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Sample records for lung infections due

  1. [Two cases of lung infection due to Mycobacterium chelonae subsp. abscessus].

    PubMed

    Kawashima, T; Kioi, S; Arakawa, M

    1994-03-01

    Two cases of lung infection due to Mycobacterium chelonae subsp. abscessus are reported. Case 1, a 50-year-old female, was a secondary infection-type, and case 2, a 53-year-old female, was a primary infection-type. The 16 cases reported, between the ages of 29 and 76 years, there were 6 males and 10 females. The roentgenographic examinations, revealed that the ratio of the primary and secondary infection-type was 3:1. Effective agents for this organism has not been yet confirmed. In the present study, we treated two patients with AMK and IPM/CS, and obtained negative conversion of the sputum culture as well as improvement of roentgenographic features. PMID:8176285

  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.

  4. Diffuse interstitial and multiple cavitary lung lesions due to Talaromyces marneffei infection in a non-HIV patient.

    PubMed

    Li, H R; Xu, N L; Lin, M; Hu, X L; Chen, J H; Chen, Y S; Cai, S X

    2015-11-01

    A 57-year-old man presented with unproductive cough and dyspnea for 6 months in Fujian Province, China. His misuse of a large amount of steroids (accumulated dose equivalent to 3530 mg prednisolone) resulted in Talaromyces marneffei infection. Chest computed tomographic scan revealed diffuse interstitial and multiple cavitary lung lesions. Treatment with amphotericin B combined with itraconazole resulted in total recovery, with marked regression of lung lesions. PMID:26550481

  5. [Lung disorders due to metals].

    PubMed

    Rüegger, M

    1995-03-11

    Though metals represent the largest group of elements they rather rarely cause respiratory diseases. This article will therefore review the most important ones caused by inhaled dusts of metals and some of their inorganic compounds, but leaving aside silicosis and silicatosis as well as iatrogenically induced metal pneumopathies. Among toxic inflammatory diseases metal fume fever, an influenza-like condition caused by zinc oxide, ranks as the commonest. Activities such as oxi-acetylene cutting and welding of zinc covered metal pieces account for about 90% of all cases compensated in Switzerland. Due to the non-recurrent character of this type of work, the typical waning of symptoms while exposure is going on has become seldom. Toxic pneumonia caused by inhaled metal fumes occurs rather seldom. However, serious cases have been reported where soldiers were exposed to zinc chloride from smoke bombs. The existence and extent of chronic airflow limitation due to occupational exposure to metallic dusts have not been widely examined but are to be assumed when there is poor occupational hygiene. Concerning asthma, there are at least four metals and several of their compounds which have been proven to cause variable airway narrowing, namely chromium, nickel, platinum and cobalt (the latter as hardmetal). Platinum complex salts (chloro-compounds) are very potent sensitizers leading to a notable prevalence of asthma among exposed workforces. Nevertheless, there have been no such cases in Switzerland for more than ten years. Hard-metal not only causes asthma but also an alveolitis-like interstitial lung disease progressing to fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

  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. Telomere Attrition Due to Infection

    PubMed Central

    Ilmonen, Petteri; Kotrschal, Alexander; Penn, Dustin J.

    2008-01-01

    Background Telomeres–the terminal caps of chromosomes–become shorter as individuals age, and there is much interest in determining what causes telomere attrition since this process may play a role in biological aging. The leading hypothesis is that telomere attrition is due to inflammation, exposure to infectious agents, and other types of oxidative stress, which damage telomeres and impair their repair mechanisms. Several lines of evidence support this hypothesis, including observational findings that people exposed to infectious diseases have shorter telomeres. Experimental tests are still needed, however, to distinguish whether infectious diseases actually cause telomere attrition or whether telomere attrition increases susceptibility to infection. Experiments are also needed to determine whether telomere erosion reduces longevity. Methodology/Principal Findings We experimentally tested whether repeated exposure to an infectious agent, Salmonella enterica, causes telomere attrition in wild-derived house mice (Mus musculus musculus). We repeatedly infected mice with a genetically diverse cocktail of five different S. enterica strains over seven months, and compared changes in telomere length with sham-infected sibling controls. We measured changes in telomere length of white blood cells (WBC) after five infections using a real-time PCR method. Our results show that repeated Salmonella infections cause telomere attrition in WBCs, and particularly for males, which appeared less disease resistant than females. Interestingly, we also found that individuals having long WBC telomeres at early age were relatively disease resistant during later life. Finally, we found evidence that more rapid telomere attrition increases mortality risk, although this trend was not significant. Conclusions/Significance Our results indicate that infectious diseases can cause telomere attrition, and support the idea that telomere length could provide a molecular biomarker for assessing

  8. Myocardial infection due to Fusobacterium nucleatum.

    PubMed

    Storm, Jeremy C; Ford, Bradley A; Streit, Judy A

    2013-12-01

    Fusobacterium nucleatum is an anaerobic gram-negative bacillus, which inhabits the oropharynx, gastrointestinal tract, and female genital tract. Infections classically affect the head and neck. We report a patient with a myocardial mass due to F. nucleatum, initially thought to be a neoplasm, and discuss anaerobic cardiac infections.

  9. 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.

  10. 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

  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. [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

  13. Foreign body infections due to Staphylococcus epidermidis.

    PubMed

    Uçkay, Ilker; Pittet, Didier; Vaudaux, Pierre; Sax, Hugo; Lew, Daniel; Waldvogel, Francis

    2009-01-01

    Staphylococcal infections are one of the main causes of complications in patients with implanted foreign prosthetic material. Implants are associated with a significant reduction of the threshold at which contaminating Gram-positive bacteria, particularly Staphylococcus epidermidis, become infectious and develop a biofilm with phenotypic resistance to almost all antibiotics. A 1000-fold increase in minimal bactericidal levels against most antibiotics except rifampin has been repeatedly observed. Since only removal of the foreign material reverses these phenomena, the clinical challenge consists in finding approaches to cure the infection without removal of the implanted device. Rifampin combinations with other antibiotics, administration of exceedingly high antibiotic concentrations in situ, and early therapy before biofilm development are efficacious. Although these strategies have dramatically improved the outcome of foreign body infections, an improved understanding of biofilm-grown S. epidermidis is necessary to develop new antibacterial agents. Here, we review the pathogenesis, prevention, and treatment of implant infections due to S. epidermidis and highlight some new compounds with already promising in vitro results.

  14. Lung cancer in HIV-infected patients

    PubMed Central

    Palacios, R; Lebrón, J; Guerrero-León, M; Del Arco, A; Colmenero, J; Márquez, M; Santos, J

    2012-01-01

    Purpose Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast Spain (study period 1992–2012) were reviewed, and all patients with a lung cancer were analysed. Results There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%), and smokers (96.6%; mean pack-years 35.2), with a median age of 48.0 (41.7–52.9) years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7%) patients were Aids cases, and 29 (47.5%) had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42–232), the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85–397), and 66.1%<350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0%) and 23 (38.3%) cases, respectively. There were 49 (80.3%) cases with advanced stages (III and IV) at diagnosis. The distribution of treatments was: only palliative 23 (39.7%), chemotherapy 14 (24.1%), surgery and chemotherapy 8 (13.8%), radiotherapy 7 (12.1%), surgery 4 (6.9%), and other combined treatments 2 (3.4%). Forty-six (76.7%) patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%). Conclusions The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis. Adenocarcinoma

  15. Endobronchial lesion due to pulmonary Fusobacterium nucleatum infection in a child.

    PubMed

    Gedik, Ahmet H; Cakir, Erkan; Soysal, Omer; Umutoğlu, Tarık

    2014-03-01

    Clinically significant infections due to the members of the genus Fusobacterium are rare. The clinical manifestations of pulmonary Fusobacterium nucleatum infections range from simple aspiration pneumonia to severe diseases as necrotizing pneumonia, lung abscess, and empyema. Endobronchial lesions and obstructions are rarely seen in children and are often a misdiagnosed result in delay of definitive treatment. Here, we report a case of endobronchial lesion due to pulmonary F. nucleatum infection in an entirely healthy child before illness. This is the first case reported in the literature of endobronchial lesion due to pulmonary F. nucleatum infection.

  16. 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

  17. 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

  18. Ventriculitis due to infection with Rhizopus arrhizus.

    PubMed

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

    2015-12-01

    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. 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

  20. 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

  1. Pulmonary infection due to Mycobacterium bovis in a black rhinoceros (Diceros bicornis minor) in South Africa.

    PubMed

    Espie, Ian W; Hlokwe, Tiny M; Gey van Pittius, Nicolaas C; Lane, Emily; Tordiffe, Adrian S W; Michel, Anita L; Müller, Annélle; Kotze, Antoinette; van Helden, Paul D

    2009-10-01

    We report a case of tuberculosis due to infection with Mycobacterium bovis in an elderly male black rhinoceros (Diceros bicornis minor) from the Limpopo Province in South Africa. The animal was euthanized due to very poor condition, old age, and dental attrition. Necropsy examination revealed two small nonencapsulated granulomas (approximately 40-mm diameter) in the dorsocaudal lobe of the left lung. Sequencing of isolated crude lung tissue PCR product and boiled lung culture samples confirmed that the causative organism was M. bovis. Genotyping revealed limited similarities with M. bovis strains isolated thus far from South African cattle or wildlife. The source of the infection could not be determined. This case illustrates that M. bovis could impact conservation of free-ranging rare and endangered species. Effective diagnostics are urgently needed for different animal species, such as white or black rhinoceroses, to certify with a reasonable degree of certainty that these animals are free of tuberculosis in natural habitats. PMID:19901395

  2. [Infections due to Mycobacterium marinum: a review].

    PubMed

    Nenoff, P; Klapper, B-M; Mayser, P; Paasch, U; Handrick, W

    2011-04-01

    Mycobacterium marinum belongs to the non-tuberculous or "atypical" mycobacteria. The reservoirs for these ubiquitous and slowly growing bacteria are both fresh water and salt water. In particular, aquaria should be considered as important source of hobby-related infections especially of fingers, hands and forearms. Affected are both immunosuppressed patients and persons with an intact immune system. Distinctive are erythematous plaques and nodules with tendency for hyperkeratosis, crusting, and superficial ulcerations, sometimes as sporotrichoid lymphocutaneous infection. The histology shows non-caseation granulomas containing epithelioid cells and Langhans giant cells. Using the Ziehl Neelsen staining, typical acid-fast rods are not always detectable. The molecular biological detection of mycobacterial DNA using polymerase chain reaction represents the standard method of diagnosis. Cryotherapy is frequently used as first treatment. For the often long-term tuberculostatic therapy, rifampicin, ethambutol, and clarithromycin are the most used agents.

  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. Early airway infection, inflammation, and lung function in cystic fibrosis

    PubMed Central

    Nixon, G; Armstrong, D; Carzino, R; Carlin, J; Olinsky, A; Robertson, C; Grimwood, K

    2002-01-01

    Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV0.5 195 ml and 236 ml respectively). Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients. PMID:12244003

  5. 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

  6. Infected abdominal aortic aneurysm due to Morganella morganii: CT findings.

    PubMed

    Kwon, Oh Young; Lee, Jong Seok; Choi, Han Sung; Hong, Hoon Pyo; Ko, Young Gwan

    2011-02-01

    An infected aortic aneurysm, or mycotic aneurysm, is a rare arterial dilatation due to destruction of the infected vessel wall. Common pathogens resulting in an infected aortic aneurysm are Salmonella and Clostridium species, as well as Staphylococcus aureus; Morganella morganii, on the other hand, is very rare. An infected abdominal aortic aneurysm has tendencies to grow rapidly and to rupture. The mortality rate is high in patients undergoing emergent surgical intervention. We report the case of a 65-year-old man who presented with an infected abdominal aortic aneurysm caused by M. morganii. A high index of suspicion and imaging tests are necessary in order to diagnose an infected aortic aneurysm.

  7. 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

  8. Disseminated Scedosporium/Pseudallescheria Infection after Double-Lung Transplantation in Patients with Cystic Fibrosis▿

    PubMed Central

    Morio, Florent; Horeau-Langlard, Delphine; Gay-Andrieu, Françoise; Talarmin, Jean-Philippe; Haloun, Alain; Treilhaud, Michelle; Despins, Philippe; Jossic, Frédérique; Nourry, Laurence; Danner-Boucher, Isabelle; Pattier, Sabine; Bouchara, Jean-Philippe; Le Pape, Patrice; Miegeville, Michel

    2010-01-01

    We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed. PMID:20220160

  9. Primary pulmonary botryomycosis: a bacterial lung infection mimicking lung cancer.

    PubMed

    Ariza-Prota, M A; Pando-Sandoval, A; García-Clemente, M; Jiménez, H; Álvarez-Álvarez, C; Casan-Clara, P

    2013-07-01

    Primary pulmonary botryomycosis, or bacterial pseudomycosis, is an unusual bacterial infection characterised by the formation of eosinophilic granules that resemble those of Actinomyces species infection. The diagnosis of botryomycosis is based on culture of the granules revealing gram-positive cocci or gram-negative bacilli. The bacterial pathogen most frequently found is Staphylococcus aureus. The pathobiology remains unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis or invasive carcinoma. Definitive treatment requires a combination of both surgical debridement and long-term antimicrobial therapy. We present a case of primary pulmonary botryomycosis in an immunocompetent patient.

  10. Necrotizing lung infection caused by the protozoan Balantidium coli

    PubMed Central

    Sharma, Sat; Harding, Godfrey

    2003-01-01

    Balantidium coli, a ciliated protozoan, is well known to cause intestinal infection in humans. Extraintestinal spread to the peritoneal cavity and genitourinary tract has rarely been reported. There have also been a few cases of lung involvement from this parasite. A case of B coli causing a thick-walled right upper lobe cavity in an organic farmer who had contact with aerosolized pig manure is reported. Bronchoalveolar lavage fluid examined for ova and parasite revealed trophozoites of B coli in large numbers. Treatment with doxycycline hyclate led to marked improvement. Necrotizing lung infection caused by the protozoan B coli should be considered in individuals who report contact with pigs. PMID:18159451

  11. Necrotizing lung infection caused by the protozoan Balantidium coli.

    PubMed

    Sharma, Sat; Harding, Godfrey

    2003-05-01

    Balantidium coli, a ciliated protozoan, is well known to cause intestinal infection in humans. Extraintestinal spread to the peritoneal cavity and genitourinary tract has rarely been reported. There have also been a few cases of lung involvement from this parasite. A case of B coli causing a thick-walled right upper lobe cavity in an organic farmer who had contact with aerosolized pig manure is reported. Bronchoalveolar lavage fluid examined for ova and parasite revealed trophozoites of B coli in large numbers. Treatment with doxycycline hyclate led to marked improvement. Necrotizing lung infection caused by the protozoan B coli should be considered in individuals who report contact with pigs. PMID:18159451

  12. Mycotic encephalitis and nephritis in a dog due to infection with Cladosporium cladosporioides.

    PubMed

    Poutahidis, T; Angelopoulou, K; Karamanavi, E; Polizopoulou, Z S; Doulberis, M; Latsari, M; Kaldrymidou, E

    2009-01-01

    The dematiaceous fungus Cladosporium cladosporioides is a widely distributed saprophyte that is reported to occasionally infect the lung, skin, eye and brain of humans. This report describes a German shepherd dog with granulomatous encephalitis and nephritis due to C. cladosporioides infection. Although the fungal organisms appeared non-pigmented in haematoxylin and eosin stained sections, they were readily identified with histochemical stains. Semi-nested polymerase chain reaction using universal fungal primers amplified fungal DNA from fixed tissue that had identity to that of C. cladosporioides on sequencing.

  13. Bacteriocin-mediated competition in cystic fibrosis lung infections

    PubMed Central

    Ghoul, Melanie; West, Stuart A.; Johansen, Helle Krogh; Molin, Søren; Harrison, Odile B.; Maiden, Martin C. J.; Jelsbak, Lars; Bruce, John B.; Griffin, Ashleigh S.

    2015-01-01

    Bacteriocins are toxins produced by bacteria to kill competitors of the same species. Theory and laboratory experiments suggest that bacteriocin production and immunity play a key role in the competitive dynamics of bacterial strains. The extent to which this is the case in natural populations, especially human pathogens, remains to be tested. We examined the role of bacteriocins in competition using Pseudomonas aeruginosa strains infecting lungs of humans with cystic fibrosis (CF). We assessed the ability of different strains to kill each other using phenotypic assays, and sequenced their genomes to determine what bacteriocins (pyocins) they carry. We found that (i) isolates from later infection stages inhibited earlier infecting strains less, but were more inhibited by pyocins produced by earlier infecting strains and carried fewer pyocin types; (ii) this difference between early and late infections appears to be caused by a difference in pyocin diversity between competing genotypes and not by loss of pyocin genes within a lineage over time; (iii) pyocin inhibition does not explain why certain strains outcompete others within lung infections; (iv) strains frequently carry the pyocin-killing gene, but not the immunity gene, suggesting resistance occurs via other unknown mechanisms. Our results show that, in contrast to patterns observed in experimental studies, pyocin production does not appear to have a major influence on strain competition during CF lung infections. PMID:26311664

  14. 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

  15. 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

  16. Bacteraemia and sinusitis due to Flavimonas oryzihabitans infection.

    PubMed

    Lejbkowicz, Flavio; Belavsky, Larissa; Kudinsky, Raya; Gery, Raphael

    2003-01-01

    Flavimonas oryzihabitans is rarely reported as a pathogen in human infections and is related to opportunistic infection. Previously reported cases of infections caused by this bacterium were nosocomially acquired, including bacteraemia in critically ill patients, catheter-related infection, and peritonitis in patients undergoing continuous ambulatory peritoneal dialysis. Three cases of F. oryzihabitans infection are presented, 1 of which was sinusitis and 2 were nosocomially acquired bacteraemia. To the authors' knowledge, this is the first reported case of sinusitis infection due to F. oryzihabitans induced by prosthetic material. Isolates from the 2 bacteraemic patients were susceptible to tazobactam, ceftazidime, cefepime, aztreonam, gentamicin, amikacin, imipenem, ciprofloxacin and levofloxacin, but resistant to cephazolin, cefuroxime and trimethoprim. The isolate from the sinus was susceptible to gentamicin, amikacin, tetracycline, ciprofloxacin and levofloxacin. After appropriate treatment all the patients recovered and no longer showed signs of the pathogen.

  17. Genomic and functional analysis of the host response to acute simian varicella infection in the lung

    PubMed Central

    Arnold, Nicole; Girke, Thomas; Sureshchandra, Suhas; Nguyen, Christina; Rais, Maham; Messaoudi, Ilhem

    2016-01-01

    Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host. PMID:27677639

  18. Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections.

    PubMed

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang; Høiby, Niels

    2012-07-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

  19. '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

  20. Postoperative infection of laparoscopic surgery wound due to Mycobacterium chelonae.

    PubMed

    Rajini, M; Prasad, S R; Reddy, R R; Bhat, R V; Vimala, K R

    2007-04-01

    We report a case of postoperative wound infection due to Mycobacterium chelonae. A 35-year-old woman presented with multiple erythematous nodules, plaques and discharging sinuses over the abdomen, 45 days after she had undergone laparoscopic ovarian cystectomy. The seropurulent discharge from the wound showed acid-fast bacilli on Ziehl- Neelsen stain and culture yielded Mycobacterium chelonae. The patient responded to clarithromycin and doxycycline. The source of infection was probably contaminated water or disinfectant solution used for sterilization of laparoscopic instruments.

  1. Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report

    PubMed Central

    Faulhaber, Gustavo Adolpho Moreira; Borges, Flavia Kessler; Ascoli, Aline Maria; Seligman, Renato; Furlanetto, Tania Weber

    2011-01-01

    We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency. PMID:22606443

  2. HIV infection in the etiology of lung cancer: confounding, causality, and consequences.

    PubMed

    Kirk, Gregory D; Merlo, Christian A

    2011-06-01

    Persons infected with HIV have an elevated risk of lung cancer, but whether the increase simply reflects a higher smoking prevalence continues to be debated. This review summarizes existing data on the association of HIV infection and lung cancer, with particular attention to study design and adjustment for cigarette smoking. Potential mechanisms by which HIV infection may lead to lung cancer are discussed. Finally, irrespective of causality and mechanisms, lung cancer represents an important and growing problem confronting HIV-infected patients and their providers. Substantial efforts are needed to promote smoking cessation and to control lung cancer among HIV-infected populations.

  3. 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

  4. 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

  5. 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

  6. MUC18 Regulates Lung Rhinovirus Infection and Inflammation

    PubMed Central

    Berman, Reena; Jiang, Di; Wu, Qun; Stevenson, Connor R.; Schaefer, Niccolette R.; Chu, Hong Wei

    2016-01-01

    Background MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection. Methods Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B. Results Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls. Conclusions Our study is the first to demonstrate MUC18’s pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection. PMID:27701461

  7. Unusual clinical presentation of infection due to Flavimonas oryzihabitans.

    PubMed

    Giacometti, A; Cirioni, O; Quarta, M; Schimizzi, A M; Del Prete, M S; Scalise, G

    1998-09-01

    Six cases of Flavimonas oryzihabitans infection are presented, four of which were community-acquired pneumonia and two of which were nosocomially acquired bacteremia. All four cases of pneumonia occurred in immunosuppressed hosts, three of whom were HIV-positive individuals and one of whom was a young man affected by chronic myeloid leukemia. Flavimonas oryzihabitans is recognized with increasing frequency as a cause of opportunistic infection, but the present cases of community-acquired pneumonia due to this organism are believed to be the first four reported in the English literature. The findings emphasize that Flavimonas oryzihabitans should be included in the list of pathogens that cause community-acquired infections in the immunocompromised host.

  8. 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

  9. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera.

    PubMed

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

    2013-06-01

    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.

  10. Corneal Transplant Infection due to Alternaria alternata: A Case Report

    PubMed Central

    Konidaris, Vasileios; Mersinoglou, Andreana; Vyzantiadis, Timoleon-Achilleas; Papadopoulou, Domniki; Boboridis, Kostas G.; Ekonomidis, Panagiotis

    2013-01-01

    Purpose. To report a case of Alternaria alternata keratitis in a patient with a corneal transplant in her right eye due to bullous pseudophakic keratopathy. Methods. A 66-year-old female underwent a full-thickness keratoplasty in her right eye due to bullous pseudophakic keratopathy. Three weeks after keratoplasty, epithelial edema and a stromal opacity with an infiltrate and development of peripheral corneal opacities appeared. The diagnosis of Alternaria alternata keratitis was made. Results. The patient underwent a second keratoplasty, due to the corneal melting as a result of the fungal infection. She was also given combined antifungal treatment locally and systematically. Conclusion. Corneal transplantation alone would not have been sufficient to keep the fungus in the anterior portion of the eye. Combined antifungal treatment, locally and systematically, was important in attempting to prevent the further spread of the fungus to the interior of the eye. To our knowledge, the case presented here is only the second one in the literature concerning a keratomycosis due to Alternaria alternata corneal transplant infection. PMID:23573439

  11. Stochastic Tracking of Infection in a CF Lung

    PubMed Central

    Zarei, Sara; Mirtar, Ali; Rohwer, Forest; Salamon, Peter

    2014-01-01

    Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scan are the two ubiquitous imaging sources that physicians use to diagnose patients with Cystic Fibrosis (CF) or any other Chronic Obstructive Pulmonary Disease (COPD). Unfortunately the cost constraints limit the frequent usage of these medical imaging procedures. In addition, even though both CT scan and MRI provide mesoscopic details of a lung, in order to obtain microscopic information a very high resolution is required. Neither MRI nor CT scans provide micro level information about the location of infection in a binary tree structure the binary tree structure of the human lung. In this paper we present an algorithm that enhances the current imaging results by providing estimated micro level information concerning the location of the infection. The estimate is based on a calculation of the distribution of possible mucus blockages consistent with available information using an offline Metropolis-Hastings algorithm in combination with a real-time interpolation scheme. When supplemented with growth rates for the pockets of mucus, the algorithm can also be used to estimate how lung functionality as manifested in spirometric tests will change in patients with CF or COPD. PMID:25360611

  12. An ALK translocation positive carcinoma of the lung presenting as uremia due to bilateral renal obstruction.

    PubMed

    Rosenberg, Shilo; Katz, Ran; Pode, Dov; Gofrit, N Ofer; Pizov, Galina; Hovav, Nechushtan

    2013-01-01

    We describe an unusual presentation of metastatic lung adenocarcinoma as malignant retroperitoneal fibrosis (MRPF). The diagnostic challenge, due to the small solitary lung mass and absence of a discrete retroperitoneal mass, was overcome by diagnostic laparoscopy. Molecular analysis of tissue acquired was positive for ALK gene rearrangement. Treatment of the patient with crizotinib reversed MRPF. He was weaned off the nephrostomy tubes and is with stable renal function 11 months after diagnosis. PMID:23914266

  13. Attributable risk of lung cancer deaths due to indoor radon exposure.

    PubMed

    Kim, Si-Heon; Hwang, Won Ju; Cho, Jeong-Sook; Kang, Dae Ryong

    2016-01-01

    Exposure to radon gas is the second most common cause of lung cancer after smoking. A large number of studies have reported that exposure to indoor radon, even at low concentrations, is associated with lung cancer in the general population. This paper reviewed studies from several countries to assess the attributable risk (AR) of lung cancer death due to indoor radon exposure and the effect of radon mitigation thereon. Worldwide, 3-20 % of all lung cancer deaths are likely caused by indoor radon exposure. These values tend to be higher in countries reporting high radon concentrations, which can depend on the estimation method. The estimated number of lung cancer deaths due to radon exposure in several countries varied from 150 to 40,477 annually. In general, the percent ARs were higher among never-smokers than among ever-smokers, whereas much more lung cancer deaths attributable to radon occurred among ever-smokers because of the higher rate of lung cancers among smokers. Regardless of smoking status, the proportion of lung cancer deaths induced by radon was slightly higher among females than males. However, after stratifying populations according to smoking status, the percent ARs were similar between genders. If all homes with radon above 100 Bq/m(3) were effectively remediated, studies in Germany and Canada found that 302 and 1704 lung cancer deaths could be prevented each year, respectively. These estimates, however, are subject to varying degrees of uncertainty related to the weakness of the models used and a number of factors influencing indoor radon concentrations.

