment should be continued until sputum cultures are consecutively negative for at least one year. PMID

  11. First Case of Lung Abscess due to Salmonella enterica Serovar Abony in an Immunocompetent Adult Patient.

    PubMed

    Pitiriga, Vassiliki; Dendrinos, John; Nikitiadis, Emanuel; Vrioni, Georgia; Tsakris, Athanassios

    2016-01-01

    In healthy individuals, nontyphoidal Salmonella species predominantly cause a self-limited form of gastroenteritis, while they infrequently invade or cause fatal disease. Extraintestinal manifestations of nontyphoidal Salmonella infections are not common and mainly occur among individuals with specific risk factors; among them, focal lung infection is a rare complication caused by nontyphoidal Salmonella strains typically occurring in immunocompromised patients with prior lung disease. We describe the first case of a localized lung abscess formation in an immunocompetent healthy female adult due to Salmonella enterica serovar Abony. The patient underwent lobectomy and was discharged after full clinical recovery. This case report highlights nontyphoidal Salmonellae infections as a potential causative agent of pleuropulmonary infections even in immunocompetent healthy adults. PMID:27429814

  12. First Case of Lung Abscess due to Salmonella enterica Serovar Abony in an Immunocompetent Adult Patient

    PubMed Central

    Dendrinos, John; Nikitiadis, Emanuel; Vrioni, Georgia; Tsakris, Athanassios

    2016-01-01

    In healthy individuals, nontyphoidal Salmonella species predominantly cause a self-limited form of gastroenteritis, while they infrequently invade or cause fatal disease. Extraintestinal manifestations of nontyphoidal Salmonella infections are not common and mainly occur among individuals with specific risk factors; among them, focal lung infection is a rare complication caused by nontyphoidal Salmonella strains typically occurring in immunocompromised patients with prior lung disease. We describe the first case of a localized lung abscess formation in an immunocompetent healthy female adult due to Salmonella enterica serovar Abony. The patient underwent lobectomy and was discharged after full clinical recovery. This case report highlights nontyphoidal Salmonellae infections as a potential causative agent of pleuropulmonary infections even in immunocompetent healthy adults. PMID:27429814

  13. Respiratory failure due to infliximab induced interstitial lung disease.

    PubMed

    Kakavas, Sotiris; Balis, Evangelos; Lazarou, Vasiliki; Kouvela, Marousa; Tatsis, Georgios

    2013-01-01

    Although poorly understood, interstitial lung disease has been reported as a possible complication of tumor necrosis factor alpha inhibitors. We report a case of interstitial lung disease in a 64-year-old man with psoriasis 3 weeks after the initiation of infliximab treatment. The patient had received two fortnightly infusions of infliximab following a short course of methotrexate. Thoracic computed tomography showed bilateral ground glass and interstitial infiltrates, while the results of microbiology and immunologic workup were negative. Likewise, bronchoalveolar lavage detected neither typical nor atypical pathogens. Infliximab-induced interstitial lung injury was suspected and corticosteroid therapy was administered which resulted in rapid clinical and radiological improvement. This is one of the few reported cases of interstitial lung disease due to infliximab in the psoriasis population. The patient had no pre-existing lung pathology, while his previous exposure to methotrexate was minimal and was not temporally associated with the induction of interstitial lung disease. PMID:23969008

  14. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    PubMed

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. PMID:25443661

  15. Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

    PubMed Central

    DING, HONGMEI; LIU, JIANHUA; XUE, RONG; ZHAO, PENG; QIN, YI; ZHENG, FANG; SUN, XUGUO

    2014-01-01

    Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. PMID:25054025

  16. A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep

    PubMed Central

    Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

    2013-01-01

    Background Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Methodology/Principal Findings Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>104 cfu/g). Conclusions/Significance The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches. PMID:23874438

  17. Case of a Lung Mass due to Melioidosis in Mexico

    PubMed Central

    Truong, Kimberly K.; Moghaddam, Samer; Saghbini, Samer Al; Saatian, Bahman

    2015-01-01

    Patient: Female, 70 Final Diagnosis: Melioidosis Symptoms: Chills • fever • neck pain • night sweats Medication: — Clinical Procedure: Incision and drainage • endobronchial ultrasound guided biopsy Specialty: Infectious Diseases Objective: Rare disease Background: Melioidosis, an infection caused by the gram-negative bacterium Burkholderia pseudomallei, is an important cause of pneumonia, skin infection, sepsis, and death in Southeast Asia and Australia, but is exceedingly rare in North America. Pulmonary melioidosis typically presents as acute bacterial pneumonia or cavitary lung lesions resembling tuberculosis. Case Report: We report melioidosis in a 70-year-old active smoker from Mexico with no history of travel to disease-endemic areas. The patient presented with a left supraclavicular abscess and a non-cavitary, left lung mass encasing a pulmonary vein. Incision and drainage of the patient’s subcutaneous abscess isolated B. pseudomallei, and fine-needle aspiration of enlarged mediastinal lymph nodes revealed the presence of intracellular gram-negative bacilli with no evidence of malignancy. Biochemical tests determined that the strain the patient acquired from Mexico is identical to only 1 other isolate from Thailand. Conclusions: This report highlights the blurring epidemiological borders of this organism, its rare presentation mimicking lung malignancy, and an aggressive antimicrobial treatment that resulted in resolution of the patient’s symptoms. PMID:25943405

  18. Ventriculitis due to infection with Rhizopus arrhizus

    PubMed Central

    Hagel, Stefan; Ewald, Christian; Doenst, Torsten; Sachse, Svea; Roedel, Jürgen; Pletz, Mathias W.

    2015-01-01

    A 52-year-old heart–lung transplant patient presented to the emergency department with acute onset of neurologic symptoms. MRI showed ballooning of the left ventricle, midline shift and contrast enhancement in the anterior horn of the left ventricle. Ventricle neuroendoscopy revealed whitish, floccose aerial structures within the left ventricle. Brain biopsy cultures grew Rhizopus arrhizus. Therapy with liposomale amphotericin B and posaconazole was performed. Except for hemianopsia and deficits in minute motor activity, the patient completely recovered. PMID:26862476

  19. Lung cancer in HIV-infected patients in the combination antiretroviral treatment era

    PubMed Central

    Moltó, José; Sirera, Guillem; Clotet, Bonaventura

    2015-01-01

    The advent of combination antiretroviral treatment (cART) has been followed by a decrease in HIV-associated morbidity and mortality, but also by an apparent increase in the incidence of non-AIDS-defining cancers (NADCs). The risk of lung cancer is substantially higher in HIV-infected patients than in the general population, in part due to aging and tobacco use, and it is the most frequent NADC. The management of lung cancer in HIV-infected patients has some peculiarities that need to be taken into account. This review focuses on the epidemiology, risk factors, and clinical management of lung cancer in HIV-infected patients. In addition, screening tools and future perspectives are also discussed. Keywords Lung cancer; non-AIDS-defining cancers (NADCs); HIV infection; antiretroviral treatment PMID:26798577

  20. Lung Infections Associated with Cystic Fibrosis

    PubMed Central

    Lyczak, Jeffrey B.; Cannon, Carolyn L.; Pier, Gerald B.

    2002-01-01

    While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host. PMID:11932230

  1. Viral infection of the lung: host response and sequelae.

    PubMed

    Yoo, Jae-Kwang; Kim, Taeg S; Hufford, Matthew M; Braciale, Thomas J

    2013-12-01

    Because of its essential role in gas exchange and oxygen delivery, the lung has evolved a variety of strategies to control inflammation and maintain homeostasis. Invasion of the lung by pathogens (and in some instances exposure to certain noninfectious particulates) disrupts this equilibrium and triggers a cascade of events aimed at preventing or limiting colonization (and more importantly infection) by pathogenic microorganisms. In this review we focus on viral infection of the lung and summarize recent advances in our understanding of the triggering of innate and adaptive immune responses to viral respiratory tract infection, mechanisms of viral clearance, and the well-recognized consequences of acute viral infection complicating underlying lung diseases, such as asthma. PMID:23915713

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

    PubMed

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

    2016-04-01

    Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function. PMID:26730551

  3. Deaths in Canada from lung cancer due to involuntary smoking.

    PubMed Central

    Wigle, D T; Collishaw, N E; Kirkbride, J; Mao, Y

    1987-01-01

    Recently published evidence indicates that involuntary smoking causes an increased risk of lung cancer among nonsmokers. Information was compiled on the proportion of people who had never smoked among victims of lung cancer, the risk of lung cancer for nonsmokers married to smokers and the prevalence of such exposure. On the basis of these data we estimate that 50 to 60 of the deaths from lung cancer in Canada in 1985 among people who had never smoked were caused by spousal smoking; about 90% occurred in women. The total number of deaths from lung cancer attributable to exposure to tobacco smoke from spouses and other sources (mainly the workplace) was derived by applying estimated age- and sex-specific rates of death from lung cancer attributable to such exposure to the population of Canadians who have never smoked; about 330 deaths from lung cancer annually are attributable to such exposure. PMID:3567810

  4. Persistent Human Cosavirus Infection in Lung Transplant Recipient, Italy

    PubMed Central

    Campanini, Giulia; Rovida, Francesca; Meloni, Federica; Cascina, Alessandro; Ciccocioppo, Rachele; Piralla, Antonio

    2013-01-01

    Human cosavirus is a novel picornavirus recently identified in feces from children in southern Asia. We report infection with human cosavirus in a patient in the Mediterranean area. The patient was an adult double lung transplant recipient who had chronic diarrhea associated with persistent infection with human cosavirus. PMID:24047954

  5. The association between human papillomavirus infection and female lung cancer

    PubMed Central

    Lin, Frank Cheau-Feng; Huang, Jing-Yang; Tsai, Stella Ching-Shao; Nfor, Oswald Ndi; Chou, Ming-Chih; Wu, Ming-Fang; Lee, Chun-Te; Jan, Cheng-Feng; Liaw, Yung-Po

    2016-01-01

    Abstract Lung cancer is the leading cause of cancer deaths among Taiwanese women. Human papillomavirus (HPV) has been detected in lung cancer tissues. The aim of this study was to investigate the association between HPV infection and lung cancer among the Taiwanese women. The analytical data were collected from the longitudinal health insurance databases (LHID 2005 and 2010) of the National Health Insurance Research Database (NHIRD). The study participants were 30 years and older and included 24,162 individuals who were identified with HPV infection from 2001 to 2004 and 1,026,986 uninfected individuals. Lung cancer incidence among infected and uninfected individuals was compared using the univariate and multivariate regression models. Among the total participants, 24,162 individuals were diagnosed with HPV. After adjusting for age, gender, low income, residential area, and comorbidity, the risk of lung cancer was higher in women (hazard ratio [HR] 1.263, 95% CI 1.015–1.571), while all cancer risks were high in both men and women with corresponding hazard ratios (HR) of 1.161 (95% CI 1.083–1.245) and HR 1.240 (95% CI 1.154–1.331), respectively. This study showed a significant increase in lung cancer risk among Taiwanese women who were exposed to HPV infection. PMID:27281096

  6. Penicillium marneffei infection in a lung transplant recipient.

    PubMed

    Stathakis, A; Lim, K P; Boan, P; Lavender, M; Wrobel, J; Musk, M; Heath, C H

    2015-06-01

    Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in individuals infected with human immunodeficiency virus-1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41-year-old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas. PMID:25809145

  7. Human Immunodeficiency Virus Infection and Host Defense in the Lungs.

    PubMed

    Charles, Tysheena P; Shellito, Judd E

    2016-04-01

    Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections. PMID:26974294

  8. Paragonimus kellicotti: A Lung Infection in Our Own Backyard.

    PubMed

    Johannesen, Eric; Nguyen, Van

    2016-01-01

    Paragonimiasis is an infection caused by the lung fluke of the genus Paragonimus. Within the United States, paragonimiasis has been commonly diagnosed in Southeast Asian immigrants infected with the Asian lung fluke Paragonimus westermani. Infections from the North American lung fluke, Paragonimus kellicotti, have been rare, although more infections have been seen in people in the Midwestern United States. A 29-year-old male with a history of pleomorphic xanthoastrocytoma presented with hemoptysis. A CT scan showed a mass in the left upper lung lobe. A biopsy showed eosinophils and parasite eggs, some with a recognizable operculum. Further investigation revealed that he takes canoe trips on rivers within Missouri and would eat crayfish caught from these rivers. A blood sample was confirmed positive for Paragonimiasis serologically at the Center for Disease Control. Paragonimus kellicotti is found in rivers within the Mississippi basin. Infection occurs by consuming uncooked or undercooked crawfish. Microscopic identification of parasite eggs has been the gold standard. Serologic tests have been developed to aid in the diagnosis. Patients typically present with fever and hemoptysis. Common CT findings include pleural effusion, a mass, and lymphadenopathy. Awareness of P. kellicotti is important to guide appropriate diagnostic testing and ensuring proper treatment. PMID:27213066

  9. Paragonimus kellicotti: A Lung Infection in Our Own Backyard

    PubMed Central

    Johannesen, Eric; Nguyen, Van

    2016-01-01

    Paragonimiasis is an infection caused by the lung fluke of the genus Paragonimus. Within the United States, paragonimiasis has been commonly diagnosed in Southeast Asian immigrants infected with the Asian lung fluke Paragonimus westermani. Infections from the North American lung fluke, Paragonimus kellicotti, have been rare, although more infections have been seen in people in the Midwestern United States. A 29-year-old male with a history of pleomorphic xanthoastrocytoma presented with hemoptysis. A CT scan showed a mass in the left upper lung lobe. A biopsy showed eosinophils and parasite eggs, some with a recognizable operculum. Further investigation revealed that he takes canoe trips on rivers within Missouri and would eat crayfish caught from these rivers. A blood sample was confirmed positive for Paragonimiasis serologically at the Center for Disease Control. Paragonimus kellicotti is found in rivers within the Mississippi basin. Infection occurs by consuming uncooked or undercooked crawfish. Microscopic identification of parasite eggs has been the gold standard. Serologic tests have been developed to aid in the diagnosis. Patients typically present with fever and hemoptysis. Common CT findings include pleural effusion, a mass, and lymphadenopathy. Awareness of P. kellicotti is important to guide appropriate diagnostic testing and ensuring proper treatment. PMID:27213066

  10. Infective endocarditis due to Leptotrichia buccalis: a case report.

    PubMed Central

    Duperval, R.; Béland, S.; Marcoux, J. A.

    1984-01-01

    A patient with Down's syndrome presented with infective endocarditis due to Leptotrichia buccalis. The source of the infection was not detected, but the predisposing factor was a complex cardiac malformation. The disease followed a subacute course, had a number of immunologic manifestations and was successfully treated with a 28-day course of penicillin G, given intravenously. L. buccalis has never been reported before as a cause of endocarditis. PMID:6692239

  11. Mycobacterial Lung Disease Complicating HIV Infection.

    PubMed

    Haas, Michelle K; Daley, Charles L

    2016-04-01

    Mycobacterial infections have caused enormous morbidity and mortality in people living with human immunodeficiency virus (HIV) infection. Of these, the most devastating has been tuberculosis (TB), the leading cause of death among HIV-positive persons globally. TB has killed more people living with HIV than any other infection. Diagnosis of latent TB infection (LTBI) is critical as treatment can prevent emergence of TB disease. Bacteriologic confirmation of TB disease should be sought whenever possible as well as drug susceptibility testing. When detected early, drug susceptible TB is curable. Similar to TB, nontuberculous mycobacteria (NTM) can also produce pulmonary and extrapulmonary infections including disseminated disease that can be fatal. Diagnosis through accurate identification of the pathogenic organism will greatly inform treatment. Depending on the NTM identified, treatment may not be curable. Ultimately, preventive strategies such as initiation of antiretroviral drugs and treatment of LTBI are interventions expected to have significant impacts on control of TB and NTM in the setting of HIV. This chapter will review the impact of pulmonary mycobacterial infections on HIV-positive individuals. PMID:26974300

  12. Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

    PubMed Central

    Restrepo-Gualteros, Sonia M.; Jaramillo-Barberi, Lina E.; Gonzalez-Santos, Monica; Rodriguez-Martinez, Carlos E.; Perez, Geovanny F.; Gutierrez, Maria J.; Nino, Gustavo

    2014-01-01

    Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes. PMID:24811320

  13. Bioengineered lysozyme in combination therapies for Pseudomonas aeruginosa lung infections.

    PubMed

    Griswold, Karl E; Bement, Jenna L; Teneback, Charlotte C; Scanlon, Thomas C; Wargo, Matthew J; Leclair, Laurie W

    2014-01-01

    There is increasing urgency in the battle against drug-resistant bacterial pathogens, and this public health crisis has created a desperate need for novel antimicrobial agents. Recombinant human lysozyme represents one interesting candidate for treating pulmonary infections, but the wild type enzyme is subject to electrostatic mediated inhibition by anionic biopolymers that accumulate in the infected lung. We have redesigned lysozyme's electrostatic potential field, creating a genetically engineered variant that is less susceptible to polyanion inhibition, yet retains potent bactericidal activity. A recent publication demonstrated that the engineered enzyme outperforms wild type lysozyme in a murine model of Pseudomonas aeruginosa lung infection. Here, we expand upon our initial studies and consider dual therapies that combine lysozymes with an antimicrobial peptide. Consistent with our earlier results, the charge modified lysozyme combination outperformed its wild type counterpart, yielding more than an order-of-magnitude reduction in bacterial burden following treatment with a single dose. PMID:24637705

  14. 'Inflammatory breast cancer' due to metastatic adenocarcinoma of lung.

    PubMed

    Ninan, Jacob; Naik, Vinay; George, Gemy Maria

    2016-01-01

    A 67-year-old woman with a history of lung adenocarcinoma presented with 3 weeks of redness, pain, swelling and skin changes in her right breast. Her vital signs and physical examination were within physiological limits except for the right breast. She had extensive red streaks radiating from the right nipple with peau d'orange appearance of her overlying skin. Her breast was tender on examination and did not have any associated cervical or axillary lymphadenopathy. Her mammography revealed thickening of the skin, increased parenchymal markings and shrinkage the breast. Multiple skin biopsies demonstrated moderately differentiated lung adenocarcinoma with lymphovascular invasion. The patient made an informed decision to undergo radiotherapy following discussion with her oncologist and breast surgeon. She succumbed to her illness 2 months after the diagnosis of metastasis to her breast. PMID:27587745

  15. Aortic rupture due to pneumococcal infection in aortoiliac stents.

    PubMed

    Mlynski, Amélie; Mordant, Pierre; Dufour, Guillaume; Augustin, Pascal; Lesèche, Guy; Castier, Yves

    2011-06-01

    We report a rare case of pneumococcal aortitis secondary to endovascular bare-metal stent infection. The patient was a 70-year-old man presenting with back pain 1 year after aortoiliac implantation of bare-metal kissing stents. Final diagnosis was microbial aortitis due to Streptococcus pneumoniae involving the stents that resulted in a contained aortic rupture requiring urgent surgical treatment. Emergency extra-anatomic revascularization, excision of the infected tissues, and appropriate antibiotic therapy led to a favorable outcome. A high index of suspicion is required in such a situation because the mortality rate is very high in the absence of appropriate treatment. PMID:21498029

  16. Interstitial Lung Disease due to Siderosis in a Lathe Machine Worker.

    PubMed

    Gothi, D; Satija, B; Kumar, S; Kaur, Omkar

    2015-01-01

    Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lung disease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker. PMID:26410982

  17. [Potential nosocomial disseminated infection due to Nocardia asteroides after a prosthesis insertion in an immunocompetent patient].

    PubMed

    Mrozek, N; Hamizi, S; Gourdon, F; Laurichesse, H; Beytout, J; Lesens, O

    2008-12-01

    Nocardia infections are rare and usually occurred in immunocompromised patients with systemic dissemination from a lung infection. We report a case of an immunocompetent patient in whom Nocardia asteroides had cause psoas and cerebral abcess without pulmonary infection, a short period after a hip prosthesis insertion. The clinical history is highly suggestive of a hospital-acquired infection. PMID:18395304

  18. Interleukin-17 Pathophysiology and Therapeutic Intervention in Cystic Fibrosis Lung Infection and Inflammation.

    PubMed

    Hsu, Daniel; Taylor, Patricia; Fletcher, Dave; van Heeckeren, Rolf; Eastman, Jean; van Heeckeren, Anna; Davis, Pamela; Chmiel, James F; Pearlman, Eric; Bonfield, Tracey L

    2016-09-01

    Cystic fibrosis (CF) is characterized by an excessive neutrophilic inflammatory response within the airway as a result of defective cystic fibrosis transmembrane receptor (CFTR) expression and function. Interleukin-17A induces airway neutrophilia and mucin production associated with Pseudomonas aeruginosa colonization, which is associated with the pathophysiology of cystic fibrosis. The objectives of this study were to use the preclinical murine model of cystic fibrosis lung infection and inflammation to investigate the role of IL-17 in CF lung pathophysiology and explore therapeutic intervention with a focus on IL-17. Cftr-deficient mice (CF mice) and wild-type mice (WT mice) infected with P. aeruginosa had robust IL-17 production early in the infection associated with a persistent elevated inflammatory response. Intratracheal administration of IL-17 provoked a neutrophilic response in the airways of WT and CF animals which was similar to that observed with P. aeruginosa infection. The neutralization of IL-17 prior to infection significantly improved the outcomes in the CF mice, suggesting that IL-17 may be a therapeutic target. We demonstrate in this report that the pathophysiological contribution of IL-17 may be due to the induction of chemokines from the epithelium which is augmented by a deficiency of Cftr and ongoing inflammation. These studies demonstrate the in vivo contribution of IL-17 in cystic fibrosis lung disease and the therapeutic validity of attenuating IL-17 activity in cystic fibrosis. PMID:27271746

  19. First Report of Ventriculoperitoneal Shunt Infection due to Cyberlindnera fabianii

    PubMed Central

    Baghdadi, Jonathan; Hemarajata, Peera; Humphries, Romney; Kelesidis, Theodoros

    2015-01-01

    Fungal infections in the central nervous system (CNS) are associated with significant morbidity and death. Transient fungemia in immunocompetent patients without any other risk factors for fungemia has been suggested as a possible mechanism that may lead to serious fungal ventriculoperitoneal (VP) shunt infections, but evidence is lacking. The clinical spectrum, diagnosis, and optimal therapy of Cyberlindnera fabianii infections remain to be determined. We describe the first case of CNS infection due to C. fabianii that occurred in an immunocompetent adult with a VP shunt. Spontaneous translocation with yeast that is not part of the normal gastrointestinal flora in the setting of ingestion of multiple servings of a fermentation product was the likely source from which Cyberlindnera fabianii gained entrance into the VP shunt system, causing meningitis in this patient. The authors conclude that, in view of the high morbidity associated with yeast infection of the CNS, long-term antifungal therapy should be strongly considered in cases where the VP shunt cannot be completely removed. Transient fungemia may lead to invasive disease in an immunocompetent host with VP shunt, even in the absence of any other risk factors for fungemia and even after remote placement of the VP shunt. PMID:26618013

  20. Modifications of lung clearance mechanisms by acute influenza A infection

    SciTech Connect

    Levandowski, R.A.; Gerrity, T.R.; Garrard, C.S.

    1985-10-01

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.

  1. Hypoxia, innate immunity and infection in the lung.

    PubMed

    Schaible, Bettina; Schaffer, Kirsten; Taylor, Cormac T

    2010-12-31

    The mucosal surface of the lung is the key interface between the external atmosphere and the bloodstream. Normally, this well oxygenated tissue is maintained in state of sterility by a number of innate immune processes. These include a physical and dynamic mucus barrier, the production of microbiocidal peptides and the expression of specific pattern recognition receptors on alveolar epithelial cells and resident macrophages and dendritic cells which recognise microbial structures and initiate innate immune responses which promote the clearance of potentially infectious agents. In a range of diseases, the mucosal surface of the lung experiences decreased oxygen tension leading to localised areas of prominent hypoxia which can impact upon innate immune and subsequent infectious and inflammatory processes. Under these conditions, the lung is generally more susceptible to infection and subsequent inflammation. In the current review, we will discuss recent data pertaining to the role of hypoxia in regulating both host and pathogen in the lung during pulmonary disease and how this contributes to innate immunity, infection and inflammation. PMID:20709192

  2. Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium

    PubMed Central

    Collie, David; Glendinning, Laura; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Doherty, Catherine; McLachlan, Gerry

    2015-01-01

    Background Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS). Methodology/Principal Findings We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota

  3. Prosthetic Valve Endocarditis and Bloodstream Infection Due to Mycobacterium chimaera

    PubMed Central

    Achermann, Yvonne; Rössle, Matthias; Hoffmann, Matthias; Deggim, Vanessa; Kuster, Stefan; Zimmermann, Dieter R.; Hombach, Michael; Hasse, Barbara

    2013-01-01

    Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected. PMID:23536407

  4. Noninvasive monitoring of infection and rejection after lung transplantation.

    PubMed

    De Vlaminck, Iwijn; Martin, Lance; Kertesz, Michael; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F; Okamoto, Jennifer; Nicolls, Mark R; Cornfield, David; Weill, David; Valantine, Hannah; Khush, Kiran K; Quake, Stephen R

    2015-10-27

    The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort. PMID:26460048

  5. Noninvasive monitoring of infection and rejection after lung transplantation

    PubMed Central

    De Vlaminck, Iwijn; Martin, Lance; Kertesz, Michael; Patel, Kapil; Kowarsky, Mark; Strehl, Calvin; Cohen, Garrett; Luikart, Helen; Neff, Norma F.; Okamoto, Jennifer; Nicolls, Mark R.; Cornfield, David; Weill, David; Valantine, Hannah; Khush, Kiran K.; Quake, Stephen R.

    2015-01-01

    The survival rate following lung transplantation is among the lowest of all solid-organ transplants, and current diagnostic tests often fail to distinguish between infection and rejection, the two primary posttransplant clinical complications. We describe a diagnostic assay that simultaneously monitors for rejection and infection in lung transplant recipients by sequencing of cell-free DNA (cfDNA) in plasma. We determined that the levels of donor-derived cfDNA directly correlate with the results of invasive tests of rejection (area under the curve 0.9). We also analyzed the nonhuman cfDNA as a hypothesis-free approach to test for infections. Cytomegalovirus is most frequently assayed clinically, and the levels of CMV-derived sequences in cfDNA are consistent with clinical results. We furthermore show that hypothesis-free monitoring for pathogens using cfDNA reveals undiagnosed cases of infection, and that certain infectious pathogens such as human herpesvirus (HHV) 6, HHV-7, and adenovirus, which are not often tested clinically, occur with high frequency in this cohort. PMID:26460048

  6. Necrotising fasciitis due to an infected sebaceous cyst

    PubMed Central

    Bosman, W M P F; Brekelmans, W; Verduijn, P S; Borger van der Burg, B L S; Ritchie, E D

    2014-01-01

    The current case presents a patient who was admitted to our hospital with the diagnosis of cellulitis of the right groin. In the following days, the patient's condition deteriorated and developed a septic shock. Exploration in the operating room showed a necrotising fasciitis of the adductor muscles, with an infected sebaceous cyst in the inguinal crest as port d'entrée. After extensive surgical debridement, antibiotic therapy, haemodynamic and respiratory support, the patient recovered. Necrotising fasciitis is a rare but very lethal condition, which necessitates aggressive surgical therapy and antibiotic support. The current case report is the first report to show a necrotising fasciitis due to an infected sebaceous cyst. PMID:24789153

  7. Man's best friend? Infective endocarditis due to Capnocytophaga canimorsus.

    PubMed

    Hayani, Omar; Higginson, Lyall A J; Toye, Baldwin; Burwash, Ian G

    2009-04-01

    Infective endocarditis caused by zoonotic microorganisms is an uncommon clinical entity. A 55-year-old man was diagnosed with endocarditis due to Capnocytophaga canimorsus, a commensal bacterium contained in the saliva of dogs, that involved the aortic and tricuspid valves and was complicated by a para-aortic valve abscess and aorta-to-right atrial fistula. The patient was successfully treated with antibiotic therapy and surgical intervention. C canimorsus endocarditis should be considered in patients with culture-negative endocarditis, particularly in immunosuppressed, asplenic or alcoholic individuals who have recently suffered a dog bite or have had close contact with dogs. PMID:19340358

  8. Modeling Granulomas in Response to Infection in the Lung.

    PubMed

    Hao, Wenrui; Schlesinger, Larry S; Friedman, Avner

    2016-01-01

    Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The 'strength' of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the 'switching time', namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. PMID:26986986

  9. Modeling Granulomas in Response to Infection in the Lung

    PubMed Central

    Hao, Wenrui; Schlesinger, Larry S.; Friedman, Avner

    2016-01-01

    Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The ‘strength’ of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the ‘switching time’, namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. PMID:26986986

  10. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    PubMed

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists. PMID:26962155

  11. Respirable bacteriophages for the treatment of bacterial lung infections.

    PubMed

    Hoe, Susan; Semler, Diana D; Goudie, Amanda D; Lynch, Karlene H; Matinkhoo, Sadaf; Finlay, Warren H; Dennis, Jonathan J; Vehring, Reinhard

    2013-12-01

    This review article discusses the development of respiratory therapeutics containing bacteriophages indicated for lung infections, specifically those that have become increasingly difficult to treat because of antibiotic resistance. Recent achievements and remaining problems are presented for each step necessary to develop a bacteriophage-containing dosage form for respiratory drug delivery, including selection of appropriate bacteriophages for therapy, processing and purification of phage preparations, formulation into a stable, solid dosage form, and delivery device selection. Safety and efficacy studies in animals and human subjects are also reviewed. PMID:23597003

  12. Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection.