  14. Attributable risk of lung cancer deaths due to indoor radon exposure.

    PubMed

    Kim, Si-Heon; Hwang, Won Ju; Cho, Jeong-Sook; Kang, Dae Ryong

    2016-01-01

    Exposure to radon gas is the second most common cause of lung cancer after smoking. A large number of studies have reported that exposure to indoor radon, even at low concentrations, is associated with lung cancer in the general population. This paper reviewed studies from several countries to assess the attributable risk (AR) of lung cancer death due to indoor radon exposure and the effect of radon mitigation thereon. Worldwide, 3-20 % of all lung cancer deaths are likely caused by indoor radon exposure. These values tend to be higher in countries reporting high radon concentrations, which can depend on the estimation method. The estimated number of lung cancer deaths due to radon exposure in several countries varied from 150 to 40,477 annually. In general, the percent ARs were higher among never-smokers than among ever-smokers, whereas much more lung cancer deaths attributable to radon occurred among ever-smokers because of the higher rate of lung cancers among smokers. Regardless of smoking status, the proportion of lung cancer deaths induced by radon was slightly higher among females than males. However, after stratifying populations according to smoking status, the percent ARs were similar between genders. If all homes with radon above 100 Bq/m(3) were effectively remediated, studies in Germany and Canada found that 302 and 1704 lung cancer deaths could be prevented each year, respectively. These estimates, however, are subject to varying degrees of uncertainty related to the weakness of the models used and a number of factors influencing indoor radon concentrations. PMID:26925236

  15. 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

  16. 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

  17. Alveolar Macrophages Are a Prominent but Nonessential Target for Murine Cytomegalovirus Infecting the Lungs

    PubMed Central

    Farrell, Helen E.; Lawler, Clara; Oliveira, Martha T.; Davis-Poynter, Nick

    2015-01-01

    ABSTRACT Cytomegaloviruses (CMVs) infect the lungs and cause pathological damage there in immunocompromised hosts. How lung infection starts is unknown. Inhaled murine CMV (MCMV) directly infected alveolar macrophages (AMs) and type 2 alveolar epithelial cells (AEC2s) but not type 1 alveolar epithelial cells (AEC1s). In contrast, herpes simplex virus 1 infected AEC1s and murid herpesvirus 4 (MuHV-4) infected AEC1s via AMs. MCMV-infected AMs prominently expressed viral reporter genes from a human CMV IE1 promoter; but most IE1-positive cells were AEC2s, and CD11c-cre mice, which express cre in AMs, switched the fluorochrome expression of <5% of floxed MCMV in the lungs. In contrast, CD11C-cre mice exhibited fluorochrome switching in >90% of floxed MuHV-4 in the lungs and 50% of floxed MCMV in the blood. AM depletion increased MCMV titers in the lung during the acute phase of infection. Thus, the influence of AMs was more restrictive than permissive. Circulating monocytes entered infected lungs in large numbers and became infected, but not directly; infection occurred mainly via AEC2s. Mice infected with an MCMV mutant lacking its m131/m129 chemokine homolog, which promotes macrophage infection, showed levels of lung infection equivalent to those of wild-type MCMV-infected mice. The level of lung infiltration by Gr-1-positive cells infected with the MCMV m131/m129-null mutant was modestly different from that for wild-type MCMV-infected lungs. These results are consistent with myeloid cells mainly disseminating MCMV from the lungs, whereas AEC2s provide local amplification. IMPORTANCE Cytomegaloviruses (CMVs) chronically and systemically infect most mammals. Human CMV infection is usually asymptomatic but causes lung disease in people with poor immune function. As human infection is hard to analyze, studies with related animal viruses provide important insights. We show that murine CMV has two targets in the lungs: macrophages and surfactant-secreting epithelial cells

  18. Laboratory diagnosis of infections due to blood and tissue parasites.

    PubMed

    Rosenblatt, Jon E

    2009-10-01

    Microscopy remains the cornerstone of the laboratory diagnosis of infections due to blood and tissue parasites. Examination of thick and thin peripheral blood smears stained with Giemsa or other appropriate stains is used for detection and identification of species of Plasmodium, Babesia, Trypanosoma, Brugia, Mansonella, and Wuchereria. Even in the hands of well-trained technologists, diagnosis may be hampered by the sparseness of organisms on the slide and by the subjective nature of differentiating similar-appearing organisms. Microscopy and/or culture of ulcer, bone marrow, tissue aspirate, and biopsy samples are useful for the diagnosis of African trypanosomiasis, onchocerciasis, trichinosis, and leishmaniasis. Serologic assays are available for the diagnosis of a number of these infections, but none of these assays are sensitive or specific enough to be used on their own to establish a diagnosis. In particular, the use of assays for the diagnosis of infection with a particular helminth will often cross-react with antibodies to a different helminth. Very sensitive polymerase chain reaction assays have been developed for a number of these parasites and are available from the Centers for Disease Control and Prevention and from several referral laboratories. PMID:19691431

  19. 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.

  20. 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

  1. Assessment of morbidity due to Schistosoma japonicum infection in China

    PubMed Central

    2014-01-01

    This paper presents a historical assessment of morbidity due to the Schistosoma japonicum infection in China. Due to the socio-economic situation, which did not allow for a control program to be implemented until the early 1950s, morbidity was serious and mortality was high before this. Based on a few investigations and published papers, it can be said that the disease caused millions of deaths, and destroyed numerous families and villages. Since the 1950s, there has been a national control program, intensive control and prevention work has been carried out, and consequently the disease is being controlled. At present, both the prevalence and the morbidity of the disease have been decreasing substantially. The morbidity of the three phases of the disease is outlined in this paper. Comparatively higher morbidity is seen in the acute and advanced phases of the disease. The four major forms of advanced schistosomiasis i.e., ascites, megalosplenia, dwarfism, and colonic tumoroid proliferation, are outlined with their characteristic clinical presentations; their proportions are different during various periods of the national control program. Ectopic schistosomiasis and the relationship between the S. japonicum infection and colorectal cancer are also discussed. Post-transmission schistosomiasis is briefly discussed (which can happen even if the disease reaches the criteria of elimination, and the infection and transmission have stopped, but yet it still develops). The problem of mammalian reservoir hosts of S. japonicum makes the epidemiology and control of schistosomiasis in China even more complicated and arduous, and the control progress in animal reservoirs is briefly presented. PMID:24529186

  2. Lung epithelial NOX/DUOX and respiratory virus infections.

    PubMed

    Grandvaux, Nathalie; Mariani, Mélissa; Fink, Karin

    2015-03-01

    Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.

  3. Risks of Lung Cancer due to Radon Exposure among the Regions of Korea.

    PubMed

    Lee, Hye Ah; Lee, Won Kyung; Lim, Dohee; Park, Su Hyun; Baik, Sun Jung; Kong, Kyoung Ae; Jung-Choi, Kyunghee; Park, Hyesook

    2015-05-01

    Radon is likely the second most common cause of lung cancer after smoking. We estimated the lung cancer risk due to radon using common risk models. Based on national radon survey data, we estimated the population-attributable fraction (PAF) and the number of lung cancer deaths attributable to radon. The exposure-age duration (EAD) and exposure-age concentration (EAC) models were used. The regional average indoor radon concentration was 37.5 95 Bq/m(3). The PAF for lung cancer was 8.3% (European Pooling Study model), 13.5% in males and 20.4% in females by EAD model, and 19.5% in males and 28.2% in females by EAC model. Due to differences in smoking by gender, the PAF of radon-induced lung cancer deaths was higher in females. In the Republic of Korea, the risk of radon is not widely recognized. Thus, information about radon health risks is important and efforts are needed to decrease the associated health problems.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. ICAM-1-dependent and ICAM-1-independent neutrophil lung infiltration by porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Liu, Jie; Hou, Make; Yan, Meiping; Lü, Xinhui; Gu, Wei; Zhang, Songlin; Gao, Jianfeng; Liu, Bang; Wu, Xiaoxiong; Liu, Guoquan

    2015-08-01

    Neutrophils are innate immune cells that play a crucial role in the first line of host defense. It is also known that neutrophil lung recruitment and infiltration may cause lung injury. The roles of neutrophils in virus infection-induced lung injury are not clear. We explore the mechanisms of neutrophil lung infiltration and the potential biomarkers for lung injury in a swine model of lung injury caused by natural or experimental porcine reproductive and respiratory syndrome virus (PRRSV) infection. Neutrophil lung infiltration was determined by measurement of myeloperoxidase expression and enzyme activity of lung tissues. Myeloperoxidase expression and enzyme activity were dramatically increased in the naturally and experimentally infected lung tissues. Chemokine analysis by quantitative PCR and ELISA showed that IL-8 expression was increased in both infections, while monocyte chemoattractant protein-1 expression was increased only in experimentally infected lung tissues. Expression of the cell adhesion molecules VCAM-1 and ICAM-1 was measured by quantitative PCR and Western blotting. VCAM-1 expression was increased in experimentally and naturally infected lungs, whereas ICAM-1 expression was increased only in the naturally infected lung samples. Our results suggest that neutrophil lung infiltrations in the infected animals are both ICAM-1- and -independent and that combined expression of VCAM-1 and IL-8 may serve as the biomarker for lung injury induced by virus infection.

  11. 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

  12. 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

    2015-12-04

    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

  13. Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends.

    PubMed

    Cross, A; Allen, J R; Burke, J; Ducel, G; Harris, A; John, J; Johnson, D; Lew, M; MacMillan, B; Meers, P

    1983-01-01

    The role of Pseudomonas aeruginosa in nosocomial infections occurring since 1975 is reviewed. Data from the National Nosocomial Infections Study conducted by the Centers for Disease Control, from individual medical centers, and from the literature were used to compare the relative frequency of occurrence of nosocomial infection caused by P. aeruginosa with that of infection caused by other gram-negative bacilli. The relative frequency of P. aeruginosa as a nosocomial pathogen has increased, although wide variations are seen among individual medical centers. P. aeruginosa continues to be a major pathogen among patients with immunosuppression, cystic fibrosis, malignancy, and trauma. While Staphylococcus aureus has become the predominant pathogen in some large burn centers, P. aeruginosa is the most important gram-negative pathogen. Periodic review of the epidemiology of P. aeruginosa infection is warranted in view of the changing incidence of infection caused by this organism.

  14. Intra-Abdominal Infections Due to Comamonas kerstersii

    PubMed Central

    Almuzara, Marisa N.; Cittadini, Rosana; Vera Ocampo, Cecilia; Bakai, Romina; Traglia, German; Ramirez, Maria S.; del Castillo, Marcelo

    2013-01-01

    Herein, we report four cases of Comamonas kerstersii intra-abdominal infections representing the first report of human infections caused by this Comamonas species. In addition, our work demonstrates the association of C. kerstersii with peritonitis secondary to appendix rupture. PMID:23576541

  15. Inflammatory damage on respiratory and nervous systems due to hRSV infection.

    PubMed

    Bohmwald, Karen; Espinoza, Janyra A; Becerra, Daniela; Rivera, Katherine; Lay, Margarita K; Bueno, Susan M; Riedel, Claudia A; Kalergis, Alexis M

    2015-10-01

    The exacerbated inflammatory response elicited by human Respiratory Syncytial Virus (hRSV) in the lungs of infected patients causes a major health burden in the pediatric and elderly population. Since the discovery of hRSV, the exacerbated host immune-inflammatory response triggered by this virus has been extensively studied. In this article, we review the effects on the airways caused by immune cells and cytokines/chemokines secreted during hRSV infection. While molecules such as interferons contribute at controlling viral infection, IL-17 and others produce damage to the hRSV-infected lung. In addition to affecting the airways, hRSV infection can cause significant neurologic abnormalities in the host, such as seizures and encephalopathy. Although the origin of these symptoms remains unclear, studies from patients suffering neurological alteration suggest an involvement of the inflammatory response against hRSV.

  16. Number of deaths due to lung diseases: How large is the problem

    SciTech Connect

    Wagener, D.K. )

    1990-06-01

    The importance of lung disease as an indicator of environmentally induced adverse health effects has been recognized by inclusion among the Health Objectives for the Nation. The 1990 Health Objectives for the Nation (US Department of Health and Human Services, 1986) includes an objective that there should be virtually no new cases among newly exposed workers for four preventable occupational lung diseases-asbestosis, byssinosis, silicosis, and coal workers' pneumoconiosis. This brief communication describes two types of cause-of-death statistics- underlying and multiple cause-and demonstrates the differences between the two statistics using lung disease deaths among adult men. The choice of statistic has a large impact on estimated lung disease mortality rates. The choice of statistics also may have large effect on the estimated mortality rates due to other chromic diseases thought to be environmentally mediated. Issues of comorbidity and the way causes of death are reported become important in the interpretation of these statistics. The choice of which statistic to use when comparing data from a study population with national statistics may greatly affect the interpretations of the study findings.

  17. 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.

  18. 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

  19. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    PubMed

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    2016-01-01

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome.

  20. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    PubMed

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    2016-01-01

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome. PMID:27629965

  1. 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

  2. Alterations in cysteine proteinase content of rat lung associated with development of Pneumocystis carinii infection.

    PubMed Central

    Hayes, D J; Stubberfield, C R; McBride, J D; Wilson, D L

    1991-01-01

    The rate of hydrolysis of three cysteine-type proteinase substrates, N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-coumarylamide (AMC) (cathepsin B), Arg-AMC (cathepsin H), and N-benzyloxycarbonyl-Phe-Arg-AMC (cathepsin L), were determined in rat lung throughout the time course of the induction of Pneumocystis carinii infection by immunosuppression. Cathepsin B-like and cathepsin L-like activities fell below control values initially, but from week 8 of the immunosuppressive treatment significant increases above the control were noted. Cathepsin H-like activity was greater than control levels from week 3, and by week 12 it was 7,600% of the mean control value. When compared with the relative degree of infection, as assessed from the number of cysts present in lung impression smears, cathepsin B-like and cathepsin L-like activities were significantly increased only at heavy parasite burdens while cathepsin H-like activity displayed a close correlation with parasite number (r = 0.884; P less than 0.001). Activity was detected in lysates of purified P. carinii with all three substrates. Treatment of heavily infected animals with co-trimoxazole cleared the lungs of P. carinii, and this was accompanied by a marked reduction in proteinase activity, in particular, cathepsin H-like activity, which fell from 108- to 3-fold the mean control value following drug treatment. Analysis of cathepsin H isozyme patterns by fluorography following isoelectric focusing revealed differences between treated and control lung samples. In the immunosuppressed group, there was a time-dependent increase in the intensity of some of the bands observed in the controls and an appearance of several novel bands which corresponded to bands observed in lysates of P. carinii. It is likely, therefore, that the increased proteinase activity observed in the treated group is due, at least in part, to isozymes from P. carinii; consequently, cathepsin H-like activity might be of use diagnostically in the

  3. Pseudomonas aeruginosa Diversification during Infection Development in Cystic Fibrosis Lungs-A Review.

    PubMed

    Sousa, Ana Margarida; Pereira, Maria Olívia

    2014-01-01

    Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according the infection stage. CF adaptation is triggered by high selective pressure of inflamed CF lungs and by antibiotic treatments. Bacteria undergo genetic, phenotypic, and physiological variations that are fastened by the repeating interplay of mutation and selection. During CF infection development, P. aeruginosa gradually shifts from an acute virulent pathogen of early infection to a host-adapted pathogen of chronic infection. This paper reviews the most common changes undergone by P. aeruginosa at each stage of infection development in CF lungs. The comprehensive understanding of the adaptation process of P. aeruginosa may help to design more effective antimicrobial treatments and to identify new targets for future drugs to prevent the progression of infection to chronic stages. PMID:25438018

  4. 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.

  5. Early infective endocarditis due to Staphylococcus aureus following dental procedures.

    PubMed

    Kasmi, Gentian; Refatllari, Etleva; Dumani, Selman; Refatllari, Ali

    2014-01-01

    Staphylococcus aureus is now the most common cause of infective endocarditis (IE) in many areas of the developed world. Patients with S. aureus IE exhibit different characteristics compared to patients with IE deriving from oth- er organisms [1]. IE in general is a complication of bacteremia following invasive procedures. PMID:25648038

  6. Clinical characteristics of infections in humans due to Staphylococcus epidermidis.

    PubMed

    Rupp, Mark E

    2014-01-01

    Staphylococcus epidermidis is the most common cause of primary bacteremia and infections of indwelling medical devices. The ability to cause disease is linked to its natural niche on human skin and ability to attach and form biofilm on foreign bodies. This review focuses on the S. epidermidis clinical syndromes most commonly encountered by clinicians and future potential treatment modalities.

  7. 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

  8. 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

  9. Lower lip numbness due to peri-radicular dental infection.

    PubMed

    Ngeow, W C

    1998-12-01

    Lower lip numbness has always been a sinister symptom. Much has been written about it being the sole symptom of pathological lesions and metastatic tumours in the mandible. It may also be a symptom of manifestations of certain systemic disorders. A case of lower lip numbness resulting from the compression of the mental nerve by a peri-radicular abscess is presented because of the unusual nature of this spread of infection. PMID:10971994

  10. Intravenous thrombolysis is unsafe in stroke due to infective endocarditis.

    PubMed

    Brownlee, W J; Anderson, N E; Barber, P A

    2014-02-01

    Embolic stroke is the most common neurological complication of infective endocarditis and a major source of morbidity and mortality. Septic embolism is considered a contraindication to intravenous thrombolysis in patients with ischaemic stroke because of concerns over an increased risk of intracranial haemorrhage. We describe a patient with occult endocarditis who was treated with thrombolysis for acute stroke and review other cases reported in the literature.

  11. [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.

  12. [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

  13. [Nosocomial infections due to human coronaviruses in the newborn].

    PubMed

    Gagneur, A; Legrand, M C; Picard, B; Baron, R; Talbot, P J; de Parscau, L; Sizun, J

    2002-01-01

    Human coronaviruses, with two known serogroups named 229-E and OC-43, are enveloped positive-stranded RNA viruses. The large RNA is surrounded by a nucleoprotein (protein N). The envelop contains 2 or 3 glycoproteins: spike protein (or protein S), matrix protein (or protein M) and a hemagglutinin (or protein HE). Their pathogen role remains unclear because their isolation is difficult. Reliable and rapid methods as immunofluorescence with monoclonal antibodies and reverse transcription-polymerase chain reaction allow new researches on epidemiology. Human coronaviruses can survive for as long as 6 days in suspension and 3 hours after drying on surfaces, suggesting that they could be a source of hospital-acquired infections. Two prospective studies conducted in a neonatal and paediatric intensive care unit demonstrated a significant association of coronavirus-positive nasopharyngal samples with respiratory illness in hospitalised preterm neonates. Positive samples from staff suggested either a patient-to-staff or a staff-to-patient transmission. No cross-infection were observed from community-acquired respiratory-syncitial virus or influenza-infected children to neonates. Universal precautions with hand washing and surface desinfection could be proposed to prevent coronavirus transmission.

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

    ClinicalTrials.gov

    2016-10-03

    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

  15. 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

  16. The balance between protective and pathogenic immune responses in the TB-infected lung.

    PubMed

    Orme, Ian M; Robinson, Richard T; Cooper, Andrea M

    2015-01-01

    Tuberculosis is a disease of the lung, and efficient transmission is dependent on the generation of a lesion in the lung, which results in a bacterium-laden cough. Mycobacterium tuberculosis (Mtb) is able to manipulate both the innate and acquired immune response of the host. This manipulation results in an effective CD4(+) T cell response that limits disease throughout the body but can also promote the development of progressively destructive lesions in the lung. In this way Mtb infection can result in an ambulatory individual who has a lesion in the lung capable of transmitting Mtb. The inflammatory environment within the lung lesion is manipulated by Mtb throughout infection and can limit the expression of acquired immunity by a variety of pathways.

  17. 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

  18. 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

  19. 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.

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

    PubMed

    Jungraithmayr, Wolfgang; Tzafos, Stefanos; 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

  1. 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

  2. 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

  3. 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

  4. Human distomatosis due to Fasciola hepatica infection in Assam, India.

    PubMed

    Narain, K; Biswas, D; Rajguru, S K; Mahanta, J

    1997-06-01

    A seven year old girl in a rural area of Upper Assam was found to be infected with Fasciola hepatica. The girl gave history of eating watercress. Besides the presence of eggs in the stools, her liver was enlarged and tender. Liver function tests revealed hepato-biliary involvement with increase in serum AKP and ALT. Ultrasonography revealed presence of adult fluke in gall bladder, and a marginal thickening of gall bladder wall. However, the echo pattern of her liver parenchyma was normal. The case is reported for its public health significance and is a maiden report from north eastern India. PMID:9282516

  5. 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.

  6. [Neuropathic pain due to herpes zoster infection with atypical localization].

    PubMed

    Sağır, Özlem; Özaslan, Sabri; Meriç, Yücel; Arslan, İsmail; Köroğlu, Ahmet

    2013-01-01

    Acute herpes zoster infection appears in the situation of depression of immune system and reactivation of varicella zoster virus which causes small pox. Pain and maculopapular lesion accompany clinical symptoms. Various pharmacological and invasive methods can be used for treatment. Efficient therapy is important for prevention of postherpetic neuralgia and cure of acute pain and dermatological lesions. A 55 years old, 160 cm height and 65 kg weight female patient with complaints of severe pain, sensation of burning, tingling at the right hand and forearm was admitted to our pain department. The patient who was diagnosed as cervical hernia at an other medical center had a normal physical servical spine examination. Patient history and physical examination findings with acute herpes zoster infection was considered. Right stellate ganglion blockade for diagnosis and treatment was performed because of regressed and atypically located lesions and a visual analog scale score of 10. VAS score decreased 50% at 9th min after block, VAS score at 2nd hour was 2. Antiviral, gabapentin, and tricyclic antidepressant treatment was started after stellat ganglion blockade and patient was discharged. After 3 months complaints dissapeared and drug doses were discreased and stopped. In conclusion we think that stellate ganglion blockade can be useful in diagnosis, acute pain control, improving patient comfort and compatibility to drug therapy in atypically located herpes zoster.

  7. 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

  8. Prosthetic joint infections with osteomyelitis due to Candida albicans.

    PubMed

    Lerch, K; Kalteis, T; Schubert, T; Lehn, N; Grifka, J

    2003-12-01

    We report the case of a 78-year-old woman who suffered from a severe soft tissue and bone infection of her left knee 3 years after a total knee-joint replacement without loosening of her endoprosthesis. Cultures from joint aspiration and tissue specimen identified Staphylococcus aureus and Candida albicans. Direct microscopic examination of vital spongy bone and fibrous tissue revealed microabscesses and seeds of yeasts inside the fatty marrow and interface. After removal of the prosthesis several soft tissue and bone specimens were taken during planned re-operations. The histological examination showed no morphological changing, no reduction or extinction of the yeast cells under fluconazole therapy with a dosage of 6 mg kg(-1) body weight (400 mg daily). Curing of the fungal infection with eradication of the yeasts in the bony specimens was achieved with higher doses of 12 mg kg(-1) body weight (800 mg day(-1)) over a 2 month regimen in combination with repeated surgical debridements.

  9. 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

  10. 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

  11. [Massive alveolar hemorrhage due to cytomegalovirus (CMV) and HIV infection].

    PubMed

    Cortés, A; Peña, E; Vega, R; Reyes, G; Bautista, E

    2011-03-01

    Alveolar hemorrhage may be a complication of diseases with local and systemic manifestations. Both share the same pathophysiological concept: damage to the alveolar microcirculation. It is a clinical entity that generates a diagnostic challenge for the physician. Early recognition favors aggressive treatment, which can improve the outcome. Despite the technological advances in its diagnosis and treatment, it is still a condition having high morbidity and mortality. We present the case of a 42-year old woman diagnosed of massive alveolar hemorrhage induced by cytomegalovirus (CMV) and HIV infection. Its presentation is atypical because most reported cases have occurred as a pneumonic process, episodes of massive hemorrhage being uncommon. The diagnosis was documented by bronchoscopy with bronchoalveolar lavage and etiological diagnosis with molecular techniques using reverse transcription polymerase chain reaction.

  12. A milk-borne outbreak of serious infection due to Streptococcus zooepidemicus (Lancefield Group C).

    PubMed Central

    Edwards, A. T.; Roulson, M.; Ironside, M. J.

    1988-01-01

    An outbreak of infection due to Streptococcus zooepidemicus (Lancefield Group C) is described. At least 11 patients were affected and the infection was responsible for, or contributed to, the deaths of seven of these. Clinical features included septicaemia, meningitis and endocarditis. The source of infection was unpasteurized milk from a dairy herd with mild intermittent mastitis. PMID:3402548

  13. No causal association identified for human papillomavirus infections in lung cancer.

    PubMed

    Anantharaman, Devasena; Gheit, Tarik; Waterboer, Tim; Halec, Gordana; Carreira, Christine; Abedi-Ardekani, Behnoush; McKay-Chopin, Sandrine; Zaridze, David; Mukeria, Anush; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Mates, Dana; Janout, Vladimir; Foretova, Lenka; Bencko, Vladimir; Rudnai, Peter; Fabianova, Eleonora; Tjønneland, Anne; Travis, Ruth C; Boeing, Heiner; Quirós, J Ramón; Johansson, Mikael; Krogh, Vittorio; Bueno-de-Mesquita, H Bas; Kotanidou, Anastasia; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Johansson, Mattias; Pawlita, Michael; Scelo, Ghislaine; Tommasino, Massimo; Brennan, Paul

    2014-07-01

    Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer.

  14. 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

  15. 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

  16. Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

    PubMed

    Hadinoto, Kunn; Cheow, Wean Sin

    2014-04-01

    Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified.

  17. 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.

  18. 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

  19. 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.

  20. Polymicrobial Infection of the Cornea Due to Contact Lens Wear

    PubMed Central

    Sızmaz, Selçuk; Bingöllü, Sibel; Erdem, Elif; Kibar, Filiz; Koltaş, Soner; Yağmur, Meltem; Ersöz, Reha

    2016-01-01

    A 38-year-old male presented with pain and redness in his left eye. He had a history of wearing contact lenses. His ophthalmic examination revealed a large corneal ulcer with surrounding infiltrate. Cultures were isolated from the contact lenses, lens solutions, storage cases, and conjunctivae of both eyes and also corneal scrapings of the left eye. Fortified vancomycin and amikacin drops were started hourly. Culture results of conjunctivae of each eye and left cornea were positive for Pseudomonas aeruginosa; cultures from the contact lenses, lens solution and storage case of both eyes revealed Pseudomonas aeruginosa and Alcaligenes xylosoxidans. Polymerase chain reaction of the corneal scraping was positive for Acanthameoba. The topical antibiotics were changed with ones that both bacteria were sensitive to and anti-amoebic therapy was added. The patient had two recurrences following initial presentation despite intensive therapy. Keratitis occurred due to multiple pathogens; the relapsing course despite adequate therapy is potentially associated with this polymicrobial etiology. PMID:27800266

  1. 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

  2. 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

  3. [Torsion of the right upper lobe due to primary lung cancer with pulmonary hypertrophic osteoarthropathy; report of a case].

    PubMed

    Matsukura, T; Hanawa, T; Kuwabara, M; Motoishi, M; Fujimoto, T; Okazaki, T; Yamashita, N; Matsubara, Y

    2006-12-01

    A 61-year-old woman was admitted due to severe coughing. Chest X-ray revealed a mass in the right lower lung field at standing position and in the right upper lung field at supine position. A position of the mass changed with change in her posture because of lobar torsion. Bronchoscopic biopsy of the polypoid tumor obstructing the right upper bronchus revealed adenocarcinoma. She had hypertrophic osteoarthropathy simultaneously. Right pneumonectomy was performed. Postoperative course has been uneventful for 3 years.

  4. 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

  5. Cytokine and Chemokine Responses of Lung Exposed to Surrogate Viral and Bacterial Infections

    PubMed Central

    Liberati, Teresa A; Trammell, Rita A; Randle, Michelle; Barrett, Sarah; Toth, Linda A

    2013-01-01

    The use of in vitro models of complex in vivo systems has yielded many insights into the molecular mechanisms that underlie normal and pathologic physiology. However although the reduced complexity of these models is advantageous with regard to some research questions, the simplification may obscure or eliminate key influences that occur in vivo. We sought to examine this possibility with regard to the lung's response to infection, which may be inherent to resident lung cells or related to the systemic response to pulmonary infection. We used the inbred mouse strains C57BL/6J, DBA/2J, and B6.129S2-IL6tm1Kopf, which differ in their response to inflammatory and infectious challenges, to assess in vivo responses of lung to surrogate viral and bacterial infection and compared these with responses of cultured lung slices and human A549 cells. Pulmonary cytokine concentrations were measured both after in vivo inoculation of mice and in vitro exposure of lung slices and A549 cells to surrogate viral and bacterial infections. The data indicate similarities and differences in early lung responses to in vivo compared with in vitro exposure to these inflammatory substances. Therefore, resident cells in the lung appear to respond to some challenges in a strain-independent manner, whereas some stimuli may elicit recruitment of peripheral inflammatory cells that generate the subsequent response in a genotype-related manner. These results add to the body of information pointing to host genotype as a crucial factor in mediating the severity of microbial infections and demonstrate that some of these effects may not be apparent in vitro. PMID:23582418

  6. Human papillomavirus infection in lung vs. oral squamous cell carcinomas: a polymerase chain reaction study.

    PubMed

    Halimi, M; Morshedi Asl, S

    2011-06-01

    The role of Human Papillomavirus (HPV) has been suspected in pathogenesis of various malignancies; however, the available data are not conclusive. This study aimed to determine and compare the frequency of HPV infection in oral and lung Squamous Cell Carcinoma (SCC) by a sensitive method. Sixty specimens of oral and lung SCC (30 cases each one) were reevaluated in Tabriz Imam Reza Centre in a 24 month period. Following genomic DNA extract, the Polymerase Chain Reaction (PCR) amplification was performed in presence of specific MY11 and MY09 primers for HPV infection. Three cervical specimens and a combination of PCR solution lacking DNA plus healthy persons' DNA samples were employed as positive and negative controls, respectively. The oral group was significantly older than the lung group (68.90 vs. 56.67 y, p < 0.001) with more males in the latter (83.3 vs. 60%; p = 0.04). Percentages of HPV infection in the oral and lung groups were comparable (20 vs. 10%, respectively; p = 0.47). Majority of patients with HPV infection were older than 60 years (88.9%) or male (88.9%). In the oral group, all these cases were well differentiated and the majority was of lower lip origin (83.3%). In the lung group, 66.7% of these specimens were moderately differentiated and the origin was bronchus in all cases. In conclusion, the rate of HPV infection in lung and oral SCC samples is rather lower than the previous reports in the literature. This rate is apparently higher in the oral than the lung SCC specimens. PMID:22235505

  7. Risk factors for revision due to infection after primary total hip arthroplasty

    PubMed Central

    2010-01-01

    Background and purpose There has been a limited amount of research on risk factors for revision due to infection following total hip arthroplasty (THA), probably due to low absolute numbers of revisions. We therefore studied patient- and surgery-related risk factors for revision due to infection after primary THA in a population-based setting. Materials and methods Using the Danish Hip Arthroplasty Registry, we identified 80,756 primary THAs performed in Denmark between Jan 1, 1995 and Dec 31, 2008. We used Cox regression analysis to compute crude and adjusted relative risk (RR) of revision due to infection. Revision was defined as extraction or exchange of any component due to infection. The median follow-up time was 5 (0–14) years. Results 597 primary THAs (0.7%) were revised due to infection. Males, patients with any co-morbidity, patients operated due to non-traumatic avascular femoral head necrosis, and patients with long duration of surgery had an increased RR of revision due to infection within the total follow-up time. A tendency of increased RR of revision was found for patients who had received cemented THA without antibiotic and hybrid THA relative to patients with cementless implants. Hip diagnosis and fixation technique were not associated with risk of revision due to infection within 1 year of surgery (short-term risk). Interpretation We identified several categories of THA patients who had a higher risk of revision due to infection. Further research is required to explain the mechanism underlying this increased risk. More attention should be paid by clinicians to infection prevention strategies in patients with THA, particularly those with increased risk. PMID:20860453

  8. The interferon-induced gene Ifi27l2a is active in lung macrophages and lymphocytes after influenza A infection but deletion of Ifi27l2a in mice does not increase susceptibility to infection.

    PubMed

    Tantawy, Mohamed A; Hatesuer, Bastian; Wilk, Esther; Dengler, Leonie; Kasnitz, Nadine; Weiß, Siegfried; Schughart, Klaus

    2014-01-01

    Interferons represent one of the first and essential host defense mechanisms after infection, and the activation of the IFN-pathway results in the transcriptional activation of hundreds of interferon-stimulated genes. The alpha-inducible protein 27 like 2A (Ifi27l2a) gene (human synonym: ISG12) is strongly up-regulated in the lung after influenza A infection in mice and has been shown in gene expression studies to be highly correlated to other activated genes. Therefore, we investigated the role of Ifi27l2a for the host defense to influenza A infections in more detail. RT-PCR analyses in non-infected mice demonstrated that Ifi27l2a was expressed in several tissues, including the lung. Detailed analyses of reporter gene expression in lungs from Ifi27l2a-LacZ mice revealed that Ifi27l2a was expressed in macrophages and lymphocytes but not in alveolar cells or bronchiolar epithelium cells. The number of macrophages and lymphocyte strongly increased in the lung after infection, but no significant increase in expression levels of the LacZ reporter gene was found within individual immune cells. Also, no reporter gene expression was found in bronchiolar epithelial cells, alveolar cells or infiltrating neutrophils after infection. Thus, up-regulation of Ifi27l2a in infected lungs is mainly due to the infiltration of macrophages and lymphocytes. Most surprisingly, deletion of Ifi27l2a in mouse knock-out lines did not result in increased susceptibility to infections with H1N1 or H7N7 influenza A virus compared to wild type C57BL/6N mice, suggesting a less important role of the gene for the host response to influenza infections than for bacterial infections. PMID:25184786

  9. Cytokine expression in lungs of calves spontaneously infected with Mycoplasma bovis.

    PubMed

    Rodríguez, Francisco; González, Jorge F; Arbelo, Manuel; Zucca, Daniele; Fernández, Antonio

    2015-03-01

    Cytokine expression in the lung can play an important role during Mycoplasma bovis infection through leukocyte recruitment and activation, and the induction of a broad array of inflammatory mediators. To gain further insight into the pathogenesis of M. bovis-associated pneumonia, cytokine expression was examined, by immunohistochemical methods in formalin-fixed, paraffin wax-embedded tissues, in the lung of 20 calves spontaneously infected. Immunolabelling for tumor necrosis factor alpha (TNF)-α, interleukin-4 (IL-4), IL-10 and interferon-gamma (IFN-γ), was usually associated with pneumonia, particularly in macrophages and lymphocytes, and with the presence of M. bovis antigen. The expression was minimal in lungs from negative controls. The results demonstrated consistent upregulation of TNF-α, IL-4, IL-10 and IFN-γ expression during M. bovis-associated pneumonic lesions. These cytokines can participate in the immune and inflammatory responses during the pulmonary defense mechanisms against M. bovis infection. PMID:25331253

  10. Immunofluorescent characterization of lymphocytes in lungs of rats infected with Mycoplasma pulmonis.

    PubMed Central

    Davis, J K; Maddox, P A; Thorp, R B; Cassell, G H

    1980-01-01

    Immunofluorescence was used to determine the relative percentages of T and B lymphocytes found in the lungs of normal and Mycoplasma pulmonis-infected F344 rats. Lymphocytes recovered from controls were approximately 25% T, 25% B, and 50% unclassified mononuclear cells. Infected animals had a 2.6-fold greater number of T cells and IgA-bearing cells, and a 1.6-fold greater number of unclassified mononuclear cells. These studies show that M. pulmonis infection significantly alters lung lymphocyte populations both quantitatively and in subpopulation distribution. Therefore, future studies of rat lung lymphocytes should utilize animals known to be free of this ubiquitous respiratory pathogen. Images Fig. 1 PMID:7358429

  11. 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

  12. Some Pathological Features of Lungs from Domestic and Wild Ruminants with Single and Mixed Protostrongylid Infections

    PubMed Central

    Panayotova-Pencheva, Mariana Stancheva; Alexandrov, Marin Tsvyatkov

    2010-01-01

    Lungs of 40 ruminants from Bulgaria with natural small lungworm (Nematoda: Protostrongylidae) infections were investigated, including 16 goats, 15 sheep, 7 mouflons, and 2 chamois. Muellerius capillaris, M. tenuispiculatus, Cystocaulus ocreatus, Neostrongylus linearis, and Protostrongylus brevispiculum infections were predominantly associated with nodular lesions, and Protostrongylus rufescens, Protostrongylus hobmaieri and Protostrongylus rupicaprae were associated with extensive lesions located mainly along the length of the large bronchi. The extent of lung abnormalities was most severe in the sheep. Alveolitis, parasite granulomas, damage of the alveolar septa, hyperplasia of the lung associated lymphoid tissue, and sclerosis of the parenchyma were found upon microscope examinations. In the goats compared to the sheep and mouflons, the terminal bronchi, bronchioles, and alveoli were more affected than the interstitium. Our research shows that the pathological lesions in the lungs of ruminants infected with protostrongylids depend on both the helminth and the host species. To our knowledge, this work is the first to provide data on the pathomorphological lesions in mouflon lungs infected with protostrongylids. PMID:20445790

  13. 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

  14. Haemophilus influenzae LicB contributes to lung damage in an aged mice co-infection model.

    PubMed

    Bondy, Jessica; Osharovich, Sofya; Storm, Julie; Durning, Graham; McAuliffe, Timothy; Fan, Xin

    2016-01-01

    Phosphorylcholine (ChoP) decoration of lipopolysaccharides is an important virulence strategy adopted by Haemophilus influenzae to establish a niche on the mucosal surface and to promote adherence to the host cells. The incorporation of ChoP on the LPS surface involves the lic1 operon, which consists of the licA, licB, licC, and licD genes. Among which, licB is a choline transporter gene required for acquisition of choline from environmental sources. In this study, we investigated the pathogenesis of the licB gene in an aged mice infection model. Due to immediate clearance of H. influenzae upon infection in mice, we employed influenza A virus and H. influenzae co-infection model. Our data showed that in the co-infection model, the secondary bacterial infection with a very low H. influenzae concentration of 100 colony forming unit is lethal to the aged mice. Although we did not observe any differences in weight loss between parent and licB mutant strains during the course of infection, a significant reduction of lung tissue damage was observed in the licB mutant infected aged mice. These results suggest that the licB gene is a virulence factor during H. influenzae infection in the lung in aged mice, possibly due to the increased binding to the host cell receptor via ChoP expression on the bacterial surface. In addition, when aged mice and mature mice were compared in the challenge experiments, we did not observe any protective immunity in the co-infection model suggesting the detrimental effects of the secondary bacterial infection on the aged mice in contrast to obvious immune-protections observed in the mature mice. The results of our experiments also implied that the co-infection model with influenza A virus and H. influenzae may be employed as a model system to study H. influenzae pathogenesis in vivo in aged mice.

  15. 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.

  16. 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

  17. Central nervous system infection due to Mycobacterium haemophilum in a patient with acquired immunodeficiency syndrome.

    PubMed

    Buppajarntham, Aubonphan; Apisarnthanarak, Anucha; Rutjanawech, Sasinuj; Khawcharoenporn, Thana

    2015-03-01

    Mycobacterium haemophilum is an environmental organism that rarely causes infections in humans. We report a patient with acquired immunodeficiency syndrome who had central nervous system infection due to M. haemophilum. The diagnosis required brain tissue procurement and molecular identification method while the treatment outcome was unfavourable.

  18. A nosocomial epidemic model with infection of patients due to contaminated rooms.

    PubMed

    Browne, Cameron; Webb, Glenn F

    2015-08-01

    A model of epidemic bacterial infections in hospitals is developed. The model incorporates the infection of patients and the contamination of healthcare workers due to environmental causes. The model is analyzed with respect to the asymptotic behavior of solutions. The model is interpreted to provide insight for controlling these nosocomial epidemics.

  19. 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

  20. 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

  1. 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

  2. Endobronchial mucosal blanching due to a post-lung transplantation pulmonary artery stenosis.

    PubMed

    Slebos, Dirk-Jan; Wolff, Rienhart F E; van der Bij, Wim

    2011-03-01

    A 45-year-old woman underwent a bronchoscopy shortly after lung transplantation. The airway mucosal appearance significantly differed between both lungs, with a pale aspect of the left bronchial tree. Computed tomography (CT) and perfusion scan confirmed a left pulmonary artery stenosis, improving with conservative treatment.

  3. 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 ...

  4. Lung cancer risk due to residential radon exposures: estimation and prevention.

    PubMed

    Truta, L A; Hofmann, W; Cosma, C

    2014-07-01

    Epidemiological studies proved that cumulative exposure to radon is the second leading cause of lung cancer, the world's most common cancer. The objectives of the present study are (i) to analyse lung cancer risk for chronic, low radon exposures based on the transformation frequency-tissue response (TF-TR) model formulated in terms of alpha particle hits in cell nuclei; (ii) to assess the percentage of attributable lung cancers in six areas of Transylvania where the radon concentration was measured and (iii) to point out the most efficient remediation measures tested on a pilot house in Stei, Romania. Simulations performed with the TF-TR model exhibit a linear dose-effect relationship for chronic, residential radon exposures. The fraction of lung cancer cases attributed to radon ranged from 9 to 28% for the investigated areas. Model predictions may represent a useful tool to complement epidemiological studies on lung cancer risk and to establish reasonable radiation protection regulations for human safety.

  5. Choriodecidual Infection Downregulates Angiogenesis and Morphogenesis Pathways in Fetal Lungs from Macaca Nemestrina

    PubMed Central

    McAdams, Ryan M.; Vanderhoeven, Jeroen; Beyer, Richard P.; Bammler, Theo K.; Farin, Federico M.; Liggitt, H. Denny; Kapur, Raj P.; Gravett, Michael G.; Rubens, Craig E.; Adams Waldorf, Kristina M.

    2012-01-01

    Background Intrauterine exposure to amniotic fluid (AF) cytokines is thought to predispose to bronchopulmonary dysplasia (BPD). We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD. Methods Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n = 5) or 2) saline (n = 5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry. Results Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening) and one control (peri-mortem hemorrhage). Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6) were detected in GBS versus controls (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05) with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development. Conclusions A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in utero to

  6. 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

  7. 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

  8. 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

  9. Cross Protective Mucosal Immunity Mediated by Memory Th17 Cells against Streptococcus pneumoniae Lung Infection

    PubMed Central

    Wang, Yan; Jiang, Bin; Guo, Yongli; Li, Wenchao; Tian, Ying; Sonnenberg, Gregory F; Weiser, Jeffery N.; Ni, Xin; Shen, Hao

    2016-01-01

    Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of current pneumonia cases result from infection by serotype strains not included in the vaccine. In this study, we asked if cross-protection against lung infection by heterologous strains can be induced and investigated the underlying immune mechanism. We found that immune mice recovered from a prior infection were protected against heterologous Sp strains in the pneumonia challenge model, as evident by accelerated bacterial clearance, reduced pathology and apoptosis of lung epithelial cells. Sp infection in the lung induced strong Th17 responses at the lung mucosal site. Transfer of CD4+ T cells from immune mice provided heterologous protection against pneumonia, and this protection was abrogated by IL-17A blockade. Transfer of memory CD4+ T cells from IL-17A knockout mice failed to provide protection. These results indicate that memory Th17 cells played a key role in providing protection against pneumonia in a serotype independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells. PMID:27118490

  10. Green herring syndrome: bacterial infection in patients with mucormycosis cavitary lung disease.

    PubMed

    Peixoto, Driele; Hammond, Sarah P; Issa, Nicolas C; Madan, Rachna; Gill, Ritu R; Milner, Danny A; Colson, Yolonda L; Koo, Sophia; Baden, Lindsey R; Marty, Francisco M

    2014-03-01

    Mucormycosis is a life-threatening fungal disease in patients with hematological malignancies. The diagnosis of pulmonary mucormycosis is particularly challenging. We describe 3 mucormycosis cases with an uncommon presentation in patients whose cavitary lung disease was attributed to well documented bacterial infection, although evolution and reassessment established mucormycosis as the underlying disease. PMID:25734087

  11. 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…

  12. Detection of Mycobacterium tuberculosis in latently infected lungs by immunohistochemistry and confocal microscopy

    PubMed Central

    Eugenin, Eliseo; Kaplan, Gilla

    2014-01-01

    Detection of latent Mycobacterium tuberculosis is a challenge in the diagnosis of asymptomatic, subclinical tuberculosis. We report the development of an immunofluorescence technique to visualize and enumerate M. tuberculosis in latently infected rabbit lungs where no acid-fast–stained organisms were seen and no cultivable bacilli were obtained by the agar-plating method. PMID:25161200

  13. Successful Nonoperative Management of Spontaneous Splenic Hematoma and Hemoperitoneum due to CMV Infection

    PubMed Central

    Lianos, Georgios; Ignatiadou, Eleftheria; Bali, Christina; Harissis, Haralampos; Katsios, Christos

    2012-01-01

    Introduction. Spontaneous splenic hematoma or splenic rupture due to CMV infection in immunocompetent adults is rare and life-threatening. Case Report. Herein we report a rare case of spontaneous splenic hematoma and hemoperitoneum due to CMV infection in a 23-year-old Caucasian male in whom conservative management was successful. Conclusion. Spontaneous splenic hematoma and spontaneous splenic rupture are extremely rare conditions during primary CMV infection. Though rare, they must be always considered by the operating surgeon, because any misinterpretation may result in unfavorable outcomes. PMID:23227374

  14. [Air Bubble in the Left Ventricle due to Computed Tomography Guided Lung Needle Biopsy].

    PubMed

    Matsuda, Eisuke; Yoshida, Kumiko; Yoshiyama, Koichi; Hayashi, Tatsuro; Tanaka, Toshiki; Tao, Hiroyuki; Okabe, Kazunori

    2015-11-01

    Computed tomography (CT) guided lung biopsy is a useful examination in diagnosing pulmonary diseases, but the complications such as pneumothorax or pulmonary hemorrhage can not be ignored. Among them, air embolization is a severe complication, although it is infrequently encountered. Forty two-year-old man admitted to our department for the examination of left lung tumor. CT guided lung biopsy was performed. After examination, the patient showed disturbance in cardiac function, which recovered in several minutes. Chest CT revealed air bubble in the left ventricle. After 2-hours head down position followed by bed rest, air bubble is confirmed to be dissappeared by CT.

  15. Combined Legionella and Escherichia coli lung infection after a tsunami disaster.

    PubMed

    Ebisawa, Kei; Yamada, Norihiro; Okada, Shinji; Suzuki, Yasuko; Satoh, Asami; Kobayashi, Makoto; Morikawa, Naoto

    2011-01-01

    Pulmonary infection after a tsunami is often polymicrobial and tends to form chronic pyogenic lung disease, necrotizing pneumonia, and empyemas. We report a combined pulmonary infection of Legionella and multiple antibiotic-resistant Escherichia coli in a previously well 75-year-old woman following immersion in tsunami waters 1 km inland from the Pacific coastline following the Tohoku Region Pacific Coast Earthquake of 2011. She needed drainage several times and the long-term use of multiple antibiotics according to the type of bacteria found and antibiotic susceptibility. We should be mindful of infections caused by multiple pathogens in the environment in Japan as a consequence of a tsunami disaster.

  16. Splenic abscess due to Brucella infection: is the splenectomy necessary? Case report and literature review.

    PubMed

    Del Arco, Alfonso; De La Torre-Lima, Javier; Prada, José Luís; Aguilar, Josefa; Ruiz-Mesa, Juan Diego; Moreno, Francisco

    2007-01-01

    The case of a woman with splenic abscess due to Brucella is reported. There was no response with antibiotics and surgical treatment was required. On the basis of this case and the literature review we consider that surgical treatment must be considered in patients with splenic abscess due to Brucella infection.