    PubMed Central

    Castranova, V; Ma, J Y; Yang, H M; Antonini, J M; Butterworth, L; Barger, M W; Roberts, J; Ma, J K

    2001-01-01

    There are at least three mechanisms by which alveolar macrophages play a critical role in protecting the lung from bacterial or viral infections: production of inflammatory cytokines that recruit and activate lung phagocytes, production of antimicrobial reactive oxidant species, and production of interferon (an antiviral agent). In this article we summarize data concerning the effect of exposure to diesel exhaust particles on these alveolar macrophage functions and the role of adsorbed organic chemicals compared to the carbonaceous core in the toxicity of diesel particles. In vitro exposure of rat alveolar macrophages to diesel exhaust particles decreased the ability of lipopolysaccharide (LPS), a bacterial product] to stimulate the production of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Methanol extract exhibited this potential but methanol-washed diesel particles did not. Exposure of rats to diesel exhaust particles by intratracheal instillation also decreased LPS-induced TNF-alpha and IL-1 production from alveolar macrophages. In contrast, carbon black did not exhibit this inhibitory effect. Exposure of rats to diesel exhaust particles by inhalation decreased the ability of alveolar macrophages to produce antimicrobial reactive oxidant species in response to zymosan (a fungal component). In contrast, exposure to coal dust increased zymosan-stimulated oxidant production. In vivo exposure to diesel exhaust particles but not to carbon black decreased the ability of the lungs to clear bacteria. Inhalation exposure of mice to diesel exhaust particles but not to coal dust depressed the ability of the lung to produce the antiviral agent interferon and increased viral multiplication in the lung. These results support the hypothesis that exposure to diesel exhaust particles increases the susceptibility of the lung to infection by depressing the antimicrobial potential of alveolar macrophages. This inhibitory effect appears

  13. Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients.

    PubMed

    Ciofu, Oana; Tolker-Nielsen, Tim; Jensen, Peter Østrup; Wang, Hengzhuang; Høiby, Niels

    2015-05-01

    Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms of biofilm formation and antimicrobial tolerance and resistance are reviewed. Potential anti-biofilm therapeutic targets such as weakening of biofilms by quorum-sensing inhibitors or antibiotic killing guided by pharmacokinetics and pharmacodynamics of antibiotics are presented. The vicious circle of adaptive evolution of the persisting bacteria imposes important therapeutic challenges and requires development of new drug delivery systems able to reach the different niches occupied by the bacteria in the lung of cystic fibrosis patients. PMID:25477303

  14. Protection against Streptococcus pneumoniae lung infection after nasopharyngeal colonization requires both humoral and cellular immune responses

    PubMed Central

    Wilson, R; Cohen, J M; Jose, R J; de Vogel, C; Baxendale, H; Brown, J S

    2015-01-01

    Streptococcus pneumoniae is a common cause of pneumonia and infective exacerbations of chronic lung disease, yet there are few data on how adaptive immunity can specifically prevent S. pneumoniae lung infection. We have used a murine model of nasopharyngeal colonization by the serotype 19F S. pneumoniae strain EF3030 followed by lung infection to investigate whether colonization protects against subsequent lung infection and the mechanisms involved. EF3030 colonization induced systemic and local immunoglobulin G against a limited number of S. pneumoniae protein antigens rather than capsular polysaccharide. During lung infection, previously colonized mice had increased early cytokine responses and neutrophil recruitment and reduced bacterial colony-forming units in the lungs and bronchoalveolar lavage fluid compared with control mice. Colonization-induced protection was lost when experiments were repeated in B-cell- or neutrophil-deficient mice. Furthermore, the improved interleukin (IL)-17 response to infection in previously colonized mice was abolished by depletion of CD4+ cells, and prior colonization did not protect against lung infection in mice depleted of CD4+ cells or IL17. Together these data show that naturally acquired protective immunity to S. pneumoniae lung infection requires both humoral and cell-mediated immune responses, providing a template for the design of improved vaccines that can specifically prevent pneumonia or acute bronchitis. PMID:25354319

  15. Presence of gas in left ventricle due to infective endocarditis.

    PubMed

    Laiq, Zenab; Yarmohammadi, Hirad; Nabeel, Yassar; Adatya, Sirtaz

    2016-01-01

    Gas in myocardium is a rare manifestation of infective endocarditis caused by gas producing bacteria. We present a case of infective endocarditis caused by Citrobacter Koseri initially diagnosed by computed tomography and confirmed with transesophageal echocardiogram. PMID:27318588

  16. Virus Infection and Titration of SARS-CoV in Mouse Lung

    PubMed Central

    Fett, Craig; Zhao, Jincun; Perlman, Stanley

    2016-01-01

    Two critical steps when investigating an animal model of a virus infection are consistently successfully infecting animals and accurately determining viral titers in tissue throughout the course of infection. Here we discuss in detail how to infect mice with SARS-CoV and then quantify the titer of virus in the lung.

  17. Spontaneous pneumothorax due to bronchopleural fistula following reirradiation for locoregionally recurrent squamous cell lung cancer.

    PubMed

    Ota, Takayo; Suzumura, Tomohiro; Sugiura, Takamune; Hasegawa, Yoshikazu; Yonesaka, Kimio; Makihara, Masaru; Tsukuda, Hiroshi; Tada, Takuhito; Fukuoka, Masahiro

    2016-05-01

    Spontaneous pneumothorax following radiotherapy for pulmonary malignancy is an unusual clinical condition. Here, we report a case of a 78-year-old male suffering from dyspnea during radiotherapy for squamous cell lung cancer of the right main bronchus. Imaging studies and fiberoptic bronchoscopy revealed that pneumothorax was due to a bronchopleural fistula. PMID:27190612

  18. Ciprofloxacin-Loaded Inorganic-Organic Composite Microparticles To Treat Bacterial Lung Infection.

    PubMed

    Tewes, Frederic; Brillault, Julien; Lamy, Barbara; O'Connell, Peter; Olivier, Jean-Christophe; Couet, William; Healy, Anne Marie

    2016-01-01

    Ciprofloxacin (CIP) is an antibiotic that has been clinically trialed for the treatment of lung infections by aerosolization. However, CIP is rapidly systemically absorbed after lung administration, increasing the risk for subtherapeutic pulmonary concentrations and resistant bacteria selection. In the presence of calcium, CIP forms complexes that reduce its oral absorption. Such complexation may slow down CIP absorption from the lung thereby maintaining high concentration in this tissue. Thus, we developed inhalable calcium-based inorganic-organic composite microparticles to sustain CIP within the lung. The aerodynamics and micromeritic properties of the microparticles were characterized. FTIR and XRD analysis suggest that the inorganic component of the particles comprised amorphous calcium carbonate and amorphous calcium formate, and that CIP and calcium interact in a 1:1 stoichiometry in the particles. CIP was completely released from the microparticles within 7 h, with profiles showing a slight dependence on pH (5 and 7.4) compared to the dissolution of pure CIP. Transport studies of CIP across Calu-3 cell monolayers, in the presence of various calcium concentrations, showed a decrease of up to 84% in CIP apparent permeability. The apparent minimum inhibitory concentration of CIP against Pseudomonas aeruginosa and Staphylococcus aureus was not changed in the presence of the same calcium concentration. These results indicate that the designed particles should provide sustained levels of CIP with therapeutic effect in the lung. With these microparticles, it should be possible to control CIP pharmacokinetics within the lung, based on controlled CIP release from the particles and reduced apparent permeability across the epithelial barrier due to the cation-CIP interaction. PMID:26641021

  19. Proposed biomolecular theory of fasting during fevers due to infection.

    PubMed

    Yarnell, E

    2001-10-01

    The folk admonition to starve a fever may have a scientific basis. Fevers due to infectious organisms that produce neuraminidase (sialidase) may contribute to the pathophysiology of autoimmune conditions. Neuraminidase unmasks host cellular lectins that interact with food lectins and can induce human leukocyte antigen type II (HLA II) expression. HLA II can then bind food lectins and serve as targets for antibody production. Some of these antibodies can then cross-react and attack healthy tissue, inducing disease. The example of insulin-dependent diabetes mellitus is discussed, helping to explain why infectious organisms and dairy product ingestion appear to be linked to some cases of this disease. Genetic variants and other factors may contribute to disease pathogenesis, so this model does not explain all instances of autoimmune disease. Fasting as a way to avoid the process by not introducing food lectins is briefly reviewed. Neuraminidase inhibitors might be useful in preventing genesis of autoimmunity during infection, although this possibility has not been formally tested. PMID:11703168

  20. Sudden infant death due to Lactococcal infective endocarditis.

    PubMed

    Taniguchi, K; Nakayama, M; Nakahira, K; Nakura, Y; Kanagawa, N; Yanagihara, I; Miyaishi, S

    2016-03-01

    Infective endocarditis (IE) of infants is rare, most of which occur associated with congenital heart disease or its cardiac surgery. We experienced a case of sudden death of a four-month-old male infant without congenital heart disease. It was elucidated by postmortem examination that the dead had suffered severe IE, which led him to death. In the microbiological genetic analysis using histological section, the pathogen causing inflammation in the present case was identified as Lactococcus lactis subspecies, although Staphylococci have been reported to be common and important one. Previously reported infectious diseases by Lactococcus lactis subspecies were all adult cases and this is the first report of an infantile death due to Lactococcal IE according to our knowledge. Any fatal disease may be included in sudden death cases targeted for forensic autopsy, even if it is rare. It is expected for forensic pathologists that they note such case and share each experience among themselves and other medical fields to develop a strategy for prevention. PMID:26277368

  1. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice

    PubMed Central

    Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

    2016-01-01

    Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future. PMID:27196107

  2. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    PubMed Central

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  3. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury

    PubMed Central

    Sugiyama, Michael G.; Gamage, Asela; Zyla, Roman; Armstrong, Susan M.; Advani, Suzanne; Advani, Andrew; Wang, Changsen

    2015-01-01

    ABSTRACT Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza. IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza

  4. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    PubMed

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2016-02-01

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  5. Lung cancer: is the increasing incidence due to radioactive polonium in cigarettes

    SciTech Connect

    Marmorstein, J.

    1986-02-01

    This paper presents clinical, experimental, and epidemiologic evidence to help explain the rapidly increasing incidence of primary lung cancer, with recently observed reversal in leading cell type from squamous cell to adenocarcinoma. It postulates that this may be due to changes in modern cigarettes, with or without filters, which allow inhalation of increased amounts of radioactive lead and polonium and decreased amounts of benzopyrene. This hypothesis is based upon measurements of increased concentrations of radioactive polonium in the lungs of cigarette smokers, in modern tobaccos grown since 1950, and in high-phosphate fertilizers used for tobacco farming in industrialized countries. Critical support for this thesis is based upon experimental animal studies in which lung cancers that resemble adenocarcinomas are induced with as little as 15 rads of radioactive polonium, equal to one fifth the dosage inhaled by cigarette smokers who average two packs a day during a 25-year period.

  6. Nitric oxide as a mediator of oxidant lung injury due to paraquat.

    PubMed Central

    Berisha, H I; Pakbaz, H; Absood, A; Said, S I

    1994-01-01

    At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either NG-nitro-L-arginine methyl ester or N omega-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury. PMID:7519778

  7. Nitric Oxide as a Mediator of Oxidant Lung Injury Due to Paraquat

    NASA Astrophysics Data System (ADS)

    Berisha, Hasan I.; Pakbaz, Hedayatollah; Absood, Afaf; Said, Sami I.

    1994-08-01

    At low concentrations, nitric oxide is a physiological transmitter, but in excessive concentrations it may cause cell and tissue injury. We report that in acute oxidant injury induced by the herbicide paraquat in isolated guinea pig lungs, nitric oxide synthesis was markedly stimulated, as evidenced by increased levels of cyclic GMP in lung perfusate and of nitrite and L-citrulline production in lung tissue. All signs of injury, including increased airway and perfusion pressures, pulmonary edema, and protein leakage into the airspaces, were dose-dependently attenuated or totally prevented by either N^G-nitro-L-arginine methyl ester or N^ω-nitro-L-arginine, selective and competitive inhibitors of nitric oxide synthase. Protection was reversed by excess L-arginine but not by its enantiomer D-arginine. When blood was added to the lung perfusate, the paraquat injury was moderated or delayed as it was when paraquat was given to anesthetized guinea pigs. The rapid onset of injury and its failure to occur in the absence of Ca2+ suggest that constitutive rather than inducible nitric oxide synthase was responsible for the stimulated nitric oxide synthesis. The findings indicate that nitric oxide plays a critical role in the production of lung tissue injury due to paraquat, and it may be a pathogenetic factor in other forms of oxidant tissue injury.

  8. Implantable cardioverter defibrillator infection due to Mycobacterium mageritense.

    PubMed

    Fukunaga, Masato; Goya, Masahiko; Ogawa, Midori; Fukuda, Kazumasa; Taniguchi, Hatsumi; Ando, Kenji; Iwabuchi, Masashi; Miyazaki, Hiroaki

    2016-03-01

    Rapidly growing non-tuberculous mycobacteria (RGM) are usually detected in blood cultures after 4-5 days of incubation, so it is important to differentiate RGM from contamination of commensal organisms on human skin. We report an unusual case of Mycobacterium mageritense bacteremia and infection of an implantable cardioverter defibrillator originally misidentified as Corynebacterium spp. or Nocardia spp. in gram-stained smears. 16S rRNA gene sequencing had utility in the definitive identification of isolates. We should be aware that RGM infection may exist in repeated implantable device infections. PMID:26719132

  9. Monte Carlo estimation of dose difference in lung from 192Ir brachytherapy due to tissue inhomogeneity.

    PubMed

    Gialousis, G; Dimitriadis, A; Yakoumakis, E

    2011-09-01

    Lung brachytherapy using high-dose rate (192)Ir technique is a well-established technique of radiation therapy. However, many commercial treatment planning systems do not have the ability to consider the inhomogeneity of lung in relation to normal tissue. Under such circumstances dose calculations for tissues and organs at risk close to the target are inaccurate. The purpose of the current study was to estimate the dose difference due to tissue inhomogeneity using the Monte Carlo simulation code MCNP-5. Results showed that there was a relative sub dosage by treatment planning systems calculations in neighbouring tissues around the radioactive source due to inhomogeneity ignorance. The presence of lung instead of normal tissue resulted in an increase in relative dose, which approached 8 % at 4-cm distance from the source. Additionally, the relative increase was small for the lung (2.1 %) and larger for organs at risk such as the heart (6.8 %) and bone marrow (7.6 %). PMID:21831865

  10. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae.

    PubMed

    Peñaloza, Hernán F; Nieto, Pamela A; Muñoz-Durango, Natalia; Salazar-Echegarai, Francisco J; Torres, Javiera; Parga, María J; Alvarez-Lobos, Manuel; Riedel, Claudia A; Kalergis, Alexis M; Bueno, Susan M

    2015-09-01

    Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inflammatory cytokine interleukin-10 (IL-10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10(-/-) mice). The IL-10(-/-) mice showed increased mortality, higher expression of pro-inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10(-/-) mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine. PMID:26032199

  11. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

    PubMed Central

    Peñaloza, Hernán F; Nieto, Pamela A; Muñoz-Durango, Natalia; Salazar-Echegarai, Francisco J; Torres, Javiera; Parga, María J; Alvarez-Lobos, Manuel; Riedel, Claudia A; Kalergis, Alexis M; Bueno, Susan M

    2015-01-01

    Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inflammatory cytokine interleukin-10 (IL-10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10−/− mice). The IL-10−/− mice showed increased mortality, higher expression of pro-inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10−/− mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine. PMID:26032199

  12. Enteric infections due to Campylobacter, Yersinia, Salmonella, and Shigella*

    PubMed Central

    1980-01-01

    This report reviews the available information on the clinical features, pathogenesis, bacteriology, and epidemiology of Campylobacter jejuni and Yersinia enterocolitica, both of which have recently been recognized as important causes of enteric infection. In the fields of salmonellosis and shigellosis, important new epidemiological and related findings that have implications for the control of these infections are described. Priority research activities in each of these areas are outlined. PMID:6969131

  13. Outbreak of Intestinal Infection Due to Rhizopus microsporus▿

    PubMed Central

    Cheng, Vincent C. C.; Chan, Jasper F. W.; Ngan, Antonio H. Y.; To, Kelvin K. W.; Leung, S. Y.; Tsoi, H. W.; Yam, W. C.; Tai, Josepha W. M.; Wong, Samson S. Y.; Tse, Herman; Li, Iris W. S.; Lau, Susanna K. P.; Woo, Patrick C. Y.; Leung, Anskar Y. H.; Lie, Albert K. W.; Liang, Raymond H. S.; Que, T. L.; Ho, P. L.; Yuen, K. Y.

    2009-01-01

    Sinopulmonary and rhinocerebral zygomycosis has been increasingly found in patients with hematological malignancies and bone marrow transplantation, but intestinal zygomycosis remains very rare in the literature. We investigated an outbreak of intestinal infection due to Rhizopus microsporus in 12 patients on treatment for hematological malignancies over a period of 6 months in a teaching hospital. The intake of allopurinol during hospitalization (P < 0.001) and that of commercially packaged ready-to-eat food items in the preceding 2 weeks (P < 0.001) were found to be independently significant risk factors for the development of intestinal zygomycosis. A total of 709 specimens, including 378 environmental and air samples, 181 food samples, and 150 drug samples, were taken for fungal culture. Among them, 16 samples of allopurinol tablets, 3 prepackaged ready-to-eat food items, and 1 pair of wooden chopsticks were positive for Rhizopus microsporus, which was confirmed by ITS1-5.8S-ITS2 rRNA gene cluster (internal transcribed spacer [ITS]) sequencing. The mean viable fungal counts of allopurinol obtained from wards and pharmacy were 4.22 × 103 CFU/g of tablet (range, 3.07 × 103 to 5.48 × 103) and 3.24 × 103 CFU/g of tablet (range, 2.68 × 103 to 3.72 × 103), respectively, which were much higher than the mean count of 2 × 102 CFU/g of food. Phylogenetic analysis by ITS sequencing showed multiple clones from isolates of contaminated allopurinol tablets and ready-to-eat food, of which some were identical to patients' isolates, and with one isolate in the cornstarch used as an excipient for manufacture of this drug. We attempted to type the isolates by random amplification of polymorphic DNA analysis, with limited evidence of clonal distribution. The primary source of the contaminating fungus was likely to be the cornstarch used in the manufacturing of allopurinol tablets or ready-to-eat food. Rhizopus microsporus is thermotolerant and can multiply even at 50

  14. Septic arthritis due to tubercular and Aspergillus co-infection.

    PubMed

    Kumar, Mukesh; Thilak, Jai; Zahoor, Adnan; Jyothi, Arun

    2016-01-01

    Aspergillus septic arthritis is a rare and serious medical and surgical problem. It occurs mainly in immunocompromised patients. Aspergillus fumigatus is the most common causative organism followed by Aspergillus flavus. The most common site affected is knee followed by shoulder, ankle, wrist, hip and sacroiliac joint. Debridement and voriconazole are primary treatment of articular aspergilosis. To the best of our knowledge, there are no reported cases of co-infection of tuberculosis (TB) and Aspergillus infecting joints. We report a case of co-infection of TB and A. flavus of hip and knee of a 60-year-old male, with type 2 diabetes mellitus. He was treated with debridement, intravenous voriconazole, and antitubercular drugs. PMID:27293296

  15. Extensive Bilateral Lemierre Syndrome due to Methicillin-Resistant Staphylococcus epidermidis in a Patient with Lung Adenocarcinoma

    PubMed Central

    Choi, Bo Mi; Son, Seong Wan; Park, Chan Kwon; Lee, Sang-Hoon

    2015-01-01

    Lemierre syndrome (LS) is a septic thrombophlebitis of the internal jugular vein (IJV) following an oropharyngeal infection. LS is commonly caused by normal anaerobic flora and treated with appropriate antibiotics and anticoagulation therapy. Although the incidence of disease is very rare, 15% cases of LS are fatal even in the antibiotic era because of disseminated septic thromboemboli. We reported a case of extensive bilateral LS due to methicillin-resistant Staphylococcus epidermidis in a 63-year-old female with lung adenocarcinoma. Initial examination revealed a retropharyngeal abscess; hence, intravenous ceftriaxone and steroid were initiated empirically. However, pulmonary thromboembolism developed and methicillin-resistant S. epidermidis was identified in the bacterial culture. Despite intensive antibiotic and anticoagulation therapies, extensive septic thrombophlebitis involving the bilateral IJV and superior vena cava developed. Adjunctive catheter-directed thrombolysis and superior vena cava stenting were performed and the patient received antibiotic therapy for an additional 4 weeks, resulting in complete recovery. PMID:26175788

  16. Subdural empyema and unilateral pansinusitis due to a tooth infection.

    PubMed

    Derin, Serhan; Sahan, Murat; Hazer, Derya Burcu; Sahan, Leyla

    2015-01-01

    Paranasal sinus infections are very common. Dental infections, tumours and anatomical malformations can cause unilateral sinusitis. Most cases can be treated without complications. However, rare life-threatening intracranial complications can occur. Generally, an intracranial complication progresses rapidly and can cause meningismus, focal neurological disorders, loss of consciousness and seizures. In such cases, an emergency craniotomy and concurrent sinus surgery are required. This article presents a 16-year-old patient with pansinusitis and subdural empyema that developed after a dental abscess. PMID:26123452

  17. Surfactant therapy restores gas exchange in lung injury due to paraquat intoxication in rats.

    PubMed

    So, K L; de Buijzer, E; Gommers, D; Kaisers, U; van Genderen, P J; Lachmann, B

    1998-08-01

    Paraquat is a weed killer which causes often fatal lung damage in humans and other animals. There is evidence that the pulmonary surfactant system is involved in the pathophysiology of respiratory failure after paraquat intoxication and, therefore, the possible therapeutic effect of intratracheal surfactant administration on gas exchange in rats with progressive lung injury induced by paraquat poisoning was studied. In one group of rats, the time course of the development of lung injury due to paraquat intoxication was characterized. In a second group of rats, 72 h after paraquat intoxication, the animals underwent mechanical ventilation and only those animals in which the arterial oxygen tension/inspiratory oxygen fraction (Pa,O2/FI,O2) decreased to below 20 kPa (150 mmHg) received exogenous surfactant (200 mg x kg(-1) body weight). Within 3 days the rats in group 1 developed progressive respiratory failure, demonstrated not only by impaired gas exchange and lung mechanics but also by increased minimal surface tension and increased protein concentration in bronchoalveolar lavage fluid. In group 2, intratracheal surfactant administration increased Pa,O2/FI,O2 significantly within 5 min (14.4+/-2.4 kPa (108+/-18 mmHg)) to (55.2+/-53 kPa (414+/-40 mmHg)) and sustained this level for at least 2 h. It is concluded that intratracheal surfactant administration is a promising approach in the treatment of severe respiratory failure caused by paraquat poisoning. PMID:9727775

  18. Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

    PubMed Central

    Hirose, Akihiko; Akashi, Toshi; Takeshita, Tomomi; Kuroki, Nao; Shibata, Asami; Hongo, Satoko; Hashiguchi, Seiko; Konno, Katsuhiko

    2013-01-01

    Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV) infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm) in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6) and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice. PMID:24369005

  19. A patient with fulminant influenza-related bacterial pneumonia due to Streptococcus pneumoniae followed by Mycobacterium tuberculosis infection.

    PubMed

    Seki, Masafumi; Suyama, Naofumi; Hashiguchi, Kohji; Hara, Atsuko; Kosai, Kosuke; Kurihara, Shintaro; Nakamura, Shigeki; Yamamoto, Kazuko; Imamura, Yoshifumi; Izumikawa, Koichi; Kakaya, Hiroshi; Yanagihara, Katsunori; Yamamoto, Yoshihiro; Mukae, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

    2008-01-01

    A 74-year-old man with poorly controlled diabetes mellitus was admitted to our hospital because of severe respiratory disturbance, fever, and sputum. We found massive consolidation of the right lung and nodular shadows on the left lung on chest X-ray, and detected influenza virus and Streptococcus pneumoniae antigen from a nasopharyngeal swab and urine sample, respectively. Co-infection with influenza virus and bacteria was suspected, and oseltamivir and biapenem were prescribed. Laboratory data improved after the addition of sivelestat sodium hydrate, an inhibitor of neutrophil-derived elastase; however, chest X-ray findings became worse on Day 8, and we administered 1 g methylprednisolone intravenously for two days. On Day 12, we detected Mycobacterium tuberculosis in the sputum, even though we did not previously detect any acid-fast bacilli, and started anti-tuberculosis drugs, such as isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide; however, the patient died 12 days later. Severe influenza-related bacterial pneumonia with Streptococcus pneumoniae and subsequently secondary tuberculosis infection were finally suspected in this case. This was a very rare case in which additional tuberculosis infection was found in a patient with fulminant pneumonia due to co-infection of influenza virus and bacteria. It is necessary to observe patients with influenza carefully, especially when steroids are used, even if antibiotics are also administered. PMID:19043258

  20. Proinflammatory and Th1 cytokine alterations following ultraviolet radiation enhancement of disease due to influenza infection in mice.

    PubMed

    Ryan, Lisa K; Copeland, Lisa R; Daniels, Mary J; Costa, Elisabeth R; Selgrade, Mary Jane K

    2002-05-01

    Exposure of rodents to immunosuppressive agents such as ozone, dioxin, or ultraviolet radiation (UVR) leads to increased morbidity and mortality following influenza virus infection. However, these adverse effects are not related to the suppression of virus-specific immune responses. Our laboratory showed that UVR increased the morbidity, mortality, and pathogenesis of influenza virus without affecting protective immunity to the virus, as measured by resistance to reinfection, suggesting that UVR and other immunosuppressive pollutants such as dioxin and ozone may exacerbate early responses that contribute to the pathogenesis of a primary viral infection. In the present study, we examined the mechanism of UVR-enhanced mortality in the absence of effects on virus-specific immunity and tested the hypothesis that modulation of cytokine levels was associated with increased deaths and body weight loss. BALB/c mice were exposed to 8.2 kJ/m(2) UVR and were infected 3 days later with a sublethal influenza virus infection (LD(40) of mouse-adapted Hong Kong influenza A/68, H(3)N(2)). Influx of inflammatory cells, proinflammatory cytokines, and cytokines produced by T-helper lymphocytes (Th1 and Th2) were measured in lung homogenates (LH) as well as in bronchoalveolar lavage fluid (BAL). UVR preexposure decreased the influenza-induced lymphocytic influx 5 days after infection, but did not alter macrophage and neutrophil influx into the lung, or increase virus titers significantly. Although interferon (IFN)-gamma, total interleukin (IL)-12, IL-6, and TNF-alpha were altered in mice that received UVR exposure prior to infection, no clear association was made that correlated with the UVR-induced increase in body weight loss and mortality due to influenza infection. PMID:11961220

  1. A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE)

    ClinicalTrials.gov

    2016-09-01

    Bloodstream Infections (BSI) Due to CRE; Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE; Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE; Complicated Urinary Tract Infection (cUTI) Due to CRE; Acute Pyelonephritis (AP) Due to CRE

  2. Bloodstream infections due to Peptoniphilus spp.: report of 15 cases

    PubMed Central

    Brown, K; Church, D; Lynch, T; Gregson, D

    2014-01-01

    Peptoniphilus spp. are Gram-positive anaerobic cocci (GPAC) that were formerly classified in the genus Peptostreptococcus. This study describes 15 cases of Peptoniphilus spp. bloodstream infection (BSI) diagnosed from 2007 to 2011 using 16S rDNA sequencing in patients with pneumonia, pre-term delivery, soft tissue infection or colon or bladder disease. Seven out of 15 (47%) of these cases had polymicrobial BSIs. One of the isolates was closely related to P. duerdenii (EU526290), while the other 14 isolates were most closely related to a Peptoniphilus sp. reference strain (ATCC 29743) and P. hareii (Y07839). Peptoniphilus is a rare but important cause of BSI. PMID:24773457

  3. [Infection due to Mycobacterium bovis in common variable immunodeficiency].

    PubMed

    Herrera-Sánchez, Diana Andrea; Castilla-Rodríguez, Jaisel Luz; Castrejón-Vázquez, María Isabel; Vargas-Camaño, María Eugenia; Medina-Torres, Edgar Alejandro; Blancas-Galicia, Lizbeth; Espinosa-Padilla, Sara Elva

    2015-01-01

    Common variable immunodeficiency (CVID) is an heterogeneous group of disorders characterized by impaired antibody production. It shows a wide spectrum of manifestations including severe and recurrent respiratory infections (Streptococcus pneumoniae, Haemophilus) and gastrointestinal (Campylobacter jejuni, rotavirus and Giardia lamblia). Viral infections caused by herpes zoster, cytomegalovirus (CMV) and hepatitis C are rare. The opportunistic agents such as CMV, Pneumocystis jirovecii, cryptococcus and atypical mycobacteria have been reported as isolated cases. This paper reports the case of a 38-year-old female patient, who began six years before with weight loss of 7 kg in six months, fatigue, weakness, sweating, fever and abdominal pain. Furthermore, patient had intestinal obstruction and abdominal CT showed mesenteric lymph growth. The mesenteric lymph node biopsy revealed positives Mycobacterium PCR, Ziehl-Neelsen staining and culture for M. bovis. In the laparotomy postoperative period was complicated with nosocomial pneumonia, requiring mechanical ventilation and tracheostomy. Two years later, she developed right renal abscess that required surgical drainage, once again with a positive culture for Mycobacterium bovis. She was referred to highly specialized hospital and we documented panhypogammaglobulinemia and lymphopenia. Secondary causes of hypogammaglobulinemia were ruled out and common variable immunodeficiency (CVID) was confirmed, we started IVIG replacement. Four years later she developed mixed cellularity Hodgkin's lymphoma. Until today she continues with IVIG and chemotherapy. This report of a patient with CVID and Mycobacterium bovis infection, a unusual association, shows the cellular immunity susceptibility in this immunodeficiency, additional to the humoral defect. PMID:25758115

  4. Chlamydial Lung Infection Induces Transient IL-9 Production Which Is Redundant for Host Defense against Primary Infection

    PubMed Central

    Peng, Ying; Gao, Xiaoling; Yang, Jie; Shekhar, Sudhanshu; Wang, Shuhe; Fan, Yijun; Yang, Xi

    2015-01-01

    IL-9/Th9 responses are recently found to be important for innate and adaptive immunity particularly in parasitic infections. To date, the study on the role of IL-9 in bacterial infections is limited and the reported data are contradictory. One reported function of IL-9/Th9 is to modulate Th1/Th17 responses. Since our and others’ previous work has shown a critical role of Th1 and Th17 cells in host defense against chlamydial lung infection, we here examined the role of IL-9 responses in Chlamydia muridarum (Cm) lung infection, particularly its effect on Th1 and Th17 responses and outcome infection. Our data showed quick but transient IL-9 production in the lung following infection, peaking at day 3 and back to baseline around day 7. CD4+ T cell was the major source of IL-9 production in the lung infection. Blockade of endogenous IL-9 using neutralizing antibody failed to change Interferon-γ (IFN-γ) and IL-17 production by cultured spleen mononuclear cells isolated from Cm infected mice. Similarly, in vivo neutralization of IL-9 failed to show significant effect on T cell (Th1 and Th17) and antibody responses (IgA, IgG1 and IgG2a). Consistently, the neutralization of IL-9 had no significant effect on disease process, including body weight change, bacterial burden and histopathological score. The data suggest that IL-9 production following chlamydial lung infection is redundant for host defense against the intracellular bacteria. PMID:25646821

  5. Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung

    PubMed Central

    Tay, Hock L.; Kaiko, Gerard E.; Plank, Maximilian; Li, JingJing; Maltby, Steven; Essilfie, Ama-Tawiah; Jarnicki, Andrew; Yang, Ming; Mattes, Joerg; Hansbro, Philip M.; Foster, Paul S.

    2015-01-01

    Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases. PMID:25894560

  6. Infections with Avian Pathogenic and Fecal Escherichia coli Strains Display Similar Lung Histopathology and Macrophage Apoptosis

    PubMed Central

    Horn, Fabiana; Corrêa, André Mendes Ribeiro; Barbieri, Nicolle Lima; Glodde, Susanne; Weyrauch, Karl Dietrich; Kaspers, Bernd; Driemeier, David; Ewers, Christa; Wieler, Lothar H.

    2012-01-01

    The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (Afecal) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic Afecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas. PMID:22848424

  7. Staphylococcal scalded skin syndrome due to burn wound infection

    PubMed Central

    Farroha, A.; Frew, Q.; Jabir, S.; Dziewulski, P.

    2012-01-01

    Summary Introduction. The staphylococcal scalded skin syndrome is an acute exfoliation of the skin caused by exfoliative toxins A and B. Although Staphylococcus aureus is a common cause of burn wound infection, SSSS following burn wound infection is rare. Method. A retrospective review of all SSSS cases admitted to a regional burns service between January 2008 and January 2012 was undertaken. Results. Two cases of SSSS were reported during this time period as occurring following burns injury. The first case was a 17-month-old boy who had been hospitalized for a conservative treatment of 6% total body surface area (TBSA) mixed depth scald burns. On day four he developed exfoliation of 85% TBSA. The second case was a ten-month-old boy who sustained a 1% TBSA scald burn and was managed conservatively in the community by his general practitioner. On day five, he developed exfoliation of 80% TBSA. Staphylococcus aureus was isolated from the burn wounds in both cases. Conclusion: These two cases show that it is vital for burns surgeons and intensive care specialists to be aware of the possibility of SSSS occurring in patients with burn injuries with its potential devastating effects. PMID:23467312

  8. Diarrhea due to Cryptosporidium infection in artificially reared lambs.

    PubMed Central

    Tzipori, S; Angus, K W; Campbell, I; Clerihew, L W

    1981-01-01

    Severe diarrhea which lasted 7 to 12 days occurred in 40 of 48 artificially reared lambs within 5 to 12 days of birth, and 16 of them died. Of 16 diarrheic fecal samples examined, 10 contained Cryptosporidium oocysts and 1 contained rotavirus, but no other known enteropathogen was detected. Upon histological examination, cryptosporidia were found in the ilea of three affected lambs, and in one of them, villous atrophy and fusion, with epithelial cross-bridging between villi, were present in distal small intestine. Diarrhea was induced in two specific pathogen-free lambs by oral inoculation with fecal homogenate containing Cryptosporidium oocysts. Both the small and large intestines became infected with the organism, and associated lesions included stunting, fusion, and deformities of villi in the distal small intestine, with replacement of columnar enterocytes by immature cuboidal cells. Subclinical infections were induced in newborn specific pathogen-free mice and rats. Judged by these data, the lamb-derived Cryptosporidium sp. is similar to those recovered from calves, deer, and humans. Images PMID:7263849

  9. Designer vaccines to prevent infections due to group B Streptococcus.

    PubMed

    Kasper, D L

    1995-10-01

    Group B streptococci (GBS) are the major cause of serious infections in neonates and an important cause of infection in adults, particularly peripartum women and patients with diabetes mellitus and malignancy. Immunity to GBS in neonates is associated with naturally acquired maternal antibodies to the type-specific capsular polysaccharides of these organisms. IgG class antibodies directed to these polysaccharides are passed transplacentally and protect the child from invasive GBS disease. Phase I and II clinical trials showed that the purified polysaccharides had limited immunogenicity. However, vaccine responders passed functional IgG class antibodies to their children. A glycoconjugate vaccine has been designed so that the type-specific polysaccharides are covalently linked to a carrier protein. This secondary amine linkage is between aldehyde groups created on the eighth carbon of a selected number of periodate-oxidized sialic acid residues of the polysaccharide and epsilon-amino groups on lysine residues of tetanus toxoid. Careful epitope mapping studies had demonstrated that modification by controlled periodate oxidation could be accomplished and that an important conformational epitope on the polysaccharide would be preserved. Preclinical testing of the glycoconjugate vaccines in animal models of GBS disease demonstrated the immunogenicity and protective efficacy of the vaccine-induced antibodies. Phase I clinical testing of the glycoconjugate vaccine is in progress, and the early results appear promising. PMID:8608425

  10. Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response.

    PubMed

    Meshi, Bernard; Vitalis, Timothy Z; Ionescu, Diana; Elliott, W Mark; Liu, Chun; Wang, Xiang-Dong; Hayashi, Shizu; Hogg, James C

    2002-01-01

    This study was designed to test the hypothesis that cigarette smoke-induced inflammation and emphysema are amplified by the presence of latent adenoviral (Ad) infection, and to determine whether this emphysematous process can be reversed by all-trans-retinoic acid (RA) treatment. The results confirm that in guinea pigs, chronic cigarette-smoke exposure caused lesions similar to human centrilobular emphysema. They also show that latent Ad infection combined with cigarette-smoke exposure caused an excess increase in lung volume (P < 0.001), air-space volume (P < 0.001), and lung weight (P < 0.01), and further decrease in surface-to-volume ratio (P < 0.001) compared with smoke exposure alone. RA treatment failed to reverse these emphysematous changes. Analysis of inflammatory response in parenchymal and airway tissue showed that smoking caused an increase of polymorphonuclear leukocytes (PMNs) (P < 0.0002), macrophages (P < 0.001), and CD4 cells (P < 0.0009), and that latent Ad infection independently increased PMNs (P < 0.001), macrophages (P = 0.003), and CD8 cells (P < 0.001). We conclude that latent Ad infection amplifies the emphysematous lung destruction and increases the inflammatory response produced by cigarette-smoke exposure. In this study, the increase in CD4 was associated with cigarette smoke and the increase in CD8 cells with latent Ad infection. PMID:11751203

  11. Scedosporium apiospermum and S. prolificans mixed disseminated infection in a lung transplant recipient: An unusual case of long-term survival with combined systemic and local antifungal therapy in intensive care unit

    PubMed Central

    Balandin, Bárbara; Aguilar, Miriam; Sánchez, Isabel; Monzón, Araceli; Rivera, Isabel; Salas, Clara; Valdivia, Miguel; Alcántara, Sara; Pérez, Aris; Ussetti, Piedad

    2016-01-01

    Infections due Scedosporium spp. in lung transplant recipients are associated with disseminated disease with high mortality rates. The adjunctive local antifungal therapy may be a useful option when systemic treatment is insufficient and/or surgery is not feasible. We present a case of mixed disseminated infection due Scedosporium apiospermum and S. prolificans in a lung transplant recipient. Combined local and systemic antifungal therapy provided an unusual long-term survival in the intensive care unit. PMID:27222774

  12. Scedosporium apiospermum and S. prolificans mixed disseminated infection in a lung transplant recipient: An unusual case of long-term survival with combined systemic and local antifungal therapy in intensive care unit.

    PubMed

    Balandin, Bárbara; Aguilar, Miriam; Sánchez, Isabel; Monzón, Araceli; Rivera, Isabel; Salas, Clara; Valdivia, Miguel; Alcántara, Sara; Pérez, Aris; Ussetti, Piedad

    2016-03-01

    Infections due Scedosporium spp. in lung transplant recipients are associated with disseminated disease with high mortality rates. The adjunctive local antifungal therapy may be a useful option when systemic treatment is insufficient and/or surgery is not feasible. We present a case of mixed disseminated infection due Scedosporium apiospermum and S. prolificans in a lung transplant recipient. Combined local and systemic antifungal therapy provided an unusual long-term survival in the intensive care unit. PMID:27222774

  13. Hemoptysis Due to Breath-Hold Diving Following Chemotherapy and Lung Irradiation

    PubMed Central

    Gutsche, Markus; Kuschner, Ware G.

    2012-01-01

    Breath-hold diving, also known as free-diving, describes the practice of intentional immersion under water without an external supply of oxygen. Pulmonary hemorrhage with hemoptysis has been reported as a complication of immersion and breath-hold diving in young healthy athletes. We report the case of a 60-year-old man with a history of radiation and chemotherapy for breast carcinoma, who developed the abrupt onset of hemoptysis in the setting of swimming and breath-hold diving. A computed tomography (CT) scan of the chest demonstrated an area of ground glass opacification, suggestive of pulmonary hemorrhage, superimposed on a background of reticular opacities within the prior radiation field. A follow-up CT scan of the chest, obtained 2 months after presentation, demonstrated resolution of the ground glass opacification, but persistence of fibrotic features attributable to prior radiation therapy. We postulate that prior irradiation of the chest resulted in lung injury and fibrosis which, in turn, rendered the affected region of the lung susceptible to “stress failure,” due to an increase in the transcapillary pressure gradient arising from immersion and breath-hold diving. Patients with a history of lung injury resulting from chest irradiation should be cautioned about pulmonary hemorrhage and hemoptysis as a potential complication of swimming and breath-hold diving. PMID:22537760

  14. ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo.

    PubMed

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R; Solouk-Saran, Djamschid; Männ, Linda; Weski, Juliane; Maurer, Andreas; Fischer, Eliane; Spycher, Philipp R; Schibli, Roger; Boschetti, Frederic; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Severin, Gregory W; Autenrieth, Stella E; Krappmann, Sven; Davies, Genna; Pichler, Bernd J; Gunzer, Matthias; Wiehr, Stefan

    2016-02-23

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [(64)Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [(64)Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [(18)F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation. PMID:26787852

  15. ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

    PubMed Central

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R.; Solouk-Saran, Djamschid; Männ, Linda; Weski, Juliane; Maurer, Andreas; Fischer, Eliane; Spycher, Philipp R.; Schibli, Roger; Boschetti, Frederic; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Severin, Gregory W.; Autenrieth, Stella E.; Krappmann, Sven; Davies, Genna; Pichler, Bernd J.; Gunzer, Matthias; Wiehr, Stefan

    2016-01-01

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [64Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [64Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [18F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation. PMID:26787852

  16. Mouse lung infection model to assess Rhodococcus equi virulence and vaccine protection.

    PubMed

    González-Iglesias, Patricia; Scortti, Mariela; MacArthur, Iain; Hapeshi, Alexia; Rodriguez, Héctor; Prescott, John F; Vazquez-Boland, José A

    2014-08-01

    The pathogenic actinomycete Rhodococcus equi causes severe purulent lung infections in foals and immunocompromised people. Although relatively unsusceptible to R. equi, mice are widely used for in vivo studies with this pathogen. The most commonly employed mouse model is based on systemic (intravenous) infection and determination of R. equi burdens in spleen and liver. Here, we investigated the murine lung for experimental infection studies with R. equi. Using a 10(7)CFU intranasal challenge in BALB/c mice, virulent R. equi consistently survived in quantifiable numbers up to 10 days in the lungs whereas virulence-deficient R. equi bacteria were rapidly cleared. An internally controlled virulence assay was developed in which the test R. equi strains are co-inoculated and monitored in the same mouse. Isogenic R. equi bacteria lacking either the plasmid vapA gene or the entire virulence plasmid were compared using this competitive assay. Both strains showed no significant differences in in vivo fitness in the lung, indicating that the single loss of the virulence factor VapA was sufficient to account for the full attenuation seen in the absence of the virulence plasmid. To test the adequacy of the lung infection model for monitoring R. equi vaccine efficacy, BALB/c mice were immunized with live R. equi and challenged intranasally. Vaccination conferred protection against acute pulmonary challenge with virulent R. equi. Our data indicate that the murine lung infection model provides a useful tool for both R. equi virulence and vaccine studies. PMID:24852140

  17. Lung cancer induced in mice by the envelope protein of jaagsiekte sheep retrovirus (JSRV) closely resembles lung cancer in sheep infected with JSRV

    PubMed Central

    Wootton, Sarah K; Metzger, Michael J; Hudkins, Kelly L; Alpers, Charles E; York, Denis; DeMartini, James C; Miller, A Dusty

    2006-01-01

    Background Jaagsiekte sheep retrovirus (JSRV) causes a lethal lung cancer in sheep and goats. Expression of the JSRV envelope (Env) protein in mouse lung, by using a replication-defective adeno-associated virus type 6 (AAV6) vector, induces tumors resembling those seen in sheep. However, the mouse and sheep tumors have not been carefully compared to determine if Env expression alone in mice can account for the disease features observed in sheep, or whether additional aspects of virus replication in sheep are important, such as oncogene activation following retrovirus integration into the host cell genome. Results We have generated mouse monoclonal antibodies (Mab) against JSRV Env and have used these to study mouse and sheep lung tumor histology. These Mab detect Env expression in tumors in sheep infected with JSRV from around the world with high sensitivity and specificity. Mouse and sheep tumors consisted mainly of well-differentiated adenomatous foci with little histological evidence of anaplasia, but at long times after vector exposure some mouse tumors did have a more malignant appearance typical of adenocarcinoma. In addition to epithelial cell tumors, lungs of three of 29 sheep examined contained fibroblastic cell masses that expressed Env and appeared to be separate neoplasms. The Mab also stained nasal adenocarcinoma tissue from one United States sheep, which we show was due to expression of Env from ovine enzootic nasal tumor virus (ENTV), a virus closely related to JSRV. Systemic administration of the AAV6 vector encoding JSRV Env to mice produced numerous hepatocellular tumors, and some hemangiomas and hemangiosarcomas, showing that the Env protein can induce tumors in multiple cell types. Conclusion Lung cancers induced by JSRV infection in sheep and by JSRV Env expression in mice have similar histologic features and are primarily characterized by adenomatous proliferation of peripheral lung epithelial cells. Thus it is unnecessary to invoke a role for

  18. Role of small colony variants in persistence of Pseudomonas aeruginosa infections in cystic fibrosis lungs

    PubMed Central

    Malone, Jacob G

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that predominates during the later stages of cystic fibrosis (CF) lung infections. Over many years of chronic lung colonization, P. aeruginosa undergoes extensive adaptation to the lung environment, evolving both toward a persistent, low virulence state and simultaneously diversifying to produce a number of phenotypically distinct morphs. These lung-adapted P. aeruginosa strains include the small colony variants (SCVs), small, autoaggregative isolates that show enhanced biofilm formation, strong attachment to surfaces, and increased production of exopolysaccharides. Their appearance in the sputum of CF patients correlates with increased resistance to antibiotics, poor lung function, and prolonged persistence of infection, increasing their relevance as a subject for clinical investigation. The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates. Here, we review the current state of research in clinical P. aeruginosa SCVs. We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment. PMID:26251621

  19. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice.

    PubMed

    Damlund, Dina Silke Malling; Christophersen, Lars; Jensen, Peter Østrup; Alhede, Morten; Høiby, Niels; Moser, Claus

    2016-06-01

    The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target. PMID:27009697

  20. [Infections due to several species of Salmonella in Mendoza, Argentina].

    PubMed

    Curi de Montbrun, S E; Ciccarelli, A S; de Ampuero, S; Fernández, R A; Benito, M A

    1981-01-01

    Fifty nine sporadic cases and forty five cases from six outbreaks of salmonellosis occurring in Mendoza, Argentina between 1972-76 are reported. All 104 patients were studied epidemiologically searching for the etiologic agent, implicated food and contacts. Stools of patients and contacts were examined. Other clinical specimens and the implicated foods were examined bacteriologically. The Salmonella isolates were classified in eleven serotypes with the following order of frequency: a) Outbreaks: S. typhimurium (50,0%), S. derby (16,7%), S. newport (16,7%), S. bredeney (16,7%), S. enteritidis (16,7%), S. cholerae-suis (16,7%) and S. oranienburg (16,7%). b) Sporadic cases; S. typhimurium (35,9%), S. newport (15,6%), S. anatum (7,8%), S. oranienburg (6,2%), S. derby (4,7%), S. java (3,1%), S. cholerae-suis (3,1%), S. bredeney (1,6%), S. enteritidis (1,6%), S. minnesota (1,6%), S. urbana (1,6%), and Salmonella spp (17,2%). These results are compared with those obtained in the same areas between 1962-71 and with the serotype frequencies from different sources of infection found in Mendoza and other regions. PMID:7346889

  1. Treatment of prosthetic joint infections due to Propionibacterium

    PubMed Central

    Van Hooff, Miranda L; Meis, Jacques F; Vos, Fidel; Goosen, Jon H M

    2016-01-01

    Background and purpose Currently, Propionibacterium is frequently recognized as a causative microorganism of prosthetic joint infection (PJI). We assessed treatment success at 1- and 2-year follow-up after treatment of Propionibacterium-associated PJI of the shoulder, hip, and knee. Furthermore, we attempted to determine whether postoperative treatment with rifampicin is favorable. Patients and methods We conducted a retrospective cohort study in which we included patients with a primary or revision joint arthroplasty of the shoulder, hip, or knee who were diagnosed with a Propionibacterium-associated PJI between November 2008 and February 2013 and who had been followed up for at least 1 year. Results We identified 60 patients with a Propionibacterium-associated PJI with a median duration of 21 (0.1–49) months until the occurrence of treatment failure. 39 patients received rifampicin combination therapy, with a success rate of 93% (95% CI: 83–97) after 1 year and 86% (CI: 71–93) after 2 years. The success rate was similar in patients who were treated with rifampicin and those who were not. Interpretation Propionibacterium-associated PJI treated with surgery in combination with long-term antibiotic administration had a successful outcome at 1- and 2-year follow-up irrespective of whether the patient was treated with rifampicin. Prospective studies are needed to determine whether the use of rifampicin is beneficial in the treatment of Propionibacterium-associated PJI. PMID:26414972

  2. Rapid Growth of Lung Nodules due to Combined Pulmonary Vasculitis, Silicoanthracosis, and Chondrocalcinosis

    PubMed Central

    Distler, Oliver; Kolios, Antonios G. A.; Weder, Walter; Franzen, Daniel

    2016-01-01

    Background. Silicoanthracosis is a pneumoconiosis due to occupational inhalation of silica and carbon dusts. Clinically, it can be associated with vasculitis or rheumatoid arthritis. In association with these diseases, silicoanthracosis can present within the lung with multiple pulmonary nodules which, as a differential diagnosis, can mimic metastatic disease or multiple abscesses. Case Presentation. We present the case of a 62-year old former pit worker with pulmonary nodules, chondrocalcinosis due to calcium pyrophosphate deposition (CPPD), and a history of renal cancer. Within a short period of time, pulmonary nodules grew rapidly. Thoracoscopically, the resected lung specimen revealed silicoanthracosis associated with small-to-medium-size vasculitis in the presence of antineutrophil cytoplasmatic autoantibodies (c-ANCA). Conclusion. Pulmonary silicoanthracotic lesions on the base of ANCA-associated vasculitis and CPPD arthritis can rapidly grow. A mutual correlation between silicoanthracosis, ANCA-associated vasculitis, and CPPD seems possible. Apart from this, consideration of metastatic disease should be obligatory in patients with a history of cancer at the same time being immunosuppressed. PMID:27478398

  3. Continuum-kinetic-microscopic model of lung clearance due to core-annular fluid entrainment

    NASA Astrophysics Data System (ADS)

    Mitran, Sorin

    2013-07-01

    The human lung is protected against aspirated infectious and toxic agents by a thin liquid layer lining the interior of the airways. This airway surface liquid is a bilayer composed of a viscoelastic mucus layer supported by a fluid film known as the periciliary liquid. The viscoelastic behavior of the mucus layer is principally due to long-chain polymers known as mucins. The airway surface liquid is cleared from the lung by ciliary transport, surface tension gradients, and airflow shear forces. This work presents a multiscale model of the effect of airflow shear forces, as exerted by tidal breathing and cough, upon clearance. The composition of the mucus layer is complex and variable in time. To avoid the restrictions imposed by adopting a viscoelastic flow model of limited validity, a multiscale computational model is introduced in which the continuum-level properties of the airway surface liquid are determined by microscopic simulation of long-chain polymers. A bridge between microscopic and continuum levels is constructed through a kinetic-level probability density function describing polymer chain configurations. The overall multiscale framework is especially suited to biological problems due to the flexibility afforded in specifying microscopic constituents, and examining the effects of various constituents upon overall mucus transport at the continuum scale.

  4. Continuum-kinetic-microscopic model of lung clearance due to core-annular fluid entrainment

    PubMed Central

    Mitran, Sorin

    2013-01-01

    The human lung is protected against aspirated infectious and toxic agents by a thin liquid layer lining the interior of the airways. This airway surface liquid is a bilayer composed of a viscoelastic mucus layer supported by a fluid film known as the periciliary liquid. The viscoelastic behavior of the mucus layer is principally due to long-chain polymers known as mucins. The airway surface liquid is cleared from the lung by ciliary transport, surface tension gradients, and airflow shear forces. This work presents a multiscale model of the effect of airflow shear forces, as exerted by tidal breathing and cough, upon clearance. The composition of the mucus layer is complex and variable in time. To avoid the restrictions imposed by adopting a viscoelastic flow model of limited validity, a multiscale computational model is introduced in which the continuum-level properties of the airway surface liquid are determined by microscopic simulation of long-chain polymers. A bridge between microscopic and continuum levels is constructed through a kinetic-level probability density function describing polymer chain configurations. The overall multiscale framework is especially suited to biological problems due to the flexibility afforded in specifying microscopic constituents, and examining the effects of various constituents upon overall mucus transport at the continuum scale. PMID:23729842

  5. Necrosis of lung epithelial cells during infection with Mycobacterium tuberculosis is preceded by cell permeation.

    PubMed

    Dobos, K M; Spotts, E A; Quinn, F D; King, C H

    2000-11-01

    Mycobacterium tuberculosis establishes infection, progresses towards disease, and is transmitted from the alveolus of the lung. However, the role of the alveolar epithelium in any of these pathogenic processes of tuberculosis is unclear. In this study, lung epithelial cells (A549) were used as a model in which to examine cytotoxicity during infection with either virulent or avirulent mycobacteria in order to further establish the role of the lung epithelium during tuberculosis. Infection of A549 cells with M. tuberculosis strains Erdman and CDC1551 demonstrated significant cell monolayer clearing, whereas infection with either Mycobacterium bovis BCG or Mycobacterium smegmatis LR222 did not. Clearing of M. tuberculosis-infected A549 cells correlated to necrosis, not apoptosis. Treatment of M. tuberculosis-infected A549 cells with streptomycin, but not cycloheximide, demonstrated a significant reduction in the necrosis of A549 cell monolayers. This mycobacterium-induced A549 necrosis did not correlate to higher levels of intracellular or extracellular growth by the mycobacteria during infection. Staining of infected cells with propidium iodide demonstrated that M. tuberculosis induced increased permeation of A549 cell membranes within 24 h postinfection. Quantitation of lactate dehydrogenase (LDH) release from infected cells further demonstrated that cell permeation was specific to M. tuberculosis infection and correlated to A549 cellular necrosis. Inactivated M. tuberculosis or its subcellular fractions did not result in A549 necrosis or LDH release. These studies demonstrate that lung epithelial cell cytotoxicity is specific to infection by virulent mycobacteria and is caused by cellular necrosis. This necrosis is not a direct correlate of mycobacterial growth or of the expression of host cell factors, but is preceded by permeation of the A549 cell membrane and requires infection with live bacilli. PMID:11035739

  6. Recurrent infective endocarditis due to Aggregatibacter aphrophilus and Staphylococcus lugdunensis.

    PubMed

    Hidalgo-García, L; Hurtado-Mingo, A; Olbrich, P; Moruno-Tirado, A; Neth, O; Obando, I

    2015-03-01

    Uncommon microorganisms are increasingly being recognized as causative agents of paediatric infectious endocarditis (IE). We report a 4-year old girl with congenital heart disease, who suffered from 2 IE episodes secondary to Aggregatibacter aphrophilus (formerly Haemophilus aphrophilus) and Staphylococcus lugdunensis, both rarely reported pathogens in this age group. The patient was initially successfully treated with prolonged intravenous antibiotic courses, however removal of the Contegra valved conduit during the second episode was required due to recurrence of fever and development of pulmonary embolism despite completion of antibiotic therapy. A. aphrohilus is a member of the fastidious gram negative microorganisms of the HACEK group (Haemophilus spp., Aggregatibacter spp, Cardiobaterium hominis, Eikenella corrodens and Kingella kingae), that colonize the oropharynx and are a recognised cause of IE. Prognosis of children with IE due to HACEK group members varies, half of them suffering from complications and mortality rates of 10-12.5%. Although S. lugdunensis belongs to coagulase negative staphylococci (CONS), it behaves more like S. aureus species rather than CONS. This microorganism is a well-described cause of endocarditis in adult patients, associated with high requirements of surgical procedures and mortality (42-78%). In conclusion, paediatric IE can be caused by uncommon microorganisms associated with severe complications and potential fatality. The isolation of S. lugdunensis or A. aphrophilus in febrile patients should be considered clinically relevant and cardiac involvement must be ruled out. Those patients with proved IE will require prolonged intravenous antibiotic courses and in complicated cases surgical intervention. PMID:25751682

  7. The association between human papillomavirus infection and female lung cancer: A population-based cohort study.

    PubMed

    Lin, Frank Cheau-Feng; Huang, Jing-Yang; Tsai, Stella Ching-Shao; Nfor, Oswald Ndi; Chou, Ming-Chih; Wu, Ming-Fang; Lee, Chun-Te; Jan, Cheng-Feng; Liaw, Yung-Po

    2016-06-01

    Lung cancer is the leading cause of cancer deaths among Taiwanese women. Human papillomavirus (HPV) has been detected in lung cancer tissues. The aim of this study was to investigate the association between HPV infection and lung cancer among the Taiwanese women. The analytical data were collected from the longitudinal health insurance databases (LHID 2005 and 2010) of the National Health Insurance Research Database (NHIRD). The study participants were 30 years and older and included 24,162 individuals who were identified with HPV infection from 2001 to 2004 and 1,026,986 uninfected individuals. Lung cancer incidence among infected and uninfected individuals was compared using the univariate and multivariate regression models. Among the total participants, 24,162 individuals were diagnosed with HPV. After adjusting for age, gender, low income, residential area, and comorbidity, the risk of lung cancer was higher in women (hazard ratio [HR] 1.263, 95% CI 1.015-1.571), while all cancer risks were high in both men and women with corresponding hazard ratios (HR) of 1.161 (95% CI 1.083-1.245) and HR 1.240 (95% CI 1.154-1.331), respectively. This study showed a significant increase in lung cancer risk among Taiwanese women who were exposed to HPV infection. PMID:27281096

  8. Study of epidemiological risk of lung cancer in Mexico due indoor radon exposure

    NASA Astrophysics Data System (ADS)

    Ángeles, A.; Espinosa, G.