  17. 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

  18. 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

  19. Serum level of substance P in patients with lung injuries due to sulfur mustard

    PubMed Central

    Najafian, Bita; Shohrati, Majid; Harandi, Ali Amini; Mahyar, Shiva; Khaheshi, Isa; Ghanei, Mostafa

    2014-01-01

    Background: Chronic bronchiolitis is the most important problems of chemical victims of mustard gas. Diverse studies suggest that substance P (SP) as a member of tachykinin neuropeptides, has a significant role in the neurogenic inflammation processes of the airways and lungs. We aimed to determine the serum level of SP in chemical victims of mustard gas and compare it with normal subjects. Materials and Methods: The chemical victims were divided into the 2 groups of 30:A group with mild to moderate pulmonary symptoms and other group with moderate to severe symptoms and compared with 3rd group as healthy controls. After preparing our samples and using the SP kit, final analysis was performed with enzyme-linked immunosorbent assay reader. Results: The Concentration of circulatory SP levels in the chemical patients was 2.86 ± 1.47 ng/ml and had not a significant difference with the control group (3.15 ± 1.03 ng/ml) (P > 0.05). The circulatory SP levels were 2.48 ± 0.92 ng/ml and 3.28 ± 1.73 ng/ml in patients with moderate to severe symptoms and mild to moderates (P < 0.05) respectively. Conclusion: The SP may have a role in pulmonary complications of mustard gas. The lower level of SP in the moderate to severe patients may be due to corticosteroid consumption in such severe cases. However, further studies are needed to clarify the roles and mechanism of SP in this setting. PMID:25161984

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. Infective endocarditis due to Enterobacter cloacae resistant to third- and fourth-generation cephalosporins.

    PubMed

    Yoshino, Yusuke; Okugawa, Shu; Kimura, Satoshi; Makita, Eiko; Seo, Kazunori; Koga, Ichiro; Matsunaga, Naohisa; Kitazawa, Takatoshi; Ota, Yasuo

    2015-04-01

    We report the case of using a long-term combination of meropenem and amikacin to treat infective endocarditis caused by Enterobacter cloacae resistant to third- and fourth-generation cephalosporins. Multi-drug resistant Gram-negative bacilli, such as the E. cloacae in our study, may become possible pathogens of infective endocarditis. Our experience with this case indicates that long-term use of a combination of β-lactam and aminoglycosides might represent a suitable management option for future infective endocarditis cases due to non-Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella spp. (HACEK group) Gram-negative bacilli such as ours.

  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. 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.

  8. Effect of a plant polyphenol-rich extract on the lung protease activities of influenza-virus-infected mice.

    PubMed

    Serkedjieva, Julia; Toshkova, Reneta; Antonova-Nikolova, Stefka; Stefanova, Tsvetanka; Teodosieva, Ani; Ivanova, Iskra

    2007-01-01

    Influenza infection was induced in white mice by intranasal inoculation of the virus A/Aichi/2/68 (H3N2). The lung protease and the protease-inhibitory activities were followed for 9 days after infection. The intranasal application of a polyphenol-rich extract (PC) isolated from Geranium sanguineum L. induced a continuous rise in the anti-protease activity but did not cause substantial changes in the lung protease activity of healthy mice. Influenza virus infection triggered a slight reduction in protease activity in the lungs at 5 and 48 h post infection (p.i.) and a marked increase at 24 h and 6 day p.i.. Protease inhibition in the lungs was reduced at 24 and 48 h p.i. and an increase was observed at 5 h and 6 and 9 days p.i.. PC treatment brought both activities to normal levels. The restoration of the examined parameters was consistent with a prolongation of mean survival time and reduction of mortality rate, infectious virus titre and lung consolidation. PC reinstated superoxide production by alveolar macrophages and increased their number in virus-infected mice. The favourable effect on the protease and the protease-inhibitory activities in the lungs of influenza-virus-infected mice apparently contributes to the overall protective effect of PC in the murine experimental influenza A/Aichi infection. The antiviral effect of the individual constituents was evaluated. PMID:17542152

  9. 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

    2013-12-01

    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.

  10. [Infections of finger and toe nails due to fungi and bacteria].

    PubMed

    Nenoff, P; Paasch, U; Handrick, W

    2014-04-01

    Infections of the finger and the toe nails are most frequently caused by fungi, primarily dermatophytes. Causative agents of tinea unguium are mostly anthropophilic dermatophytes. Both in Germany, and worldwide, Trichophyton rubrum represents the main important causative agent of onychomycoses. Yeasts are isolated from fungal nail infections, both paronychia and onychomycosis far more often than generally expected. This can represent either saprophytic colonization as well as acute or chronic infection of the nail organ. The main yeasts causing nail infections are Candida parapsilosis, and Candida guilliermondii; Candida albicans is only in third place. Onychomycosis due to molds, or so called non-dermatophyte molds (NDM), are being increasingly detected. Molds as cause of an onychomycosis are considered as emerging pathogens. Fusarium species are the most common cause of NDM onychomycosis; however, rare molds like Onychocola canadensis may be found. Bacterial infections of the nails are caused by gram negative bacteria, usually Pseudomonas aeruginosa (recognizable because of green or black coloration of the nails) but also Klebsiella spp. and gram positive bacteria like Staphylococcus aureus. Treatment of onychomycosis includes application of topical antifungal agents (amorolfine, ciclopirox). If more than 50 % of the nail plate is affected or if more than three out of ten nails are affected by the fungal infection, oral treatment using terbinafine (in case of dermatophyte infection), fluconazole (for yeast infections), or alternatively itraconazole are recommended. Bacterial infections are treated topically with antiseptic agents (octenidine), and in some cases with topical antibiotics (nadifloxacin, gentamicin). Pseudomonas infections of the nail organ are treated by ciprofloxacin; other bacteria are treated according to the results of culture and sensitivity testing.

  11. 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

  12. Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria

    PubMed Central

    Falagas, Matthew E; Bliziotis, Ioannis A; Kasiakou, Sofia K; Samonis, George; Athanassopoulou, Panayiota; Michalopoulos, Argyris

    2005-01-01

    Background The increasing problem of infections due to multidrug-resistant Gram-negative bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-negative bacteria that are resistant to all available antibiotics, including polymyxins. Methods We present a case series of patients with infections due to pathogens resistant to all antimicrobial agents tested, including polymyxins. An isolate was defined as pandrug-resistant (PDR) if it exhibited resistance to all 7 anti-pseudomonal antimicrobial agents, i.e. antipseudomonal penicillins, cephalosporins, carbapenems, monobactams, quinolones, aminoglycosides, and polymyxins. Results Clinical cure of the infection due to pandrug-resistant (PDR) Gram-negative bacteria, namely Pseudomonas aeruginosa or Klebsiella pneumoniae was observed in 4 out of 6 patients with combination of colistin and beta lactam antibiotics. Conclusion Colistin, in combination with beta lactam antibiotics, may be a useful agent for the management of pandrug-resistant Gram-negative bacterial infections. The re-use of polymyxins, an old class of antibiotics, should be done with caution in an attempt to delay the rate of development of pandrug-resistant Gram-negative bacterial infections. PMID:15819983

  13. Mixed Fungal Lung Infection with Aspergillus Fumigatus and Candida Albicans in a Immunocomprimised Patient: Case Report

    PubMed Central

    Vipparti, Haritha

    2014-01-01

    The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades. In the immune-compromised host, many fungi, including species of fungi typically considered non-pathogenic, have the potential to cause serious morbidity and mortality. Here we report a rare case of mixed fungal infection of the lung with Candida albicans and Aspergillus fumigatus in a patient on prolonged steroid therapy. PMID:24959447

  14. Intrinsic and environmental mutagenesis drive diversification and persistence of Pseudomonas aeruginosa in chronic lung infections.

    PubMed

    Rodríguez-Rojas, Alexandro; Oliver, Antonio; Blázquez, Jesús

    2012-01-01

    Pseudomonas aeruginosa is a versatile opportunistic pathogen causing a wide variety of hospital-acquired acute infections in immunocompromised patients as well as chronic respiratory infections in patients suffering from cystic fibrosis or other chronic respiratory diseases. Several traits contribute to its ability to colonize and persist in the lungs of chronically infected patients, including development of high resistance to antimicrobials and hypermutability, biofilm growth, and alginate hyperproduction, or a customized pathogenicity, which may include the loss of classical virulence factors and metabolic changes. Here we argue that a combination of both intrinsic and environmental mutagenesis leads to a high number of mutant variants in the population. The conducive environment then triggers a positive feedback loop leading to adaptation and persistence of P. aeruginosa, rendering these chronic infections almost impossible to eradicate. PMID:22080096

  15. Demyelinating lesions due to Theiler's virus are associated with ongoing central nervous system infection.

    PubMed

    Chamorro, M; Aubert, C; Brahic, M

    1986-03-01

    We used in situ hybridization and immunocytochemistry to look for a correlation between virus expression and white matter lesions during late demyelinating disease due to persistent Theiler's virus infection. We found the following. (i) Tissue lesions developed at the site of virus infection. This correlation was not explained by infection of lymphocytes and macrophages. (ii) Large differences in the extent of pathology existed between mice. The amount of inflammation paralleled the number of cells containing viral RNA or viral capsid antigens. (iii) C57BL/6 mice, which are resistant to demyelination, were able to eradicate the infection. Our results are strongly in favor of a mechanism of demyelination in which viral gene products play a central role.

  16. Massive Alimentary Tract Bleeding due to Cytomegalovirus Infection in an Elderly Patient.

    PubMed

    Koc, Bora; Bircan, Huseyin Yuce; Altaner, Semsi; Cinar, Ozlem; Ozcelik, Umit; Yavuz, Alpaslan; Kemik, Ozgur

    2014-08-13

    In recent years, cytomegalovirus (CMV) has been recognized as an important common pathogen in immunocompromized patients. This is due to the increasing number of immunosuppressive medications, intensive cancer chemotherapy use, recurrent transplantations, progressively aging population, and the higher number of human immunodeficiency virus infections. Cytomegalovirus infection especially interests the gastrointestinal tract, anywhere, from the mouth to the anus. Namely, the most commonly affected area is the colon, followed by duodenum, stomach, esophagus and small intestine. The most frequent manifestations of CMV colitis are: diarrhea, fever, gastrointestinal bleeding and abdominal pain. We report here the case of an 82-year-old woman, who was treated for non-Hodgkin lymphoma; she was admitted to the emergency department for abdominal pain and diffuse arthralgia, following massive upper- and lower- gastrointestinal bleeding, due to duodenal and colonic ulcers related to CMV infection. PMID:25276331

  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. [Toll-like receptors expression in the lungs of human metapneumovirus infected mice and the effects of polyI:C on viral infection].

    PubMed

    Dou, Ying; Zhao, Yao; Zhang, Zhi-Yong; Zhao, Xiao-Dong

    2010-01-01

    To investigate the expression changes of Toll-like receptors (TLR) in the lungs of human metapneumovirus infected BALB/c mice, and to explore the effects of PolyI:C on viral replication, HMPV-infected group, PolyI:C+hMPV group, PolyI:C+DMED group and DMEM control group were set up for this study. All mice were sacrificed on day 1, 3, 5, 7, 9 and 16 post inoculation. Lungs were used for viral titration, pulmonary histopathology and detection of TLRs mRNA expression by RT-PCR and real-time PCR. Results showed that the levels of viral replication in the lungs of PolyI:C+hMPV infected mice were significantly decreased and lung inflammation were also lessened compared with those of hMPV infected mice. RT-PCR detection showed that mRNA levels of most TLRs were up-regulated (P < 0.05) in the lungs of hMPV infected group compared with DMEM group. Real time PCR assay showed that TLR7-8 mRNA significantly increased in hMPV infected group in a time-dependent manner. The level of TLR3 mRNA was significantly up-regulated in PolyI:C+hMPV group at the 24 hour after intranasal inoculation. The results showed that hMPV infection up-regulated the expression of TLRs in lungs of BALB/c mice and TLR7/8 pathway might play an important role in the start of natural immune response. PolyI:C was capable of inhibiting viral replication in the lung of mice and reducing lung inflammation probably through the early activation of TLR3.

  20. 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

  1. 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.

  2. Bioassay by intratracheal instillation for detection of lung toxicity due to fine particles in F344 male rats.

    PubMed

    Yokohira, Masanao; Takeuchi, Hijiri; Yamakawa, Keiko; Saoo, Kousuke; Matsuda, Yoko; Zeng, Yu; Hosokawa, Kyoko; Imaida, Katsumi

    2007-01-01

    We have established and documented an in vivo bioassay for detection of hazards with intratracheally instilled fine particles, which can be used for risk assessment of toxicity of materials inhaled into deep lung tissue of humans (Yokohira et al. Establishment of a bioassay system for detection of lung toxicity due to fine particle instillation: sequential histopathological changes with acute and subacute lung damage due to intratracheal instillation of quartz in F344 male rats. J Toxicol Pathol 2005;18:13-8). For validation we here examined toxicity of fine particles from quartz, hydrotalcite, potassium octatitanate, palladium oxide and carbon black with this bioassay. A total of 108, 10-week-old F344/DuCrj male rats were randomly divided into 8 groups. Groups 1 to 5 underwent intratracheal instillation of the 5 test particles (4 mg/rat) suspended in 0.2 ml vehicle (saline or 10% propylene glycol and 1% sodium carboxymethyl cellulose in saline: PG-CMC) with a specially designed aerolizer, and subgroups of 7 rats were killed on Days 1 and 28 thereafter. Groups 6 and 7 similarly were exposed to saline and PG-CMC, respectively, as vehicle controls, while group 8 was maintained untreated. Using histopathological changes and immunohistochemically assessed bromodeoxyuridine (BrdU) labeling indices, inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-3 (MMP-3) levels as end points, the quartz treated group exhibited high toxicity, while the values for the other particle-treated groups pointed to only slight effects. Although additional efforts are needed to establish advantages and disadvantages with our bioassay, models featuring intratracheal instillation clearly can be useful for detection of acute or subacute lung toxicity due to inhaled fine particles by using histopathological scoring and markers like BrdU and iNOS for screening purposes in short-term studies.

  3. 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

  4. Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung.

    PubMed

    Vidaña, Beatriz; Martínez, Jorge; Martínez-Orellana, Pamela; García Migura, Lourdes; Montoya, María; Martorell, Jaime; Majó, Natàlia

    2014-01-01

    The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts' capacities to mount efficient immune responses to control viral infection of the lung.

  5. 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

  6. Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections.

    PubMed Central

    Franchini, M; Walker, C; Henrard, D R; Suter-Gut, D; Braun, P; Villiger, B; Suter, M

    1995-01-01

    The lung is continuously exposed to infectious and non-infectious agents causing cell activation. Activated cells in the lung such as antigen-presenting cells which harbour HIV may favour this organ as a site for virus production. To test this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV-infected patients and healthy controls were obtained and the activation of the cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA-1. The HIV-infected individuals were subdivided into 'lung symptomatic' or 'lung asymptomatic' patients, depending on the presence or absence of secondary lung diseases besides HIV. All HIV-infected individuals demonstrated a decreased number of CD4+ lymphocytes in blood; however, normal numbers of these cells were found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and BAL was higher in lymphocytes from HIV-infected patients compared with controls. The activation state was highest in the lung symptomatic group. Lung symptomatic patients and lung asymptomatic patients with extrapulmonary infections had increased levels of free virus in plasma. Four out of four individuals without or with only low amounts of cell-free HIV in plasma belonged to the symptom-free subgroup. These results suggest that microorganisms other than HIV may promote viral replication via antigen-driven accumulation and activation of CD4+ cells in the lung or other organs, and thus may be responsible for the loss of helper T cells and the progression of the disease. PMID:7586671

  7. 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

  8. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

    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.

  10. Postmortem endogenous ethanol production and diffusion from the lung due to aspiration of wood chip dust in the work place.

    PubMed

    Furumiya, Junichi; Nishimura, Hiroyuki; Nakanishi, Akinori; Hashimoto, Yoshiaki

    2011-07-01

    We report an autopsy case of postmortem ethanol diffusion into the cardiac blood after aspiration of wood chips, although antemortem ethanol consumption was not evident. A man in his twenties, who was loading a truck with small wood chips in a hot, humid storehouse, was accidentally buried in a heap of chips. At the time the body was discovered, 20 h after the accident, rectal temperature was 36°C. Autopsy showed the cause of death to be asphyxia due to obstruction of the airway by aspiration of wood chips. The ethanol and n-propanol levels were significantly higher in the lungs (left, 0.603 and 0.009 mg/g; right, 0.571 and 0.006 mg/g) than in other tissues. A significant difference in ethanol concentration was observed between the left cardiac blood (0.243 mg/g) and the right femoral blood (0.042 mg/g). Low levels of ethanol and n-propanol were detected in the stomach contents (0.105 and 0.001 mg/g, respectively). In order to determine whether aspiration of wood chips affects postmortem ethanol production in the lung, we measured the ethanol and n-propanol levels of homogenized rabbit lung tissue incubated with autoclaved or non-autoclaved wood chips. Levels of ethanol and n-propanol were significantly higher in the homogenates incubated with non-autoclaved chips for 24h. The results of this animal experiment suggested that the ethanol detected in the lung was produced by putrefactive bacteria within the wood chips. After death, the ethanol produced endogenously in the lung appears to have diffused and affected the ethanol concentration of the left cardiac blood.

  11. Endovascular intervention for acute stroke due to infective endocarditis: case report.

    PubMed

    Dababneh, Haitham; Hedna, V Shushrutha; Ford, Jenna; Taimeh, Ziad; Peters, Keith; Mocco, J; Waters, Michael F

    2012-02-01

    The overall incidence of neurological complications due to infective endocarditis is as high as 40%, with embolic infarcts more common than hemorrhagic strokes. The standard of care for typical strokes does not apply to infective endocarditis because there is a substantial risk of hemorrhage with thrombolysis. In the last decade there have been multiple case reports of intravenous and intraarterial thrombolysis with successful outcomes for acute strokes with related infective endocarditis, but successful endovascular interventions for acute strokes associated with infective endocarditis are rarely reported. To the authors' knowledge, this report is the first case in the literature to use a mechanical retrieval device in successful vegetation retrieval in an infective endocarditis acute stroke. Although an interventional approach for treatment of acute stroke related to infective endocarditis is a promising option, it is controversial and a cautious clinical decision should be made on a case-by-case basis. The authors conclude that this approach can be tested in a case series with matched controls, because this condition is rare and a randomized clinical trial is not a realistic option.

  12. Hospital-acquired infections due to multidrug-resistant organisms in Hungary, 2005-2010.

    PubMed

    Caini, S; Hajdu, A; Kurcz, A; Borocz, K

    2013-01-10

    Healthcare-associated infections caused by multidrug-resistant organisms are associated with prolonged medical care, worse outcome and costly therapies. In Hungary, hospital-acquired infections (HAIs) due to epidemiologically important multidrug-resistant organisms are notifiable by law since 2004. Overall, 6,845 case-patients (59.8% men; median age: 65 years) were notified in Hungary from 2005 to 2010. One third of case-patients died in hospital. The overall incidence of infections increased from 5.4 in 2005 to 14.7 per 100,000 patient-days in 2010. Meticillin-resistant Staphylococcus aureus (MRSA) was the most frequently reported pathogen (52.2%), but while its incidence seemed to stabilise after 2007, notifications of multidrug-resistant Gram-negative organisms have significantly increased from 2005 to 2010. Surgical wound and bloodstream were the most frequently reported sites of infection. Although MRSA incidence has seemingly reached a plateau in recent years, actions aiming at reducing the burden of HAIs with special focus on Gram-negative multidrug-resistant organisms are needed in Hungary. Continuing promotion of antimicrobial stewardship, infection control methodologies, reinforced HAI surveillance among healthcare and infection control practitioners, and engagement of stakeholders, hospital managers and public health authorities to facilitate the implementation of existing guidelines and protocols are essential.

  13. 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

  14. Neonatal pneumococcal colonisation caused by Influenza A infection alters lung function in adult mice

    PubMed Central

    FitzPatrick, Meaghan; Royce, Simon G.; Langenbach, Shenna; McQualter, Jonathan; Reading, Patrick C.; Wijburg, Odilia; Anderson, Gary P.; Stewart, Alastair; Bourke, Jane; Bozinovski, Steven

    2016-01-01

    There is emerging epidemiological data to suggest that upper respiratory tract bacterial colonisation in infancy may increase the risk of developing respiratory dysfunction later in life, and respiratory viruses are known to precipitate persistent colonisation. This study utilized a neonatal mouse model of Streptococcus pneumonia (SP) and influenza A virus (IAV) co-infection, where bronchoalveolar leukocyte infiltration had resolved by adulthood. Only co-infection resulted in persistent nasopharyngeal colonisation over 40 days and a significant increase in airway resistance in response to in vivo methacholine challenge. A significant increase in hysteresivity was also observed in IAV and co-infected mice, consistent with ventilatory heterogeneity and structural changes in the adult lung. Airway hyper-responsiveness was not associated with a detectable increase in goblet cell transdifferentiation, peribronchial smooth muscle bulk or collagen deposition in regions surrounding the airways. Increased reactivity was not observed in precision cut lung slices challenged with methacholine in vitro. Histologically, the airway epithelium appeared normal and expression of epithelial integrity markers (ZO-1, occludin-1 and E-cadherin) were not altered. In summary, neonatal co-infection led to persistent nasopharyngeal colonisation and increased airway responsiveness that was not associated with detectable smooth muscle or mucosal epithelial abnormalities, however increased hysteresivity may reflect ventilation heterogeneity. PMID:26940954

  15. Alteration of pressure-volume characteristics due to different types of edema induction in isolated rabbit lungs.

    PubMed

    Seeger, W; Wolf, H R; Stähler, G; Neuhof, H

    1983-01-01

    In a model of isolated, ventilated and perfused rabbit lungs the influence of a fixed amount of edema (standardized at 7 g weight gain/kg body weight) on the pressure-volume characteristics of the isolated lungs was investigated. Periodical stimulation with A 23187 or A 23187 plus indomethacin or A 23187 plus indomethacin plus glutathione evokes an increase in vascular permeability with subsequent severe alterations of the pressure-volume characteristics, reflecting a disturbance in the alveolar surfactant system, which is more extensive the more rapidly the edema develops. The alterations caused this way are markedly more severe than those caused by the same amount of weight gain due to mechanically increased capillary filtration pressure. PMID:6410476

  16. The risk of biomaterial-associated infection after revision surgery due to an experimental primary implant infection.

    PubMed

    Engelsman, Anton F; Saldarriaga-Fernandez, Isabel C; Nejadnik, M Reza; van Dam, Gooitzen M; Francis, Kevin P; Ploeg, Rutger J; Busscher, Henk J; van der Mei, Henny C

    2010-10-01

    The fate of secondary biomaterial implants was determined by bio-optical imaging and plate counting, after antibiotic treatment of biomaterials-associated-infection (BAI) and surgical removal of an experimentally infected, primary implant. All primary implants and tissue samples from control mice showed bioluminescence and were culture-positive. In an antibiotic treated group, no bioluminescence was detected and only 20% of all primary implants and no tissue samples were culture-positive. After revision surgery, bioluminescence was detected in all control mice. All the implants and 80% of all tissue samples were culture-positive. In contrast, in the antibiotic treated group, 17% of all secondary implants and 33% of all tissue samples were culture-positive, despite antibiotic treatment. The study illustrates that due to the BAI of a primary implant, the infection risk of biomaterial implants is higher in revision surgery than in primary surgery, emphasizing the need for full clearance of the infection, as well as from surrounding tissues prior to implantation of a secondary implant.

  17. Immunization protected well nourished mice but not undernourished ones from lung injury in Methicillin-resistant Staphylococcus aureus (MRSA) infection

    PubMed Central

    2009-01-01

    Background Staphylococcus aureus methicillin-resistant (MRSA) has been frequently isolated from endotracheal and lung puncture aspirates in malnourished children with pneumonia. In this work we evaluated the susceptibility of undernourished BALB/c mice and its ability to mount a protective immunity against MRSA with emphasis on the lung involvement. Results BALB/c mice submitted to a 20% dietary restriction during 20 days presented a significant decrease in body weight, lymphocyte number and also atrophy in thymus and intestinal epithelium. Determination of bacterial load by the number of colony forming units (CFU) indicated a similar susceptibility whereas the findings of Gram stain clearly suggested a higher amount of bacteria in the lungs of normal mice than in the undernourished ones. Immunization reduced bacterial growth in the lungs of normal mice but not in the undernourished ones. Histopathological analysis showed that inflammation appeared in the lungs from normal mice only after infection and that immunization prevented this pulmonary inflammatory process. On the other hand, undernourished mice presented lung inflammation even before infection. In addition, the degree of this inflammatory process did not change with infection or previous immunization. Conclusion Our results indicated that lung injury during MRSA infection is prevented by previous immunization in well nourished but not in undernourished mice. PMID:19930660

  18. 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

  19. 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

  20. Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection.

    PubMed

    Kumar, Pankaj; Khanna, Madhu; Srivastava, Vikram; Tyagi, Yogesh Kumar; Raj, Hanumanthrao G; Ravi, K

    2005-06-01

    In the mice, instillation of influenza virus A/Udorn/317/72(H3N2) intranasally resulted in a significant decrease in the pulmonary concentrations of catalase, reduced glutathione, and superoxide dismutase. There was a decrease in vitamin E level also. These effects were observed on the 5th day after viral instillation. Oral supplementation with quercetin simultaneous with viral instillation produced significant increases in the pulmonary concentrations of catalase, reduced glutathione, and superoxide dismutase. However, quercetin did not reverse the fall in vitamin E level associated with the viral infection. It is concluded that during influenza virus infection, there is "oxidative stress." Because quercetin restored the concentrations of many antioxidants, it is proposed that it may be useful as a drug in protecting the lung from the deleterious effects of oxygen derived free radicals released during influenza virus infection.