    2014-07-01

    In this work the lifetime relative risks (LRR) of lung cancer due to exposure to indoor 222Rn on the Mexican population is calculated. Cigarette smoking is the number one risk factor for lung cancer (LC), because that, to calculate the number of cases of LC due to exposure to 222Rn is necessary considers the number of cases of LC for smoking cigarette. The lung cancer mortality rates published by the "Secretaría de Salud" (SSA), the mexican population data published by the "Consejo Nacional de Población" (CONAPO), smoking data in the mexican population, published by the "Comisión Nacional Contra las Adicciones" (CONADIC), the "Organización Panamericana de la Salud" (OPS) and indoor 222Rn concentrations in Mexico published in several recent studies are used. To calculate the lifetime relative risks (LRR) for different segments of the Mexican population, firstly the Excess Relative Risk (ERR) is calculated using the method developed by the BEIR VI committee and subsequently modified by the USEPA and published in the report "EPA Assessment of Risks from Radon in Homes". The excess relative risks were then used to calculate the corresponding lifetime relative risks, again using the method developed by the BEIR VI committee. The lifetime relative risks for Mexican male and female eversmokers and Mexican male and female never-smokers were calculated for radon concentrations spanning the range found in recent studies of indoor radon concentrations in Mexico. The lifetime relative risks of lung cancer induced by lifetime exposure to the mexican average indoor radon concentration were estimated to be 1.44 and 1.40 for never-smokers mexican females and males respectively, and 1.19 and 1.17 for ever-smokers Mexican females and males respectively. The Mexican population LRR values obtained in relation to the USA and Canada LRR published values in ever-smokers for both gender are similar with differences less than 4%, in case of never-smokers in relation with Canada

  9. Loss of social behaviours in populations of Pseudomonas aeruginosa infecting lungs of patients with cystic fibrosis.

    PubMed

    Jiricny, Natalie; Molin, Søren; Foster, Kevin; Diggle, Stephen P; Scanlan, Pauline D; Ghoul, Melanie; Johansen, Helle Krogh; Santorelli, Lorenzo A; Popat, Roman; West, Stuart A; Griffin, Ashleigh S

    2014-01-01

    Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as the result of adaptation to the lung environment. Typically, chronic strains carry mutations in global regulation factors that could effect reduced expression of social traits, raising the possibility that competitive dynamics between cooperative and selfish, cheating strains could also drive changes in P. aeruginosa infections. We compared the expression of cooperative traits - biofilm formation, secretion of exo-products and quorum sensing (QS) - in P. aeruginosa isolates that were estimated to have spent different lengths of time in the lung based on clinical information. All three exo-products involved in nutrient acquisition were produced in significantly smaller quantities with increased duration of infection, and patterns across four QS signal molecules were consistent with accumulation over time of mutations in lasR, which are known to disrupt the ability of cells to respond to QS signal. Pyocyanin production, and the proportion of cells in biofilm relative to motile, free-living cells in liquid culture, did not change. Overall, our results confirm that the loss of social behaviour is a consistent trend with time spent in the lung and suggest that social dynamics are potentially relevant to understanding the behaviour of P. aeruginosa in lung infections. PMID:24454693

  10. Mycobacterium avium genotype is associated with the therapeutic response to lung infection.

    PubMed

    Kikuchi, T; Kobashi, Y; Hirano, T; Tode, N; Santoso, A; Tamada, T; Fujimura, S; Mitsuhashi, Y; Honda, Y; Nukiwa, T; Kaku, M; Watanabe, A; Ichinose, M

    2014-03-01

    Factors that can interfere with the successful treatment of Mycobacterium avium lung infection have been inadequately studied. To identify a potent predictor of therapeutic responses of M. avium lung infection, we analyzed variable number tandem repeats (VNTR) at 16 minisatellite loci of M. avium clinical isolates. Associations between the VNTR profiling data and a therapeutic response were evaluated in 59 subjects with M. avium lung infection. M. avium lung infection of 30 subjects in whom clarithromycin-containing regimens produced microbiological and radiographic improvement was defined as responsive disease, while that of the remaining 29 subjects was defined as refractory disease. In phylogenetic analysis using the genotypic distance aggregated from 16-dimensional VNTR data, 59 M. avium isolates were divided into three clusters, which showed a nearly significant association with therapeutic responses (p 0.06). We then subjected the raw 16-dimensional VNTR data directly to principal component analysis, and identified the genetic features that were significantly associated with the therapeutic response (p <0.05). By further analysis of logistic regression with a stepwise variable-selection, we constructed the highest likelihood multivariate model, adjusted for age, to predict a therapeutic response, using VNTR data from only four minisatellite loci. In conclusion, we identified four mycobacterial minisatellite loci that together were associated with the therapeutic response of M. avium lung infections. PMID:23829301

  11. Infections after lung transplantation: time of occurrence, sites, and microbiologic etiologies

    PubMed Central

    Yun, Ji Hyun; Jo, Kyung-Wook; Choi, Se Hoon; Lee, Jina; Chae, Eun Jin; Do, Kyung-Hyun; Choi, Dae-Kee; Choi, In-Cheol; Hong, Sang-Bum; Shim, Tae Sun; Kim, Hyeong Ryul; Kim, Dong Kwan; Park, Seung-Il

    2015-01-01

    Background/Aims Infections are major causes of both early and late death after lung transplantation (LT). The development of prophylaxis strategies has altered the epidemiology of post-LT infections; however, recent epidemiological data are limited. We evaluated infections after LT at our institution by time of occurrence, site of infections, and microbiologic etiologies. Methods All consecutive patients undergoing lung or heart-lung transplantation between October 2008 and August 2014 at our institution were enrolled. Cases of infections after LT were initially identified from the prospective registry database, which was followed by a detailed review of the patients' medical records. Results A total of 108 episodes of post-LT infections (56 bacterial, 43 viral, and nine fungal infections) were observed in 34 LT recipients. Within 1 month after LT, the most common bacterial infections were catheter-related bloodstream infections (42%). Pneumonia was the most common site of bacterial infection in the 2- to 6-month period (28%) and after 6 months (47%). Cytomegalovirus was the most common viral infection within 1 month (75%) and in the 2- to 6-month period (80%). Respiratory viruses were the most common viruses after 6 months (48%). Catheter-related candidemia was the most common fungal infection. Invasive pulmonary aspergillosis developed after 6 months. Survival rates at the first and third years were 79% and 73%, respectively. Conclusions Although this study was performed in a single center, we provide valuable and recent detailed epidemiology data for post-LT infections. A further multicenter study is required to properly evaluate the epidemiology of post-LT infections in Korea. PMID:26161017

  12. In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans.

    PubMed

    Liew, Kah Leong; Jee, Jap Meng; Yap, Ivan; Yong, Phelim Voon Chen

    2016-01-01

    Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection. PMID:27054608

  13. In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans

    PubMed Central

    2016-01-01

    Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection. PMID:27054608

  14. Symptomatic Peripheral Mycotic Aneurysms Due to Infective Endocarditis

    PubMed Central

    González, Isabel; Sarriá, Cristina; López, Javier; Vilacosta, Isidre; San Román, Alberto; Olmos, Carmen; Sáez, Carmen; Revilla, Ana; Hernández, Miguel; Caniego, Jose Luis; Fernández, Cristina

    2014-01-01

    Abstract Peripheral mycotic aneurysms (PMAs) are a relatively rare but serious complication of infective endocarditis (IE). We conducted the current study to describe and compare the current epidemiologic, microbiologic, clinical, diagnostic, therapeutic, and prognostic characteristics of patients with symptomatic PMAs (SPMAs). A descriptive, comparative, retrospective observational study was performed in 3 tertiary hospitals, which are reference centers for cardiac surgery. From 922 definite IE episodes collected from 1996 to 2011, 18 patients (1.9%) had SPMAs. Because all SPMAs developed in left-sided IE, we performed a comparative study between 719 episodes of left-sided IE without SPMAs and 18 episodes with SPMAs. We found a higher frequency of intravenous drug abuse, native valve IE, intracranial bleeding, septic emboli, multiple embolisms, and IE diagnostic delay >30 days in patients with SPMAs than in patients without SPMAs. The causal microorganisms were gram-positive cocci (n =10), gram-negative bacilli (n = 2), gram-positive bacilli (n = 3), Bartonella henselae (n = 1), Candida albicans (n = 1), and negative culture (n = 1). The median IE diagnosis delay was 15 days (interquartile range [IQR], 13–33 d) in the case of high-virulence microorganisms versus 45 days (IQR, 30–240 d) in the case of low- to medium-virulence microorganisms. Twelve SPMAs were intracranial and 6 were extracranial. In 10 cases (8 intracranial and 2 extracranial), SPMAs were the initial presentation of IE; the remaining cases developed symptoms during or after finishing parenteral antibiotic treatment. The initial diagnosis of intracranial SPMAs was made by computed tomography (CT) or magnetic resonance imaging in 6 unruptured aneurysms and by angiography in 6 ruptured aneurysms. The initial test in extracranial SPMAs was Doppler ultrasonography in limbs, CT in liver, and coronary angiography in heart. Four (3 intracranial, 1 extracranial) of 7 (6 intracranial, 1 extracranial

  15. Automatic implantable cardioverter defibrillator pocket infection due to Providencia rettgeri: a case report.

    PubMed

    Marull, Jorge Manuel; De Benedetti, Maria Elena

    2009-01-01

    Coagulase-negative staphylococci and Staphylococcus aureus are the commonest pathogens involved in infections of pacemaker-defibrillator systems. Among causative Gram-negative bacteria, infections due to Klebsiella, Serratia, Pseudomonas, Acinetobacter and other species have been reported. We report herein a unique case of an automatic implantable cardioverter defibrillator infection due to Providencia rettgeri in a 65-year-old male who was admitted to our service with bacteremia and infection of the generator and subcutaneous array in a recently implanted device. PMID:19918391

  16. Automatic implantable cardioverter defibrillator pocket infection due to Providencia rettgeri: a case report

    PubMed Central

    De Benedetti, Maria Elena

    2009-01-01

    Coagulase-negative staphylococci and Staphylococcus aureus are the commonest pathogens involved in infections of pacemaker-defibrillator systems. Among causative Gram-negative bacteria, infections due to Klebsiella, Serratia, Pseudomonas, Acinetobacter and other species have been reported. We report herein a unique case of an automatic implantable cardioverter defibrillator infection due to Providencia rettgeri in a 65-year-old male who was admitted to our service with bacteremia and infection of the generator and subcutaneous array in a recently implanted device. PMID:19918391

  17. Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C

    PubMed Central

    Kamar, Fareed B.; Hawkins, T. Lee-Ann

    2016-01-01

    While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID:27366166

  18. Antineutrophil Cytoplasmic Antibody Induction due to Infection: A Patient with Infective Endocarditis and Chronic Hepatitis C.

    PubMed

    Kamar, Fareed B; Hawkins, T Lee-Ann

    2016-01-01

    While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID:27366166

  19. Successful cinacalcet treatment of refractory secondary hyperparathyroidism due to multiple lung parathyroid adenomas

    PubMed Central

    Sugi, Orie; Kimata, Naoki; Miwa, Naoko; Otsubo, Shigeru; Nitta, Kosaku; Akiba, Takashi

    2010-01-01

    We describe a 56-year-old woman who presented with end-stage renal disease due to pregnancy-induced hypertension and secondary hyperparathyroidism (sHPT). She had started hemodialysis and underwent a subtotal parathyroidectomy (PTx). However, intact parathyroid hormone (iPTH) levels increased gradually. Eventually, she underwent a second PTx. However, therapy failed to significantly decrease iPTH levels. A third PTx was performed, but no pathological parathyroid tissue was found. Computed tomography scan indicated the presence of multiple ectopic lung nodules and 26 nodules were surgically removed from the left lung. Despite surgical treatment, iPTH levels remained high. Additional maxacalcitol failed to decrease iPTH levels, cinacalcet was then started. iPTH levels decreased and the cinacalcet dose could be reduced to maintenance doses of 60 mg/day. Throughout the 1.6 years of treatment, serum iPTH, alkaline phosphatase (ALP) and bone alkaline phosphatase (BAP) were normalized. As a consequence, bone pain gradually disappeared. Bone mineral density (BMD) was improved by administration of cinacalcet. In conclusion, cinacalcet was effective in this patient with refractory and inoperable sHPT. In addition, it improves their BMD and relieves bone pain. PMID:25984040

  20. Ileal Intussusception Due to Metastasis from Squamous Cell Carcinoma of the Lung Resected 12 Years Previously.

    PubMed

    Nakamura, Tomoki; Chino, Osamu; Tajima, Takayuki; Tanaka, Yoichi; Yokoyama, Daiki; Hanashi, Tomoko; Sadahiro, Sotaro; Makuuchi, Hiroyasu

    2015-12-01

    An 88-year-old woman, with a history of resection of stage IIA lung cancer in 1998, was referred to our hospital in August 2010 complaining of upper abdominal pain, vomiting, and dark brown stools. After endoscopic examination, she was admitted with a diagnosis of Mallory-Weiss syndrome. Vomiting occurred when food intake was resumed after fasting. Intestinal obstruction was suspected on abdominal radiography, and complete small bowel obstruction was confirmed by contrast-enhanced imaging after placement of an ileus tube. A small intestinal tumor with intussusception was detected by computed tomography. At laparotomy, there was no ascites. Intussusception was found due to an ileal tumor located approximately 50 cm from the ileocecal valve, and we performed partial small bowel resection. The resected small intestine contained a submucosal tumor approximately 40 mm in diameter that had penetrated the bowel wall to reach the serosa. Pathological examination revealed a submucosal tumor that showed poor continuity with the surrounding mucosa, while the histology was squamous cell carcinoma. Immunohistochemistry showed that the tumor was CK7 positive, CK20 negative, TTF-1 negative, and CK10 positive. Based on these findings, we made a diagnosis of small intestinal metastasis at 12 years after radical resection of squamous cell carcinoma of the lung. PMID:26662663

  1. Phantom tumour of the lung in a patient with renal failure misdiagnosed as chest infection

    PubMed Central

    Althomali, Sarah Ali; Almalki, Mazen Mohammed; Mohiuddin, Syed Atif

    2014-01-01

    Phantom or vanishing tumour of the lung is a rare finding on chest radiographs that has been reported secondary to heart failure or chronic kidney disease. It has been described as an interlobular effusion of the transverse or oblique fissure of the right lung. Although it is uncommon, it should always be considered as a differential diagnosis for a radiographic opacity of the right-middle lung zone because it can be easily mistaken for a lung mass or infiltration. We herein present a case involving a patient with chronic kidney disease and a radiographic opacity of the right-middle lung that was diagnosed as a chest infection. The patient did not respond to various antibiotics and showed a poor response to diuretics, the standard treatment for phantom tumour. However, the patient markedly improved after dialysis, and the radiographic chest opacity disappeared. PMID:24943144

  2. Phantom tumour of the lung in a patient with renal failure misdiagnosed as chest infection.

    PubMed

    Althomali, Sarah Ali; Almalki, Mazen Mohammed; Mohiuddin, Syed Atif

    2014-01-01

    Phantom or vanishing tumour of the lung is a rare finding on chest radiographs that has been reported secondary to heart failure or chronic kidney disease. It has been described as an interlobular effusion of the transverse or oblique fissure of the right lung. Although it is uncommon, it should always be considered as a differential diagnosis for a radiographic opacity of the right-middle lung zone because it can be easily mistaken for a lung mass or infiltration. We herein present a case involving a patient with chronic kidney disease and a radiographic opacity of the right-middle lung that was diagnosed as a chest infection. The patient did not respond to various antibiotics and showed a poor response to diuretics, the standard treatment for phantom tumour. However, the patient markedly improved after dialysis, and the radiographic chest opacity disappeared. PMID:24943144

  3. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens.

    PubMed

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions. PMID:25699030

  4. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    PubMed Central

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  5. Expression of Suppressor of Cytokine Signaling 1 (SOCS1) Impairs Viral Clearance and Exacerbates Lung Injury during Influenza Infection

    PubMed Central

    Sun, Keer; Salmon, Sharon; Yajjala, Vijaya Kumar; Bauer, Christopher; Metzger, Dennis W.

    2014-01-01

    Suppressor of cytokine signaling (SOCS) proteins are inducible feedback inhibitors of cytokine signaling. SOCS1−/− mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation. Since it is well established that IFN-γ is dispensable for protection against influenza infection, we generated SOCS1−/−IFN-γ−/− mice to determine whether SOCS1 regulates antiviral immunity in vivo. Here we show that SOCS1−/−IFN-γ−/− mice exhibited significantly enhanced resistance to influenza infection, as evidenced by improved viral clearance, attenuated acute lung damage, and consequently increased survival rates compared to either IFN-γ−/− or WT animals. Enhanced viral clearance in SOCS1−/−IFN-γ−/− mice coincided with a rapid onset of adaptive immune responses during acute infection, while their reduced lung injury was associated with decreased inflammatory cell infiltration at the resolution phase of infection. We further determined the contribution of SOCS1-deficient T cells to antiviral immunity. Anti-CD4 antibody treatment of SOCS1−/−IFN-γ−/− mice had no significant effect on their enhanced resistance to influenza infection, while CD8+ splenocytes from SOCS1−/−IFN-γ−/− mice were sufficient to rescue RAG1−/− animals from an otherwise lethal infection. Surprisingly, despite their markedly reduced viral burdens, RAG1−/− mice reconstituted with SOCS1−/−IFN-γ−/− adaptive immune cells failed to ameliorate influenza-induced lung injury. In conclusion, in the absence of IFN-γ, the cytoplasmic protein SOCS1 not only inhibits adaptive antiviral immune responses but also exacerbates inflammatory lung damage. Importantly, these detrimental effects of SOCS1 are conveyed through discrete cell populations. Specifically, while SOCS1 expression in adaptive immune cells is sufficient to inhibit antiviral immunity, SOCS1 in innate/stromal cells is responsible for aggravated lung injury. PMID:25500584

  6. Inducible Innate Resistance of Lung Epithelium to Infection

    PubMed Central

    Evans, Scott E.; Xu, Yi; Tuvim, Michael J.; Dickey, Burton F.

    2015-01-01

    Most studies of innate immunity have focused on leukocytes such as neutrophils, macrophages and natural killer cells. However, epithelial cells play key roles in innate defenses that include providing a mechanical barrier to microbial entry, signaling to leukocytes, and directly killing pathogens. Importantly, all of these defenses are highly inducible in response to the sensing of microbial and host products. In healthy lungs, the level of innate immune epithelial function is low at baseline, as indicated by low levels of spontaneous microbial killing and cytokine release, reflecting low constitutive stimulation in the nearly sterile lower respiratory tract when mucociliary clearance mechanisms are functioning effectively. This contrasts with the colon, where bacteria are continuously present and epithelial cells are constitutively activated. While the surface area of the lungs presents a large target for microbial invasion, activated lung epithelial cells that are closely apposed to deposited pathogens are ideally positioned for microbial killing. PMID:20148683

  7. Pharmacodynamics of the New Fluoroquinolone Gatifloxacin in Murine Thigh and Lung Infection Models

    PubMed Central

    Andes, D.; Craig, W. A.

    2002-01-01

    Gatifloxacin is a new 8-methoxy fluoroquinolone with enhanced activity against gram-positive cocci. We used the neutropenic murine thigh infection model to characterize the time course of antimicrobial activity of gatifloxacin and determine which pharmacokinetic (PK)-pharmacodynamic (PD) parameter best correlated with efficacy. The thighs of mice were infected with 106.5 to 107.4 CFU of strains of Staphylococcus aureus, Streptococcus pneumoniae, or Escherichia coli, and the mice were then treated for 24 h with 0.29 to 600 mg of gatifloxacin per kg of body weight per day, with the dose fractionated for dosing every 3, 6, 12, and 24 h. Levels in serum were measured by microbiologic assay. In vivo postantibiotic effects (PAEs) were calculated from serial values of the log10 numbers of CFU per thigh 2 to 4 h after the administration of doses of 8 and 32 mg/kg. Nonlinear regression analysis was used to determine which PK-PD parameter best correlated with the numbers of CFU per thigh at 24 h. Pharmacokinetic studies revealed peak/dose values of 0.23 to 0.32, area under the concentration-time curve (AUC)/dose values of 0.47 to 0.62, and half-lives of 0.6 to 1.1 h. Gatifloxacin produced in vivo PAEs of 0.2 to 3.1 h for S. pneumoniae and 0.4 to 2.3 h for S. aureus. The 24-h AUC/MIC was the PK-PD parameter that best correlated with efficacy (R2 = 90 to 94% for the three organisms, whereas R2 = 70 to 81% for peak level/MIC and R2 = 48 to 73% for the time that the concentration in serum was greater than the MIC). There was some reduced activity when dosing every 24 h was used due to the short half-life of gatifloxacin in mice. In subsequent studies we used the neutropenic and nonneutropenic murine thigh and lung infection models to determine if the magnitude of the AUC/MIC needed for the efficacy of gatifloxacin varied among pathogens (including resistant strains) and infection sites. The mice were infected with 106.5 to 107.4 CFU of four isolates of S. aureus (one methicillin

  8. Pulmonary infection due to Pseudozyma aphidis in a patient with Burkitt lymphoma: first case report.

    PubMed

    Parahym, Ana Maria Rabelo de Carvalho; da Silva, Carolina Maria; Domingos, Igor de Farias; Gonçalves, Sarah Santos; Rodrigues, Márcia de Melo; de Morais, Vera Lúcia Lins; Neves, Rejane Pereira

    2013-01-01

    Fungal infections are being increasingly reported in patients with malignancies. Pseudozyma aphidis is an opportunistic yeast usually isolated from plants and rarely from human samples. In this study, we report the first case of pulmonary infection due to P. aphidis in a Burkitt lymphoma patient. PMID:23182077

  9. Dengue viruses can infect human primary lung epithelia as well as lung carcinoma cells, and can also induce the secretion of IL-6 and RANTES.

    PubMed

    Lee, Ying-Ray; Su, Ching-Yao; Chow, Nan-Haw; Lai, Wu-Wei; Lei, Huan-Yao; Chang, Chia-Lun; Chang, Tsuey-Yu; Chen, Shun-Hua; Lin, Yee-Shin; Yeh, Trai-Ming; Liu, Hsiao-Sheng

    2007-06-01

    Dengue viruses (DENV) are herein demonstrated for the first time as being able to infect and replicate in human primary lung epithelium and various lung cancer cell lines. The detection of dengue virus particles and viral negative strand RNA synthesis in the cell, in conjunction with the release of viral progenies in culture supernatants, support the notion that lung cells are susceptible to dengue virus infection. The replication efficiency of DENV in lung cancer cells from high to low is: DEN-2 (dengue virus type-2), DEN-3, DEN-4 and DEN-1. Moreover, the susceptibility of the six lung cancer cell lines to DEN-2 infection is: SW1573>A549>H1435; H23; H520; Bes2B. DEN-2 infection significantly increased the expression levels of IL-6 and RANTES in four of the six lung cancer cell lines, which is consistent with the high expression levels of these molecules in DHF/DSS patients. IL-6 expression induced by DEN-2 infection was NF-kappaB dependent. In summary, our results indicate that lung epithelial cell is a possible target of dengue viruses and IL-6 and RANTES may play pivotal roles in lung related immuno-pathogenesis. PMID:17416433

  10. Bloodstream Infection Due to Brachyspira pilosicoli in a Patient with Multiorgan Failure▿

    PubMed Central

    Prim, Núria; Pericas, Roser; Español, Montse; Rivera, Alba; Mirelis, Beatriz; Coll, Pere

    2011-01-01

    Brachyspira pilosicoli is an etiological agent of human intestinal spirochetosis. Bloodstream infection due to this microorganism is rare. We report a case of B. pilosicoli bacteremia in a 70-year-old patient who presented with multiorgan failure. PMID:21832021

  11. Epithelial anion transporter pendrin contributes to inflammatory lung pathology in mouse models of Bordetella pertussis infection.

    PubMed

    Scanlon, Karen M; Gau, Yael; Zhu, Jingsong; Skerry, Ciaran; Wall, Susan M; Soleimani, Manoocher; Carbonetti, Nicholas H

    2014-10-01

    Pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. However, there are currently no effective treatments for pertussis. We previously studied the role of pertussis toxin (PT), an important Bordetella pertussis virulence factor, in lung transcriptional responses to B. pertussis infection in mouse models. One of the genes most highly upregulated in a PT-dependent manner encodes an epithelial transporter of bicarbonate, chloride, and thiocyanate, named pendrin, that contributes to asthma pathology. In this study, we found that pendrin expression is upregulated at both gene and protein levels in the lungs of B. pertussis-infected mice. Pendrin upregulation is associated with PT production by the bacteria and with interleukin-17A (IL-17A) production by the host. B. pertussis-infected pendrin knockout (KO) mice had higher lung bacterial loads than infected pendrin-expressing mice but had significantly reduced levels of lung inflammatory pathology. However, reduced pathology did not correlate with reduced inflammatory cytokine expression. Infected pendrin KO mice had higher levels of inflammatory cytokines and chemokines than infected pendrin-expressing mice, suggesting that these inflammatory mediators are less active in the airways in the absence of pendrin. In addition, treatment of B. pertussis-infected mice with the carbonic anhydrase inhibitor acetazolamide reduced lung inflammatory pathology without affecting pendrin synthesis or bacterial loads. Together these data suggest that PT contributes to pertussis pathology through the upregulation of pendrin, which promotes conditions favoring inflammatory pathology. Therefore, pendrin may represent a novel therapeutic target for treatment of pertussis disease. PMID:25069981

  12. Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection

    PubMed Central

    Peteranderl, Christin; Morales-Nebreda, Luisa; Lecuona, Emilia; Vadász, István; Morty, Rory E.; Schmoldt, Carole; Bespalowa, Julia; Pleschka, Stephan; Mayer, Konstantin; Gattenloehner, Stefan; Fink, Ludger; Lohmeyer, Juergen; Seeger, Werner; Sznajder, Jacob I.; Mutlu, Gökhan M.; Budinger, G.R. Scott

    2016-01-01

    Influenza A viruses (IAV) can cause lung injury and acute respiratory distress syndrome (ARDS), which is characterized by accumulation of excessive fluid (edema) in the alveolar airspaces and leads to hypoxemia and death if not corrected. Clearance of excess edema fluid is driven mostly by the alveolar epithelial Na,K-ATPase and is crucial for survival of patients with ARDS. We therefore investigated whether IAV infection alters Na,K-ATPase expression and function in alveolar epithelial cells (AECs) and the ability of the lung to clear edema. IAV infection reduced Na,K-ATPase in the plasma membrane of human and murine AECs and in distal lung epithelium of infected mice. Moreover, induced Na,K-ATPase improved alveolar fluid clearance (AFC) in IAV-infected mice. We identified a paracrine cell communication network between infected and noninfected AECs and alveolar macrophages that leads to decreased alveolar epithelial Na,K-ATPase function and plasma membrane abundance and inhibition of AFC. We determined that the IAV-induced reduction of Na,K-ATPase is mediated by a host signaling pathway that involves epithelial type I IFN and an IFN-dependent elevation of macrophage TNF-related apoptosis–inducing ligand (TRAIL). Our data reveal that interruption of this cellular crosstalk improves edema resolution, which is of biologic and clinical importance to patients with IAV-induced lung injury. PMID:26999599

  13. Lipoxin Signaling in Murine Lung Host Responses to Cryptococcus neoformans Infection.

    PubMed

    Colby, Jennifer K; Gott, Katherine M; Wilder, Julie A; Levy, Bruce D

    2016-01-01

    Lipoxins (LX) are proresolving mediators that augment host defense against bacterial infection. Here, we investigated roles for LX in lung clearance of the fungal pathogen Cryptococcus neoformans (Cne). After intranasal inoculation of 5,000 CFU Cne, C57BL/6 and C.B-17 mice exhibited strain-dependent differences in Cne clearance, immunologic responses, and lipoxin A4 (LXA4) formation and receptor (ALX/FPR2) expression. Compared with C.B-17 mice, C57BL/6 lungs had increased and persistent Cne infection 14 days after inoculation, increased eosinophils, and distinct profiles of inflammatory cytokines. Relative to C.B-17 mice, bronchoalveolar lavage fluid levels of LXA4 were increased before and after infection in C57BL/6. The kinetics for 15-epi-LXA4 production were similar in both strains. Lung basal expression of the LX biosynthetic enzyme Alox12/15 (12/15-lipoxygenase) was increased in C57BL/6 mice and further increased after Cne infection. In contrast, lung basal expression of the LXA4 receptor Alx/Fpr2 was higher in C.B-17 relative to C57BL/6 mice, and after Cne infection, Alx/Fpr2 expression was significantly increased in only C.B-17 mice. Heat-killed Cne initiated lung cell generation of IFN-γ and IL-17 and was further increased in C.B-17 mice by 15-epi-LXA4. A trend toward reduced Cne clearance and IFN-γ production was observed upon in vivo administration of an ALX/FPR2 antagonist. Together, these findings provide the first evidence that alterations in cellular immunity against Cne are associated with differences in LXA4 production and receptor expression, suggesting an important role for ALX/FPR2 signaling in the regulation of pathogen-mediated inflammation and antifungal lung host defense. PMID:26039320

  14. Locally extensive angio-invasive Scedosporium prolificans infection following resection for squamous cell lung carcinoma

    PubMed Central

    Holmes, Natasha E.; Trevillyan, Janine M.; Kidd, Sarah E.; Leong, Trishe Y.-M.

    2013-01-01

    We report a case of Scedosporium prolificans infection in a patient following surgery for squamous cell lung carcinoma. Combination therapy with voriconazole and terbinafine was commenced for intrathoracic infection and mycotic vasculitis. In spite of antifungal treatment, he developed culture-positive sternal and rib osteomyelitis four months later. Scedosporiosis is not commonly reported in patients with solid organ malignancies, and this case highlights its aggressive nature and propensity for direct local invasion. PMID:24432228

  15. Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes

    SciTech Connect

    Antonini, James M. . E-mail: jga6@cdc.gov; Taylor, Michael D.; Millecchia, Lyndell; Bebout, Alicia R.; Roberts, Jenny R.

    2004-11-01

    Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10{sup 3} Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-{alpha}, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-{alpha} and IL-6) after infection, which are likely

  16. Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes.

    PubMed

    Antonini, James M; Taylor, Michael D; Millecchia, Lyndell; Bebout, Alicia R; Roberts, Jenny R

    2004-11-01

    Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-alpha, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-alpha and IL-6) after infection, which are likely responsible for

  17. The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection

    PubMed Central

    Traboulsi, Hussein; Cloutier, Alexandre; Boyapelly, Kumaraswamy; Bonin, Marc-André; Marsault, Éric; Cantin, André M.

    2015-01-01

    The host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+ effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus. PMID:26248373

  18. Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

    PubMed

    Song, Z; Johansen, H K; Moser, C; Høiby, N

    1996-05-01

    The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable. PMID:8703440

  19. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    PubMed Central

    Cipolla, David; Blanchard, Jim; Gonda, Igor

    2016-01-01

    Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin®) that are in development by Aradigm Corporation are described here. PMID:26938551

  20. Development of Liposomal Ciprofloxacin to Treat Lung Infections.

    PubMed

    Cipolla, David; Blanchard, Jim; Gonda, Igor

    2016-01-01

    Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin(®) and Pulmaquin(®)) that are in development by Aradigm Corporation are described here. PMID:26938551

  1. Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections

    PubMed Central

    Winstanley, Craig; O’Brien, Siobhan; Brockhurst, Michael A.

    2016-01-01

    Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification. PMID:26946977

  2. Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections.

    PubMed

    Winstanley, Craig; O'Brien, Siobhan; Brockhurst, Michael A

    2016-05-01

    Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification. PMID:26946977

  3. Effects of Marijuana on the Lung and Its Defenses against Infection and Cancer.

    ERIC Educational Resources Information Center

    Tashkin, Donald P.

    1999-01-01

    Examines the many effects of marijuana use on the lungs. States that patients with pre-existing immune deficits are particularly vulnerable to marijuana-related pulmonary infections. However, warns that habitual use of marijuana may lead to respiratory cancer must await epidemiological studies, which are now possible since 30 years have passed…

  4. Detecting bacterial lung infections: in vivo evaluation of in vitro volatile fingerprints.

    PubMed

    Zhu, Jiangjiang; Bean, Heather D; Wargo, Matthew J; Leclair, Laurie W; Hill, Jane E

    2013-03-01

    The identification of bacteria by their volatilomes is of interest to many scientists and clinicians as it holds the promise of diagnosing infections in situ, particularly lung infections via breath analysis. While there are many studies reporting various bacterial volatile biomarkers or fingerprints using in vitro experiments, it has proven difficult to translate these data to in vivo breath analyses. Therefore, we aimed to create secondary electrospray ionization-mass spectrometry (SESI-MS) pathogen fingerprints directly from the breath of mice with lung infections. In this study we demonstrated that SESI-MS is capable of differentiating infected versus uninfected mice, P. aeruginosa-infected versus S. aureus-infected mice, as well as distinguish between infections caused by P. aeruginosa strains PAO1 versus FRD1, with statistical significance (p < 0.05). In addition, we compared in vitro and in vivo volatiles and observed that only 25-34% of peaks are shared between the in vitro and in vivo SESI-MS fingerprints. To the best of our knowledge, these are the first breath volatiles measured for P. aeruginosa PAO1, FRD1, and S. aureus RN450, and the first comparison of in vivo and in vitro volatile profiles from the same strains using the murine infection model. PMID:23307645

  5. Lung transplantation in patients with cystic fibrosis: special focus to infection and comorbidities.

    PubMed

    Dorgan, Daniel J; Hadjiliadis, Denis

    2014-06-01

    Despite advances in medical care, patients with cystic fibrosis still face limited life expectancy. The most common cause of death remains respiratory failure. End-stage cystic fibrosis can be treated with lung transplantation and is the third most common reason for which the procedure is performed. Outcomes for cystic fibrosis are better than most other lung diseases, but remain limited (5-year survival 60%). For patients with advanced disease lung transplantation appears to improve survival. Outcomes for patients with Burkholderia cepacia remain poor, although they are better for patients with certain genomovars. Controversy exists about Mycobacterium abscessus infection and appropriateness for transplant. More information is also becoming available for comorbidities, including diabetes and pulmonary hypertension among others. Extra-corporeal membrane oxygenation is used more frequently for end-stage disease as a bridge to lung transplantation and will likely be used more in the future. PMID:24655065

  6. Gene mutation discovery research of non-smoking lung cancer patients due to indoor radon exposure.

    PubMed

    Choi, Jung Ran; Park, Seong Yong; Noh, O Kyu; Koh, Young Wha; Kang, Dae Ryong

    2016-01-01

    Although the incidence and mortality for most cancers such as lung and colon are decreasing in several countries, they are increasing in several developed countries because of an unhealthy western lifestyles including smoking, physical inactivity and consumption of calorie-dense food. The incidences for lung and colon cancers in a few of these countries have already exceeded those in the United States and other western countries. Among them, lung cancer is the main cause of cancer death in worldwide. The cumulative survival rate at five years differs between 13 and 21 % in several countries. Although the most important risk factors are smoking for lung cancer, however, the increased incidence of lung cancer in never smokers(LCINS) is necessary to improve knowledge concerning other risk factors. Environmental factors and genetic susceptibility are also thought to contribute to lung cancer risk. Patients with lung adenocarcinoma who have never smoking frequently contain mutation within tyrosine kinase domain of the epidermal growth factor receptor(EGFR) gene. Also, K-ras mutations are more common in individuals with a history of smoking use and are related with resistance to EFGR-tyrosine kinase inhibitors. Recently, radon(Rn), natural and noble gas, has been recognized as second common reason of lung cancer. In this review, we aim to know whether residential radon is associated with an increased risk for developing lung cancer and regulated by several genetic polymorphisms. PMID:26985396

  7. Airway CD8(+) T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection.

    PubMed

    Connors, Thomas J; Ravindranath, Thyyar M; Bickham, Kara L; Gordon, Claire L; Zhang, Feifan; Levin, Bruce; Baird, John S; Farber, Donna L

    2016-06-01

    Infants and young children are disproportionately susceptible to severe complications from respiratory viruses, although the underlying mechanisms remain unknown. Recent studies show that the T cell response in the lung is important for protective responses to respiratory infections, although details on the infant/pediatric respiratory immune response remain sparse. The objectives of the present study were to characterize the local versus systemic immune response in infants and young children with respiratory failure from viral respiratory tract infections and its association to disease severity. Daily airway secretions were sampled from infants and children 4 years of age and younger receiving mechanical ventilation owing to respiratory failure from viral infection or noninfectious causes. Samples were examined for immune cell composition and markers of T cell activation. These parameters were then correlated with clinical disease severity. Innate immune cells and total CD3(+) T cells were present in similar proportions in airway aspirates derived from infected and uninfected groups; however, the CD8:CD4 T cell ratio was markedly increased in the airways of patients with viral infection compared with uninfected patients, and specifically in infected infants with acute lung injury. T cells in the airways were phenotypically and functionally distinct from those in blood with activated/memory phenotypes and increased cytotoxic capacity. We identified a significant increase in airway cytotoxic CD8(+) T cells in infants with lung injury from viral respiratory tract infection that was distinct from the T cell profile in circulation and associated with increasing disease severity. Airway sampling could therefore be diagnostically informative for assessing immune responses and lung damage. PMID:26618559

  8. Extracellular Adenosine Protects against Streptococcus pneumoniae Lung Infection by Regulating Pulmonary Neutrophil Recruitment.

    PubMed

    Bou Ghanem, Elsa N; Clark, Stacie; Roggensack, Sara E; McIver, Sally R; Alcaide, Pilar; Haydon, Philip G; Leong, John M

    2015-08-01

    An important determinant of disease following Streptococcus pneumoniae (pneumococcus) lung infection is pulmonary inflammation mediated by polymorphonuclear leukocytes (PMNs). We found that upon intratracheal challenge of mice, recruitment of PMNs into the lungs within the first 3 hours coincided with decreased pulmonary pneumococci, whereas large numbers of pulmonary PMNs beyond 12 hours correlated with a greater bacterial burden. Indeed, mice that survived infection largely resolved inflammation by 72 hours, and PMN depletion at peak infiltration, i.e. 18 hours post-infection, lowered bacterial numbers and enhanced survival. We investigated host signaling pathways that influence both pneumococcus clearance and pulmonary inflammation. Pharmacologic inhibition and/or genetic ablation of enzymes that generate extracellular adenosine (EAD) (e.g. the ectoenzyme CD73) or degrade EAD (e.g. adenosine deaminase) revealed that EAD dramatically increases murine resistance to S. pneumoniae lung infection. Moreover, adenosine diminished PMN movement across endothelial monolayers in vitro, and although inhibition or deficiency of CD73 had no discernible impact on PMN recruitment within the first 6 hours after intratracheal inoculation of mice, these measures enhanced PMN numbers in the pulmonary interstitium after 18 hours of infection, culminating in dramatically elevated numbers of pulmonary PMNs at three days post-infection. When assessed at this time point, CD73-/- mice displayed increased levels of cellular factors that promote leukocyte migration, such as CXCL2 chemokine in the murine lung, as well as CXCR2 and β-2 integrin on the surface of pulmonary PMNs. The enhanced pneumococcal susceptibility of CD73-/- mice was significantly reversed by PMN depletion following infection, suggesting that EAD-mediated resistance is largely mediated by its effects on PMNs. Finally, CD73-inhibition diminished the ability of PMNs to kill pneumococci in vitro, suggesting that EAD alters

  9. Localized lipidomics in cystic fibrosis: TOF-SIMS imaging of lungs from Pseudomonas aeruginosa-infected mice.

    PubMed

    Desbenoit, Nicolas; Saussereau, Emilie; Bich, Claudia; Bourderioux, Matthieu; Fritsch, Janine; Edelman, Aleksander; Brunelle, Alain; Ollero, Mario

    2014-07-01

    A consistent body of research has linked cystic fibrosis (CF) with variations in the tissue and fluid content in a number of lipid molecules. However, little is known about the spatial localization of those variations. We have recently applied TOF-SIMS mass spectrometry imaging to detect differential lipid signatures at the colon epithelium between normal and cftr-/- mice. In the present work we have used this technology to investigate potential differences in the spatial distribution of lipids due to Pseudomonas aeruginosa (P.a.) infection in mouse lung expressing or not cftr. Wild-type and exon 10 cftr knockout mice were subjected to intranasal infection with a clinical strain of P.a. Lung cryosections from infected and non-infected mice were subjected to cluster TOF-SIMS analysis in the negative ion mode. We observed a highly specific localization of a phosphoinositol fragment ion at m/z 299.1 in bronchial epithelium. Using this ion to delineate a region of interest, we studied the relative abundance of ions below m/z 1500. We found a significant increase in m/z 465.4 (identified as cholesteryl sulfate) in cftr-/- epithelium and in response to bacterial infection, as well as a decrease in most carboxylic ions. In conclusion, the m/z 299.1 ion can be used as a marker of bronchial epithelium, where P.a. infection leads to increased presence of cholesteryl sulfate in this tissue. TOF-SIMS imaging reveals as a valuable tool for the study of respiratory epithelium. PMID:24513532

  10. Lung gallium scan

    MedlinePlus

    ... inflammation in the lungs, most often due to sarcoidosis or a certain type of pneumonia. Normal Results ... up very little gallium. What Abnormal Results Mean Sarcoidosis Other respiratory infections, most often pneumocystis jirovecii pneumonia ...

  11. Influenza Infects Lung Microvascular Endothelium Leading to Microvascular Leak: Role of Apoptosis and Claudin-5

    PubMed Central

    Armstrong, Susan M.; Wang, Changsen; Tigdi, Jayesh; Si, Xiaoe; Dumpit, Carlo; Charles, Steffany; Gamage, Asela; Moraes, Theo J.; Lee, Warren L.

    2012-01-01

    Severe influenza infections are complicated by acute lung injury, a syndrome of pulmonary microvascular leak. The pathogenesis of this complication is unclear. We hypothesized that human influenza could directly infect the lung microvascular endothelium, leading to loss of endothelial barrier function. We infected human lung microvascular endothelium with both clinical and laboratory strains of human influenza. Permeability of endothelial monolayers was assessed by spectrofluorimetry and by measurement of the transendothelial electrical resistance. We determined the molecular mechanisms of flu-induced endothelial permeability and developed a mouse model of severe influenza. We found that both clinical and laboratory strains of human influenza can infect and replicate in human pulmonary microvascular endothelium, leading to a marked increase in permeability. This was caused by apoptosis of the lung endothelium, since inhibition of caspases greatly attenuated influenza-induced endothelial leak. Remarkably, replication-deficient virus also caused a significant degree of endothelial permeability, despite displaying no cytotoxic effects to the endothelium. Instead, replication-deficient virus induced degradation of the tight junction protein claudin-5; the adherens junction protein VE-cadherin and the actin cytoskeleton were unaffected. Over-expression of claudin-5 was sufficient to prevent replication-deficient virus-induced permeability. The barrier-protective agent formoterol was able to markedly attenuate flu-induced leak in association with dose-dependent induction of claudin-5. Finally, mice infected with human influenza developed pulmonary edema that was abrogated by parenteral treatment with formoterol. Thus, we describe two distinct mechanisms by which human influenza can induce pulmonary microvascular leak. Our findings have implications for the pathogenesis and treatment of acute lung injury from severe influenza. PMID:23115643

  12. Sexual dimorphism in lung function responses to acute influenza A infection

    PubMed Central

    Larcombe, Alexander N.; Foong, Rachel E.; Bozanich, Elizabeth M.; Berry, Luke J.; Garratt, Luke W.; Gualano, Rosa C.; Jones, Jessica E.; Dousha, Lovisa F.; Zosky, Graeme R.; Sly, Peter D.

    2011-01-01

    Please cite this paper as: Larcombe et al. (2011) Sexual dimorphism in lung function responses to acute influenza A infection. Influenza and Other Respiratory Viruses 5(5), 334–342. Background  Males are generally more susceptible to respiratory infections; however, there are few data on the physiological responses to such infections in males and females. Objectives  To determine whether sexual dimorphism exists in the physiological/inflammatory responses of weanling and adult BALB/c mice to influenza. Methods  Weanling and adult mice of both sexes were inoculated with influenza A or appropriate control solution. Respiratory mechanics, responsiveness to methacholine (MCh), viral titre and bronchoalveolar lavage (BAL) cellular inflammation/cytokines were measured 4 (acute) and 21 (resolution) days post‐inoculation. Results  Acute infection impaired lung function and induced hyperresponsiveness and cellular inflammation in both sexes at both ages. Males and females responded differently with female mice developing greater abnormalities in tissue damping and elastance and greater MCh responsiveness at both ages. BAL inflammation, cytokines and lung viral titres were similar between the sexes. At resolution, all parameters had returned to baseline levels in adults and weanling males; however, female weanlings had persisting hyperresponsiveness. Conclusions  We identified significant differences in the physiological responses of male and female mice to infection with influenza A, which occurred in the absence of variation in viral titre and cellular inflammation. PMID:21668688

  13. Toll-Like Receptor 4 Agonistic Antibody Promotes Host Defense against Chronic Pseudomonas aeruginosa Lung Infection in Mice.

    PubMed

    Nakamura, Shigeki; Iwanaga, Naoki; Seki, Masafumi; Fukudome, Kenji; Oshima, Kazuhiro; Miyazaki, Taiga; Izumikawa, Koichi; Yanagihara, Katsunori; Miyazaki, Yoshitsugu; Mukae, Hiroshi; Kohno, Shigeru

    2016-07-01

    Chronic lower respiratory tract infection with Pseudomonas aeruginosa is difficult to treat due to enhanced antibiotic resistance and decreased efficacy of drug delivery to destroyed lung tissue. To determine the potential for restorative immunomodulation therapies, we evaluated the effect of Toll-like receptor 4 (TLR4) stimulation on the host immune response to Pseudomonas infection in mice. We implanted sterile plastic tubes precoated with P. aeruginosa in the bronchi of mice, administered the TLR4/MD2 agonistic monoclonal antibody UT12 intraperitoneally every week, and subsequently analyzed the numbers of viable bacteria and inflammatory cells and the levels of cytokines. We also performed flow cytometry-based phagocytosis and opsonophagocytic killing assays in vitro using UT12-treated murine peritoneal neutrophils. UT12-treated mice showed significantly enhanced bacterial clearance, increased numbers of Ly6G(+) neutrophils, and increased concentrations of macrophage inflammatory protein 2 (MIP-2) in the lungs (P < 0.05). Depletion of CD4(+) T cells eliminated the ability of the UT12 treatment to improve bacterial clearance and promote neutrophil recruitment and MIP-2 production. Additionally, UT12-pretreated peritoneal neutrophils exhibited increased opsonophagocytic killing activity via activation of the serine protease pathway, specifically neutrophil elastase activity, in a TLR4-dependent manner. These data indicated that UT12 administration significantly augmented the innate immune response against chronic bacterial infection, in part by promoting neutrophil recruitment and bactericidal function. PMID:27091927

  14. Cytokines transcript levels in lung and lymphoid organs during genotype 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection.

    PubMed

    García-Nicolás, Obdulio; Quereda, Juan José; Gómez-Laguna, Jaime; Salguero, Francisco Javier; Carrasco, Librado; Ramis, Guillermo; Pallarés, Francisco José

    2014-07-15

    Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the most economically important diseases of swine. PRRS virus (PRRSV) infection in the pig is characterized by a weak or absent host innate immune response. The underlying mechanisms of PRRSV pathogenesis are still unclear. The analysis of transcript levels represents an alternative to immunoassays for the detection of cytokines that sometimes are difficult to detect due to their low amounts. This study sets out to determine the differences in pathogenesis and the immune response between lung, tonsil, tracheobronchial lymph node (Tb-LN) and retropharyngeal LN (Rf-LN) of PRRSV 2982 strain infected pigs. PRRSV strain 2982 avoided the onset of an effective innate immune response, especially in PRRSV main target (lung) and reservoir (tonsil) organs. PRRSV lead to an impaired expression of IFN-α and TNF-α gene expression, which finally induced a weak and delayed adaptive immune response through an inefficient IL-12 and IFN-γ expression. Finally, PRRSV replication favored the expression of the anti-inflammatory IL-10 cytokine in infected pigs. PMID:24726859

  15. Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair

    PubMed Central

    Quantius, Jennifer; Schmoldt, Carole; Vazquez-Armendariz, Ana I.; Becker, Christin; El Agha, Elie; Wilhelm, Jochen; Morty, Rory E.; Vadász, István; Mayer, Konstantin; Gattenloehner, Stefan; Fink, Ludger; Matrosovich, Mikhail; Li, Xiaokun; Seeger, Werner; Lohmeyer, Juergen; Bellusci, Saverio; Herold, Susanne

    2016-01-01

    Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4)+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC), and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of alveolar Fgf10

  16. Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair.

    PubMed

    Quantius, Jennifer; Schmoldt, Carole; Vazquez-Armendariz, Ana I; Becker, Christin; El Agha, Elie; Wilhelm, Jochen; Morty, Rory E; Vadász, István; Mayer, Konstantin; Gattenloehner, Stefan; Fink, Ludger; Matrosovich, Mikhail; Li, Xiaokun; Seeger, Werner; Lohmeyer, Juergen; Bellusci, Saverio; Herold, Susanne

    2016-06-01

    Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4)+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC), and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of alveolar Fgf10

  17. A rare case of urinary tract infection due to Trichosporonasahii in a diabetic patient

    PubMed Central

    Iken, Maryem; Belkouch, Ahmed; Bellarj, Badia; Naoui, Hafida; Boumhil, Laila; El Bouti, Anass; Jidane, Said; Belyamani, Lahcen; Lmimouni, Badreddine

    2015-01-01

    Trichosporonasahii is a basidiomycete yeast responsible for white piedra and onychomycosis in the immunocompetent host. In the immunocompromised patients, invasive infections are reported; their diagnosis is difficult and they are associated with high mortality rate. Urinary infection due to Trichosporon Asahi is rare but its incidenceis increasing. We report the case of a 58 year old diabetic patient. The yeast was isolated from urine samples of three consecutive crops in pure form. The patient improved after antifungal therapy. PMID:26097631

  18. A rare case of urinary tract infection due to Trichosporon asahii in a diabetic patient.

    PubMed

    Iken, Maryem; Belkouch, Ahmed; Bellarj, Badia; Naoui, Hafida; Boumhil, Laila; El Bouti, Anass; Jidane, Said; Belyamani, Lahcen; Lmimouni, Badreddine

    2015-01-01

    Trichosporon asahii is a basidiomycete yeast responsible for white piedra and onychomycosis in the immunocompetent host. In the immunocompromised patients, invasive infections are reported; their diagnosis is difficult and they are associated with high mortality rate. Urinary infection due to Trichosporon Asahi is rare but its incidence increasing. We report the case of a 58 year old diabetic patient. The yeast was isolated from urine samples of three consecutive crops in pure form. The patient improved after antifungal therapy. PMID:26097631

  19. Infective endocarditis and meningitis due to Scedosporium prolificans in a renal transplant recipient.

    PubMed

    Uno, Kenji; Kasahara, Kei; Kutsuna, Satoshi; Katanami, Yuichi; Yamamoto, Yoshifumi; Maeda, Koichi; Konishi, Mitsuru; Ogawa, Taku; Yoneda, Tatsuo; Yoshida, Katsunori; Kimura, Hiroshi; Mikasa, Keiichi

    2014-02-01

    Scedosporium prolificans is a ubiquitous filamentous fungi that may cause disseminated diseases in neutropenic patients with hematological malignancies. We report a fatal case of renal transplant recipient who developed both infective endocarditis and meningitis due to S. prolificans during treatment with micafungin and itraconazole for chronic necrotizing aspergillosis. Breakthrough Scedosporium infection should be considered among differential diagnosis of invasive fungal diseases in patients with renal transplant recipients receiving antifungal agents. PMID:24462439

  20. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses

    PubMed Central

    Gandhale, Pradeep N.; Kumar, Himanshu; Kulkarni, Diwakar D.

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens. PMID:27071061

  1. Antibiotic management of lung infections in cystic fibrosis. II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi.

    PubMed

    Chmiel, James F; Aksamit, Timothy R; Chotirmall, Sanjay H; Dasenbrook, Elliott C; Elborn, J Stuart; LiPuma, John J; Ranganathan, Sarath C; Waters, Valerie J; Ratjen, Felix A

    2014-10-01

    Airway infections are a key component of cystic fibrosis (CF) lung disease. Whereas the approach to common pathogens such as Pseudomonas aeruginosa is guided by a significant body of evidence, other infections often pose a considerable challenge to treating physicians. In Part I of this series on the antibiotic management of difficult lung infections, we discussed bacterial organisms including methicillin-resistant Staphylococcus aureus, gram-negative bacterial infections, and treatment of multiple bacterial pathogens. Here, we summarize the approach to infections with nontuberculous mycobacteria, anaerobic bacteria, and fungi. Nontuberculous mycobacteria can significantly impact the course of lung disease in patients with CF, but differentiation between colonization and infection is difficult clinically as coinfection with other micro-organisms is common. Treatment consists of different classes of antibiotics, varies in intensity, and is best guided by a team of specialized clinicians and microbiologists. The ability of anaerobic bacteria to contribute to CF lung disease is less clear, even though clinical relevance has been reported in individual patients. Anaerobes detected in CF sputum are often resistant to multiple drugs, and treatment has not yet been shown to positively affect patient outcome. Fungi have gained significant interest as potential CF pathogens. Although the role of Candida is largely unclear, there is mounting evidence that Scedosporium species and Aspergillus fumigatus, beyond the classical presentation of allergic bronchopulmonary aspergillosis, can be relevant in patients with CF and treatment should be considered. At present, however there remains limited information on how best to select patients who could benefit from antifungal therapy. PMID:25167882

  2. Activity and local delivery of azithromycin in a mouse model of Haemophilus influenzae lung infection.

    PubMed Central

    Vallée, E; Azoulay-Dupuis, E; Pocidalo, J J; Bergogne-Bérézin, E

    1992-01-01

    We compared the activities of azithromycin and erythromycin against Haemophilus influenzae in a mouse model of nonparenchymatous lower respiratory tract infection. In vitro and in vivo efficacy data for both drugs were analyzed relative to their pharmacokinetics in lungs and in vivo uptake by phagocytes. Aged C57BL/6 mice (mean age, 15.1 +/- 1.9 months) were infected intratracheally with 10(8) CFU of H. influenzae serotype b. Oral drug administration was initiated 4 h after infection by various dosage regimens. In terms of bacterial killing in the lung, azithromycin was much more active than erythromycin (P less than 0.01). Its in vivo activity was also more durable after a single administration relative to the durability of three doses of erythromycin given at 6-h intervals. The MIC of azithromycin was eightfold lower than that of erythromycin, and better penetration and a longer half-life in lung tissue were achieved after a single oral administration. Phagocytes delivered increased amounts of both drugs to the infected lungs, particularly at the site of infection (bronchoalveolar airspaces), and detectable levels of azithromycin were maintained locally for long periods. The fact that the efficacy of azithromycin coincided with the arrival of large numbers of polymorphonuclear leukocytes within the airspaces suggests that active extracellular concentrations were provided by the release of azithromycin from these cells. This further supports the potential value of once-daily azithromycin regimens for the treatment of lower respiratory tract infections in humans, provided that inhibitory concentrations against common pathogens such as H. influenzae are maintained for adequate periods of time. PMID:1324644

  3. Effect of Bacterial Pneumonia on Lung SIV Replication in Alcohol Consuming SIV Infected Rhesus Macaques

    PubMed Central

    Nelson, Steve; Happel, Kyle I.; Zhang, Ping; Myers, Leann; Dufour, Jason P.; Bagby, Gregory J.

    2013-01-01

    Background Opportunistic infections in HIV-infected persons have been shown to increase the rate of HIV replication. In populations where prophylaxis against Pneumocystis pneumonia is utilized, bacterial pneumonia is now the leading cause of lower respiratory tract infection in HIV+ patients. Our prior studies have shown that chronic alcohol consumption in simian demarcated immunodeficiency virus (SIV) infected rhesus macaques increases plasma viral load set point and accelerates progression to end-stage AIDS. While chronic alcohol abuse is well-known to increase the incidence and severity of bacterial pneumonia, the impact of alcohol consumption on local and systemic SIV/HIV burden during lung infection is unknown. Therefore, we utilized the macaque SIV infection model to examine the effect of chronic ethanol feeding on SIV burden during the course of pulmonary infection with Streptococcus pneumoniae, the most commonly identified etiology of bacterial pneumonia in HIV+ and HIV- persons in developed countries. Methods Alcohol was administered starting 3 months before SIVMac251 inoculation to the end of the study via an indwelling intragastric catheter to achieve a plasma alcohol concentration of 50–60 mM. Control animals received isocaloric sucrose. Four months after SIV infection, the right lung was inoculated with 2 × 106 CFU S. pneumoniae. Results Leukocyte recruitment into the lung, pulmonary bacterial clearance, and clinical course were similar between ethanol and control groups. While plasma SIV viral load was similar between groups post-pneumonia, chronic ethanol-fed macaques showed a prolonged increase in SIV RNA in bronchoalveolar lavage (BAL) fluid. Alveolar macrophages isolated from ethanol-fed macaques one day post-pneumonia showed greater nuclear factor kappa beta (NF-kB) activation. Conclusions This study indicates that chronic ethanol feeding results in enhanced local, but not systemic, SIV replication following pneumococcal pneumonia. Increased

  4. Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection

    NASA Astrophysics Data System (ADS)

    Yin, Lu; Xu, Shuoyu; Cheng, Jierong; Zheng, Dahai; Limmon, Gino V.; Leung, Nicola H. N.; Rajapakse, Jagath C.; Chow, Vincent T. K.; Chen, Jianzhu; Yu, Hanry

    2013-04-01

    Lung injury caused by influenza virus infection is widespread. Understanding lung damage and repair progression post infection requires quantitative spatiotemporal information on various cell types mapping into the tissue structure. Based on high content images acquired from an automatic slide scanner, we have developed algorithms to quantify cell infiltration in the lung, loss and recovery of Clara cells in the damaged bronchioles and alveolar type II cells (AT2s) in the damaged alveolar areas, and induction of pro-surfactant protein C (pro-SPC)-expressing bronchiolar epithelial cells (SBECs). These quantitative analyses reveal: prolonged immune cell infiltration into the lung that persisted long after the influenza virus was cleared and paralleled with Clara cell recovery; more rapid loss and recovery of Clara cells as compared to AT2s; and two stages of SBECs from Scgb1a1+ to Scgb1a1-. These results provide evidence supporting a new mechanism of alveolar repair where Clara cells give rise to AT2s through the SBEC intermediates and shed light on the understanding of the lung damage and repair process. The approach and algorithms in quantifying cell-level changes in the tissue context (cell-based tissue informatics) to gain mechanistic insights into the damage and repair process can be expanded and adapted in studying other disease models.

  5. Vaccine-generated lung tissue–resident memory T cells provide heterosubtypic protection to influenza infection

    PubMed Central

    Zens, Kyra D.; Chen, Jun Kui; Farber, Donna L.

    2016-01-01

    Tissue-resident memory T cells (TRM) are a recently defined, noncirculating subset with the potential for rapid in situ protective responses, although their generation and role in vaccine-mediated immune responses is unclear. Here, we assessed TRM generation and lung-localized protection following administration of currently licensed influenza vaccines, including injectable inactivated influenza virus (IIV, Fluzone) and i.n. administered live-attenuated influenza virus (LAIV, FluMist) vaccines. We found that, while IIV preferentially induced strain-specific neutralizing antibodies, LAIV generated lung-localized, virus-specific T cell responses. Moreover, LAIV but not IIV generated lung CD4+ TRM and virus-specific CD8+ TRM, similar in phenotype to those generated by influenza virus infection. Importantly, these vaccine-generated TRM mediated cross-strain protection, independent of circulating T cells and neutralizing antibodies, which persisted long-term after vaccination. Interestingly, intranasal administration of IIV or injection of LAIV failed to elicit T cell responses or provide protection against viral infection, demonstrating dual requirements for respiratory targeting and a live-attenuated strain to establish TRM. The ability of LAIV to generate lung TRM capable of providing long-term protection against nonvaccine viral strains, as demonstrated here, has important implications for protecting the population against emergent influenza pandemics by direct fortification of lung-specific immunity. PMID:27468427

  6. Urinary tract infections due to Trichosporon spp. in severely ill patients in an intensive care unit

    PubMed Central

    Mattede, Maria das Graças Silva; Piras, Cláudio; Mattede, Kelly Dematte Silva; Ferrari, Aline Trugilho; Baldotto, Lorena Simões; Assbu, Michel Silvestre Zouain

    2015-01-01

    Objective To evaluate the incidence of urinary tract infections due to Trichosporon spp. in an intensive care unit. Methods This descriptive observational study was conducted in an intensive care unit between 2007 and 2009. All consecutive patients admitted to the intensive care unit with a confirmed diagnosis were evaluated. Results Twenty patients presented with urinary tract infections due to Trichosporon spp. The prevalence was higher among men (65%) and among individuals > 70 years of age (55%). The mortality rate was 20%. The average intensive care unit stay was 19.8 days. The onset of infection was associated with prior use of antibiotics and was more frequent in the fall and winter. Conclusion Infection due to Trichosporon spp. was more common in men and among those > 70 years of age and was associated with the use of an indwelling urinary catheter for more than 20 days and with the use of broadspectrum antibiotics for more than 14 days. In addition, patients with urinary infection due to Trichosporon spp. were most often hospitalized in intensive care units in the fall and winter periods. PMID:26465246

  7. IL-10 Restrains IL-17 to Limit Lung Pathology Characteristics following Pulmonary Infection with Francisella tularensis Live Vaccine Strain

    PubMed Central

    Slight, Samantha R.; Monin, Leticia; Gopal, Radha; Avery, Lyndsay; Davis, Marci; Cleveland, Hillary; Oury, Tim D.; Rangel-Moreno, Javier; Khader, Shabaana A.

    2014-01-01

    IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10–deficient mice (Il10−/−), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10−/−-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain. PMID:24007881

  8. Role of Mutant CFTR in Hypersusceptibility of Cystic Fibrosis Patients to Lung Infections

    NASA Astrophysics Data System (ADS)

    Pier, Gerald B.; Grout, Martha; Zaidi, Tanweer S.; Olsen, John C.; Johnson, Larry G.; Yankaskas, James R.; Goldberg, Joanna B.

    1996-01-01

    Cystic fibrosis (CF) patients are hypersusceptible to chronic Pseudomonas aeruginosa lung infections. Cultured human airway epithelial cells expressing the ΔF508 allele of the cystic fibrosis transmembrane conductance regulator (CFTR) were defective in uptake of P. aeruginosa compared with cells expressing the wild-type allele. Pseudomonas aeruginosa lipopolysaccharide (LPS)-core oligosaccharide was identified as the bacterial ligand for epithelial cell ingestion; exogenous oligosaccharide inhibited bacterial ingestion in a neonatal mouse model, resulting in increased amounts of bacteria in the lungs. CFTR may contribute to a host-defense mechanism that is important for clearance of P. aeruginosa from the respiratory tract.