  1. [Ciprofloxacin and therapy of urinary tract infections, including those due to Staphylococcus saprophyticus].

    PubMed

    Ivanov, D V; Budanov, S V

    2006-01-01

    Staphylococcus saprophyticus is one of the main pathogens of cystitis in young women. The human biotopes are contaminated by the staphylococcus on direct contacts with domestic animals or after using not properly cooked food of animal origin. Young women are more susceptible to colonization of the urinary tract by S. saprophyticus vs. the other contingents. Sexual intercourse is conducive to the colonization and infection. Shifts in the urinary tract microflora due to the use of spermicide, as well as candidiasis promote colonization of the urinary tract by S. saprophyticus. At present fluoroquinolones are considered as a significant independent group of chemotherapeutics within the class of quinolones, inhibitors of DNA gyrase, characterized by high clinical efficacy in the treatment of urinary tract infections. Especially significant clinical experience with ciprofloxacin in the therapy of urinary tract infections is available.

  2. Enhanced delivery of gentamicin to infection foci due to Staphylococcus aureus using gold nanorods.

    PubMed

    Salouti, Mojtaba; Heidari, Zahra; Ahangari, Azam; Zare, Somayeh

    2016-01-01

    Bacterial infections continue to be one of the major causes of morbidity and mortality. Although many methods for diagnosing and treating of infectious diseases currently exist, there is an urgent need for new and improved approaches for bacterial destruction. The present study focuses on the conjugation of gold nanorods (GNRs) with gentamicin via the Nanothink acid linker and its application in delivery of gentamicin to infection foci due to Staphylococcus aureus. The interaction between gentamicin and gold nanorods was confirmed by FT-IR spectroscopy. The high performance liquid chromatography (HPLC) and atomic absorption spectroscopy analyses showed that 2050 gentamicin molecules were attached to each gold nanorod. The minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of gentamicin-GNRs conjugate showed the enhancement of antibacterial effect of gentamicin. The biodistribution study demonstrated localization of the complex at the site of Staphylococcal infection with high sensitivity in mouse model.

  3. Ventriculoatrial shunt infection due to Cryptococcus neoformans: an ultrastructural and quantitative microbiological study.

    PubMed

    Walsh, T J; Schlegel, R; Moody, M M; Costerton, J W; Salcman, M

    1986-03-01

    A 28-year-old man presented with hydrocephalus due to an infection by Cryptococcus neoformans involving his ventriculoatrial shunt. Ultrastructural studies of the ventriculoatrial shunt demonstrated yeastlike organisms consistent with C. neoformans within a biofilm on the appliance. Quantitative microbiological studies of segments of the shunt demonstrated C. neoformans in a concentration gradient from 9 X 10(6) colony-forming units (CFU)/0.5-cm section involving the ventricular portion of the catheter to 1 X 10(2) CFU/0.5-cm section at the vascular tip. The clinical, microbiological, and ultrastructural data suggest that this cryptococcal infection started as a ventriculitis or encephalitis with extension to the meningeal surface. Future application of these methods may further elucidate the pathogenesis of ventriculoatrial shunt infections.

  4. An outbreak of nosocomial infection due to multiply resistant Serratia marcescens: evidence of interhospital spread.

    PubMed

    Schaberg, D R; Alford, R H; Anderson, R; Farmer, J J; Melly, M A; Schaffner, W

    1976-08-01

    Interhospital spread appeared to be responsible for a large epidemic of infections due to a strain of Serratia marcescens that was resistant to all currently available parenteral antibiotics. Between April 1, 1973 and January 1, 1975, 210 patients in four geographically separate hospitals in Nashville, Tennessee, were infected with the epidemic strain; 21 patients were bacteremic and eight died. Catheter-associated urinary tract infection accounted for the majority of isolates, and broad-spectrum antibiotic exposure appeared to promote the acquisition of the epidemic strain. The serotype (O1:H7) and phage type (186) of the organism were identical in all four hospitals, but background, sensitive strains of S. marcesens yielded a variety of other serotypes. Carriage on the hands of hospital personnel was implicated as the mode of spread within the hospital and apparently was the mode of transmission between the hospitals. Antibiotic resistance was largely episomally mediated, but resistance to gentamicin, cephalothin, and colistin was not transferable.

  5. 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

  6. 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

  7. Effect of Quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection.

    PubMed

    Kumar, Pankaj; Sharma, Sonal; Khanna, MadhU; Raj, Hanumantharao Guru

    2003-06-01

    Influenza virus infection, induced experimentally in mice, was associated with marked changes in lung morphology viz. epithelial damage with focal areas of reactive papillary hyperplasia, infiltration of leukocytes and development of oxidative stress, as evidenced by increased superoxide radical production and lipid peroxidation (LPO) products by alveolar macrophages. These effects were observed on the 5th day after virus instillation. The levels of superoxide and LPO were measured spectrophotometrically by the nitroblue tetrazolium (NBT) assay and thiobarbituric acid reactive species (TBARS) assay, respectively. The former increased by 1.5-2 fold and the latter was raised by 85% when compared with normal control. Supplementation of intranasal viral instillation with the anti-oxidant, Quercetin, given orally, resulted in a significant decrease in the levels of both superoxide radicals and LPO products. There was also a significant decrease in the number of infiltrating cells. A mild to moderate protective effect was observed in lung morphology. Thus, Quercetin may be useful as a drug in reducing the oxidative stress induced by influenza virus infection in the lung, and protect it from the toxic effects of the free radicals.

  8. Alterations in lung clearance mechanisms due to single and repeated nitrogen dioxide exposures in the rabbit

    SciTech Connect

    Vollmuth, T.A.

    1986-01-01

    Tracheobronchial mucociliary clearance was assessed following single, two-hour exposures to either 0.3, 1.0, 3.0, or 10.0 ppm NO/sub 2/, or 14 daily two hour exposures to 0.3, 1.0, 3.0 ppm NO/sub 2/. No significant changes in the mean residence time of tracer particles in the tracheobronchial region were produced under any exposure condition, indicating no effect upon mucociliary clearance. Macrophage functional properties were examined in vitro at select times following single, two hour in vivo exposures to 1.0 and 10.0 ppm NO/sub 2/. Macrophage number and viability were not affected; however, significant dose-related differences in phagocytosis and mobility were observed. These changes were associated with altered in vivo alveolar clearance patterns. Additional studies examined the effects of in vitro exposure to nitrite and hydrogen ion, two known NO/sub 2/ reaction products in the lung, on macrophage phagocytosis. While hydrogen ion had no effect at the levels used, nitrate was shown to enhance phagocytosis. These results demonstrate that alveolar clearance and macrophage function are altered by short-term NO/sub 2/ exposure at realistic, environmental levels. These data also provide insight into the mechanisms of NO/sub 2/-induced alteration in lung clearance pathways.

  9. Comparison of four lung scoring systems for the assessment of the pathological outcomes derived from Actinobacillus pleuropneumoniae experimental infections

    PubMed Central

    2014-01-01

    Background In this study, four lung lesion scoring methods (Slaughterhouse Pleurisy Evaluation System [SPES], Consolidation Lung Lesion Score [LLS], Image analyses [IA] and Ratio of lung weight/body weight [LW/BW]) were compared for the assessment of the different pathological outcomes derived from an Actinobacillus pleuropneumoniae (App) experimental infection model. Moreover, pathological data was coupled with clinical (fever, inappetence and clinical score), production (average daily weigh gain [ADWG]) and diagnostic (PCR, ELISA and bacterial isolation) parameters within the four infection outcomes (peracute, acute, subclinically infected and non-infected). Results From the 61 inoculated animals, 9 were classified as peracute (presence of severe App-like clinical signs and lesions and sudden death or euthanasia shortly after inoculation), 31 as acutely affected (presence of App-like clinical signs and lesions and survival until the end of the experiment), 12 as subclinically infected (very mild or no clinical signs but App infection confirmed) and 9 as non-infected animals (lack of App-like clinical signs and lack of evidence of App infection). A significant correlation between all lung lesion scoring systems was found with the exception of SPES score versus LW/BW. SPES showed a statistically significant association with all clinical, production and diagnostic (with the exception of PCR detection of App in the tonsil) variables assessed. LLS and IA showed similar statistically significant associations as SPES, with the exception of seroconversion against App at necropsy. In contrast, LW/BW was statistically associated only with App isolation in lungs, presence of App-like lesions and ELISA OD values at necropsy. Conclusions In conclusion, SPES, LLS and IA are economic, fast and easy-to-perform lung scoring methods that, in combination with different clinical and diagnostic parameters, allow the characterization of different outcomes after App infection. PMID

  10. Premature delivery due to intrauterine Candida infection that caused neonatal congenital cutaneous candidiasis: a case report.

    PubMed

    Ito, Fumitake; Okubo, Tomoharu; Yasuo, Tadahiro; Mori, Taisuke; Iwasa, Koichi; Iwasaku, Kazuhiro; Kitawaki, Jo

    2013-01-01

    Congenital cutaneous candidiasis is a very rare disease with less than 100 cases published in the medical literature. Neonates having this disease present with systemic skin lesions caused by intrauterine Candida infections. We present a case of threatened premature delivery due to Candida chorioamnionitis, which caused both maternal postpartum endometritis and neonatal congenital cutaneous candidiasis. A 34-year-old woman who was admitted for fetal membrane bulging at 20 weeks of gestation underwent McDonald cervical cerclage. We diagnosed threatened premature delivery due to intrauterine infection; therefore, we terminated the gestation by cesarean section at 24 weeks of gestation. Fungi-like yeast was detected in infantile gastric juice. Histopathological findings of the placenta revealed that Candida albicans mycelium invaded the placenta, chorioamniotic membrane and umbilical cord.

  11. 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

  12. Unorthodox long-term aerosolized ampicillin use for methicillin-susceptible Staphylococcus aureus lung infection in a cystic fibrosis patient.

    PubMed

    Máiz, Luis; Lamas, Adelaida; Fernández-Olmos, Ana; Suárez, Lucrecia; Cantón, Rafael

    2009-05-01

    Staphylococcus aureus is a significant cause of pulmonary colonization in cystic fibrosis (CF) patients. The optimal strategy of therapy in chronically infected patients with this pathogen is not yet established. We report a successful long-term aerosolized ampicillin treatment of a 14-year-old girl with chronic symptomatic S. aureus lung infection.

  13. Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs.

    PubMed

    Cardenas, Silvia; Scuri, Mario; Samsell, Lennie; Ducatman, Barbara; Bejarano, Pablo; Auais, Alexander; Doud, Melissa; Mathee, Kalai; Piedimonte, Giovanni

    2010-09-01

    Early-life respiratory infection with Pseudomonas aeruginosa is common in children with cystic fibrosis or immune deficits. Although many of its clinical manifestations involve neural reflexes, little information is available on the peripheral nervous system of infected airways. This study sought to determine whether early-life infection triggers a neurogenic-mediated immunoinflammatory response, the mechanisms of this response, and its relationship with other immunoinflammatory pathways. Weanling and adult rats were inoculated with suspensions containing P. aeruginosa (PAO1) coated on alginate microspheres suspended in Tris-CaCl(2) buffer. Five days after infection, rats were injected with capsaicin to stimulate nociceptive nerves in the airway mucosa, and microvascular permeability was measured using Evans blue as a tracer. PAO1 increased neurogenic inflammation in the extra- and intrapulmonary compartments of weanlings but not in adults. The mechanism involves selective overexpression of NGF, which is critical for the local increase in microvascular permeability and for the infiltration of polymorphonuclear leukocytes into infected lung parenchyma. These effects are mediated in part by induction of downstream inflammatory cytokines and chemokines, especially IL-1beta, IL-18, and leptin. Our data suggest that neurogenic-mediated immunoinflammatory mechanisms play important roles in airway inflammation and hyperreactivity associated with P. aeruginosa when infection occurs early in life. PMID:20543002

  14. Antipseudomonal Bacteriophage Reduces Infective Burden and Inflammatory Response in Murine Lung

    PubMed Central

    Pabary, Rishi; Singh, Charanjit; Morales, Sandra; Bush, Andrew; Alshafi, Khalid; Bilton, Diana; Alton, Eric W. F. W.; Smithyman, Anthony

    2015-01-01

    As antibiotic resistance increases, there is a need for new therapies to treat infection, particularly in cystic fibrosis (CF), where Pseudomonas aeruginosa is a ubiquitous pathogen associated with increased morbidity and mortality. Bacteriophages are an attractive alternative treatment, as they are specific to the target bacteria and have no documented side effects. The efficacy of phage cocktails was established in vitro. Two P. aeruginosa strains were taken forward into an acute murine infection model with bacteriophage administered either prophylactically, simultaneously, or postinfection. The infective burden and inflammation in bronchoalveolar lavage fluid (BALF) were assessed at various times. With low infective doses, both control mice and those undergoing simultaneous phage treatment cleared P. aeruginosa infection at 48 h, but there were fewer neutrophils in BALF of phage-treated mice (median, 73.2 × 104/ml [range, 35.2 to 102.1 × 104/ml] versus 174 × 104/ml [112.1 to 266.8 × 104/ml], P < 0.01 for the clinical strain; median, 122.1 × 104/ml [105.4 to 187.4 × 104/ml] versus 206 × 104/ml [160.1 to 331.6 × 104/ml], P < 0.01 for PAO1). With higher infective doses of PAO1, all phage-treated mice cleared P. aeruginosa infection at 24 h, whereas infection persisted in all control mice (median, 1,305 CFU/ml [range, 190 to 4,700 CFU/ml], P < 0.01). Bacteriophage also reduced CFU/ml in BALF when administered postinfection (24 h) and both CFU/ml and inflammatory cells in BALF when administered prophylactically. A reduction in soluble inflammatory cytokine levels in BALF was also demonstrated under different conditions. Bacteriophages are efficacious in reducing both the bacterial load and inflammation in a murine model of P. aeruginosa lung infection. This study provides proof of concept for future clinical trials in patients with CF. PMID:26574007

  15. Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung disease.

    PubMed

    Zamora-Legoff, Jorge A; Krause, Megan L; Crowson, Cynthia S; Ryu, Jay H; Matteson, Eric L

    2016-10-01

    The objective of this study is to assess the occurrence of and risk factors for serious infections in rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). All patients with RA-ILD (ACR 1987 criteria for RA) seen at a single center from 1998 to 2014 were identified and manually screened for study inclusion. Follow-up data were abstracted until death or December 31, 2015. Serious infection was defined as requiring antimicrobial therapy and hospitalization. Risk of infection was analyzed by person-year (py) methods using time-dependent covariates started when the medication was first used and stopped 30 days after the medication was discontinued. Of the 181 included patients, 87 (48 %) were female. The mean age at ILD diagnosis was 67.4 (±9.9) years, and median follow-up time was 3.1 (range: 0.01 to 14.8) years. Higher infection rates were observed during the first year after ILD diagnosis (14.1 per 100 py) than subsequently (5.7 per 100 py; p = 0.001). Pneumonia was the most common (3.9 per 100 py). Overall infection risk was higher in organizing pneumonia (OP) (27.1 per 100 py) than usual interstitial pneumonia (7.7 per 100 py) or non-specific interstitial pneumonia (5.5 per 100 py) (p < 0.001). The highest infection rate observed was with a daily prednisone use >10 mg per day (15.4 per 100 py). Patients with RA-ILD are at risk of serious infection. Prednisone use >10 mg per day was associated with higher rates of infection. Immunosuppressive drug use governed by concern for risk of infection in patients with ILD resulting in channeling bias cannot be excluded. PMID:27448151

  16. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome

    PubMed Central

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G.; Britton, Steven L.; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses. PMID:25978669

  17. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    PubMed

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G; Britton, Steven L; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  18. Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis.

    PubMed

    Vazquez-Espinosa, E; Marcos, C; Alonso, T; Giron, R M; Gomez-Punter, R M; Garcia-Castillo, E; Zamora, E; Cisneros, C; Garcia, J; Valenzuela, C; Ancochea, J

    2016-01-01

    Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.

  19. Primary orbital chronic granulomatous reaction to deep staphylococcal infection due to trauma in immunocompetent.

    PubMed

    Rao, Lavanya G; Gonsalves, Sarita R J; Pathan, Atiya; Sinha, Akansha

    2013-01-01

    A 53-year-old man presented with a slow-growing mass in the right orbit and temporal area of 1 year duration following a road traffic accident. Examination revealed a nodular fungating mass involving the orbit, right temporal area with multiple discharging sinuses causing proptosis and restricted ocular motility. The patient denied light perception in the right eye. There was exposure keratopathy and optic atrophy. Imaging showed mass lesion of the orbit extending intracranially. Tissue biopsy and culture revealed a chronic granulomatous reaction due to deep infection with coagulase-positive staphylococci. The patient showed remarkable improvement to systemic antibiotics and anticonvulsants. Mortality is high in such cases due to intracranial extension if there is a delay in treatment. This case report summarises a rare aetiology and successful treatment of a case of chronic granulomatous reaction due to deep bacterial infection following trauma and is deemed rare as cases of primary orbital infection in immunocompetent have not been reported so far. PMID:23904427

  20. 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.

  1. 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.

  2. Changes in Immunohistochemical Protein Levels in Anaplastic Lymphoma Kinase-positive Lung Adenocarcinoma Possibly due to Chemo-radiotherapy.

    PubMed

    Taniguchi, Hirokazu; Ikeda, Takaya; Soda, Hiroshi; Fukuda, Yuichi; Kitazaki, Takeshi; Nakamura, Yoichi; Kohno, Shigeru

    2016-01-01

    To detect the anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are the standard methods. However, there are discrepancies between them. We herein report a 40-year-old woman with ALK fusion-positive adenocarcinoma that changed from positive to negative in IHC due to chemo-radiotherapy. Recurrence of the disease restored the IHC expression, whereas FISH was positive throughout the entire clinical course. Our experience suggests that we should therefore carefully evaluate samples after chemotherapy and radiotherapy. PMID:27374682

  3. Isolation and purification of Mycobacterium tuberculosis from H37Rv infected guinea pig lungs.

    PubMed

    Shi, Libin; Ryan, Gavin J; Bhamidi, Suresh; Troudt, JoLynn; Amin, Anita; Izzo, Angelo; Lenaerts, Anne J; McNeil, Michael R; Belisle, John T; Crick, Dean C; Chatterjee, Delphi

    2014-09-01

    Evidence suggests that Mycobacterium tuberculosis grown in vivo may have a different phenotypic structure from its in vitro counterpart. In order to study the differences between in vivo and in vitro grown bacilli, it is important to establish a reliable method for isolating and purifying M. tuberculosis from infected tissue. In this study, we developed an optimal method to isolate bacilli from the lungs of infected guinea pigs, which was also shown to be applicable to the interferon-γ gene knockout mouse model. Briefly, 1) the infected lungs were thoroughly homogenized; 2) a four step enzymatic digestion was utilized to reduce the bulk of the host tissue using collagenase, DNase I and pronase E; 3) residual contamination by the host tissue debris was successfully reduced using percoll density gradient centrifugation. These steps resulted in a protocol such that relatively clean, viable bacilli can be isolated from the digested host tissue homogenate in about 50% yield. These bacilli can further be used for analytical studies of the more stable cellular components such as lipid, peptidoglycan and mycolic acid.

  4. 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

  5. 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

  6. 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

  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. 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

  9. Genome-Wide Identification of Klebsiella pneumoniae Fitness Genes during Lung Infection

    PubMed Central

    Breen, Paul; Deornellas, Valerie; Mu, Qiao; Zhao, Lili; Wu, Weisheng; Cavalcoli, James D.; Mobley, Harry L. T.

    2015-01-01

    ABSTRACT Klebsiella pneumoniae is an urgent public health threat because of resistance to carbapenems, antibiotics of last resort against Gram-negative bacterial infections. Despite the fact that K. pneumoniae is a leading cause of pneumonia in hospitalized patients, the bacterial factors required to cause disease are poorly understood. Insertion site sequencing combines transposon mutagenesis with high-throughput sequencing to simultaneously screen thousands of insertion mutants for fitness defects during infection. Using the recently sequenced K. pneumoniae strain KPPR1 in a well-established mouse model of pneumonia, insertion site sequencing was performed on a pool of >25,000 transposon mutants. The relative fitness requirement of each gene was ranked based on the ratio of lung to inoculum read counts and concordance between insertions in the same gene. This analysis revealed over 300 mutants with at least a 2-fold fitness defect and 69 with defects ranging from 10- to >2,000-fold. Construction of 6 isogenic mutants for use in competitive infections with the wild type confirmed their requirement for lung fitness. Critical fitness genes included those for the synthesis of branched-chain and aromatic amino acids that are essential in mice and humans, the transcriptional elongation factor RfaH, and the copper efflux pump CopA. The majority of fitness genes were conserved among reference strains representative of diverse pathotypes. These results indicate that regulation of outer membrane components and synthesis of amino acids that are essential to its host are critical for K. pneumoniae fitness in the lung. PMID:26060277

  10. Six-Month Multicenter Study on Invasive Infections Due to Group B Streptococci in Argentina

    PubMed Central

    Lopardo, Horacio A.; Vidal, Patricia; Jeric, Paola; Centron, Daniela; Paganini, Hugo; Facklam, Richard R.; Elliott, John

    2003-01-01

    There is little information about invasive infections by group B streptococci (GBS) and their antimicrobial susceptibilities in Latin America. We performed a prospective multicenter study to determine the serotype distribution and the antimicrobial susceptibility of GBS in Argentina. We identified 58 cases, but only 44 had sufficient data to be evaluated. Eight early-, four late-, and one fatal late, late-onset neonatal infections due to GBS were found. A total of 31 patients were adults with bacteremia, skin and soft tissue infections, osteomyelitis, arthritis, meningitis, abdominal infections, and renal abscess. Serotype III was prevalent in late-onset neonatal disease, and several serotypes (Ia/c, III, Ia, and II) were involved in early-onset neonatal infections. Serotypes II, Ia/c, III, and IV were commonly found in adults, with serotype II prevalent in younger adults (18 to 69 years old) and serotype Ia/c prevalent in elderly adults (>70 years old). The mortality rate attributable to GBS infections was 10.8%. All GBS were susceptible to penicillin and ceftriaxone. Resistance to clindamycin (1.7%), erythromycin (5.2%), azithromycin (5.2%), minocycline (69%), and tetracycline (72.4%), to high levels of kanamycin and amikacin (1.7%), and to intermediately high levels of gentamicin (1.7%) was observed. The bifunctional enzyme AAC6′-APH2" was detected in the isolate resistant to aminoglycosides, and other genetic determinants were identified in other resistant isolates: tetM and tetO in tetracycline-resistant streptococci and mefA and ermTR for efflux-mediated and inducible macrolide-lincosamide-streptogramin B-resistant streptococci, respectively. For clinical purposes and rapid and easy detection of high-level aminoglycoside-resistant GBS, a screening method that used 1,000-μg kanamycin disks is proposed. PMID:14532204

  11. In Vivo Activity of Ceftobiprole in Murine Skin Infections Due to Staphylococcus aureus and Pseudomonas aeruginosa▿

    PubMed Central

    Fernandez, Jeffrey; Hilliard, Jamese J.; Abbanat, Darren; Zhang, Wenyan; Melton, John L.; Santoro, Colleen M.; Flamm, Robert K.; Bush, Karen

    2010-01-01

    Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in a subcutaneous skin infection model with Staphylococcus aureus Smith OC 4172 (methicillin-susceptible S. aureus [MSSA]), S. aureus OC 8525 (MRSA), Pseudomonas aeruginosa OC 4351 (having an inducible AmpC β-lactamase), and P. aeruginosa OC 4354 (overproducing AmpC β-lactamase). In the MSSA and MRSA infection models, ceftobiprole, administered as the prodrug ceftobiprole medocaril, was more effective in reducing CFU/g skin (P < 0.001) than were cefazolin, vancomycin, or linezolid based on the dose-response profiles. Skin lesion volumes in MSSA-infected animals treated with ceftobiprole were 19 to 29% lower than those for cefazolin-, vancomycin-, or linezolid-treated animals (P < 0.001). In MRSA infections, lesion size in ceftobiprole-treated mice was 34% less than that with cefazolin or linezolid treatment (P < 0.001). Against P. aeruginosa, ceftobiprole at similar doses was as effective as meropenem-cilastatin in reductions of CFU/g skin, despite 8- and 32-fold-lower MICs for meropenem; both treatments were more effective than was cefepime (P < 0.001) against the inducible and overproducing AmpC β-lactamase strains of P. aeruginosa. Ceftobiprole was similar to meropenem-cilastatin and 47 to 54% more effective than cefepime (P < 0.01) in reducing the size of the lesion caused by either strain of P. aeruginosa in this study. These studies indicate that ceftobiprole is effective in reducing both bacterial load and lesion volume associated with infections due to MSSA, MRSA, and P. aeruginosa in this murine model of skin and soft tissue infection. PMID:19884364

  12. Pseudomonas aeruginosa Uses Multiple Pathways To Acquire Iron during Chronic Infection in Cystic Fibrosis Lungs

    PubMed Central

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

    2013-01-01

    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. 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

  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. 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.