  9. Environmental exposure and HPV infection may act synergistically to induce lung tumorigenesis in nonsmokers

    PubMed Central

    Cheng, Ya-Wen; Lin, Frank Cheau-Feng; Chen, Chih-Yi; Hsu, Nan-Yung

    2016-01-01

    Most studies of lung tumorigenesis have focused on smokers rather than nonsmokers. In this study, we used human papillomavirus (HPV)-positive and HPV-negative lung cancer cells to test the hypothesis that HPV infection synergistically increases DNA damage induced by exposure to the carcinogen benzo[a]pyrene (B[a]P), and contributes to lung tumorigenesis in nonsmokers. DNA adduct levels induced by B[a]P in HPV-positive cells were significantly higher than in HPV-negative cells. The DNA adduct formation was dependent on HPV E6 oncoprotein expression. Gene and protein expression of two DNA repair genes, XRCC3 and XRCC5, were lower in B[a]P-treated E6-positive cells than in E6-negative lung cancer cells. The reduced expression was also detected immunohistochemically and was caused by increased promoter hypermethylation. Moreover, mutations of p53 and epidermal growth factor receptor (EGFR) genes in lung cancer patients were associated with XRCC5 inactivation. In sum, our study indicates that HPV E6-induced promoter hypermethylation of the XRCC3 and XRCC5 DNA repair genes and the resultant decrease in their expression increases B[a]P-induced DNA adducts and contributes to lung tumorigenesis in nonsmokers. PMID:26918347

  10. GENETIC BASIS OF MURINE ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL LUNG INFECTION

    EPA Science Inventory

    To evaluate the effect of genetic background and toll-like receptor 2 on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6

  11. Enteral ecoimmunonutrition reduced enteral permeability and serum ghrelin activity in severe cerebral stroke patients with lung infection.

    PubMed

    Xu, Xiao-Di; Shao, Feng

    2015-01-01

    The study analyzed how enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension (TPF), can impact on the enteral permeability and serum Ghrelin activity in severe cerebral stroke patients with lung infection. Among 190 severe cerebral stroke patients with tolerance to TPF, they were randomized into control and treatment groups after antibiotics treatment due to lung infections. There were 92 patients in the control group and 98 patients in treatment group. The control group was treated with TPF and the treatment group was treated with enteral ecoimmunonutrition, which comprises probiotics, glutamine, fish oil, and Enteral Nutritional Suspension. All patients received continuous treatments through nasoenteral or nasogastric tubes. 7, 14, and 21 days after the treatments, the enteral tolerance to nutrition was observed in both groups. The tests included abdominal pain, bloating, diarrhea, and lactulose/mannitol (L/M) ratio. Serum Ghrelin levels were determined by ELISA. The incidence of abdominal pain, bloating, diarrhea was lower in the treatment group and enteral tolerance to nutrition was also superior to the control group. No difference in serum Ghrelin level was observed between the control and treatment groups with enteral intolerance to nutrition. However, in patients with enteral tolerance to nutrition, the treatment group showed lower enteral nutrition and lower enteral permeability compared to the control group. In severe cerebral stroke patients with lung infection, enteral ecoimmunonutrition after antibiotics treatment improved enteral tolerance to nutrition and reduced enteral permeability; meanwhile, it lowered the serum Ghrelin activity, which implied the high serum Ghrelin reduces enteral permeability. PMID:25142270

  12. Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice.

    PubMed

    Chen, Ting; Chen, Chang; Zhang, Zongze; Zou, Yufeng; Peng, Mian; Wang, Yanlin

    2016-08-01

    Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system, and increasing evidence supports its role in inflammation, stress, and tissue injury, including injury to the lung and brain. We aimed to investigate the effects of TLR4 on neuroinflammation due to the lung-brain interaction in mechanically ventilated mice. Male wild-type (WT) C57BL/6 and TLR4 knockout (TLR4 KO) mice were divided into three groups: (1) control group (C): spontaneous breathing; (2) anesthesia group (A): spontaneous breathing under anesthesia; and (3) mechanical ventilation group (MV): 6h of MV under anesthesia. The behavioral responses of mice were tested with fear conditioning tests. The histological changes in the lung and brain were assessed using hematoxylin-eosin (HE) staining. The level of TLR4 mRNA in tissue was measured using reverse transcription-polymerase chain reaction (RT-PCR). The levels of inflammatory cytokines were measured with an enzyme-linked immunosorbent assay (ELISA). Microgliosis, astrocytosis, and the TLR4 immunoreactivity in the hippocampus were measured by double immunofluorescence. MV mice exhibited impaired cognition, and this impairment was less severe in TLR4 KO mice than in WT mice. In WT mice, MV increased TLR4 mRNA expression in the lung and brain. MV induced mild lung injury, which was prevented in TLR4 KO mice. MV mice exhibited increased levels of inflammatory cytokines, increased microglia and astrocyte activation. Microgliosis was alleviated in TLR4 KO mice. MV mice exhibited increased TLR4 immunoreactivity, which was expressed in microglia and astrocytes. These results demonstrate that TLR4 is involved in neuroinflammation due to the lung-brain interaction and that TLR4 KO ameliorates neuroinflammation due to lung-brain interaction after prolonged MV. In addition, Administration of a TLR4 antagonist (100μg/mice) to WT mice also significantly attenuated neuroinflammation of lung-brain interaction due to prolonged MV. TLR4 antagonism

  13. Skin Infection due to Trichophyton tonsurans Still Occurs in People in Korea but not as Outbreaks

    PubMed Central

    2016-01-01

    Since 1995, Trichophyton tonsurans has been one of the causative agents of dermatophytosis in Korea. Herein we evaluate 77 patients infected with T. tonsurans who visited an outpatient clinic between 2004 and 2014. Infections due to T. tonsurans were diagnosed by mycological examination, which included direct microscopic examination using 15% KOH and culture in potato dextrose agar complemented with 0.5% chloramphenicol. The annual prevalence of infection due to T. tonsurans was the highest in 2014 (15 cases) but remained constant in non-gladiators between 2004 and 2014. The ratio of male to female patients was 1:0.3. The spring season presented the highest incidence compared with other seasons, with 27 cases. The incidence of infections due to T. tonsurans among gladiators was highest in spring compared with the other seasons whereas the incidence in non-gladiators was the highest in the winter. The body site most commonly affected was the face. Tinea corporis was the most common subtype of dermatophytosis caused by T. tonsurans. Herein, we demonstrate that the prevalence of infection with T. tonsurans remain constant throughout the study period in Korea. PMID:26839486

  14. Skin Infection due to Trichophyton tonsurans Still Occurs in People in Korea but not as Outbreaks.

    PubMed

    Lee, Weon Ju; Sim, Hyun Bo; Jang, Yong Hyun; Lee, Seok-Jong; Kim, Do Won; Jun, Jae Bok; Bang, Yong Jun

    2016-02-01

    Since 1995, Trichophyton tonsurans has been one of the causative agents of dermatophytosis in Korea. Herein we evaluate 77 patients infected with T. tonsurans who visited an outpatient clinic between 2004 and 2014. Infections due to T. tonsurans were diagnosed by mycological examination, which included direct microscopic examination using 15% KOH and culture in potato dextrose agar complemented with 0.5% chloramphenicol. The annual prevalence of infection due to T. tonsurans was the highest in 2014 (15 cases) but remained constant in non-gladiators between 2004 and 2014. The ratio of male to female patients was 1:0.3. The spring season presented the highest incidence compared with other seasons, with 27 cases. The incidence of infections due to T. tonsurans among gladiators was highest in spring compared with the other seasons whereas the incidence in non-gladiators was the highest in the winter. The body site most commonly affected was the face. Tinea corporis was the most common subtype of dermatophytosis caused by T. tonsurans. Herein, we demonstrate that the prevalence of infection with T. tonsurans remain constant throughout the study period in Korea. PMID:26839486

  15. Sacroiliac joint pain due to bacterial infection: a report of two cases

    PubMed Central

    Burns, SH; Mierau, DR; Howlett, E

    1995-01-01

    Isolated infection of the sacroiliac joint is a rare cause of low back pain. Delayed diagnosis can result in significant morbidity. The diagnosis may be missed initially if physicians do not consider the possibility of infection. The clinical index of suspicion should increase in the presence of certain historical and examination findings. These include intravenous drug use, immunosuppression, recent infection elsewhere, fever and warmth or swelling over the sacroiliac joint. Two cases of sacroiliac joint pain due to Staphylococcus aureus infection are presented, with an overview of the etiology, diagnosis and management of the disorder. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6(a)Figure 6(b)Figure 7Figure 8

  16. A retrospective study of abattoir condemnation due to parasitic infections: economic importance in Ahwaz, southwestern Iran.

    PubMed

    Borji, Hassan; Azizzadeh, Mohammad; Kamelli, Mehrab

    2012-10-01

    A 5-yr retrospective study in livestock slaughtered in abattoirs was carried out in Khuzestan Province (southwestern Iran) to determine the prevalence of parasitic infections responsible for condemnation of slaughtered animals' carcasses and viscera. The economic importance of such infections in terms of lost meat and offal were also estimated. Between 20 March 2006 and 19 March 2011, 125,593 cattle, 1,191,871 sheep, 240,221 goats, and 25,010 buffalos were slaughtered in the study area; the livers of 58,753 (3.7%; 95% confidence interval [CI]: 3.7-3.8%), the lungs of 34,522 (2.2%; 95% CI: 2.1-2.2%), and the carcasses of 78 (0.0049% 95% CI: 0.0048-0.0049%) of these animals were condemned. Proportions of liver, lung, and carcass condemnations during the 5-yr study period in buffalos were significantly greater than the other species (P < 0.001). Frequency of liver condemnation during the 5-yr period for cattle was greater than sheep and goats (P < 0.001), but condemnation of lungs in goat was significantly greater than sheep and cattle (P < 0.001). The parasitic lesions observed in the condemned livers were attributed to Echinococcus granulosus, Fasciola hepatica, or Dicrocoelium dendriticum, or some combination of these species. All the parasitic lesions observed in the condemned lungs from cattle, sheep, goats, and buffalos are ascribed to E. granulosus. Sarcocystis spp. cysts were found in ovine and buffalo muscles, whereas Taenia sp. cysticerci were detected in bovine muscle. Muscles of goats were devoid of any parasitic lesions. Parasites were responsible for 54.1% of the condemned organs or carcasses, with a retail value (based on market prices in 2011) of $1,148,181 (U.S.) ($137,880 for cattle, $602,699 for sheep, $280,955 for goats, and $126,647 for buffalos). The parasites contributing most to the condemnation of otherwise marketable organs and flesh were E. granulosus (29.2%) and F. hepatica (18.6%). These parasites clearly remain the most common, causing

  17. Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies.

    PubMed

    Parahym, Ana Maria Rabelo de Carvalho; Rolim Neto, Pedro José; da Silva, Carolina Maria; Domingos, Igor de Farias; Gonçalves, Sarah Santos; Leite, Edinalva Pereira; de Morais, Vera Lúcia Lins; Macêdo, Danielle Patrícia Cerqueira; de Lima Neto, Reginaldo Gonçalves; Neves, Rejane Pereira

    2015-06-01

    We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole. PMID:26273269

  18. Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies

    PubMed Central

    Parahym, Ana Maria Rabelo de Carvalho; Rolim, Pedro José; da Silva, Carolina Maria; Domingos, Igor de Farias; Gonçalves, Sarah Santos; Leite, Edinalva Pereira; de Morais, Vera Lúcia Lins; Macêdo, Danielle Patrícia Cerqueira; de Lima, Reginaldo Gonçalves; Neves, Rejane Pereira

    2015-01-01

    We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole. PMID:26273269

  19. Extremely increased serum carbohydrate antigen 19-9 levels caused by new or resistant infections to previous antibiotics in chronic lung diseases.

    PubMed

    Shin, Ji Young; Yoo, Su Jin; Park, Bo Mi; Jung, Sung Su; Kim, Ju Ock; Lee, Jeong Eun

    2013-09-01

    In this paper, we describe 72-year-old female patient without evidence of malignant disease presented with significantly elevated serum carbohydrate antigen (CA) 19-9 levels by respiratory infections. She was diagnosed with respiratory infections due to Mycobacterium avium complex and Pseudomonas aeruginosa. The serum CA 19-9 levels remarkably increased (1,453-5,300 U/mL; reference range, <37 U/mL) by respiratory infection and abruptly decreased (357-534 U/mL) whenever infection was controlled by specific treatments. This case suggests that serum CA 19-9 levels may be used as a diagnostic marker to indicate new or resistant infections to previous antibiotics in chronic lung diseases without significant changes in chest X-ray findings. PMID:24101938

  20. Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections.

    PubMed

    Hauck, C; Cober, E; Richter, S S; Perez, F; Salata, R A; Kalayjian, R C; Watkins, R R; Scalera, N M; Doi, Y; Kaye, K S; Evans, S; Fowler, V G; Bonomo, R A; van Duin, D

    2016-06-01

    Patients infected or colonized with carbapenem-resistant Klebsiella pneumoniae (CRKp) are often chronically and acutely ill, which results in substantial mortality unrelated to infection. Therefore, estimating excess mortality due to CRKp infections is challenging. The Consortium on Resistance against Carbapenems in K. pneumoniae (CRACKLE) is a prospective multicenter study. Here, patients in CRACKLE were evaluated at the time of their first CRKp bloodstream infection (BSI), pneumonia or urinary tract infection (UTI). A control cohort of patients with CRKp urinary colonization without CRKp infection was constructed. Excess hospital mortality was defined as mortality in cases after subtracting mortality in controls. In addition, the adjusted hazard ratios (aHR) for time-to-hospital-mortality at 30 days associated with infection compared with colonization were calculated in Cox proportional hazard models. In the study period, 260 patients with CRKp infections were included in the BSI (90 patients), pneumonia (49 patients) and UTI (121 patients) groups, who were compared with 223 controls. All-cause hospital mortality in controls was 12%. Excess hospital mortality was 27% in both patients with BSI and those with pneumonia. Excess hospital mortality was not observed in patients with UTI. In multivariable analyses, BSI and pneumonia compared with controls were associated with aHR of 2.59 (95% CI 1.52-4.50, p <0.001) and 3.44 (95% CI 1.80-6.48, p <0.001), respectively. In conclusion, in patients with CRKp infection, pneumonia is associated with the highest excess hospital mortality. Patients with BSI have slightly lower excess hospital mortality rates, whereas excess hospital mortality was not observed in hospitalized patients with UTI. PMID:26850824

  1. Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

    PubMed

    Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline

    2013-01-01

    EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed. PMID:24289102

  2. Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: a review.

    PubMed

    Ghanei, Mostafa; Harandi, Ali Amini

    2011-06-01

    Sulfur mustard (SM), a potent chemical weapon agent, was used by Iraqi forces against Iranian in the Iraq-Iran war (1981-1989). Chronic obstructive pulmonary disease (COPD) is a late toxic pulmonary consequence after SM exposure. The COPD observed in these patients is unique (described as Mustard Lung) and to some extent different from COPD resulted from other well-known causes. Several mechanisms have been hypothesized to contribute to the pathogenesis of COPD including oxidative stress, disruption of the balance between apoptosis and replenishment, proteinase-antiproteinase imbalance and inflammation. However, it is not obvious which of these pathways are relevant to the pathogenesis of mustard lung. In this paper, we reviewed studies addressing the pathogenicity of mustard lung, and reduced some recent ambiguities in this field. There is ample evidence in favor of crucial role of both oxidative stress and apoptosis as two known mechanisms that are more involved in pathogenesis of mustard lung comparing to COPD. However, according to available evidences there are no such considerable data supporting neither proteolytic activity nor inflammation mechanism as the main underlying pathogenesis in Mustard Lung. PMID:21639706

  3. Transcriptional profiling of host gene expression in chicken embryo lung cells infected with laryngotracheitis virus

    PubMed Central

    2010-01-01

    Background Infection by infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) causes acute respiratory diseases in chickens often with high mortality. To better understand host-ILTV interactions at the host transcriptional level, a microarray analysis was performed using 4 × 44 K Agilent chicken custom oligo microarrays. Results Microarrays were hybridized using the two color hybridization method with total RNA extracted from ILTV infected chicken embryo lung cells at 0, 1, 3, 5, and 7 days post infection (dpi). Results showed that 789 genes were differentially expressed in response to ILTV infection that include genes involved in the immune system (cytokines, chemokines, MHC, and NF-κB), cell cycle regulation (cyclin B2, CDK1, and CKI3), matrix metalloproteinases (MMPs) and cellular metabolism. Differential expression for 20 out of 789 genes were confirmed by quantitative reverse transcription-PCR (qRT-PCR). A bioinformatics tool (Ingenuity Pathway Analysis) used to analyze biological functions and pathways on the group of 789 differentially expressed genes revealed that 21 possible gene networks with intermolecular connections among 275 functionally identified genes. These 275 genes were classified into a number of functional groups that included cancer, genetic disorder, cellular growth and proliferation, and cell death. Conclusion The results of this study provide comprehensive knowledge on global gene expression, and biological functionalities of differentially expressed genes in chicken embryo lung cells in response to ILTV infections. PMID:20663125

  4. Complicated Catheter-Associated Urinary Tract Infections Due to Escherichia coli and Proteus mirabilis

    PubMed Central

    Jacobsen, S. M.; Stickler, D. J.; Mobley, H. L. T.; Shirtliff, M. E.

    2008-01-01

    Catheter-associated urinary tract infections (CAUTIs) represent the most common type of nosocomial infection and are a major health concern due to the complications and frequent recurrence. These infections are often caused by Escherichia coli and Proteus mirabilis. Gram-negative bacterial species that cause CAUTIs express a number of virulence factors associated with adhesion, motility, biofilm formation, immunoavoidance, and nutrient acquisition as well as factors that cause damage to the host. These infections can be reduced by limiting catheter usage and ensuring that health care professionals correctly use closed-system Foley catheters. A number of novel approaches such as condom and suprapubic catheters, intermittent catheterization, new surfaces, catheters with antimicrobial agents, and probiotics have thus far met with limited success. While the diagnosis of symptomatic versus asymptomatic CAUTIs may be a contentious issue, it is generally agreed that once a catheterized patient is believed to have a symptomatic urinary tract infection, the catheter is removed if possible due to the high rate of relapse. Research focusing on the pathogenesis of CAUTIs will lead to a better understanding of the disease process and will subsequently lead to the development of new diagnosis, prevention, and treatment options. PMID:18202436

  5. Pulmonary migratory infiltrates due to mycoplasma infection: case report and review of the literature

    PubMed Central

    You, Wenjie; Chen, Bi; Li, Jing; Shou, Juan; Xue, Shan; Liu, Xueqing

    2016-01-01

    Pulmonary migratory infiltrates (PMI) are observed in a few diseases. We report here a case of PMI attributed to Mycoplasma pneumonia (Mp) infection. The patient’s past medical history was characterized by fleeting and/or relapses of patchy opacification or infiltrates of parenchyma throughout the whole lung field except for left lower lobe radiographically. Serological assays revealed an elevation of IgG antibody specific to Mp and its fourfold increase in convalescent serum. Histopathological findings showed polypoid plugs of fibroblastic tissue filling and obliterating small air ways and interstitial infiltrates of mononuclear inflammatory cells in the vicinal alveolar septa. The patient was treated with azithromycin which resulted in a dramatic improvement clinically and imageologically. In spite of the increasing incidence of Mp, the possible unusual imaging manifestation and underlying mechanism haven’t attracted enough attention. To our knowledge, there are rare reports of such cases. PMID:27293865

  6. Pulmonary migratory infiltrates due to mycoplasma infection: case report and review of the literature.

    PubMed

    You, Wenjie; Chen, Bi; Li, Jing; Shou, Juan; Xue, Shan; Liu, Xueqing; Jiang, Handong

    2016-06-01

    Pulmonary migratory infiltrates (PMI) are observed in a few diseases. We report here a case of PMI attributed to Mycoplasma pneumonia (Mp) infection. The patient's past medical history was characterized by fleeting and/or relapses of patchy opacification or infiltrates of parenchyma throughout the whole lung field except for left lower lobe radiographically. Serological assays revealed an elevation of IgG antibody specific to Mp and its fourfold increase in convalescent serum. Histopathological findings showed polypoid plugs of fibroblastic tissue filling and obliterating small air ways and interstitial infiltrates of mononuclear inflammatory cells in the vicinal alveolar septa. The patient was treated with azithromycin which resulted in a dramatic improvement clinically and imageologically. In spite of the increasing incidence of Mp, the possible unusual imaging manifestation and underlying mechanism haven't attracted enough attention. To our knowledge, there are rare reports of such cases. PMID:27293865

  7. Mycobacterium sherrisii Lung Infection in a Brazilian Patient with Silicosis and a History of Pulmonary Tuberculosis

    PubMed Central

    de Oliveira Abrão, Carolina; de Araújo Filho, João Alves

    2015-01-01

    Nontuberculous mycobacteria (NTM) diseases became relevant with the emergence and spread of HIV and are also related to lung infection in non-HIV individuals with structural lung diseases. Mycobacterium sherrisii is a NTM first characterized in 2004. Only a few cases have been reported. The aim of this case report is to describe the first detailed case of infection with M. sherrisii in a patient with silicosis and history of pulmonary tuberculosis. A 50-year-old HIV-negative white male, previous smoker, with silicosis and a history of treated pulmonary tuberculosis developed a worsening of cough and expectoration pattern, and two sputum samples were positive for acid-fast bacilli. Presumptive treatment for pulmonary tuberculosis was initiated with rifampin, isoniazid, pyrazinamide, and ethambutol, but, at month 5 of treatment, despite correct medication intake and slight improvement of symptoms, sputum bacilloscopy remained positive. Sputum cultures were positive Mycobacterium sherrisii. Treatment regimen was altered to streptomycin (for 2 months), ethambutol, clarithromycin, rifabutin, and trimethoprim-sulfamethoxazole. M. sherrisii should be considered a possible etiological agent of lung infections in patients with pneumoconiosis and history of tuberculosis. PMID:26557395

  8. Dynamics of bovine intramammary infections due to coagulase-negative staphylococci on four farms.

    PubMed

    Bexiga, Ricardo; Rato, Márcia G; Lemsaddek, Abdelhak; Semedo-Lemsaddek, Teresa; Carneiro, Carla; Pereira, Helena; Mellor, Dominic J; Ellis, Kathryn A; Vilela, Cristina L

    2014-05-01

    The objectives of this study were to compare the impact of different coagulase-negative species (CNS) on udder health measured in terms of individual quarter milk somatic cell count (SCC) and duration of intramammary infection, and to get some insight into most likely routes of infection for different CNS species. This longitudinal observational study was performed on four farms that were sampled at 4-week intervals for a total of 12 visits each. Quarters infected with CNS were followed through time with milk samples being submitted for bacteriological culture and SCC determination. PCR amplification of the internal transcribed spacer region and sequencing of the sodA and rpoB genes were used for species allocation. Pulsed-field gel electrophoresis (PFGE) was performed to assess strain identity. The percentage of quarters affected per farm varied between 6 and 35%, with the most frequently isolated CNS species being Staphylococcus epidermidis, followed by Staph. simulans, Staph. chromogenes and Staph. haemolyticus. It was possible to follow 111 intramammary infections due to CNS through time. Duration of infection had a mean of 188 d and was not significantly different between CNS species. Geometric mean quarter SCC overall was 132 000 cells/ml and was also not significantly different between CNS species. Despite the possibility of a different epidemiology of infection, the impact in terms of udder health seems to be similar for different CNS species. PMID:24594229

  9. Lung Diseases

    MedlinePlus

    ... many disorders affecting the lungs, such as asthma, COPD, infections like influenza, pneumonia and tuberculosis, lung cancer, and many other breathing problems. Some lung diseases can lead to respiratory failure. Dept. of Health and Human Services Office on Women's Health

  10. T-bet Regulates Immunity to Francisella tularensis Live Vaccine Strain Infection, Particularly in Lungs

    PubMed Central

    Melillo, Amanda A.; Foreman, Oded; Bosio, Catharine M.

    2014-01-01

    Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis. Thus, to determine if this mediator had direct consequences in immunity to LVS, we examined its role in infection. Despite substantial in vivo gamma interferon (IFN-γ) levels, T-bet-knockout (KO) mice infected intradermally (i.d.) or intranasally (i.n.) with LVS succumbed to infection with doses 2 log units less than those required for their wild-type (WT) counterparts, and exhibited significantly increased bacterial burdens in the lung and spleen. Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice. LVS-vaccinated T-bet-KO mice survived lethal LVS intraperitoneal secondary challenge but not high doses of LVS i.n. challenge, independently of the route of vaccination. Immune T lymphocytes from the spleens of i.d. LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-γ and increased amounts of tumor necrosis factor alpha. In contrast, immune T-bet-KO lung lymphocytes were greatly impaired in controlling intramacrophage growth of LVS; this functional defect is the likely mechanism underpinning the lack of respiratory protection. Taken together, T-bet is important in host resistance to primary LVS infection and i.n. secondary challenge. Thus, T-bet represents a true, useful correlate for immunity to LVS. PMID:24421047

  11. T-bet regulates immunity to Francisella tularensis live vaccine strain infection, particularly in lungs.

    PubMed

    Melillo, Amanda A; Foreman, Oded; Bosio, Catharine M; Elkins, Karen L

    2014-04-01

    Upregulation of the transcription factor T-bet is correlated with the strength of protection against secondary challenge with the live vaccine strain (LVS) of Francisella tularensis. Thus, to determine if this mediator had direct consequences in immunity to LVS, we examined its role in infection. Despite substantial in vivo gamma interferon (IFN-γ) levels, T-bet-knockout (KO) mice infected intradermally (i.d.) or intranasally (i.n.) with LVS succumbed to infection with doses 2 log units less than those required for their wild-type (WT) counterparts, and exhibited significantly increased bacterial burdens in the lung and spleen. Lungs of LVS-infected T-bet-KO mice contained fewer lymphocytes and more neutrophils and interleukin-17 than WT mice. LVS-vaccinated T-bet-KO mice survived lethal LVS intraperitoneal secondary challenge but not high doses of LVS i.n. challenge, independently of the route of vaccination. Immune T lymphocytes from the spleens of i.d. LVS-vaccinated WT or KO mice controlled intracellular bacterial replication in an in vitro coculture system, but cultures with T-bet-KO splenocyte supernatants contained less IFN-γ and increased amounts of tumor necrosis factor alpha. In contrast, immune T-bet-KO lung lymphocytes were greatly impaired in controlling intramacrophage growth of LVS; this functional defect is the likely mechanism underpinning the lack of respiratory protection. Taken together, T-bet is important in host resistance to primary LVS infection and i.n. secondary challenge. Thus, T-bet represents a true, useful correlate for immunity to LVS. PMID:24421047

  12. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

    PubMed Central

    Dutta, Avijit; Huang, Ching-Tai; Lin, Chun-Yen; Chen, Tse-Ching; Lin, Yung-Chang; Chang, Chia-Shiang; He, Yueh-Chia

    2016-01-01

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity. PMID:27596047

  13. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs.

    PubMed

    Dutta, Avijit; Huang, Ching-Tai; Lin, Chun-Yen; Chen, Tse-Ching; Lin, Yung-Chang; Chang, Chia-Shiang; He, Yueh-Chia

    2016-01-01

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity. PMID:27596047

  14. Vitamin E protects against lipid peroxidation due to cold-SO2 coexposure in mouse lung.

    PubMed

    Ergonul, Zuhal; Erdem, Ayşen; Balkanci, Zeynep Dicle; Kilinc, Kamer

    2007-02-01

    Exposure to sulfur dioxide (SO2) and cold increases especially in the winter. SO2 or cold exposure destroys the oxidant/antioxidant balance and increases lipid peroxidation. However, the effect of coexistence of both factors has not been studied yet. Therefore, we investigated the effect of SO2 and/or repeated short-term cold exposure on the oxidant-antioxidant status and the possible protective role of vitamin E in the cardiopulmonary tissues of mice. Swiss albino mice of both sexes were assigned to eight groups. Four groups were kept at room temperature, injected either with saline or vitamin E (100 mg/kg) in the presence or absence of SO2 exposure (10 ppm, 1 h/day, 30 days). The remaining four groups received the same protocol but were exposed to cold (4 +/- 1 degrees C, 1 h/days, 30 days) instead of room temperature. On day 30, the lung and heart tissues were removed for biochemical analysis. SO2 and cold coexposure increased lactate level in the lung, and elevated thiobarbituric acid-reactive substance (TBARS) and reduced glutathione levels in both tissues, while vitamin E treatment reversed TBARS increment predominantly in the lung. In conclusion, cold and SO2 coexposure exerts more deleterious effects in the cardiopulmonary tissues, while vitamin E treatment seems to be protective, particularly in the lung. PMID:17169863

  15. Lung edema due to hydrogen peroxide is independent of cyclooxygenase products

    SciTech Connect

    Burghuber, O.; Mathias, M.M.; McMurtry, I.F.; Reeves, J.T.; Voelkel, N.F.

    1984-01-01

    Active oxygen species can cause lung injury. Although a direct action on endothelial cells is proposed, the possibility exists that they might cause injury via mediators. We considered that active oxygen species would stimulate the generation of cyclooxygenase metabolites, which then alter pulmonary vasoreactivity and cause edema. We chemically produced hydrogen peroxide by adding glucose oxidase to a plasma- and cell-free, but ..beta..-D-glucose-containing, solution, which perfused isolated rat lungs. Addition of glucose oxidase to the perfusate caused a marked decrease in pulmonary vasoreactivity, accompanied by an increase in the concentrations of prostacyclin, thromboxane A/sub 2/, and prostaglandin F/sub 2..cap alpha../. Pretreatment with catalase, a specific scavenger of hydrogen peroxide, preserved pulomonary vasoreactivity, inhibited the increase of the concentration of the measured prostaglandins, and prevented edema formation. Indomethacin effectively blocked lung prostaglandin production but neither prevented the decrease in vasoreactivity nor inhibited edema formation. From these data we conclude the hydrogen peroxide impaired pulmonary vasoreactivity and subsequently caused edema. Depsite the fact that hydrogen peroxide stimulated lung prostaglandin production, cyclooxygenase-derived products neither caused the decrease in vasoreactivity nor the development of edema.