  16. [Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection].

    PubMed

    Carella, E; Moschini, G L; Romanelli, F; Bossalini, G; Alberici, F; Viale, P; Ratti, G

    1997-05-01

    We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.

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

    PubMed Central

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

    2015-01-01

    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

  18. Inhibition of autophagy ameliorates acute lung injury caused by avian influenza A H5N1 infection.

    PubMed

    Sun, Yang; Li, Chenggang; Shu, Yuelong; Ju, Xiangwu; Zou, Zhen; Wang, Hongliang; Rao, Shuan; Guo, Feng; Liu, Haolin; Nan, Wenlong; Zhao, Yan; Yan, Yiwu; Tang, Jun; Zhao, Chen; Yang, Peng; Liu, Kangtai; Wang, Shunxin; Lu, Huijun; Li, Xiao; Tan, Lei; Gao, Rongbao; Song, Jingdong; Gao, Xiang; Tian, Xinlun; Qin, Yingzhi; Xu, Kai-Feng; Li, Dangsheng; Jin, Ningyi; Jiang, Chengyu

    2012-02-21

    The threat of a new influenza pandemic has existed since 1997, when the highly pathogenic H5N1 strain of avian influenza A virus infected humans in Hong Kong and spread across Asia, where it continued to infect poultry and people. The human mortality rate of H5N1 infection is about 60%, whereas that of seasonal H1N1 infection is less than 0.1%. The high mortality rate associated with H5N1 infection is predominantly a result of respiratory failure caused by acute lung injury; however, how viral infection contributes to this disease pathology is unclear. Here, we used electron microscopy to show the accumulation of autophagosomes in H5N1-infected lungs from a human cadaver and mice, as well as in infected A549 human epithelial lung cells. We also showed that H5N1, but not seasonal H1N1, induced autophagic cell death in alveolar epithelial cells through a pathway involving the kinase Akt, the tumor suppressor protein TSC2, and the mammalian target of rapamycin. Additionally, we suggest that the hemagglutinin protein of H5N1 may be responsible for stimulating autophagy. When applied prophylactically, reagents that blocked virus-induced autophagic signaling substantially increased the survival rate of mice and substantially ameliorated the acute lung injury and mortality caused by H5N1 infection. We conclude that the autophagic cell death of alveolar epithelial cells likely plays a crucial role in the high mortality rate of H5N1 infection, and we suggest that autophagy-blocking agents might be useful as prophylactics and therapeutics against infection of humans by the H5N1 virus. PMID:22355189

  19. Systems Medicine for Lung Diseases: Phenotypes and Precision Medicine in Cancer, Infection, and Allergy.

    PubMed

    Schmeck, Bernd; Bertrams, Wilhelm; Lai, Xin; Vera, Julio

    2016-01-01

    Lung diseases cause an enormous socioeconomic burden. Four of them are among the ten most important causes of deaths worldwide: Pneumonia has the highest death toll of all infectious diseases, lung cancer kills the most people of all malignant proliferative disorders, chronic obstructive pulmonary disease (COPD) ranks third in mortality among the chronic noncommunicable diseases, and tuberculosis is still one of the most important chronic infectious diseases. Despite all efforts, for example, by the World Health Organization and clinical and experimental researchers, these diseases are still highly prevalent and harmful. This is in part due to the specific organization of tissue homeostasis, architecture, and immunity of the lung. Recently, several consortia have formed and aim to bring together clinical and molecular data from big cohorts of patients with lung diseases with novel experimental setups, biostatistics, bioinformatics, and mathematical modeling. This "systems medicine" concept will help to match the different disease modalities with adequate therapeutic and possibly preventive strategies for individual patients in the sense of precision medicine.

  20. 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

  1. Use of an artificial neural network to predict risk factors of nosocomial infection in lung cancer patients.

    PubMed

    Chen, Jie; Pan, Qin-Shi; Hong, Wan-Dong; Pan, Jingye; Zhang, Wen-Hui; Xu, Gang; Wang, Yu-Min

    2014-01-01

    Statistical methods to analyze and predict the related risk factors of nosocomial infection in lung cancer patients are various, but the results are inconsistent. A total of 609 patients with lung cancer were enrolled to allow factor comparison using Student's t-test or the Mann-Whitney test or the Chi-square test. Variables that were significantly related to the presence of nosocomial infection were selected as candidates for input into the final ANN model. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of nosocomial infection from lung cancer in this entire study population was 20.1% (165/609), nosocomial infections occurring in sputum specimens (85.5%), followed by blood (6.73%), urine (6.0%) and pleural effusions (1.82%). It was shown that long term hospitalization (≥ 22 days, P= 0.000), poor clinical stage (IIIb and IV stage, P=0.002), older age (≥ 61 year old, P=0.023), and use the hormones were linked to nosocomial infection and the ANN model consisted of these four factors .The artificial neural network model with variables consisting of age, clinical stage, time of hospitalization, and use of hormones should be useful for predicting nosocomial infection in lung cancer cases.

  2. Guillain-Barré Syndrome in a Boy With Lung Fluke Infection: Case Report and Literature Review.

    PubMed

    Yang, Cui-Wei; Gao, Feng; Xia, Zhe-Zhi

    2015-08-01

    Guillain-Barré syndrome is the most common acute peripheral neuropathy in children in most countries. The cause and pathogenesis of the disease have yet to be clarified. There have been only a few reports of Guillain-Barré syndrome resulting from parasite infections worldwide, no cases of Guillain-Barré syndrome after lung fluke infection have been reported. We report a case of an 8-year-old male patient with Guillain-Barré syndrome after lung fluke infection. The child had a history of consumption of undercooked crabs. He was diagnosed with paragonimiasis. The patient experienced paralysis of and pain in the lower limbs about 3 weeks after symptom onset. Neurologic and electrophysiologic examination findings supported the diagnosis of Guillain-Barré syndrome. Parasitic infections should also be considered when determining which antecedent infection is associated with Guillain-Barré syndrome.

  3. Risk Factors and Outcomes for Patients with Bloodstream Infection Due to Acinetobacter baumannii-calcoaceticus Complex

    PubMed Central

    Marchaim, Dror; Johnson, Paul C.; Awali, Reda A.; Doshi, Hardik; Chalana, Indu; Davis, Naomi; Zhao, Jing J.; Pogue, Jason M.; Parmar, Sapna; Kaye, Keith S.

    2014-01-01

    Identifying patients at risk for bloodstream infection (BSI) due to Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ABC) and providing early appropriate therapy are critical for improving patient outcomes. A retrospective matched case-control study was conducted to investigate the risk factors for BSI due to ABC in patients admitted to the Detroit Medical Center (DMC) between January 2006 and April 2009. The cases were patients with BSI due to ABC; the controls were patients not infected with ABC. Potential risk factors were collected 30 days prior to the ABC-positive culture date for the cases and 30 days prior to admission for the controls. A total of 245 case patients were matched with 245 control patients. Independent risk factors associated with BSI due to ABC included a Charlson's comorbidity score of ≥3 (odds ratio [OR], 2.34; P = 0.001), a direct admission from another health care facility (OR, 4.63; P < 0.0001), a prior hospitalization (OR, 3.11; P < 0.0001), the presence of an indwelling central venous line (OR, 2.75; P = 0.011), the receipt of total parenteral nutrition (OR, 21.2; P < 0.0001), the prior receipt of β-lactams (OR, 3.58; P < 0.0001), the prior receipt of carbapenems (OR, 3.18; P = 0.006), and the prior receipt of chemotherapy (OR, 15.42; P < 0.0001). The median time from the ABC-positive culture date to the initiation of the appropriate antimicrobial therapy was 2 days (interquartile range [IQR], 1 to 3 days). The in-hospital mortality rate was significantly higher among case patients than among control patients (OR, 3.40; P < 0.0001). BSIs due to ABC are more common among critically ill and debilitated institutionalized patients, who are heavily exposed to health care settings and invasive devices. PMID:24890594

  4. 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

  5. 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

  6. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge.

  7. Investigating the role of nucleotide-binding oligomerization domain-like receptors in bacterial lung infection.

    PubMed

    Leissinger, Mary; Kulkarni, Ritwij; Zemans, Rachel L; Downey, Gregory P; Jeyaseelan, Samithamby

    2014-06-15

    Lower respiratory tract infections (LRTIs) are a persistent and pervasive public health problem worldwide. Pneumonia and other LRTIs will be among the leading causes of death in adults, and pneumonia is the single largest cause of death in children. LRTIs are also an important cause of acute lung injury and acute exacerbations of chronic obstructive pulmonary disease. Because innate immunity is the first line of defense against pathogens, understanding the role of innate immunity in the pulmonary system is of paramount importance. Pattern recognition molecules (PRMs) that recognize microbial-associated molecular patterns are an integral component of the innate immune system and are located in both cell membranes and cytosol. Toll-like receptors and nucleotide-binding oligomerization domain-like receptors (NLRs) are the major sensors at the forefront of pathogen recognition. Although Toll-like receptors have been extensively studied in host immunity, NLRs have diverse and important roles in immune and inflammatory responses, ranging from antimicrobial properties to adaptive immune responses. The lung contains NLR-expressing immune cells such as leukocytes and nonimmune cells such as epithelial cells that are in constant and close contact with invading microbes. This pulmonary perspective addresses our current understanding of the structure and function of NLR family members, highlighting advances and gaps in knowledge, with a specific focus on immune responses in the respiratory tract during bacterial infection. Further advances in exploring cellular and molecular responses to bacterial pathogens are critical to develop improved strategies to treat and prevent devastating infectious diseases of the lung. PMID:24707903

  8. Detection of Quiescent Infections with Multiple Elephant Endotheliotropic Herpesviruses (EEHVs), Including EEHV2, EEHV3, EEHV6, and EEHV7, within Lymphoid Lung Nodules or Lung and Spleen Tissue Samples from Five Asymptomatic Adult African Elephants

    PubMed Central

    Zong, Jian-Chao; Heaggans, Sarah Y.; Long, Simon Y.; Latimer, Erin M.; Nofs, Sally A.; Bronson, Ellen; Casares, Miguel; Fouraker, Michael D.; Pearson, Virginia R.; Richman, Laura K.

    2015-01-01

    ABSTRACT More than 80 cases of lethal hemorrhagic disease associated with elephant endotheliotropic herpesviruses (EEHVs) have been identified in young Asian elephants worldwide. Diagnostic PCR tests detected six types of EEHV in blood of elephants with acute disease, although EEHV1A is the predominant pathogenic type. Previously, the presence of herpesvirus virions within benign lung and skin nodules from healthy African elephants led to suggestions that African elephants may be the source of EEHV disease in Asian elephants. Here, we used direct PCR-based DNA sequencing to detect EEHV genomes in necropsy tissue from five healthy adult African elephants. Two large lung nodules collected from culled wild South African elephants contained high levels of either EEHV3 alone or both EEHV2 and EEHV3. Similarly, a euthanized U.S. elephant proved to harbor multiple EEHV types distributed nonuniformly across four small lung nodules, including high levels of EEHV6, lower levels of EEHV3 and EEHV2, and a new GC-rich branch type, EEHV7. Several of the same EEHV types were also detected in random lung and spleen samples from two other elephants. Sanger PCR DNA sequence data comprising 100 kb were obtained from a total of 15 different strains identified, with (except for a few hypervariable genes) the EEHV2, EEHV3, and EEHV6 strains all being closely related to known genotypes from cases of acute disease, whereas the seven loci (4.0 kb) obtained from EEHV7 averaged 18% divergence from their nearest relative, EEHV3. Overall, we conclude that these four EEHV species, but probably not EEHV1, occur commonly as quiescent infections in African elephants. IMPORTANCE Acute hemorrhagic disease characterized by high-level viremia due to infection by members of the Proboscivirus genus threatens the future breeding success of endangered Asian elephants worldwide. Although the genomes of six EEHV types from acute cases have been partially or fully characterized, lethal disease predominantly

  9. Birth weight, childhood lower respiratory tract infection, and adult lung function

    PubMed Central

    Shaheen, S; Sterne, J; Tucker, J; Florey, C

    1998-01-01

    BACKGROUND—Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland.
METHODS—In 1985-86 a follow up study was carried out of 1070 children who had been born in St Andrew's from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured.
RESULTS—There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of −0.39 litres (95% confidence interval (CI) −0.67, −0.11; p = 0.007) and in mean forced vital capacity (FVC) of −0.60 litres (95% CI −0.92, −0.28; p<0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1.
CONCLUSIONS—The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.

 PMID:9797752

  10. Pharmacokinetic/pharmacodynamic evaluation of sulbactam against Acinetobacter baumannii in in vitro and murine thigh and lung infection models.

    PubMed

    Yokoyama, Yuta; Matsumoto, Kazuaki; Ikawa, Kazuro; Watanabe, Erika; Shigemi, Akari; Umezaki, Yasuhiro; Nakamura, Koyo; Ueno, Keiichiro; Morikawa, Norifumi; Takeda, Yasuo

    2014-06-01

    Acinetobacter baumannii is a pathogen that has become globally associated with nosocomial infections. Sulbactam, a potent inhibitor of β-lactamases, was previously shown to be active against A. baumannii strains in vitro and effective against A. baumannii infections. However, a pharmacokinetic/pharmacodynamic (PK/PD) analysis of sulbactam against A. baumannii infections has not yet been performed. This is necessary because optimisation of dosing regimens should be based on PK/PD analysis. Therefore, in vitro and in vivo PK/PD analyses of sulbactam were performed using murine thigh and lung infection models of A. baumannii to evaluate the pharmacokinetics and pharmacodynamics of sulbactam. Sulbactam showed time-dependent bactericidal activity in vitro against A. baumannii. The PK/PD index that best correlated with its in vivo effects was the time that the free drug concentration remained above the minimum inhibitory concentration (fT>MIC) both in the thigh (R(2)=0.95) and lung (R(2)=0.96) infection models. Values of fT>MIC for a static effect and 1, 2 and 3log10 kill, respectively, were 21.0%, 32.9%, 43.6% and 57.3% in the thigh infection model and 20.4%, 24.5%, 29.3% and 37.3% in the lung infection model. Here we report the in vitro and in vivo time-dependent activities of sulbactam against A. baumannii infection and demonstrate that sulbactam was sufficiently bactericidal when an fT>MIC of >60% against A. baumannii thigh infection and >40% against A. baumannii lung infection was achieved.

  11. A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice.

    PubMed

    Choi, Jin-A; Jeong, Yu-Jin; Kim, Jae-Eun; Kang, Min-Jung; Kim, Jee-Cheon; Oh, Sang-Muk; Lee, Kyung-Bok; Kim, Dong-Hyun; Kim, Dong-Jae; Park, Jong-Hwan

    2016-02-01

    Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4-deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-α and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection. PMID:26851596

  12. Direct observation of phagocytosis and NET-formation by neutrophils in infected lungs using 2-photon microscopy.

    PubMed

    Hasenberg, Mike; Köhler, Anja; Bonifatius, Susanne; Jeron, Andreas; Gunzer, Matthias

    2011-06-02

    After the gastrointestinal tract, the lung is the second largest surface for interaction between the vertebrate body and the environment. Here, an effective gas exchange must be maintained, while at the same time avoiding infection by the multiple pathogens that are inhaled during normal breathing. To achieve this, a superb set of defense strategies combining humoral and cellular immune mechanisms exists. One of the most effective measures for acute defense of the lung is the recruitment of neutrophils, which either phagocytose the inhaled pathogens or kill them by releasing cytotoxic chemicals. A recent addition to the arsenal of neutrophils is their explosive release of extracellular DNA-NETs by which bacteria or fungi can be caught or inactivated even after the NET releasing cells have died. We present here a method that allows one to directly observe neutrophils, migrating within a recently infected lung, phagocytosing fungal pathogens as well as visualize the extensive NETs that they have produced throughout the infected tissue. The method describes the preparation of thick viable lung slices 7 hours after intratracheal infection of mice with conidia of the mold Aspergillus fumigatus and their examination by multicolor time-lapse 2-photon microscopy. This approach allows one to directly investigate antifungal defense in native lung tissue and thus opens a new avenue for the detailed investigation of pulmonary immunity.

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

    PubMed Central

    Broome, Jacqueline E.; Lis, Agnieszka

    2016-01-01

    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

  14. 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

  15. Assessment of risk of infection due to Cryptosporidium parvum in drinking water.

    PubMed

    Masago, Y; Katayama, H; Hashimoto, A; Hirata, T; Ohgaki, S

    2002-01-01

    The risk of infection of Cryptosporidium via drinking water was assessed using Monte Carlo simulation with the field survey data of the Sagami River watershed. The levels of Cryptosporidium in this river were found to follow the lognormal distribution. From the counted data, the median level of the Miyayama sampling point was estimated to be 5.7 oocysts per 100L. To calculate the annual risk of infection due to Cryptosporidium in drinking water, the Cryptosporidium level of Miyayama sampling point was used as the water source of the waterworks. The 95% percentile of the annual risk of infection was found to be 10(-2.60). If the daily risk was eliminated when the level of Cryptosporidium in treated water exceeded 1 oocyst per 20L, the 95% percentile of the annual risk was reduced by about 1 log. To reduce the 95% value of the annual risk lower than 10(-4), the risk of days with levels of Cryptosporidium in treated water exceeding 1 oocyst per 80L should be eliminated.

  16. Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention.

    PubMed

    Tzialla, Chryssoula; Borghesi, Alessandro; Pozzi, Margherita; Stronati, Mauro

    2015-12-01

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units. The benefits of antibiotic therapy when indicated are clearly enormous, but the continued and widespread use of antibiotics has generated over the years a strong selective pressure on microorganisms, favoring the emergence of resistant strains. Health agencies worldwide are galvanizing attention toward antibiotic resistance in gram-positive and gram-negative bacteria. Infections in neonatal units due to multidrug and extensively multidrug resistant bacteria are rising and are already seriously challenging antibiotic treatment options. While there is a growing choice of agents against multi-resistant gram-positive bacteria, new options for multi-resistant gram-negative bacteria in the clinical practice have decreased significantly in the last 20 years making the treatment of infections caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment options are currently limited and will be some years before any new treatment for neonates become available for clinical use, if ever. The aim of the review is to highlight the current knowledge on antibiotic resistance in the neonatal population, the possible therapeutic choices, and the prevention strategies to adopt in order to reduce the emergency and spread of resistant strains.

  17. Recurrent complicated urinary tract infection due to rare pathogen Sphingomonas paucimobilis: contamination or real deal?

    PubMed

    Demir, Tulin; Dadali, Mumtaz

    2016-09-01

    Sphingomonas paucimobilis is an aerobic, oxidase-positive, yellow-pigmented, non-fermentative, Gram-negative opportunistic pathogen that rarely causes infections in humans. It is commonly found in nosocomial environments and, despite its low clinical virulence, it can be responsible for several different infections especially among patients with underlying disease. Here we describe a clinical case of a 46-year-old male paraplegic patient with a history of neurogenic bladder due to insulin-dependent diabetes mellitus and renal failure who was admitted to the urology clinic of a university hospital in Kirsehir, Turkey, with the complaints of urinary tract infection (UTI) including fever, chills, dysuria, abdominal and back pain. The urine culture was positive for Sphingomonas paucimobilis identified by the Vitek-2 system and the patient was successfully treated with oral co-trimoxazole 800/160 mg twice a day for ten days associated to cefixime and fosfomycin. A literature review of UTIs associated to Sphingomonas paucimobilis is reported as well. PMID:27668907

  18. Recurrent complicated urinary tract infection due to rare pathogen Sphingomonas paucimobilis: contamination or real deal?

    PubMed

    Demir, Tulin; Dadali, Mumtaz

    2016-09-01

    Sphingomonas paucimobilis is an aerobic, oxidase-positive, yellow-pigmented, non-fermentative, Gram-negative opportunistic pathogen that rarely causes infections in humans. It is commonly found in nosocomial environments and, despite its low clinical virulence, it can be responsible for several different infections especially among patients with underlying disease. Here we describe a clinical case of a 46-year-old male paraplegic patient with a history of neurogenic bladder due to insulin-dependent diabetes mellitus and renal failure who was admitted to the urology clinic of a university hospital in Kirsehir, Turkey, with the complaints of urinary tract infection (UTI) including fever, chills, dysuria, abdominal and back pain. The urine culture was positive for Sphingomonas paucimobilis identified by the Vitek-2 system and the patient was successfully treated with oral co-trimoxazole 800/160 mg twice a day for ten days associated to cefixime and fosfomycin. A literature review of UTIs associated to Sphingomonas paucimobilis is reported as well.

  19. 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

  20. 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.

  1. 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

  2. [A Case of Hyperammonemia Caused by Urinary Tract Infection Due to Urease-Producing Bacteria].

    PubMed

    Emura, Masahiro; Tsuchihashi, Kazunari; Shimizu, Yosuke; Kanamaru, Sojun; Matoba, Shun; Ito, Noriyuki

    2016-08-01

    We present here a rare case of hyperammonemia without liver dysfunction or portal-systemic shunting. The patient was an 80-year-old woman with a history of neurogenic bladder. She was admitted to a nearby hospital for vomiting, diarrhea and consciousness disturbance. Two days after admission, she was transferred to our hospital because of persistant consciousness disturbance. Laboratory data revealed hyperammonemia, but there was no indication of liver dysfunction. Moreover abdominal computed tomography did not reveal any clear finding of liver disease or portal-systemic shunting, but we noted multiple large bladder diverticula. Antibiotic therapy, tracheal intubation, ventilator management and bladder catheterization were performed. The patient's level of consciousness improved rapidly. Urinary culture revealed Bacteroides ureolyticus (urease-producing bacteria). The patient was diagnosed with hyperammonemia and a urinary tract infection due to urease-producing bacteria. Thus, physicians should be aware that obstructive urinary tract infections due to urease-producing bacteria can also be the cause of hyperammonemia. PMID:27624109

  3. Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4).

    PubMed

    Derda, Monika; Wojtkowiak-Giera, Agnieszka; Kolasa-Wołosiuk, Agnieszka; Kosik-Bogacka, Danuta; Hadaś, Edward; Jagodziński, Paweł P; Wandurska-Nowak, Elżbieta

    2016-06-01

    Toll-like receptors (TLRs) play a key role in the innate immune responses to a variety of pathogens including parasites. TLRs are among the most highly conserved in the evolution of the receptor family, localized mainly on cells of the immune system and on other cells such as lung cells. The aim of this study was to determine for the first time the expression of TLR2 and TLR4 in the lung of Acanthamoeba spp. infected mice using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemical (IHC) staining. The Acanthamoeba spp. were isolated from a patient with Acanthamoeba keratitis (AK) (strain Ac 55) and from environmental samples of water from Malta Lake (Poznań, Poland - strain Ac 43). We observed a significantly increased level of expression of TLR2 as well as TLR4 mRNA from 2 to 30 days post Acanthamoeba infection (dpi) in the lungs of mice infected with Ac55 (KP120880) and Ac43 (KP120879) strains. According to our observations, increased TLR2 and TLR4 expression in the pneumocytes, interstitial cells and epithelial cells of the bronchial tree may suggest an important role of these receptors in protective immunity against Acanthamoeba infection in the lung. Moreover, increased levels of TLR2 and TLR4 mRNA expression in infected Acanthamoeba mice may suggest the involvement of these TLRs in the recognition of this amoeba pathogen-associated molecular pattern (PAMP). PMID:26940205

  4. Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis

    PubMed Central

    Oslund, Karen L.; Yang, Xiao-wei; Adamson, Lourdes; Ravindran, Resmi; Canfield, Don R.; Tarara, Ross; Hirst, Linda; Christensen, Miles; Lerche, Nicholas W.; Offenstein, Heather; Lewinsohn, David; Ventimiglia, Frank; Brignolo, Laurie; Wisner, Erik R.; Hyde, Dallas M.

    2011-01-01

    Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of three-dimensional objects from two-dimensional sections and thus is suited to quantify histological lesions. We have developed a protocol for stereological analysis of the lung in rhesus macaques inoculated with a pathogenic clinical strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of infection and tuberculosis similar to that of naturally infected humans. Conditions were optimized for collecting lung samples in a nonbiased, random manner. Bacterial load in these samples was assessed by a standard plating assay, and granulomas were graded and enumerated microscopically. Stereological analysis provided quantitative data that supported a significant correlation between bacterial load and lung granulomas. Thus this stereological approach enables a quantitative, statistically valid analysis of the impact of M. tuberculosis infection in the lung and will serve as an essential tool for objectively comparing the efficacy of drugs and vaccines. PMID:21873450

  5. Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4).