  16. Lung edema due to hydrogen peroxide is independent of cyclooxygenase products.

    PubMed

    Burghuber, O; Mathias, M M; McMurtry, I F; Reeves, J T; Voelkel, N F

    1984-04-01

    Active oxygen species can cause lung injury. Although a direct action on endothelial cells is proposed, the possibility exists that they might cause injury via mediators. We considered that active oxygen species would stimulate the generation of cyclooxygenase metabolites, which then alter pulmonary vasoreactivity and cause edema. We chemically produced hydrogen peroxide by adding glucose oxidase to a plasma- and cell-free, but beta-D-glucose-containing, solution, which perfused isolated rat lungs. Addition of glucose oxidase to the perfusate caused a marked decrease in pulmonary vasoreactivity, accompanied by an increase in the concentrations of prostacyclin, thromboxane A2, and prostaglandin F2 alpha. Pretreatment with catalase, a specific scavenger of hydrogen peroxide, preserved pulmonary vasoreactivity, inhibited the increase of the concentration of the measured prostaglandins, and prevented edema formation. Indomethacin effectively blocked lung prostaglandin production but neither prevented the decrease in vasoreactivity nor inhibited edema formation. From these data we conclude that hydrogen peroxide impaired pulmonary vasoreactivity and subsequently caused edema. Despite the fact that hydrogen peroxide stimulated lung prostaglandin production, cyclooxygenase-derived products neither caused the decrease in vasoreactivity nor the development of edema. PMID:6427146

  17. 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. PMID:25537798

  18. Acute cervical artery dissection after a dental procedure due to a second inferior molar infection.

    PubMed

    Delgado, Montserrat G; Riesco, Nuria; Murias, Eduardo; Calleja, Sergio

    2015-01-01

    Periodontal infections might represent one of the causative factors for cervical artery dissection. We present a case of a 49-year-old woman admitted due to headache. The patient had been suffering from a right second inferior molar infection with a cervical phlegmon for 1 week prior to admission. On 2 October 2014, the patient went to the dentist and a molar extraction was performed in the morning. In the afternoon, the patient began to experience right hemifacial pain that progressed towards an intense and bilateral headache. Neurological status at the time of admission revealed right miosis, ptosis and conjuntival hyperaemia. A CT angiography showed a right internal carotid artery dissection provoking a high-degree stenosis. The relationship between periodontal infection and vascular disease has been previously presented. Microbial agents may directly, and inflammatory and immunological host response indirectly, influence inflammatory changes in cervical arteries favouring dissections with minor traumas. PMID:26038385

  19. Postoperative infection in patients undergoing inspection of orthopedic damage due to external fixation☆

    PubMed Central

    Foni, Noel Oizerovici; Batista, Felipe Augusto Ribeiro; Rossato, Luís Henrique Camargo; Hungria, José Octavio Soares; Mercadante, Marcelo Tomanik; Christian, Ralph Walter

    2015-01-01

    Objective To conduct a retrospective analysis on cases undergoing inspection of orthopedic damage, at an orthopedic emergency service in a teaching hospital, with the aim of evaluating patients with postoperative infection after conversion to internal osteosynthesis. Methods This was a retrospective analysis covering the period from June 2012 to June 2013, on patients who underwent inspection of orthopedic damage due to external fixation and subsequently were converted to definitive osteosynthesis using a nail or plate. Results We found an infection rate of 13.3% in our sample and, furthermore, found that there had been technical errors in setting up the fixator in 60.4% of the cases. Conclusion We found an infection rate that we considered high, along with inadequacies in constructing the external fixator. We emphasize that this procedure is not risk-free and that training for physicians who perform this procedure should be mandatory.

  20. Immunohistochemical expression of nuclear factor erythroid-2-related factor 2 and heme oxygenase 1 in normal bovine lung and bovine lung infected with Mannheimia haemolytica

    PubMed Central

    Moussa, Amira Talaat; Singh, Baljit; Al-Dissi, Ahmad N.

    2015-01-01

    Mannheimia haemolytica is an important cause of pneumonia in feedlot cattle. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for the induction of antioxidant enzymes, such as heme oxygenase 1 (HO-1), within the lung. The expression of Nrf2 and HO-1 was immunohistochemically evaluated in 4 calves 24 h after experimental infection with M. haemolytica. Calves receiving normal saline served as controls. In the infected lungs, cytoplasmic Nrf2 expression was high in macrophages and bronchioles and low in alveolar epithelium, whereas nuclear expression was high in endothelial cells, macrophages, and bronchioles and lowest in alveolar epithelium. Normal lung samples displayed only faint Nrf2 cytoplasmic staining within bronchiolar epithelium. Expression of HO-1 was detected within the cytoplasm of macrophages and bronchiolar epithelial cells in all infected lung samples, whereas normal lungs displayed only weak cytoplasmic staining in bronchiolar epithelial cells. These findings suggest that bronchiolar epithelial cells and macrophages up-regulate Nrf2 expression early in the course of infection, which results in increased expression of HO-1 within these cells. PMID:25852222

  1. Epidemiological Aspects of Neonatal Mortality Due To Intrauterine Infection in Kazakhstan

    PubMed Central

    MAMYRBAYEVA, Marzya; IGISSINOV, Nurbek; ZHUMAGALIYEVA, Galina; SHILMANOVA, Akmanat

    2015-01-01

    Background: In this study, we examined the epidemiological aspects of neonatal mortality due to intrauterine infections with regard to regional characteristics. Methods: Consolidated report of the Ministry of Health and Social Development of the Republic of Kazakhstan on children deceased during their first 28 days of life due to intrauterine infections (P23 – congenital pneumonia, P35–39 – infectious diseases specific to the perinatal period) in the country and its regions for 2010 – 2014 was used in this investigation. Descriptive and analytical methods of medical statistics and epidemiology were used as the main method of this 5-year (2010–2014) retrospective study. Results: Overall, 3,298 neonatal deaths from intrauterine infections were recorded in Kazakhstan during the period of 2010–2014, 1,925 of which were early and 1,373 were late neonatal deaths. The average annual rate of neonatal mortality rate from intrauterine infection in the country amounted to 1.73±0.23‰ (95% CI=1.27–2.19‰), whereas trends during the study period decreased (T=−15.3%). Regional characteristics of neonatal mortality were established. Different levels for cartograms of neonatal mortality from intrauterine infections were defined: low (up to 1.28‰), average (from 1.28‰ to 2.12‰) and high (by 2.12‰ and above). Neonatal mortality in the early and late periods was also analyzed. Conclusion: This is the first epidemiological study of neonatal mortality from intrauterine infection, which contains a detailed space-time evaluation. The results of this investigation can be used to improve the state program to combat infant mortality. PMID:26576344

  2. Infections due to Lancefield group F and related Streptococci (S. milleri, S. anginosus).

    PubMed

    Shlaes, D M; Lerner, P I; Wolinsky, E; Gopalakrishna, K V

    1981-05-01

    We can no longer accept classification of streptococci solely on the basis of hemolytic reactions or Lancefield agglutinations. While the "viridans" streptococci cannot be serologically differentiated, physiological separation of the species offers a satisfactory method of classifying human isolates. We review the microbiology of Lancefield group F and related streptococci (S. milleri, S. anginosus), emphasizing microbial ecology and current taxonomic considerations. A series of 28 patients infected with these organisms is presented. There was a striking male predominance in the series (6:1) as well as an obvious association with underlying diseases and/or antecedent trauma. The most remarkable feature of these pathogens is their predilection for abscess formation, confirming their overdue recognition as the most common "viridans" streptococcus recovered from abscesses within internal organs. We observed purulent disease of the nervous and skeletal systems, oral cavity, lung and pleural space, abdomen and subcutaneous tissues. Microbial synergy (i.e. polymicrobic infection) was not a requisite for abscess formation. Four of the five deaths in this series occurred in patients 60 years of age of older. Some degree of variability in antimicrobial susceptibility was noted, so speciation alone may not always provide sufficient information on which to base a therapeutic decision. PMID:7231153

  3. Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae

    PubMed Central

    Qin, Xuan; Oron, Assaf P.; Adler, Amanda L.; Wolter, Daniel J.; Berry, Jessica E.; Hoffman, Lucas; Weissman, Scott J.

    2014-01-01

    The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae, but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred. PMID:24798269

  4. Contribution of alpha- and beta-defensins to lung function decline and infection in smokers: an association study

    PubMed Central

    Wallace, Alison M; He, Jian-Qing; Burkett, Kelly M; Ruan, Jian; Connett, John E; Anthonisen, Nicholas R; Paré, Peter D; Sandford, Andrew J

    2006-01-01

    Background Alpha-defensins, which are major constituents of neutrophil azurophilic granules, and beta-defensins, which are expressed in airway epithelial cells, could contribute to the pathogenesis of chronic obstructive pulmonary disease by amplifying cigarette smoke-induced and infection-induced inflammatory reactions leading to lung injury. In Japanese and Chinese populations, two different beta-defensin-1 polymorphisms have been associated with chronic obstructive pulmonary disease phenotypes. We conducted population-based association studies to test whether alpha-defensin and beta-defensin polymorphisms influenced smokers' susceptibility to lung function decline and susceptibility to lower respiratory infection in two groups of white participants in the Lung Health Study (275 = fast decline in lung function and 304 = no decline in lung function). Methods Subjects were genotyped for the alpha-defensin-1/alpha-defensin-3 copy number polymorphism and four beta-defensin-1 polymorphisms (G-20A, C-44G, G-52A and Val38Ile). Results There were no associations between individual polymorphisms or imputed haplotypes and rate of decline in lung function or susceptibility to infection. Conclusion These findings suggest that, in a white population, the defensin polymorphisms tested may not be of importance in determining who develops abnormally rapid lung function decline or is susceptible to developing lower respiratory infections. PMID:16700921

  5. Yersinia pseudotuberculosis uses Ail and YadA to circumvent neutrophils by directing Yop translocation during lung infection.

    PubMed

    Paczosa, Michelle K; Fisher, Michael L; Maldonado-Arocho, Francisco J; Mecsas, Joan

    2014-02-01

    A Yersinia pseudotuberculosis (Yptb) murine model of lung infection was previously developed using the serotype III IP2666NdeI strain, which robustly colonized lungs but only sporadically disseminated to the spleen and liver. We demonstrate here that a serotype Ib Yptb strain, IP32953, colonizes the lungs at higher levels and disseminates more efficiently to the spleen and liver compared with IP2666NdeI . The role of adhesins was investigated during IP32953 lung infection by constructing isogenic Δail, Δinv, ΔpsaE and ΔyadA mutants. An IP32953ΔailΔyadA mutant initially colonized but failed to persist in the lungs and disseminate to the spleen and liver. Yptb expressing these adhesins selectively bound to and targeted neutrophils for translocation of Yops. This selective targeting was critical for virulence because persistence of the ΔailΔyadA mutant was restored following intranasal infection of neutropenic mice. Furthermore, Ail and YadA prevented killing by complement-mediated mechanisms during dissemination to and/or growth in the spleen and liver, but not in the lungs. Combined, these results demonstratethat Ail and YadA are critical, redundant virulence factors during lung infection, because they thwart neutrophils by directing Yop-translocation specifically into these cells. PMID:24119087

  6. Diffuse alveolar hemorrhage due to metastatic angiosarcoma of the lung: A case report

    PubMed Central

    PAN, ZHIJIE; AN, ZHOU; LI, YANYUAN; ZHOU, JIANYING

    2015-01-01

    Angiosarcoma is a rare, heterogeneous malignant tumor that derives from endothelial cells, and it has aggressive characteristics with a marked tendency for distant metastasis. Diffuse alveolar hemorrhage (DAH) is a catastrophic clinical syndrome, however, it is rare as the presentation of pulmonary angiosarcoma. To increase awareness with regard to angiosarcoma and DAH, the current study presents a case of angiosarcoma that originated from the subcutaneous soft tissue of the mastoid process, but was subject to a delayed diagnosis and rapid invasion into the brain and lung. The metastatic angiosarcoma of the lung presented with DAH as the initial manifestation. The pathological examination of a biopsy of the subcutaneous mass and pulmonary lesions confirmed the diagnosis of angiosarcoma. The patient succumbed to respiratory failure at 1 month post-diagnosis. PMID:26788222

  7. Early cardiac tamponade due to tension pneumopericardium after bilateral lung transplantation.

    PubMed

    Lasocki, Sigismond; Castier, Yves; Geffroy, Arnaud; Mal, Hervé; Brugière, Olivier; Lesèche, Guy; Montravers, Philippe

    2007-10-01

    We report the case of a 42-year-old woman who developed severe hemodynamic instability with marked arterial pulsed pressure variation in the early course of bilateral lung transplantation. The diagnosis of tension pneumopericardium was made on Day 2 post-operatively based on chest X-ray and echocardiography. Transoesophageal echocardiography revealed both a cardiac tamponade and a right-to-left shunt via a patent foramen ovale. The treatment and mechanisms of these two rare complications are discussed. PMID:17919630

  8. Beneficial Effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection.

    PubMed

    Wanke-Jellinek, Lorenz; Keegan, Joshua W; Dolan, James W; Guo, Fei; Chen, Jianfei; Lederer, James A

    2016-01-15

    Although Streptococcus pneumoniae is usually found as a commensal in healthy individuals, it can act as a pathogen in trauma patients, causing such complications as early-onset pneumonia and sepsis. We discovered that treating mice with an A-class CpG-oligodeoxynucleotide (ODN) at 2 h after traumatic injury significantly improved mouse survival following early-onset secondary lung infection with S. pneumoniae. This study used mass cytometry (cytometry by time-of-flight) and Luminex technologies to characterize the cellular immune response to secondary S. pneumoniae lung infection at 1 and 3 d postinfection. We found increased expression of CD14, CD64, and PD-L1 on F4-80(+) and F4-80(+)CD11c(+) macrophages, CD11c(+) dendritic cells, and CD14(+)CD172a(+) cells after burn-injury and infection, supporting previous reports of innate immune cell activation in sepsis. CpG-ODN treatment at 2 h after burn-injury reversed these effects; improved pathogen clearance; and led to an increased expression of CD25, CD27, MHCII, and IL-17 on or in TCRγδ cells at 1 d postinfection. At 3 d postinfection, CpG-ODN treatment increased the expression of PD-L1 on innate cell subsets. Furthermore, we analyzed cytokine levels in lung-washout samples of TCRγδ cell-depleted (TCRγδ(-)) mice to demonstrate that the effects of CpG-ODN on cytokine expression after burn-injury and S. pneumoniae infection rely on functional TCRγδ cells. In summary, we demonstrate that cytometry by time-of-flight provides an effective strategy to systematically identify specific cellular phenotypic responses to trauma and bacterial pneumonia and to discover changes in immune system phenotypes associated with beneficial immunotherapy. PMID:26673136

  9. Early changes in lung gene expression due to high tidal volume.

    PubMed

    Copland, Ian B; Kavanagh, Brian P; Engelberts, Doreen; McKerlie, Colin; Belik, Jaques; Post, Martin

    2003-11-01

    The purpose of this study was to use gene expression profiling to understand how adult rat lung responds to high tidal volume (HV) ventilation in vivo. HV ventilation for 30 minutes did not cause discernable lung injury (in terms of altered mechanics or histology) but caused obvious injury when continued for 90 minutes. However, at 30-minute ventilation, HV caused significant upregulation of 10 genes and suppression of 12 genes. Among the upregulated genes were transcription factors, stress proteins, and inflammatory mediators; the downregulated genes were exemplified by metabolic regulatory genes. On the basis of cluster analysis, we studied Egr-1, c-Jun, heat shock protein 70, and interleukin (IL)-1beta in further detail. Temporal studies demonstrated that Egr-1 and c-Jun were increased early and before heat shock protein 70 and IL-1beta. Spatial studies using in situ hybridization and laser capture microscopy revealed that all four genes were upregulated primarily in the bronchiolar airway epithelium. Furthermore, at 90 minutes of HV ventilation, a significant increase in intracellular IL-1beta protein was observed. Although there are limitations to gene array methodology, the current data suggest a global hypothesis that (1). the effects of HV are cumulative; (2). specific patterns of gene activation and suppression precede lung injury; and (3). alteration of gene expression after mechanical stretch is pathogenic. PMID:12816737

  10. Parasitic infestation of lung: An unusual cause of interstitial pneumonitis

    PubMed Central

    Shah, Parth; Kate, Arvind H; Nester, Nora; Patole, Kamlakar; Leuppi, Joerg D; Chhajed, Prashant N

    2016-01-01

    Parasite infections are increasing worldwide due to increasing migration and traveling. Parasitic infections can affect lungs and present as a focal or diffuse lung diseases. High index of suspicion and detailed history are most important. We present a case of interstitial pneumonitis caused by parasite infestation, which was diagnosed on transbronchial lung biopsy. PMID:27051117

  11. Infectious Triggers of Chronic Lung Allograft Dysfunction.

    PubMed

    Gregson, Aric L

    2016-07-01

    Survival after lung transplantation is limited in large part due to the high incidence of chronic rejection, known as chronic lung allograft dysfunction (CLAD). Pulmonary infections are a frequent complication in lung transplant recipients, due both to immunosuppressive medications and constant exposure of the lung allograft to the external environment via the airways. Infection is a recognized risk factor for the development of CLAD, and both acute infection and chronic lung allograft colonization with microorganisms increase the risk for CLAD. Acute infection by community acquired respiratory viruses, and the bacteria Pseudomonas aeruginosa and Staphylococcus aureus are increasingly recognized as important risk factors for CLAD. Colonization by the fungus Aspergillus may also augment the risk of CLAD. Fostering this transition from healthy lung to CLAD in each of these infectious episodes is the persistence of an inflammatory lung allograft environment. PMID:27221821

  12. Genome-wide host responses against infectious laryngotracheitis virus vaccine infection in chicken embryo lung cells

    PubMed Central

    2012-01-01

    Background Infectious laryngotracheitis virus (ILTV; gallid herpesvirus 1) infection causes high mortality and huge economic losses in the poultry industry. To protect chickens against ILTV infection, chicken-embryo origin (CEO) and tissue-culture origin (TCO) vaccines have been used. However, the transmission of vaccine ILTV from vaccinated- to unvaccinated chickens can cause severe respiratory disease. Previously, host cell responses against virulent ILTV infections were determined by microarray analysis. In this study, a microarray analysis was performed to understand host-vaccine ILTV interactions at the host gene transcription level. Results The 44 K chicken oligo microarrays were used, and the results were compared to those found in virulent ILTV infection. Total RNAs extracted from vaccine ILTV infected chicken embryo lung cells at 1, 2, 3 and 4 days post infection (dpi), compared to 0 dpi, were subjected to microarray assay using the two color hybridization method. Data analysis using JMP Genomics 5.0 and the Ingenuity Pathway Analysis (IPA) program showed that 213 differentially expressed genes could be grouped into a number of functional categories including tissue development, cellular growth and proliferation, cellular movement, and inflammatory responses. Moreover, 10 possible gene networks were created by the IPA program to show intermolecular connections. Interestingly, of 213 differentially expressed genes, BMP2, C8orf79, F10, and NPY were expressed distinctly in vaccine ILTV infection when compared to virulent ILTV infection. Conclusions Comprehensive knowledge of gene expression and biological functionalities of host factors during vaccine ILTV infection can provide insight into host cellular defense mechanisms compared to those of virulent ILTV. PMID:22530940

  13. Ten-Year Experience of Cutaneous and/or Subcutaneous Infections Due to Coelomycetes in France.

    PubMed

    Guégan, Sarah; Garcia-Hermoso, Dea; Sitbon, Karine; Ahmed, Sarah; Moguelet, Philippe; Dromer, Françoise; Lortholary, Olivier

    2016-04-01

    Background.  Coelomycetes are rarely but increasingly reported in association with human infections involving mostly skin and subcutaneous tissues, both in immunocompetent and immunocompromised patients. Coelomycetes constitute a heterogeneous group of filamentous fungi with distinct morphological characteristics in culture, namely an ability to produce asexual spores within fruit bodies. Methods.  We included all cases of proven primary cutaneous and/or subcutaneous infections due to coelomycetes received for identification at the French National Reference Center for Invasive Mycoses and Antifungals between 2005 and 2014. Eumycetoma, chromoblastomycosis, and disseminated infections were excluded. Results.  Eighteen cases were analyzed. The median age was 60.5 years. In all cases, patients originated from tropical or subtropical areas. An underlying immunodepression was present in 89% of cases. Cutaneous and/or subcutaneous lesions, mainly nodules, abscesses, or infiltrated plaques, were observed in distal body areas. Isolates of different genera of coelomycetes were identified: Medicopsis (6), Paraconiothyrium (3), Gloniopsis (3), Diaporthe (3), Peyronellaea (2), Lasiodiplodia (1). Lesion treatment consisted of complete (10) or partial (2) surgical excision and/or the use of systemic antifungal therapy, namely voriconazole (5) and posaconazole (4). Literature review yielded 48 additional cases of cutaneous and/or subcutaneous infections due to coelomycetes. Conclusions.  Infectious diseases physicians should suspect coelomycetes when observing cutaneous and/or subcutaneous infections in immunocompromised hosts from tropical areas; a sequence-based approach is crucial for strains identification but must be supported by consistent phenotypic features; surgical treatment should be favored for solitary, well limited lesions; new triazoles may be used in case of extensive lesions, especially in immunocompromised patients. PMID:27419178

  14. Ten-Year Experience of Cutaneous and/or Subcutaneous Infections Due to Coelomycetes in France

    PubMed Central

    Guégan, Sarah; Garcia-Hermoso, Dea; Sitbon, Karine; Ahmed, Sarah; Moguelet, Philippe; Dromer, Françoise; Lortholary, Olivier

    2016-01-01

    Background. Coelomycetes are rarely but increasingly reported in association with human infections involving mostly skin and subcutaneous tissues, both in immunocompetent and immunocompromised patients. Coelomycetes constitute a heterogeneous group of filamentous fungi with distinct morphological characteristics in culture, namely an ability to produce asexual spores within fruit bodies. Methods. We included all cases of proven primary cutaneous and/or subcutaneous infections due to coelomycetes received for identification at the French National Reference Center for Invasive Mycoses and Antifungals between 2005 and 2014. Eumycetoma, chromoblastomycosis, and disseminated infections were excluded. Results. Eighteen cases were analyzed. The median age was 60.5 years. In all cases, patients originated from tropical or subtropical areas. An underlying immunodepression was present in 89% of cases. Cutaneous and/or subcutaneous lesions, mainly nodules, abscesses, or infiltrated plaques, were observed in distal body areas. Isolates of different genera of coelomycetes were identified: Medicopsis (6), Paraconiothyrium (3), Gloniopsis (3), Diaporthe (3), Peyronellaea (2), Lasiodiplodia (1). Lesion treatment consisted of complete (10) or partial (2) surgical excision and/or the use of systemic antifungal therapy, namely voriconazole (5) and posaconazole (4). Literature review yielded 48 additional cases of cutaneous and/or subcutaneous infections due to coelomycetes. Conclusions. Infectious diseases physicians should suspect coelomycetes when observing cutaneous and/or subcutaneous infections in immunocompromised hosts from tropical areas; a sequence-based approach is crucial for strains identification but must be supported by consistent phenotypic features; surgical treatment should be favored for solitary, well limited lesions; new triazoles may be used in case of extensive lesions, especially in immunocompromised patients. PMID:27419178

  15. Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

    PubMed Central

    Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

    2015-01-01

    Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

  16. Microbial growth inhibition by alternating electric fields in mice with Pseudomonas aeruginosa lung infection.

    PubMed

    Giladi, Moshe; Porat, Yaara; Blatt, Alexandra; Shmueli, Esther; Wasserman, Yoram; Kirson, Eilon D; Palti, Yoram

    2010-08-01

    High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2 degrees C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality. PMID:20547811

  17. Evaluation of brachytherapy lung implant dose distributions from photon-emitting sources due to tissue heterogeneities

    SciTech Connect

    Yang Yun; Rivard, Mark J.

    2011-11-15

    Purpose: Photon-emitting brachytherapy sources are used for permanent implantation to treat lung cancer. However, the current brachytherapy dose calculation formalism assumes a homogeneous water medium without considering the influence of radiation scatter or tissue heterogeneities. The purpose of this study was to determine the dosimetric effects of tissue heterogeneities for permanent lung brachytherapy. Methods: The MCNP5 v1.40 radiation transport code was used for Monte Carlo (MC) simulations. Point sources with energies of 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV were simulated to cover the range of pertinent brachytherapy energies and to glean dosimetric trends independent of specific radionuclide emissions. Source positions from postimplant CT scans of five patient implants were used for source coordinates, with dose normalized to 200 Gy at the center of each implant. With the presence of fibrosis (around the implant), cortical bone, lung, and healthy tissues, dose distributions and {sub PTV}DVH were calculated using the MCNP *FMESH4 tally and the NIST mass-energy absorption coefficients. This process was repeated upon replacing all tissues with water. For all photon energies, 10{sup 9} histories were simulated to achieve statistical errors (k = 1) typically of 1%. Results: The mean PTV doses calculated using tissue heterogeneities for all five patients changed (compared to dose to water) by only a few percent over the examined photon energy range, as did PTV dose at the implant center. The {sub PTV}V{sub 100} values were 81.2%, 90.0% (as normalized), 94.3%, 93.9%, 92.7%, and 92.2% for 0.02, 0.03, 0.05, 0.1, 0.2, and 0.4 MeV source photons, respectively. Relative to water, the maximum bone doses were higher by factors of 3.7, 5.1, 5.2, 2.4, 1.2, and 1.0 The maximum lung doses were about 0.98, 0.94, 0.91, 0.94, 0.97, and 0.99. Relative to water, the maximum healthy tissue doses at the mediastinal position were higher by factors of 9.8, 2.2, 1.3, 1.1, 1.1, and

  18. Integrating Murine Gene Expression Studies to Understand Obstructive Lung Disease Due to Chronic Inhaled Endotoxin

    PubMed Central

    Lai, Peggy S.; Hofmann, Oliver; Baron, Rebecca M.; Cernadas, Manuela; Meng, Quanxin Ryan; Bresler, Herbert S.; Brass, David M.; Yang, Ivana V.; Schwartz, David A.; Christiani, David C.; Hide, Winston

    2013-01-01

    Rationale Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD). These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. Methods We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. Results A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. Conclusions Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene expression were observed

  19. Ochroconis gallopavum infection in a lung transplant recipient: report of a case.

    PubMed

    Brokalaki, E I; Sommerwerck, U; von Heinegg, E H; Hillen, U

    2012-11-01

    Disseminated phaeohyphomycoses are rare infections caused by dematiaceous fungi. Ochroconis gallopavum is a neurotropic dematiaceous mold responsible for life-threatening respiratory and central nervous system infections in domestic poultry and in immunologically compromised humans. The world literature describes only 13 previous O gallopavum infections in solid organ transplant recipients. We report herein an O gallopavum phaeohyphomycosis with involvement of skin in a transplant recipient. A 69-year-old white man with a history of bilateral lung transplantation 6 years ago presented with acute onset of severe respiratory distress. Chest X-ray showed no evidence of pneumonia. Lung function showed bronchiolitis obliterans syndrome. Excision biopsy was performed because of a suspected pigmented basal cell carcinoma. Histopathology revealed dermal granulomatous dermatitis, focally suppurative, dominated by epitheloid cells with brownish round fungi. Further microbiological work-up of the biopsy specimen subsequently revealed O gallopavum as the causative organism. No brain involvement was observed. Antimycotic therapy with voriconazole 200 mg twice a day was immediately initiated and the patient was treated for 3 months. Additional intravenous therapy with tobramycin and imipenem was started upon detection of Enterobacter clocae and Enterococci in the sputum. The patient recovered during the next few weeks and was discharged on day 26. PMID:23146522

  20. Variation in biogenic volatile organic compound emission pattern of Fagus sylvatica L. due to aphid infection

    NASA Astrophysics Data System (ADS)

    Joó, É.; Van Langenhove, H.; Šimpraga, M.; Steppe, K.; Amelynck, C.; Schoon, N.; Müller, J.-F.; Dewulf, J.

    2010-01-01

    Volatile organic compounds (VOCs) have been the focus of interest to understand atmospheric processes and their consequences in formation of ozone or aerosol particles; therefore, VOCs contribute to climate change. In this study, biogenic VOCs (BVOCs) emitted from Fagus sylvatica L. trees were measured in a dynamic enclosure system. In total 18 compounds were identified: 11 monoterpenes (MT), an oxygenated MT, a homoterpene (C 14H 18), 3 sesquiterpenes (SQT), isoprene and methyl salicylate. The frequency distribution of the compounds was tested to determine a relation with the presence of the aphid Phyllaphis fagi L. It was found that linalool, (E)-β-ocimene, α-farnesene and a homoterpene identified as (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT), were present in significantly more samples when infection was present on the trees. The observed emission spectrum from F. sylvatica L. shifted from MT to linalool, α-farnesene, (E)-β-ocimene and DMNT due to the aphid infection. Sabinene was quantitatively the most prevalent compound in both, non-infected and infected samples. In the presence of aphids α-farnesene and linalool became the second and third most important BVOC emitted. According to our investigation, the emission fingerprint is expected to be more complex than commonly presumed.

  1. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma

    PubMed Central

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  2. Diffuse cystic lung disease due to pulmonary metastasis of colorectal carcinoma.