    PubMed

    Derda, Monika; Wojtkowiak-Giera, Agnieszka; Kolasa-Wołosiuk, Agnieszka; Kosik-Bogacka, Danuta; Hadaś, Edward; Jagodziński, Paweł P; Wandurska-Nowak, Elżbieta

    2016-06-01

    Toll-like receptors (TLRs) play a key role in the innate immune responses to a variety of pathogens including parasites. TLRs are among the most highly conserved in the evolution of the receptor family, localized mainly on cells of the immune system and on other cells such as lung cells. The aim of this study was to determine for the first time the expression of TLR2 and TLR4 in the lung of Acanthamoeba spp. infected mice using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemical (IHC) staining. The Acanthamoeba spp. were isolated from a patient with Acanthamoeba keratitis (AK) (strain Ac 55) and from environmental samples of water from Malta Lake (Poznań, Poland - strain Ac 43). We observed a significantly increased level of expression of TLR2 as well as TLR4 mRNA from 2 to 30 days post Acanthamoeba infection (dpi) in the lungs of mice infected with Ac55 (KP120880) and Ac43 (KP120879) strains. According to our observations, increased TLR2 and TLR4 expression in the pneumocytes, interstitial cells and epithelial cells of the bronchial tree may suggest an important role of these receptors in protective immunity against Acanthamoeba infection in the lung. Moreover, increased levels of TLR2 and TLR4 mRNA expression in infected Acanthamoeba mice may suggest the involvement of these TLRs in the recognition of this amoeba pathogen-associated molecular pattern (PAMP).

  6. Plasminogen activator inhibitor-1 in cigarette smoke exposure and influenza A virus infection-induced lung injury.

    PubMed

    Bhandary, Yashodhar P; Shetty, Shwetha K; Marudamuthu, Amarnath S; Midde, Krishna K; Ji, Hong-Long; Shams, Homoyoun; Subramaniam, Renuka; Fu, Jian; Idell, Steven; Shetty, Sreerama

    2015-01-01

    Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE), which contributes to chronic obstructive pulmonary disease (COPD). Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV) infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT) mice with passive CSE (PCSE), p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC apoptosis and lung inflammation. Further, inhibition of p53-mediated induction of PAI-1 by treatment of WT mice with caveolin-1 scaffolding domain peptide (CSP) reduced PCSE-induced lung inflammation and reversed PCSE-induced suppression of eosinophil-associated RNase1 (EAR1). Competitive inhibition of the p53-PAI-1 mRNA interaction by expressing p53-binding 3'UTR sequences of PAI-1 mRNA likewise suppressed CS-induced PAI-1 and AEC apoptosis and restored EAR1 expression. Consistent with PCSE-induced lung injury, IAV infection increased p53, PAI-1 and apoptosis in AECs in association with pulmonary inflammation. Lung inflammation induced by PCSE was worsened by subsequent exposure to IAV. Mice lacking PAI-1 that were exposed to IAV showed minimal viral burden based on M2 antigen and hemagglutination analyses, whereas transgenic mice that overexpress PAI-1 without PCSE showed increased M2 antigen and inflammation after IAV infection. These observations indicate that increased PAI-1 expression promotes AEC apoptosis and exacerbates lung inflammation induced by IAV following PCSE.

  7. Plasminogen Activator Inhibitor-1 in Cigarette Smoke Exposure and Influenza A Virus Infection-Induced Lung Injury

    PubMed Central

    Bhandary, Yashodhar P.; Shetty, Shwetha K.; Marudamuthu, Amarnath S.; Midde, Krishna K.; Ji, Hong-Long; Shams, Homoyoun; Subramaniam, Renuka; Fu, Jian; Idell, Steven; Shetty, Sreerama

    2015-01-01

    Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE), which contributes to chronic obstructive pulmonary disease (COPD). Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV) infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT) mice with passive CSE (PCSE), p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC apoptosis and lung inflammation. Further, inhibition of p53-mediated induction of PAI-1 by treatment of WT mice with caveolin-1 scaffolding domain peptide (CSP) reduced PCSE-induced lung inflammation and reversed PCSE-induced suppression of eosinophil-associated RNase1 (EAR1). Competitive inhibition of the p53-PAI-1 mRNA interaction by expressing p53-binding 3’UTR sequences of PAI-1 mRNA likewise suppressed CS-induced PAI-1 and AEC apoptosis and restored EAR1 expression. Consistent with PCSE-induced lung injury, IAV infection increased p53, PAI-1 and apoptosis in AECs in association with pulmonary inflammation. Lung inflammation induced by PCSE was worsened by subsequent exposure to IAV. Mice lacking PAI-1 that were exposed to IAV showed minimal viral burden based on M2 antigen and hemagglutination analyses, whereas transgenic mice that overexpress PAI-1 without PCSE showed increased M2 antigen and inflammation after IAV infection. These observations indicate that increased PAI-1 expression promotes AEC apoptosis and exacerbates lung inflammation induced by IAV following PCSE. PMID:25932922

  8. Intussusception of small intestine due to metastasis of large cell carcinoma of the lung with a rhabdoid phenotype.

    PubMed

    Otera, H; Ikeda, F; Nakagawa, S; Kono, Y; Sakurai, T; Tada, K; Hashimoto, K; Ikeda, A

    2010-09-01

    Large cell carcinoma of the lung with a rhabdoid phenotype is a rare type of lung cancer, and does not commonly metastasize to the small intestine. Herein we describe a 63-yr-old Japanese male with ileus resulting from small intestinal metastasis from lung cancer. Tumour enlargement was rapid and could not be treated with chemotherapy.

  9. Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

    PubMed

    Camberlein, Emilie; Cohen, Jonathan M; José, Ricardo; Hyams, Catherine J; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad; Brown, Jeremy S

    2015-03-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. PMID:25583525

  10. Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

    PubMed

    Camberlein, Emilie; Cohen, Jonathan M; José, Ricardo; Hyams, Catherine J; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad; Brown, Jeremy S

    2015-03-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae.

  11. Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

    PubMed Central

    Lugade, Amit A.; Bogner, Paul N.; Thatcher, Thomas H.; Sime, Patricia J.; Phipps, Richard P.; Thanavala, Yasmin

    2014-01-01

    The detrimental impact of tobacco on human health is clearly recognized and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease (COPD) are susceptible to recurrent respiratory infections with pathogens, including non-typeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. As mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study to investigate chronic infection and the generation of adaptive immune responses to NTHI following chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of antibodies against outer membrane lipoprotein P6, with impaired IgG1, IgG2a and IgA class-switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke exposed mice exhibited a similar defect in the generation of adaptive immunity following immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes COPD patients to recurrent infections, leading to exacerbations and contributing to mortality. PMID:24752444

  12. Systemic inflammatory response syndrome in adult patients with nosocomial bloodstream infections due to enterococci

    PubMed Central

    Bar, Katharine; Wisplinghoff, Hilmar; Wenzel, Richard P; Bearman, Gonzalo ML; Edmond, Michael B

    2006-01-01

    Background Enterococci are the third leading cause of nosocomial bloodstream infection (BSI). Vancomycin resistant enterococci are common and provide treatment challenges; however questions remain about VRE's pathogenicity and its direct clinical impact. This study analyzed the inflammatory response of Enterococcal BSI, contrasting infections from vancomycin-resistant and vancomycin-susceptible isolates. Methods We performed a historical cohort study on 50 adults with enterococcal BSI to evaluate the associated systemic inflammatory response syndrome (SIRS) and mortality. We examined SIRS scores 2 days prior through 14 days after the first positive blood culture. Vancomycin resistant (n = 17) and susceptible infections (n = 33) were compared. Variables significant in univariate analysis were entered into a logistic regression model to determine the affect on mortality. Results 60% of BSI were caused by E. faecalis and 34% by E. faecium. 34% of the isolates were vancomycin resistant. Mean APACHE II (A2) score on the day of BSI was 16. Appropriate antimicrobials were begun within 24 hours in 52%. Septic shock occurred in 62% and severe sepsis in an additional 18%. Incidence of organ failure was as follows: respiratory 42%, renal 48%, hematologic 44%, hepatic 26%. Crude mortality was 48%. Progression to septic shock was associated with death (OR 14.9, p < .001). There was no difference in A2 scores on days -2, -1 and 0 between the VRE and VSE groups. Maximal SIR (severe sepsis, septic shock or death) was seen on day 2 for VSE BSI vs. day 8 for VRE. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that AP2>18 at BSI onset, and respiratory, cardiovascular, renal, hematologic and hepatic failure were associated with death, but time to appropriate therapy >24 hours, age, and infection due to VRE were not. Multivariate analysis revealed that hematologic (OR 8.4, p = .025

  13. Fatal Scopulariopsis Infection in a Lung Transplant Recipient: Lessons of Organ Procurement

    PubMed Central

    Shaver, C. M.; Castilho, J. L.; Cohen, D. N.; Grogan, E. L.; Miller, G. G.; Dummer, J. S.; Gray, J.N.; Lambright, E. S.; Loyd, J.E.; Robbins, I. M.

    2014-01-01

    Seventeen days after double lung transplantation, a 56-year-old patient with idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed bilateral pulmonary infiltrates with pleural effusions and physical examination demonstrated sternal instability. Broad-spectrum antibacterial and antifungal therapy was initiated and bilateral thoracotomy tubes were placed. Both right and left pleural cultures grew a mold subsequently identified as Scopulariopsis brumptii. The patient underwent pleural irrigation and sternal debridement three times but pleural and wound cultures continued to grow S. brumptii. Despite treatment with five antifungal agents, the patient succumbed to his illness sixty-seven days after transplantation. Autopsy confirmed the presence of markedly invasive fungal disease and pleural rind formation. The patient’s organ donor had received bilateral thoracostomy tubes during resuscitation in a wilderness location. There were no visible pleural abnormalities at the time of transplantation. However, the patient’s clinical course and the location of the infection, in addition to the lack of similar infection in other organ recipients, strongly suggest that Scopulariopsis was introduced into the pleural space during pre-hospital placement of thoracostomy tubes. This case of lethal infection transmitted through transplantation highlights the unique risk of using organs from donors who are resuscitated in an outdoor location. PMID:25376207

  14. Decrease in the ability to detect elevated lung thallium due to delay in commencing imaging after exercise

    SciTech Connect

    Rothendler, J.A.; Boucher, C.A.; Strauss, H.W.; Pohost, G.M.; Okada, R.D.

    1985-10-01

    Post-exercise elevation of the lung/myocardial thallium ratio and a high lung clearance rate between initial and delayed images have been reported to be markers for exercise-induced left ventricular (LV) dysfunction associated with coronary artery disease (CAD). The authors performed thallium exercise tests on 60 patients, 42 with CAD, in order to determine the effect of delaying initial imaging on detection of elevated lung thallium. In addition to images obtained at 2 minutes and at 2 hours after exercise, 18-minute images were also obtained to simulate such a delay. Because of rapid isotope clearance in those with initially elevated lung activity, there was decreased sensitivity of both the initial lung/myocardial ratio and lung thallium clearance for detecting CAD, using the 18-minute image as the initial post exercise study. They conclude that initial imaging should be done in the anterior view early after exercise to optimize detection of elevated lung thallium.

  15. Prostate adenocarcinoma associated with prostatic infection due to Schistosoma haematobium. Case report and systematic review.

    PubMed

    Figueiredo, Jacinta Chaves; Richter, Joachim; Borja, Nilo; Balaca, Antonino; Costa, Sandra; Belo, Silvana; Grácio, Maria Amélia

    2015-02-01

    Schistosomiasis affects more than 240 million people worldwide, an infection which may cause urogenital manifestations including, among others, squamous bladder cancer and prostate involvement. We describe the first case of a prostate adenocarcinoma associated with prostatic Schistosoma haematobium infection occurring in Angola. Prostate carcinoma was suspected because of high levels of prostate-specific antigen. This observation prompted us to review the literature on schistosomiaisis with respect to genital pathology and prostate cancer. Described genital manifestations in men include funiculitis, epididymitis, granulomata of the seminal vesicles, testicular masses, and prostate lesions which may cause haematospermia and infertility. In contrast to bladder cancer, only 12 reports including the present case on 17 cases on prostate carcinoma associated with schistosomiasis have been published worldwide. The rarity of reports on prostate carcinoma associated with schistosomiasis is partly due to diagnostic constraints, and its incidence is underestimated. However, in emerging countries, the incidence of prostate cancer appears to increase mainly as a result of urbanization and improved access to health care where schistosomiasis prevalence is decreasing.

  16. Sudden psychotic episode probably due to meningoencephalitis and Chlamydia pneumoniae acute infection

    PubMed Central

    2005-01-01

    Background Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection. Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm. Case report We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation. Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids. Conclusion This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis. PMID:16164756

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

    PubMed

    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

    2015-02-14

    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. PMID:25573163

  18. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2015-12-07

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

  19. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2016-02-01

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. PMID:26644379

  20. A two-dimensional simulation of plasma leakage due to dengue infection

    NASA Astrophysics Data System (ADS)

    Nuraini, N.; Windarto, Jayanti, Swarna; Soewono, Edy

    2014-03-01

    Dengue Hemorrhagic Fever (DHF) is a disease caused by Dengue virus infection. One major characteristic in a patient with DHF is the occurrence of plasma leakage. Plasma leakage is a consequence of the immune system mechanism which activates cytokine. As a result, permeability of vascular will increase. Another characteristic in a DHF patient is hypoalbuminea (decreasing of albumin concentration). Plasma leakage can be modelled by constructing mathematical model of albumin concentration in plasma blood due to increasing of cytokine. In this paper, decreasing of albumin concentration in blood plasma is modelled using diffusion equation. In addition, two-dimensional numerical simulations of albumin concentration are also presented. From the simulation, it is found that the greater leakage rate or the wider leakage area, the greater decreasing albumin concentration will be. Furthermore, when time t increases, the albumin concentration decreases to zero.

  1. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge. PMID:26179097

  2. Type I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

    PubMed Central

    Foronjy, Robert F.; Taggart, Clifford C.; Dabo, Abdoulaye J.; Weldon, Sinéad; Cummins, Neville; Geraghty, Patrick

    2014-01-01

    The role of proteases in viral infection of the lung is poorly understood. Thus, we examined MMP and cathepsin proteases in respiratory syncytial virus (RSV) infected mouse lungs. RSV induced gene expression for matrix metalloproteinases (MMP) -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, -28 and cathepsins B, C, E, G, H, K, L1, S, W and Z in the airways of FVB/NJ mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (Mavs) and Trif deficient mice were exposed to RSV. Mavs deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13 and -28 and cathepsins C, G, K, S, W and Z. In lung epithelial cells, retinoic acid–inducible gene-1 (RIG-I) was identified as the major RIG-I- like receptor (RLR) required for RSV induced protease expression via MAVS. Overexpression of RIG-I or treatment with IFN-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV infected mice. PMID:25005357

  3. [Correlation analysis on combined medication with of Xiyanping injection in treatment of lung infection in real world].

    PubMed

    Yin, Xiu-ping; Xie, Yan-ming; Zhi, Ying-jie; Yang, Wei; Wang, Zhi-fei; Huo, Jian

    2015-06-01

    To analyze the regularity in combined medication with Xiyanping injection (Xiyanping for short) in the real world by as- sociation rules. Totally 5 822 patients using Xiyanping injection was collected from the 18 Class III Grade I hospitals nationwide to study the combined medication information of the patient with lung infection and make the analysis by using association rules and Apriori. According to the results, major drugs combined with Xiyanping in treatment of lung infection included compound amino acid, inosine, coenzyme A, cytidine triphosphate, vitamin C. Common drugs combined with Xiyanping can be divided into 5 categories: nutrition support therapy (vitamin C, compound amino acid) , coenzymes (coenzyme A, cytidine triphosphate, inosine), expectorants and antiasthmatics (ambroxol, salbutamol, doxofylline), hormones (dexamethasone, budesonide), antibiotics (mainly cefminox). The main combined medicines mostly conformed to the regularity for drugs treating lung infection. In addition, there were two most common medical combination models: the model for Xiyanping combined a single medicine is Xiyanping + nutrition support therapy, while the model for Xiyanping combined two or more than two medicines is Xiyanping + nutrition support therapy + coenzyme. Pharmacologically, Xiyanping is mostly combined with western medicines with similar pharmacological effects to substitute or supplement the antibiotic effect in treating lung infection. However, further studies shall be conducted for the safety and rationality of the combined medication based on clinical practices, in order to provide reference for clinical medication. PMID:26591539

  4. Inducible Expression of Inflammatory Chemokines in Respiratory Syncytial Virus-Infected Mice: Role of MIP-1α in Lung Pathology

    PubMed Central

    Haeberle, Helene A.; Kuziel, William A.; Dieterich, Hans-Juergen; Casola, Antonella; Gatalica, Zoran; Garofalo, Roberto P.

    2001-01-01

    Lower respiratory tract disease caused by respiratory syncytial virus (RSV) is characterized by profound airway mucosa inflammation, both in infants with naturally acquired infection and in experimentally inoculated animal models. Chemokines are central regulatory molecules in inflammatory, immune, and infectious processes of the lung. In this study, we demonstrate that intranasal infection of BALB/c mice with RSV A results in inducible expression of lung chemokines belonging to the CXC (MIP-2 and IP-10), CC (RANTES, eotaxin, MIP-1β, MIP-1α, MCP-1, TCA-3) and C (lymphotactin) families. Chemokine mRNA expression occurred as early as 24 h following inoculation and persisted for at least 5 days in mice inoculated with the highest dose of virus (107 PFU). In general, levels of chemokine mRNA and protein were dependent on the dose of RSV inoculum and paralleled the intensity of lung cellular inflammation. Immunohisthochemical studies indicated that RSV-induced expression of MIP-1α, one of the most abundantly expressed chemokines, was primarily localized in epithelial cells of the alveoli and bronchioles, as well as in adjoining capillary endothelium. Genetically altered mice with a selective deletion of the MIP-1α gene (−/− mice) demonstrated a significant reduction in lung inflammation following RSV infection, compared to control littermates (+/+ mice). Despite the paucity of infiltrating cells, the peak RSV titer in the lung of −/− mice was not significantly different from that observed in +/+ mice. These results provide the first direct evidence that RSV infection may induce lung inflammation via the early production of inflammatory chemokines. PMID:11134301

  5. Expression of Toll-like receptor 4 in lungs of immune-suppressed rat with Acinetobacter baumannii infection

    PubMed Central

    Wang, Yanmei; Zhang, Xiaohong; Feng, Xuanlin; Liu, Xiaoshu; Deng, Lei; Liang, Zong-An

    2016-01-01

    Toll-like receptor 4 (TLR4) is involved in the regulation of host responses to Acinetobacter baumannii (A. baumannii). The aim of the present study was to examine the function of TLR4 in lung inflammation in immune-suppressed rats with A. baumannii infection. A total of 72 Sprague-Dawley male rats were randomly divided into the control, A. baumannii infection and immune-suppressed infection groups. The immune-suppressed infection group was treated with 100 mg/kg hydrocortisone by subcutaneous injection every other day for 2 weeks prior to A. baumannii infection. Lung tissue was obtained on the 3rd and 7th day after tracheal inoculation with A. baumannii. The expression of TLR4 in bronchial and alveolar epithelial cells, and alveolar macrophage was examined using immunohistochemistry. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid were detected using ELISA. The results showed that in the control group, the expression of TLR4 was upregulated in the bronchial and alveolar epithelial, and alveolar macrophages, and the levels of IL-6 and TNF-α were increased in the early phase of A. baumannii infection. On the 7th day, no significant difference in the levels of IL-6 and TNF-α was observed between the A. baumannii infection and control groups. Conversely, the expression of TLR4 was downregulated in the immune-suppressed group, and the levels of IL-6 and TNF-α were reduced on the 3rd day after infection. In the subsequent observation period, the expression of TLR4 was upregulated and the levels of IL-6 and TNF-α were increased. In conclusion, the results show a critical role of TLR4 in mediating effective immune response in the lung of rat with A. baumannii infection. PMID:27703512

  6. Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung

    PubMed Central

    Talker, Stephanie C.; Stadler, Maria; Koinig, Hanna C.; Mair, Kerstin H.; Rodríguez-Gómez, Irene M.; Graage, Robert; Zell, Roland; Dürrwald, Ralf; Starick, Elke; Harder, Timm; Weissenböck, Herbert; Lamp, Benjamin; Hammer, Sabine E.; Ladinig, Andrea; Saalmüller, Armin

    2016-01-01

    ABSTRACT Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67+) CD8+ T cells with an early effector phenotype (perforin+ CD27+) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4+ and CD8+ T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4+ and CD8+ T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4+ and CD8+ memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs. IMPORTANCE Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we

  7. Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

    PubMed Central

    Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

    2011-01-01

    Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently

  8. [Calculation of the incidence of primary care visits due to acute respiratory infections].

    PubMed

    Uphoff, H; Buchholz, U; Lang, A; Haas, W; Stilianakis, N

    2004-03-01

    Data collected by the German influenza sentinel of the Working Group on Influenza (AGI) do not allow calculation of the incidence of primary care visits due to acute respiratory infections (ARI). Because patients do not have to register with a particular general practitioner, the population covered by primary care physicians is unknown. Until now the incidence of primary care visits due to ARI is estimated indirectly by extrapolating the sentinel sample of physicians to the total number of primary care physicians caring for the total population. However, distortions of the estimated incidence occur in weeks with public holidays (particularly around Christmas and New Year) and when many physicians close their practice simultaneously because of vacation. We have attempted to quantify the shortage of medical services and established thresholds to correct for situations where service by medical providers is extraordinarily reduced. The suggested method avoids distortions to a large extent and makes interpretation of data during those critical periods possible. A second subject of the paper is the validation of the estimated ARI incidence in primary care practices by comparing the data to other sources such as sick leave statistics of health insurance as well as ICD-based data from a primary care network. We found that the estimated ARI incidence in primary care practices was in line with data from other sources and appears plausible.

  9. Soft tissue infection due to Mycobacterium fortuitum following acupuncture: a case report and review of the literature.

    PubMed

    Guevara-Patiño, Armando; Sandoval de Mora, Marisol; Farreras, Aileen; Rivera-Olivero, Ismar; Fermin, Danibeth; de Waard, Jacobus H

    2010-09-03

    We report the first case of a post-acupuncture soft tissue infection due to Mycobacterium fortuitum. Two months after finishing an acupuncture treatment session, an immunocompetent 23-year-old woman developed cellulitis at the side of the needle insertions and the acid-fast bacillus was isolated from a closed abscess. The patient was successfully treated with a proper drug combination. We review the literature concerning the infection source and the risks for skin and soft tissue infection due to mycobacteria after acupuncture. The infection source in most cases is unknown but is probably associated with the inadequate sterilization of the needles or the puncture site. We show that these infections are not rare but difficult to diagnose. To avoid delays in the definitive diagnosis, infection with mycobacteria should be considered for skin and soft tissue infections, in particular late-onset infections, which are negative for routine bacterial cultures and without a clinical response to antibiotics used for acute pyogenic infections. Bacterial cultures from this lesion should be maintained for at least six weeks before discharged as negative.

  10. Experience with Fosfomycin for Treatment of Urinary Tract Infections Due to Multidrug-Resistant Organisms

    PubMed Central

    Sekeres, Jennifer; Hall, Gerri S.; van Duin, David

    2012-01-01

    Fosfomycin has shown promising in vitro activity against multidrug-resistant (MDR) urinary pathogens; however, clinical data are lacking. We conducted a retrospective chart review to describe the microbiological and clinical outcomes of urinary tract infections (UTIs) with MDR pathogens treated with fosfomycin tromethamine. Charts for 41 hospitalized patients with a urine culture for an MDR pathogen who received fosfomycin tromethamine from 2006 to 2010 were reviewed. Forty-one patients had 44 urinary pathogens, including 13 carbapenem-resistant Klebsiella pneumoniae (CR-Kp), 8 Pseudomonas aeruginosa, and 7 vancomycin-resistant Enterococcus faecium (VRE) isolates, 7 extended-spectrum beta-lactamase (ESBL) producers, and 9 others. In vitro fosfomycin susceptibility was 86% (median MIC, 16 μg/ml; range, 0.25 to 1,024 μg/ml). Patients received an average of 2.9 fosfomycin doses per treatment course. The overall microbiological cure was 59%; failure was due to either relapse (24%) or reinfection UTI (17%). Microbiological cure rates by pathogen were 46% for CR-Kp, 38% for P. aeruginosa, 71% for VRE, 57% for ESBL producers, and 100% for others. Microbiological cure (n = 24) was compared to microbiological failure (n = 17). There were significantly more solid organ transplant recipients in the microbiological failure group (59% versus 21%; P = 0.02). None of the patients in the microbiological cure group had a ureteral stent, compared to 24% of patients within the microbiological failure group (P = 0.02). Fosfomycin demonstrated in vitro activity against UTIs due to MDR pathogens. For CR-KP, there was a divergence between in vitro susceptibility (92%) and microbiological cure (46%). Multiple confounding factors may have contributed to microbiological failures, and further data regarding the use of fosfomycin for UTIs due to MDR pathogens are needed. PMID:22926565

  11. Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection

    PubMed Central

    Dudek, M; Puttur, F; Arnold-Schrauf, C; Kühl, A A; Holzmann, B; Henriques-Normark, B; Berod, L; Sparwasser, T

    2016-01-01

    The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)– and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity. PMID:26627460

  12. Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.