    PubMed

    Fielli, Mariano; Avila, Fabio; Saino, Agustina; Seimah, Deborah; Fernández Casares, Marcelo

    2016-01-01

    The diffuse cystic lung diseases (DCLDs) are a pathophysiologically heterogeneous processes characterized by the presence of multiple thin-walled, air-filled spaces within the pulmonary parenchyma. The most common causes of DCLD are lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH). DCLD develops rarely as a result of malignancy, typically secondary to metastases from peripheral sarcomas and mesenchymal tumors. DCLD have also been reported in a variety of other metastatic disease such as adenocarcinoma. Our case describes a patient with DCLD as a result of metastatic colorectal adenocarcinoma. PMID:27222791

  3. Increased lung epithelial permeability in HIV-infected patients with isolated cytotoxic T-lymphocytic alveolitis

    SciTech Connect

    Meignan, M.; Guillon, J.M.; Denis, M.; Joly, P.; Rosso, J.; Carette, M.F.; Baud, L.; Parquin, F.; Plata, F.; Debre, P. )

    1990-05-01

    HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection or tumor. In some of them a fraction of alveolar lymphocytes are HIV-specific cytotoxic T-lymphocytes (CTL) bearing the CD8 and D44 cell surface markers and capable of killing HIV-infected alveolar macrophages. In order to evaluate the in vivo effect of these CTL on lung function, we measured the pulmonary clearance of aerosolized 99mTc-diethylene triamine penta-acetate (DTPA-CI) on 24 occasions in 22 patients with lymphocytic alveolitis. DTPA-CI has been selected as a highly sensitive test to detect injury of the lung epithelium. In 13 of the patients, we found a high DTPA-CI of 4.56 +/- 2.54%.min-1 (mean +/- SD), suggesting an increase of the epithelial permeability. The lymphocytic alveolitis was then characterized by a high cellularity, a high proportion of lymphocytes (59 +/- 18%), mainly composed of CD8+D44+ T-lymphocytes (149 +/- 109 cells/mm3), which spontaneously exhibited a cytolytic activity against the autologous alveolar macrophages in a standard 51Cr release assay. In the remaining 11 patients, DTPA-CI was normal (less than 1.78%.min-1), lymphocytic alveolitis being characterized by a low number or an absence of CD8+D44+ alveolar lymphocytes (9 +/- 13 cells/mm3) with no significant cytolytic activity. In the whole group, a significant correlation (r = 0.74, p = 0.0004) was found between the DTPA-CI and the number of CD8+D44+ lymphocytes and their cytotoxic activity against alveolar macrophages. Altogether, these results suggest that an injury of the lung epithelium could result from a HIV-specific CTL-induced immunologic conflict.

  4. Regulation of proinflammatory cytokines in human lung epithelial cells infected with Mycoplasma pneumoniae.

    PubMed

    Yang, Jun; Hooper, W Craig; Phillips, Donald J; Talkington, Deborah F

    2002-07-01

    Mycoplasma pneumoniae is a small bacterium without a cell wall that causes tracheobronchitis and atypical pneumonia in humans. It has also been associated with chronic conditions, such as arthritis, and extrapulmonary complications, such as encephalitis. Although the interaction of mycoplasmas with respiratory epithelial cells is a critical early phase of pathogenesis, little is known about the cascade of events initiated by infection of respiratory epithelial cells by mycoplasmas. Previous studies have shown that M. pneumoniae can induce proinflammatory cytokines in several different study systems including cultured murine and human monocytes. In this study, we demonstrate that M. pneumoniae infection also induces proinflammatory cytokine expression in A549 human lung carcinoma cells. Infection of A549 cells resulted in increased levels of interleukin-8 (IL-8) and tumor necrosis factor alpha mRNA, and both proteins were secreted into culture medium. IL-1 beta mRNA also increased after infection and IL-1 beta protein was synthesized, but it remained intracellular. In contrast, levels of IL-6 and gamma interferon mRNA and protein remained unchanged or undetectable. Using protease digestion and antibody blocking methods, we found that M. pneumoniae cytoadherence is important for the induction of cytokines. On the other hand, while M. pneumoniae protein synthesis and DNA synthesis do not appear to be prerequisites for the induction of cytokine gene expression, A549 cellular de novo protein synthesis is responsible for the increased cytokine protein levels. These results suggest a novel role for lung epithelial cells in the pathogenesis of M. pneumoniae infection and provide a better understanding of M. pneumoniae pathology at the cellular level. PMID:12065506

  5. Affecting Pseudomonas aeruginosa Phenotypic Plasticity by Quorum Sensing Dysregulation Hampers Pathogenicity in Murine Chronic Lung Infection

    PubMed Central

    Bondí, Roslen; Messina, Marco; De Fino, Ida; Bragonzi, Alessandra; Rampioni, Giordano; Leoni, Livia

    2014-01-01

    In Pseudomonas aeruginosa quorum sensing (QS) activates the production of virulence factors, playing a critical role in pathogenesis. Multiple negative regulators modulate the timing and the extent of the QS response either in the pre-quorum or post-quorum phases of growth. This regulation likely increases P. aeruginosa phenotypic plasticity and population fitness, facilitating colonization of challenging environments such as higher organisms. Accordingly, in addition to the factors required for QS signals synthesis and response, also QS regulators have been proposed as targets for anti-virulence therapies. However, while it is known that P. aeruginosa mutants impaired in QS are attenuated in their pathogenic potential, the effect of mutations causing a dysregulated timing and/or magnitude of the QS response has been poorly investigated so far in animal models of infection. In order to investigate the impact of QS dysregulation on P. aeruginosa pathogenesis in a murine model of lung infection, the QteE and RsaL proteins have been selected as representatives of negative regulators controlling P. aeruginosa QS in the pre- and post-quorum periods, respectively. Results showed that the qteE mutation does not affect P. aeruginosa lethality and ability to establish chronic infection in mice, despite causing a premature QS response and enhanced virulence factors production in test tube cultures compared to the wild type. Conversely, the post-quorum dysregulation caused by the rsaL mutation hampers the establishment of P. aeruginosa chronic lung infection in mice without affecting the mortality rate. On the whole, this study contributes to a better understanding of the impact of QS regulation on P. aeruginosa phenotypic plasticity during the infection process. Possible fallouts of these findings in the anti-virulence therapy field are also discussed. PMID:25420086

  6. Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

    PubMed

    Rasmuson, J; Pourazar, J; Mohamed, N; Lejon, K; Evander, M; Blomberg, A; Ahlm, C

    2016-04-01

    Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments. PMID:26873376

  7. Pharmacodynamics of Ceftazidime and Avibactam in Neutropenic Mice with Thigh or Lung Infection

    PubMed Central

    Melchers, Maria J.; van Mil, Anita C.; Lagarde, Claudia M.; Schuck, Virna J.; Nichols, Wright W.

    2015-01-01

    Avibactam is a new non-β-lactam β-lactamase inhibitor that shows promising restoration of ceftazidime activity against microorganisms producing Ambler class A extended-spectrum β-lactamases (ESBLs) and carbapenemases such as KPCs, class C β-lactamases (AmpC), and some class D enzymes. To determine optimal dosing combinations of ceftazidime-avibactam for treating infections with ceftazidime-resistant Pseudomonas aeruginosa, pharmacodynamic responses were explored in murine neutropenic thigh and lung infection models. Exposure-response relationships for ceftazidime monotherapy were determined first. Subsequently, the efficacy of adding avibactam every 2 h (q2h) or q8h to a fixed q2h dose of ceftazidime was determined in lung infection for two strains. Dosing avibactam q2h was significantly more efficacious, reducing the avibactam daily dose for static effect by factors of 2.7 and 10.1, whereas the mean percentage of the dosing interval that free drug concentrations remain above the threshold concentration of 1 mg/liter (%fT>CT 1 mg/liter) yielding bacteriostasis was similar for both regimens, with mean values of 21.6 (q2h) and 18.5 (q8h). Dose fractionation studies of avibactam in both the thigh and lung models indicated that the effect of avibactam correlated well with %fT>CT 1 mg/liter. This parameter of avibactam was further explored for four P. aeruginosa strains in the lung model and six in the thigh model. Parameter estimates of %fT>CT 1 mg/liter for avibactam ranged from 0 to 21.4% in the lung model and from 14.1 to 62.5% in the thigh model to achieve stasis. In conclusion, addition of avibactam enhanced the effect of ceftazidime, which was more pronounced at frequent dosing and well related with %fT>CT 1 mg/liter. The thigh model appeared more stringent, with higher values, ranging up to 62.5% fT>CT 1 mg/liter, required for a static effect. PMID:26525790

  8. Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection.

    PubMed

    Erickson, John J; Rogers, Meredith C; Tollefson, Sharon J; Boyd, Kelli L; Williams, John V

    2016-07-01

    Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections. PMID:27259857

  9. Acute Compartment Syndrome of the Foot due to Infection After Local Hydrocortisone Injection: A Case Report.

    PubMed

    Patil, Sampat Dumbre; Patil, Vaishali Dumbre; Abane, Sachin; Luthra, Rohit; Ranaware, Abhijit

    2015-01-01

    High-energy trauma associated with calcaneal fracture or Lisfranc fracture dislocation and midfoot crushing injuries are known causes of compartment syndrome in the foot. Suppurative infection in the deep osseofascial compartments can also cause compartment syndrome. We describe the case of a 29-year-old female who had developed a suppurative local infection that resulted in acute compartment syndrome after receiving a local hydrocortisone injection for plantar fasciitis. We diagnosed the compartment syndrome, and fasciotomy was promptly undertaken. After more than 2 years of follow-up, she had a satisfactory functional outcome without substantial morbidity. To our knowledge, no other report in the English-language studies has described compartment syndrome due to abscess formation after a local injection of hydrocortisone. The aim of our report was to highlight this rare, but serious, complication of a routine outpatient clinical procedure. PMID:24838218

  10. [Bile duct obstruction due to non-Hodkin's lymphoma in patients with HIV infection].

    PubMed

    Gómez-Domínguez, E; Rodríguez Serrano, D A; Mendoza, J; Iscar, T; Sarriá, C; García-Buey, L

    2003-12-01

    Acquired immune deficiency syndrome increases the risk of developing non-Hodgkin's B-cell lymphoma (NHL) (relative risk over 100). NHL tend to be high-grade and to affect the central nervous system and digestive tract. Biliary tract compression is usually due to external compression from enlarged lymph nodes, but is not usually the first manifestation.We describe 2 cases of bile duct obstruction secondary to NHL in patients diagnosed with HIV infection. Histological diagnosis of the lymphoma can be difficult but is necessary so that these patients do not undergo highly aggressive surgical treatment instead of chemotherapy, which currently produces the best results. Therefore, we emphasize the importance of including lymphomas in the differential diagnosis of bile duct obstruction in patients with HIV infection. PMID:14670238

  11. The prevention and management of infections due to multidrug resistant organisms in haematology patients.

    PubMed

    Trubiano, Jason A; Worth, Leon J; Thursky, Karin A; Slavin, Monica A

    2015-02-01

    Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens. PMID:24341410

  12. Pseudomonas aeruginosa uses multiple pathways to acquire iron during chronic infection in cystic fibrosis lungs.

    PubMed

    Konings, Anna F; Martin, Lois W; Sharples, Katrina J; Roddam, Louise F; Latham, Roger; Reid, David W; Lamont, Iain L

    2013-08-01

    Pseudomonas aeruginosa chronically infects the lungs of more than 80% of adult patients with cystic fibrosis (CF) and is a major contributor to the progression of disease pathology. P. aeruginosa requires iron for growth and has multiple iron uptake systems that have been studied in bacteria grown in laboratory culture. The purpose of this research was to determine which of these are active during infection in CF. RNA was extracted from 149 sputum samples obtained from 23 CF patients. Reverse transcription-quantitative real-time PCR (RT-qPCR) was used to measure the expression of P. aeruginosa genes encoding transport systems for the siderophores pyoverdine and pyochelin, for heme, and for ferrous ions. Expression of P. aeruginosa genes could be quantified in 89% of the sputum samples. Expression of genes associated with siderophore-mediated iron uptake was detected in most samples but was at low levels in some samples, indicating that other iron uptake mechanisms are active. Expression of genes encoding heme transport systems was also detected in most samples, indicating that heme uptake occurs during infection in CF. feoB expression was detected in all sputum samples, implying an important role for ferrous ion uptake by P. aeruginosa in CF. Our data show that multiple P. aeruginosa iron uptake mechanisms are active in chronic CF infection and that RT-qPCR of RNA extracted from sputum provides a powerful tool for investigating bacterial physiology during infection in CF. PMID:23690396

  13. Skin and Soft Tissue Infections due to Shewanella algae – An Emerging Pathogen

    PubMed Central

    Pillai, Meera; Vinod, Vivek; Dinesh, R. Kavitha

    2015-01-01

    Introduction: Shewanella spp. are emerging human pathogens, the predominant species being Shewanella algae. Shewanella skin and soft tissue infections are more commonly seen in immunocompromised patients with a pre-existing cutaneous ulcer and most often associated with exposure to marine environments. Aim: The study was conducted to investigate the epidemiological and clinical characteristics of Shewanella skin and soft tissue infections (SSTIs) for a period of five years. Materials and Methods: All Gram-negative non-fermenting motile isolates which produced pigmented colonies and positive for oxidase and H2S were further identified with Vitek 2 system. Results: A total of 16 patients with SSTIs due to Shewanella species were identified during the period from 2010 to 2014. Majority of patients were urban, elderly and fisher men. Shewanella algae (n=12, 75%) was the predominant isolate. Skin or mucosal portal of entry was found in all patients and seawater contact was recorded in 56.25% of the patients. 81% of infections were polymicrobial, common concomitant pathogens being gut and marine flora. Peripheral vascular diseases were the predominant risk factors with comorbidities like diabetes, hypertension and hepatobiliary diseases. Third generation cephalosporins, meropenem and gentamicin were the most effective antibiotics while two of the isolates were multidrug resistant. 75% of the infected patients recovered completely and three patients died of complications. Conclusion: Shewanella algae should be considered as an emerging pathogen of SSTIs mainly in patients with chronic ulcers and at times be multidrug resistant. These infections have a good clinical outcome if prompt medical, surgical and supportive treatment is offered. PMID:25859455

  14. Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina

    PubMed Central

    McAdams, Ryan M.; Bierle, Craig J.; Boldenow, Erica; Weed, Samantha; Tsai, Jesse; Beyer, Richard P.; MacDonald, James W.; Bammler, Theo K.; Liggitt, H. Denny; Farin, Federico M.; Vanderhoeven, Jeroen

    2015-01-01

    The mechanisms underlying fetal lung injury remain poorly defined. MicroRNAs (miRNAs) are small noncoding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. Using a nonhuman primate model of choriodecidual infection, we sought to determine if differentially expressed miRNAs were associated with acute fetal lung injury. After inoculating 10 chronically catheterized pregnant monkeys (Macaca nemestrina) with either group B streptococcus (GBS) at 1 × 106 CFU (n = 5) or saline (n = 5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled the changes in expression by microarray analysis. We identified 9 differentially expressed miRNAs in GBS-exposed fetal lungs, but of these, only miR-155-5p was validated by quantitative reverse transcription-PCR (P = 0.02). Significantly elevated miR-155-5p expression was also observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]). Overexpression of miR-155-5p in FeAE cells in turn increased the production of IL-6 and CXCL10/gamma interferon-induced protein 10, which are implicated in leukocyte recruitment but also in protection from lung injury. Interestingly, while miR-155-5p decreased fibroblast growth factor 9 (FGF9) expression in a luciferase reporter assay, FGF9 levels were actually increased in GBS-exposed fetal lungs in vivo. FGF9 overexpression is associated with abnormal lung development. Thus, upregulation of miR-155-5p may serve as a compensatory mechanism to lessen the increase in FGF9 and prevent aberrant lung development. Understanding the complicated networks regulating lung development in the setting of infection is a key step in identifying how to prevent fetal lung injury leading to bronchopulmonary dysplasia. PMID:26195546

  15. Lung and skeleton malignant tumor induction due to high let emitters

    SciTech Connect

    Buldakov, L.A.; Lyubchansky, E.R.; Kalmikova, Z.I.; Buhtoyarova, Z.M.

    1992-06-01

    Experimental studies show that malignant tumor induction is of primary importance in regard to the biological action of transuranium elements on the animal body. Clarification of quantitative relationship between these parameters for low-level radiation is aproblem to be solved by health physics. This report aims at analysis of the dose-response relationship following rat exposure to PU-239, Am-241, and NP-237 over a wide range of doses, and also at comparison between risk fact obtained experimentally and tose recommended by the ICRP. The biological effect of transuranium elements was investigated regarding malignant tumor incidence in rat bone for all the pathways of intake covered and in the lung for intakes of radionuclides into the respiratory system.

  16. Alveolar echinococcosis of liver presenting with neurological symptoms due to brain metastases with simultaneous lung metastasis: a case report.

    PubMed

    Aydinli, Bülent; Aydin, Unal; Yazici, Pinar; Oztürk, Gürkan; Onbaş, Omer; Polat, K Yalçin

    2008-01-01

    Alveolar echinococcosis (AE) is a chronic and serious, even lethal, parasitic infection caused by the helminth Echinococcus multilocularis (EM). AE is an endemic disease in Turkey and it is particularly common in people living in the eastern Anatolia Region. In addition to various clinical presentations, symptoms which lead to diagnosis, however, are usually associated with the metastatic lesions. We herein reported a 62-year-old man who had liver alveolar hydatid disease with simultaneous lung and brain metastasis. We think there was only one therapeutic option, namely medical treatment with albendazol, which is the usual treatment for patients living in eastern Anatolia and who are admitted late resulting in a subsequent inoperable situation. Thus, radiological screening studies for the public in this region may increase the possibility of surgical treatment for alveolar hydatid disease. PMID:19156614

  17. Invasive Microascus trigonosporus Species Complex Pulmonary Infection in a Lung Transplant Recipient

    PubMed Central

    Schoeppler, Kelly E.; Zamora, Martin R.; Northcutt, Noelle M.; Barber, Gerard R.; O'Malley-Schroeder, Gayle; Lyu, Dennis M.

    2015-01-01

    Because of the high incidence of morbidity and mortality associated with invasive fungal infections, antifungal prophylaxis is often used in solid organ transplant recipients. However, this prophylaxis is not universally effective and may contribute to the selection of emerging, resistant pathogens. Here we present a rare case of invasive infection caused by Microascus trigonosporus species complex in a human, which developed during voriconazole prophylaxis in a lung transplant recipient. Nebulized liposomal amphotericin B was used in addition to systemic therapy in order to optimize antifungal drug exposure; this regimen appeared to reduce the patient's fungal burden. Despite this apparent improvement, the patient's pulmonary status progressively declined in the setting of multiple comorbidities, ultimately leading to respiratory failure and death. PMID:26075134

  18. Invasive Microascus trigonosporus Species Complex Pulmonary Infection in a Lung Transplant Recipient.

    PubMed

    Schoeppler, Kelly E; Zamora, Martin R; Northcutt, Noelle M; Barber, Gerard R; O'Malley-Schroeder, Gayle; Lyu, Dennis M

    2015-01-01

    Because of the high incidence of morbidity and mortality associated with invasive fungal infections, antifungal prophylaxis is often used in solid organ transplant recipients. However, this prophylaxis is not universally effective and may contribute to the selection of emerging, resistant pathogens. Here we present a rare case of invasive infection caused by Microascus trigonosporus species complex in a human, which developed during voriconazole prophylaxis in a lung transplant recipient. Nebulized liposomal amphotericin B was used in addition to systemic therapy in order to optimize antifungal drug exposure; this regimen appeared to reduce the patient's fungal burden. Despite this apparent improvement, the patient's pulmonary status progressively declined in the setting of multiple comorbidities, ultimately leading to respiratory failure and death. PMID:26075134

  19. State of the art: why do the lungs of patients with cystic fibrosis become infected and why can't they clear the infection?

    PubMed

    Chmiel, James F; Davis, Pamela B

    2003-01-01

    Cystic Fibrosis (CF) lung disease, which is characterized by airway obstruction, chronic bacterial infection, and an excessive inflammatory response, is responsible for most of the morbidity and mortality. Early in life, CF patients become infected with a limited spectrum of bacteria, especially P. aeruginosa. New data now indicate that decreased depth of periciliary fluid and abnormal hydration of mucus, which impede mucociliary clearance, contribute to initial infection. Diminished production of the antibacterial molecule nitric oxide, increased bacterial binding sites (e.g., asialo GM-1) on CF airway epithelial cells, and adaptations made by the bacteria to the airway microenvironment, including the production of virulence factors and the ability to organize into a biofilm, contribute to susceptibility to initial bacterial infection. Once the patient is infected, an overzealous inflammatory response in the CF lung likely contributes to the host's inability to eradicate infection. In response to increased IL-8 and leukotriene B4 production, neutrophils infiltrate the lung where they release mediators, such as elastase, that further inhibit host defenses, cripple opsonophagocytosis, impair mucociliary clearance, and damage airway wall architecture. The combination of these events favors the persistence of bacteria in the airway. Until a cure is discovered, further investigations into therapies that relieve obstruction, control infection, and attenuate inflammation offer the best hope of limiting damage to host tissues and prolonging survival. PMID:14511398

  20. Papular dermatitis due to Leishmania infantum infection in seventeen dogs: diagnostic features, extent of the infection and treatment outcome

    PubMed Central

    2014-01-01

    Background This study describes immunological responses, diagnostic features, follow up and treatment outcomes from seventeen dogs with papular dermatitis due to Leishmania infection diagnosed by cytology or real time-PCR. Methods Specific Leishmania humoral and cellular immune responses were evaluated by means of an immunofluorescence antibody test in all cases and a delayed-type hypersensitivity (DTH) reaction to leishmanin in eight cases. The extent of infection was studied in several tissues including blood, lymph node, conjunctival and oral swabs, by means of PCR, at the time of diagnosis and during follow-up. Culture was performed on nine dogs from cutaneous lesions and lymph node aspirates and molecular typing was carried out on isolates based on ITS-1, ITS-2 and Haspb gene sequencing analysis. Results Cytological and molecular results from fine needle aspirates of papules were diagnostic in 8 out of 13 (61.5%) cases and in 14 out of 15 dogs (93.3%), respectively. In all dogs, specific anti-Leishmania antibody levels were low or absent. Blood and lymph node PCRs and lymph node culture were negative in all dogs. Three out of the nine dogs (33%) were positive by culture from cutaneous lesions. The three isolates were identified as ITS type A, however, polymorphism was observed in the Haspb gene (PCR products of 626 bp, 962 bp and 371 bp). DTH response was positive in all tested dogs at the time of diagnosis. The majority of dogs were successfully treated with only N-methylglucamine antimoniate, after which cutaneous lesions disappeared or were reduced to depigmented, flattened scars. All dogs remained seronegative and the majority of dogs were negative by PCR in several tissues during follow-up. Conclusions This study points out that papular dermatitis due to L. infantum is probably an underestimated benign cutaneous problem, associated with a parasite specific cell mediated immunity and a poor humoral immune response. Papular dermatitis is seen in young dogs

  1. Fas/FasL pathway participates in regulation of antiviral and inflammatory response during mousepox infection of lungs.

    PubMed

    Bień, Karolina; Sokołowska, Justyna; Bąska, Piotr; Nowak, Zuzanna; Stankiewicz, Wanda; Krzyzowska, Malgorzata

    2015-01-01

    Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response. PMID:25873756

  2. Fas/FasL Pathway Participates in Regulation of Antiviral and Inflammatory Response during Mousepox Infection of Lungs

    PubMed Central

    Bień, Karolina; Sokołowska, Justyna; Bąska, Piotr; Nowak, Zuzanna; Stankiewicz, Wanda; Krzyzowska, Malgorzata

    2015-01-01

    Fas receptor-Fas ligand (FasL) signalling is involved in apoptosis of immune cells as well as of the virus infected target cells but increasing evidence accumulates on Fas as a mediator of apoptosis-independent processes such as induction of activating and proinflammatory signals. In this study, we examined the role of Fas/FasL pathway in inflammatory and antiviral response in lungs using a mousepox model applied to C57BL6/J, B6. MRL-Faslpr/J, and B6Smn.C3-Faslgld/J mice. Ectromelia virus (ECTV) infection of Fas- and FasL-deficient mice led to increased virus titers in lungs and decreased migration of IFN-γ expressing NK cells, CD4+ T cells, CD8+ T cells, and decreased IL-15 expression. The lungs of ECTV-infected Fas- and FasL-deficient mice showed significant inflammation during later phases of infection accompanied by decreased expression of anti-inflammatory IL-10 and TGF-β1 cytokines and disturbances in CXCL1 and CXCL9 expression. Experiments in vitro demonstrated that ECTV-infected cultures of epithelial cells, but not macrophages, upregulate Fas and FasL and are susceptible to Fas-induced apoptosis. Our study demonstrates that Fas/FasL pathway during ECTV infection of the lungs plays an important role in controlling local inflammatory response and mounting of antiviral response. PMID:25873756

  3. Biological Activities of Uric Acid in Infection Due to Enteropathogenic and Shiga-Toxigenic Escherichia coli.

    PubMed

    Crane, John K; Broome, Jacqueline E; Lis, Agnieszka

    2016-04-01

    In previous work, we identified xanthine oxidase (XO) as an important enzyme in the interaction between the host and enteropathogenic Escherichia coli(EPEC) and Shiga-toxigenic E. coli(STEC). Many of the biological effects of XO were due to the hydrogen peroxide produced by the enzyme. We wondered, however, if uric acid generated by XO also had biological effects in the gastrointestinal tract. Uric acid triggered inflammatory responses in the gut, including increased submucosal edema and release of extracellular DNA from host cells. While uric acid alone was unable to trigger a chloride secretory response in intestinal monolayers, it did potentiate the secretory response to cyclic AMP agonists. Uric acid crystals were formed in vivo in the lumen of the gut in response to EPEC and STEC infections. While trying to visualize uric acid crystals formed during EPEC and STEC infections, we noticed that uric acid crystals became enmeshed in the neutrophilic extracellular traps (NETs) produced from host cells in response to bacteria in cultured cell systems and in the intestine in vivo Uric acid levels in the gut lumen increased in response to exogenous DNA, and these increases were enhanced by the actions of DNase I. Interestingly, addition of DNase I reduced the numbers of EPEC bacteria recovered after a 20-h infection and protected against EPEC-induced histologic damage. PMID:26787720

  4. Therapy of Infections due to Carbapenem-Resistant Gram-Negative Pathogens

    PubMed Central

    Lee, Chang-Seop

    2014-01-01

    The prevalence of carbapenem-resistant gram-negative bacterial pathogens (CRGNs) has increased dramatically during the last 10 years, but the optimal treatment for CRGN infections is not well established due to the relative scarcity of robust clinical data. The polymyxins remain the most consistently active agents against CRGNs in vitro. Tigecycline, based on its in vitro antibacterial spectrum, could also be considered as a therapeutic option in the treatment of infections caused by certain CRGNs. Other agents, including aminoglycosides, rifampin, trimethoprim-sulfamethoxazole, fosfomycin and fluoroquinolones, could be considered as monotherapy or combination therapy against CRGNs in appropriate contexts, as combination therapy with two or more in vitro active drugs appears to be more effective than monotherapy based on some clinical data. Several promising new agents are in late-stage clinical development, including ceftolozane-tazobactam, ceftazidime-avibactam and plazomicin. Given the shortage of adequate treatment options, containment of CRGNs should be pursued through implementation of adequate infection prevention procedures and antimicrobial stewardship to reduce the disease burden and prevent future outbreaks of CRGNs. PMID:25298904

  5. Outcomes of Lung Transplantation in Recipients With Hepatitis C Virus Infection.

    PubMed

    Doucette, K E; Halloran, K; Kapasi, A; Lien, D; Weinkauf, J G

    2016-08-01

    Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5-year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx. PMID:26998739

  6. Diagnosis and prevalence of ovine pulmonary adenocarcinoma in lung tissues of naturally infected farm sheep

    PubMed Central

    Sonawane, Ganesh G.; Tripathi, Bhupendra Nath; Kumar, Rajiv; Kumar, Jyoti

    2016-01-01

    Aim: This study was aimed to detect ovine pulmonary adenocarcinoma (OPA) in sheep flocks affected with pulmonary disorders at organized farm. Materials and Methods: A total of 75 sheep died naturally were thoroughly examined for the lesions of OPA during necropsy. Tissue sections from affected portion of the lungs from each animal were collected aseptically and divided into two parts; one each for polymerase chain reaction (PCR) and another for histopathology. Results: On PCR examination of lung tissues, six sheep (8%) were found to be positive for JSRV. Two of them were 3-6 months of age and did not show clinical signs/gross lesions of OPA. Four adult sheep positive on PCR revealed characteristic lesions of OPA on gross and histopathological examination. Conclusion: In the absence of known specific antibody response to the infection with JSRV, there is no diagnostic serological test available. The PCR assay employed in this study on lung tissues, using primers based on the U3 region of the viral long terminal repeat for JSRV would be helpful in the screening of preclinical and clinical cases of OPA in sheep. PMID:27182131

  7. Therapeutic options for acute cough due to upper respiratory infections in children.

    PubMed

    Paul, Ian M

    2012-02-01

    Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families. Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives. PMID:21892785

  8. Natural killer cells regulate Th1/Treg and Th17/Treg balance in chlamydial lung infection.

    PubMed

    Li, Jing; Dong, Xiaojing; Zhao, Lei; Wang, Xiao; Wang, Yan; Yang, Xi; Wang, Hong; Zhao, Weiming

    2016-07-01

    Natural killer (NK) cell is an important component in innate immunity, playing a critical role in bridging innate and adaptive immunity by modulating the function of other immune cells including T cells. In this study, we focused on the role of NK cells in regulating Th1/Treg and Th17/Treg balance during chlamydial lung infection. We found that NK cell-depleted mice showed decreased Th1 and Th17 cells, which was correlated with reduced interferon-γ, interleukin (IL)-12, IL-17 and IL-22 production as well as T-bet and receptor-related orphan receptor gamma t expression compared with mice treated with the isotype control antibody. In contrast, NK cell depletion significantly increased Treg in cell number and related transcription factor (Foxp3) expression. The opposite trends of changes of Th1/Th17 and Treg led to significant reduction in the Th1/Treg and Th17/Treg ratios. The data implicate that NK cells play an important role in host defence against chlamydial lung infection, mainly through maintaining Th1/Treg and Th17/Treg balance. PMID:27028780

  9. Lung fluke (Paragonimus africanus) infects Nigerian red-capped mangabeys and causes respiratory disease

    PubMed Central

    Friant, Sagan; Brown, Kelsey; Saari, Mason T.; Segel, Nicholas H.; Slezak, Julia; Goldberg, Tony L.

    2015-01-01

    Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus) in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re-emerging human pathogens, in wildlife reservoirs. PMID:26543803

  10. Degradable polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections

    NASA Astrophysics Data System (ADS)

    Zhang, Fuwu; Smolen, Justin A.; Zhang, Shiyi; Li, Richen; Shah, Parth N.; Cho, Sangho; Wang, Hai; Raymond, Jeffery E.; Cannon, Carolyn L.; Wooley, Karen L.

    2015-01-01

    In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate. Electronic supplementary information (ESI) available: Materials, experimental details, and characterization. See DOI: 10.1039/c4nr07103d