    PubMed

    Locke, Landon W; Myerburg, Michael M; Weiner, Daniel J; Markovetz, Matthew R; Parker, Robert S; Muthukrishnan, Ashok; Weber, Lawrence; Czachowski, Michael R; Lacy, Ryan T; Pilewski, Joseph M; Corcoran, Timothy E

    2016-05-01

    Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previous Pseudomonas aeruginosa infection. Cystic fibrosis subjects without P. aeruginosa had similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated with P. aeruginosa infection. ABS is consistently increased in cystic fibrosis.

  13. Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.

    PubMed

    Dudek, M; Puttur, F; Arnold-Schrauf, C; Kühl, A A; Holzmann, B; Henriques-Normark, B; Berod, L; Sparwasser, T

    2016-09-01

    The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity. PMID:26627460

  14. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice

    PubMed Central

    Shi, Hengfei; Ren, Ke; Lv, Baojie; Zhang, Wei; Zhao, Ying; Tan, Ren Xiang; Li, Erguang

    2016-01-01

    The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC50) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect. PMID:27767097

  15. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria

    PubMed Central

    2014-01-01

    Introduction The high incidence of multidrug-resistant (MDR) bacteria among patients admitted to ICUs has determined an increase of tigecycline (TGC) use for the treatment of severe infections. Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed. Our purpose is to investigate TGC safety and efficacy at higher than standard doses. Methods We conducted a retrospective study of prospectively collected data in the ICU of a teaching hospital in Rome. Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed. The safety profile and efficacy of high dosing regimen use were investigated. Results Over the study period, 54 patients (pts) received TGC at a standard dose (SD group: 50 mg every 12 hours) and 46 at a high dose (HD group: 100 mg every 12 hours). Carbapenem-resistant Acinetobacter.baumannii (blaOXA-58 and blaOXA-23 genes) and Klebsiella pneumoniae (blaKPC-3 gene) were the main isolated pathogens (n = 79). There were no patients requiring TGC discontinuation or dose reduction because of adverse events. In the ventilation-associated pneumonia population (VAP) subgroup (63 patients: 30 received SD and 33 HD), the only independent predictor of clinical cure was the use of high tigecycline dose (odds ratio (OR) 6.25; 95% confidence interval (CI) 1.59 to 24.57; P = 0.009) whilst initial inadequate antimicrobial treatment (IIAT) (OR 0.18; 95% CI 0.05 to 0.68; P = 0.01) and higher Sequential Organ Failure Assessment (SOFA) score (OR 0.66; 95% CI 0.51 to 0.87; P = 0.003) were independently associated with clinical failure. Conclusions TGC was well tolerated at a higher than standard dose in a cohort of critically ill patients with severe infections. In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria. PMID:24887101

  16. Tropical parasitic lung diseases.

    PubMed

    Vijayan, V K

    2008-01-01

    Though parasitic lung diseases are frequently seen in tropical countries, these are being increasingly reported from many parts of the world due to globalisation and travel across the continents. In addition, the emergence of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS), the frequent use of immunosuppressive drugs in many diseases and the increasing numbers of organ transplantations have resulted in a renewed interest in many tropical parasitic lung diseases. This review outlines the recent developments in the pathogenesis, diagnosis and management of common and rare parasitic lung diseases.

  17. Oxidative stress in rat liver and lung induced by furanoterpenoids isolated from Fusarium solani infected sweet potatoes.

    PubMed

    Rajendran, S; Parasakthy, K; Deepalakshmi, P D; Devaraj, S N

    1996-01-01

    A crude extract containing some toxic furanoterpenoids was isolated from F. solani infected sweet potatoes. Chronic administration of the crude extract to male albino rats at a dosage of 1 mg/kg body weight/day for 21 days brought about a sharp increase in the thiobarbituric acid reactive substances and a depression of glutathione levels in the lung and liver homogenates. The antioxidant defense system was affected as evident from a significant fall in the activities of the enzymes, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase. Such an alteration could be the reason for the lung and liver damage caused by these toxic furanoterpenoids.

  18. [Two cases of lung injury due to inhalation of waterproofing spray--with special reference to pulmonary function disorder].

    PubMed

    Hashimoto, Kazunori; Arita, Kenichi; Kajihara, Toshiki; Nitta, Tomoko; Mito, Akiko; Awaya, Hirokazu; Yamasaki, Masahiro; Ohashi, Nobuyuki

    2009-05-01

    CASE 1: A 57-year-old man experienced severe dyspnea 24 hours after inhalation of waterproofing spray. Computed tomography (CT) revealed diffuse ground glass opacities in bilateral lungs. Pulmonary function tests showed mixed ventilatory disturbance with a low expiratory flow rate near the end of forced expiration and a normal diffusing capacity with normal functional residual capasity. The pulmonary function disorder was quickly improved by steroid therapy. CASE 2: A 59-year-old man smoked after inhaling waterproofing spray and soon developed dyspnea. The findings of CT were similar to those of case 1. His pulmonary function test revealed restrictive ventilatory disturbance and normal pulmonary diffusing capacity with low functional residual capacity. These findings improved without steroid treatment. However, it took more time for the pulmonary function to recover. There was probably specific inflammation around bronchioles, and the inflammation might have spread to the alveolar region in such cases with severe pulmonary function disorder. Steroid treatment seems to be useful to improve both the pulmonary function disorder and the clinical feature due to inhalation of waterproofing spray.

  19. Downregulation of super oxide dismutase level in protein might be due to sulfur mustard induced toxicity in lung.

    PubMed

    Mirbagheri, Leila; Habibi Roudkenar, Mehryar; Imani Fooladi, Abbas Ali; Ghanei, Mostafa; Nourani, Mohammad Reza

    2013-05-15

    Sulfur mustard (SM) has been identified as an important chemical weapon. During the Iran-Iraq war of 1980-88, the extensive usage of SM against Iranian civilians and military forces was proven. This agent has been shown to cause severe damage mainly in the skin, eyes, lungs, and respiratory tract in Iranian veterans. The most common disease is bronchiolitis obliterans (BO)). SM increases the endogenous production of reactive oxygen species (ROS). Superoxide dismutases (SODs) are known as protective antioxidants against the harmful effects of ROS. Twenty exposed SM individuals (43.2±6.4 years), and 10 normal controls (41.3±2.5 years) were enrolled in this study. Evaluation of SODs was performed by semiquantitative RT-PCR and immunohistochemistry. Our results demonstrated that CuZnSOD and MnSOD mRNA were up-regulated 2.79±1.09 and 2.49±1.11 folds, respectively in SM-injured patients in comparison with control levels. In contrast, Immunohistochemistry results showed downregulation of CuZnSOD protein expression in SM injured patients. Our results revealed that SODs may play an important role in cellular protection against oxidative stress due to mustard gas toxicity in airway wall of SM exposed patients.

  20. Challenges in measuring complications and death due to invasive Salmonella infections.

    PubMed

    Qamar, Farah Naz; Azmatullah, Asma; Bhutta, Zulfiqar A

    2015-06-19

    Despite the highest burden of Typhoid fever in children globally, exact estimates of morbidity and mortality are lacking due to scarcity of published data. Despite a high prevalence and a socioeconomic burden in developing countries, published data with morbidity and mortality figures are limited especially Africa and South American regions. Data from the community is insufficient and most case fatality estimates are extrapolations from hospital based studies that do not cover all geographical regions, and include cases which may or not be culture confirmed, MDR resistant or sensitive cases, or from mixed populations of age (adults and children). Complications of typhoid such as intestinal perforation, bone marrow suppression, and encephalopathy are dependent on MDR/Fluoroquinolone resistant Salmonella infection, comorbidities such as malnutrition, and health-care access. Data is again insufficient to estimate the true burden of Typhoid Fever in different regions and groups of populations. Although there has been a rapid decline in cases in developed countries with the advent of improved sanitization, timely and easy access to health care and laboratories, this is still not the case in the developing countries where Typhoid deaths are still occurring. The way forward is to develop rapid and cost effective point of care diagnostic tests, put in place validated clinical algorithms for suspected clinical cases, and design prospective, and community based studies in different groups, implement maintenance of electronic health records in large public sector hospitals and regions to identify populations that will benefit most from the implementation of vaccine. Policies on public health education and typhoid vaccine may help to reduce morbidity and mortality due to the disease.

  1. Pathogenic Potential of Novel Chlamydiae and Diagnostic Approaches to Infections Due to These Obligate Intracellular Bacteria

    PubMed Central

    Corsaro, Daniele; Greub, Gilbert

    2006-01-01

    Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology. PMID:16614250

  2. Pathogenic potential of novel Chlamydiae and diagnostic approaches to infections due to these obligate intracellular bacteria.

    PubMed

    Corsaro, Daniele; Greub, Gilbert

    2006-04-01

    Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and Chlamydophila species. They also exhibit an obligate biphasic intracellular life cycle within eukaryote host cells. Some of these new chlamydiae are currently considered potential emerging human and/or animal pathogens. Parachlamydia acanthamoebae and Simkania negevensis are both emerging respiratory human pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and Piscichlamydia salmonis has recently been identified as an agent of the gill epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp. seem to be confined to arthropods, but some evidence for human exposure exists. In this review, we first summarize the data supporting a pathogenic potential of the novel chlamydiae for humans and other vertebrates and the interactions that most of these chlamydiae have with free-living amoebae. We then review the diagnostic approaches to infections potentially due to the novel chlamydiae, especially focusing on the currently available PCR-based protocols, mammalian cell culture, the amoebal coculture system, and serology.

  3. [Anesthetic management of a patient with severe subcutaneous and mediastinal emphysema due to pertussis infection].

    PubMed

    Ideno, Satoshi; Miyazawa, Noriko; Ishikawa, Saki; Wakamiya, Rie; Shinto, Atsushi; Mikasa, Hiromi; Yamamoto, Shinichi

    2014-06-01

    A 20-month-old girl, with respiratory failure due to severe subcutaneous and mediastinal emphysema, was scheduled to undergo percutaneous drainage of emphysema and induction of extracorporeal membrane oxygenation. Paroxysm, a symptom of the infection of Bordetella pertussis, was the cause of emphysema. In patients with severe neck subcutaneous emphysema, management of difficult airway is the most important safety issue in the practice of anesthesia. Following the American Society of Anesthesiologist (ASA) guidelines for management of difficult airway, we prepared various types of equipment to facilitate intubation and surgeons were beside the patient during induction of anesthesia for emergency invasive airway access. To prevent the progression of emphysema, preservation of spontaneous breathing during the perioperative period was also important. Combined with propofol and midazolam, pethidine was an effective agent for safe anesthetic induction because it produces less respiratory depression compared to other opiate analgesics. In conclusion, this case demonstrates the importance of prediction of and preparation for difficult airway. Furthermore, anesthesiologists should consider the optimization of anesthesia to avoid progression of emphysema.

  4. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection.

    PubMed

    Hansen, Susse Kirkelund; Rau, Martin Holm; Johansen, Helle Krogh; Ciofu, Oana; Jelsbak, Lars; Yang, Lei; Folkesson, Anders; Jarmer, Hanne Østergaard; Aanæs, Kasper; von Buchwald, Christian; Høiby, Niels; Molin, Søren

    2012-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to establish under which conditions the switch to chronic infection takes place. In association with a recently established sinus surgery treatment program for CF patients at the Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa has been investigated, paralleled by sampling of sputum from the same patients. On the basis of genotyping and phenotypic characterization including transcription profiling, the diversity of the P. aeruginosa populations in the sinuses and the lower airways was investigated and compared. The observations made from several children show that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections.

  5. [Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi].

    PubMed

    Nenoff, P; Reinel, D; Krüger, C; Grob, H; Mugisha, P; Süß, A; Mayser, P

    2015-07-01

    Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic

  6. [Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi].

    PubMed

    Nenoff, P; Reinel, D; Krüger, C; Grob, H; Mugisha, P; Süß, A; Mayser, P

    2015-07-01

    Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic

  7. Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection

    PubMed Central

    McCaughey, Laura C.; Ritchie, Neil. D.; Douce, Gillian R.; Evans, Thomas J.; Walker, Daniel

    2016-01-01

    Protein antibiotics, known as bacteriocins, are widely produced by bacteria for intraspecies competition. The potency and targeted action of bacteriocins suggests that they could be developed into clinically useful antibiotics against highly drug resistant Gram-negative pathogens for which there are few therapeutic options. Here we show that Pseudomonas aeruginosa specific bacteriocins, known as pyocins, show strong efficacy in a murine model of P. aeruginosa lung infection, with the concentration of pyocin S5 required to afford protection from a lethal infection at least 100-fold lower than the most commonly used inhaled antibiotic tobramycin. Additionally, pyocins are stable in the lung, poorly immunogenic at high concentrations and efficacy is maintained in the presence of pyocin specific antibodies after repeated pyocin administration. Bacteriocin encoding genes are frequently found in microbial genomes and could therefore offer a ready supply of highly targeted and potent antibiotics active against problematic Gram-negative pathogens. PMID:27444885

  8. Bilateral Conjunctivitis Due to Trichomonas vaginalis without Genital Infection: an Unusual Presentation in an Adult Man

    PubMed Central

    Croucher, Adam; Roushan, Azita; Gaydos, Charlotte A.

    2013-01-01

    We report an unusual case of extragenital infection with Trichomonas vaginalis of the conjunctiva of a 32-year-old man. Only one other similar case has been reported in the English language literature. The present report reinforces the widening pathologic spectrum of trichomonads in humans, especially in the context of emerging extragenital infections. PMID:23843487

  9. Bilateral conjunctivitis due to Trichomonas vaginalis without genital infection: an unusual presentation in an adult man.

    PubMed

    Abdolrasouli, Alireza; Croucher, Adam; Roushan, Azita; Gaydos, Charlotte A

    2013-09-01

    We report an unusual case of extragenital infection with Trichomonas vaginalis of the conjunctiva of a 32-year-old man. Only one other similar case has been reported in the English language literature. The present report reinforces the widening pathologic spectrum of trichomonads in humans, especially in the context of emerging extragenital infections. PMID:23843487

  10. Prosthetic joint infection due to Lysobacter thermophilus diagnosed by 16S rRNA gene sequencing.

    PubMed

    Dhawan, B; Sebastian, S; Malhotra, R; Kapil, A; Gautam, D

    2016-01-01

    We report the first case of prosthetic joint infection caused by Lysobacter thermophilus which was identified by 16S rRNA gene sequencing. Removal of prosthesis followed by antibiotic treatment resulted in good clinical outcome. This case illustrates the use of molecular diagnostics to detect uncommon organisms in suspected prosthetic infections.

  11. Regional distribution of nosocomial infections due to ESBL-positive Enterobacteriaceae in Germany: data from the German National Reference Center for the Surveillance of Nosocomial Infections (KISS).

    PubMed

    Leistner, R; Schröder, C; Geffers, C; Breier, A-C; Gastmeier, P; Behnke, M

    2015-03-01

    Surveillance systems for hospital infections are reporting increasing rates of extended-spectrum β-lactamase (ESBL)-positive Enterobacteriaceae in Europe. We aimed to perform a national survey on this trend and on the regional distribution of nosocomial infections due to ESBL-positive Enterobacteriaceae in German hospitals. Data from 2007 to 2012 from two components of the German national nosocomial infection surveillance system were used for this analysis. The data derive from intensive care units and surgical departments. Independent factors determining the proportion of ESBL-positive Enterobacteriaceae among nosocomial infections due to Enterobacteriaceae and changes in its regional distribution (broken down into German federal states) were calculated by regression analysis. From 2007 to 2012, the data showed a significantly increasing proportion of ESBL-positive Enterobacteriaceae in surgical site infections (from 11.46 to 15.38, 134%, p 0.003), urinary tract infections (9.36 to 16.56, 177%, p <0.001) and lower respiratory tract infections (11.91 to 14.70, 123%, p <0.001) due to Enterobacteriaceae. Factors independently associated with a growing proportion were: Thuringia (p 0.009; odds ratio (OR) 1.53), North Rhine-Westphalia (p <0.001; OR 1.41) and general surgery ward (p 0.002; OR 1.47). The proportion of ESBL-positive Enterobacteriaceae in nosocomial infections has significantly increased in Germany over the last 6 years. Hospitals in Central Germany and surgical departments in all of Germany are especially affected by this development.

  12. Change in spectrum of Brownian fluctuations of optically trapped red blood cells due to malarial infection

    NASA Astrophysics Data System (ADS)

    Saraogi, Vishal; Padmapriya, P.; Paul, Apurba; Tatu, Utpal S.; Natarajan, Vasant

    2010-05-01

    We study the properties of single red blood cells (RBCs) held in an optical-tweezers trap. We observe a change in the spectrum of Brownian fluctuations between RBCs from normal and malaria-infected samples. The change, caused by infection-induced structural changes in the cell, appears as a statistical increase in the mean (by 25%) and standard deviation (by 200%) of the corner frequency measured over ~100 cells. The increase is observed even though the ensemble of cells being measured consists mostly of cells that do not actually host the parasite, but are from an infected pool. This bystander effect appears to vindicate other observations that infected cells can affect the biomechanical properties of uninfected cells. The change is also observed to be independent of the stage of infection and its duration, highlighting its potential for disease detection.

  13. Detection of C-type virus by immunoferritin technique in bat lung cell line chronically infected with bovine leucosis virus.

    PubMed

    Mihailescu, D; Patrascu, I V; Apostol, I; Mazilu, M

    1980-01-01

    Reported in this paper are morphological studies and tests for the detection of Type-C particles from a line of bat lung cells chronically infected with bovine leucosis virus. The immunoferritin technique was used. Ferritin labelling of Type-C particles was regularly accompanied by black-spot arrangement of ferritin around the virus envelope, which provided evidence to the specificity of this immunochemical technique. PMID:6260052

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  15. Lung Infection by Human Bocavirus Induces the Release of Profibrotic Mediator Cytokines In Vivo and In Vitro

    PubMed Central

    Karagiannidis, Christian; Bayh, Inga; Brockmann, Michael; Pieper, Monika; Windisch, Wolfram; Schildgen, Oliver; Schildgen, Verena

    2016-01-01

    Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV-negative patients were analysed by semi-quantitative Western spot blot analyses. Although lots of cytokines were regulated independently of HBoV status, several cytokines associated with lung fibrosis and tumour development, e.g., EGF, VEGF, TARC (CCL17), TNF-α, TNF-β, TIMP-1, were clearly upregulated in the HBoV-positive cohort. These findings suggest that the development of lung fibrosis might be triggered by HBoV induced cytokine expression. PMID:26807786

  16. Foot infections due to Hendersonula toruloidea and Scytalidium hyalinum in coal miners.

    PubMed

    Gugnani, H C; Oyeka, C A

    1989-01-01

    A total of 250 coal miners were screened for mycotic skin infections. Sixty-six (34.8%) miners had clinical lesions on their feet which proved to be of mycotic etiology by direct microscopy and culture. Hendersonula toruloidea, the commonest etiological agent, was the sole agent recovered from 23 (34.8%) of the positive cases and was also isolated from three (4.5%) cases of mixed infection with dermatophytes (two cases with Trichophyton rubrum and one with Trichophyton mentagrophytes var. mentagrophytes). Scytalidium hyalinum was recovered as the sole causal agent in four (6.1%) patients and from one case of mixed infection with T. mentagrophytes var. mentagrophytes. The dermatophytes isolated as sole etiological agents included T. mentagrophytes var. mentagrophytes (13 isolates) T. rubrum (10), Trichophyton tonsurans (5), Epidermophyton floccosum (4) and Microsporum gypseum (3). The toe web was invariably involved in all cases of H. toruloidea and S. hyalinum infection and was also the commonest site of infection by dermatophytes. Occasionally the sole, toe and finger nails were also involved. Other body sites were infrequently involved and then only in infections caused by dermatophytes. The epidemiology of H. toruloidea and S. hyalinum infections is reviewed.

  17. A pilot study—is there a role for mitoxantrone pleurodesis in the management of pleural effusion due to lung cancer?

    PubMed Central

    Sreter, Katherina-Bernadette; Jakopovic, Marko; Janevski, Zoran; Samarzija, Miroslav; Kioumis, Ioannis; Mparmpetakis, Nikolaos; Pataka, Athanasia; Zarogoulidis, Konstantinos; Tsiouda, Theodora; Kosmidis, Christoforos; Mpaka, Sofia; Huang, Haidong; Hohenforst-Schmidt, Wolfgang; Charalampidis, Charalampos; Machairiotis, Nikolaos; Zaric, Bojan; Milovancev, Aleksandar

    2016-01-01

    Background Lung cancer is the leading cause of malignant pleural effusion (MPE). Management of MPEs remains a clinical challenge due to recurrence and poor quality of life. An ideal sclerosing agent has yet to be found. The aim of this cohort pilot study was to evaluate the role of mitoxantrone pleurodesis (MP) as an alternative to talc sclerotherapy for managing MPEs in lung cancer patients. Methods A retrospective chart review was conducted on consecutively admitted patients with MPE to the Department of Post-Intensive Care at the Clinic for Respiratory Diseases “Jordanovac”, University Hospital Centre Zagreb, in Croatia. Results Of 34 patients with MPE, twenty-one (64.8±9.46 years; 47–84 years) with primary lung carcinoma who received MP (30 mg of mitoxantrone) between December 2003 and February 2009 were included in this study. Chest radiographs taken prior to sclerotherapy and at 1-, 2-, and 3-month follow-up were compared. At the post-sclerotherapy evaluation periods, overall success (OS) rates of MP were 88.2% [17.6%, complete response (CR); 70.6%, partial response (PR)], 53.9% (7.7% CR; 46.2% PR), and 45.5% (PR), respectively. Kaplan-Meier median survival from MP until death was 5.2 months, while that from diagnosis of primary lung cancer was 12.3 months. Conclusions MP may be a safe and effective method of managing MPE due to lung cancer. Future randomized controlled studies comparing mitoxantrone and talc pleurodesis in lung cancer patients are warranted to elucidate whether a significant difference exists between these agents. Factors affecting success, survival probability, and quality of life also require further investigation. PMID:27275475

  18. Profile of cytokines in the lungs of BALB/c mice after intra-nasal infection with Histoplasma capsulatum mycelial propagules.

    PubMed

    Sahaza, Jorge Humberto; Suárez-Alvarez, Roberto; Estrada-Bárcenas, Daniel Alfonso; Pérez-Torres, Armando; Taylor, Maria Lucia

    2015-08-01

    The host pulmonary response to the fungus Histoplasma capsulatum was evaluated, through the profile of cytokines detected by the MagPix magnetic beads platform in lung homogenates and by lung-granulomas formation, from mice intra-nasally infected with mycelial propagules (M-phase) of two virulent H. capsulatum strains, EH-46 and G-217B. Results highlight that mice lung inflammatory response depends on the H. capsulatum strain used, during the first step of the fungal infection. IL-1β and TNF-α increased their concentrations in mice infected with both strains. The highest levels of IL-6, IL-17, and IL-23 were found in EH-46-infected mice, whereas levels of IL-22 were variable at all post-infection times for both strains. Significant increases of IL-12, IFN-γ, IL-4, and IL-10 were associated to EH-46-infected mice. Histological lung findings from EH-46-infected mice revealed incipient and numerous well-developed granulomas, distributed in lung-lobes at the 14th and the 21st days after infection, according to cytokine profiles.

  19. Severe haemolytic anaemia due to cold anti-'i' antibodies associated with cytomegalovirus infection.

    PubMed Central

    Aguado, J. M.; Castrillo, J. M.; Sanz, J.; Serrano, J.

    1990-01-01

    A 66 year old patient with multiple myeloma and monoclonal cryoglobulinaemia who developed a severe haemolytic anaemia following a cytomegalovirus infection is reported. The presence of a high titre of anti-'i' cold antibody of IgM subclass is demonstrated. Anti-'i' antibody disappeared when complement-fixation antibody titres against cytomegalovirus decreased. Various pathogenetic mechanisms involved in the development of haemolytic anaemia associated with cytomegalovirus infection are discussed. To our knowledge, this is the first case described in the English language publications associating severe haemolytic anaemia with an anti-'i' antibody after a cytomegalovirus infection in an immunocompromised patient. PMID:2164663

  20. Severe haemolytic anaemia due to cold anti-'i' antibodies associated with cytomegalovirus infection.

    PubMed

    Aguado, J M; Castrillo, J M; Sanz, J; Serrano, J

    1990-05-01

    A 66 year old patient with multiple myeloma and monoclonal cryoglobulinaemia who developed a severe haemolytic anaemia following a cytomegalovirus infection is reported. The presence of a high titre of anti-'i' cold antibody of IgM subclass is demonstrated. Anti-'i' antibody disappeared when complement-fixation antibody titres against cytomegalovirus decreased. Various pathogenetic mechanisms involved in the development of haemolytic anaemia associated with cytomegalovirus infection are discussed. To our knowledge, this is the first case described in the English language publications associating severe haemolytic anaemia with an anti-'i' antibody after a cytomegalovirus infection in an immunocompromised patient.

  1. Pathogenesis of respiratory infections due to influenza virus: Implications for developing countries

    SciTech Connect

    Leigh, M.W.; Carson, J.L.; Denny, F.W. Jr. )

    1991-05-01

    The influenza viruses have an important and distinctive place among respiratory viruses: they change antigenic character at irregular intervals, infect individuals of all ages, cause illnesses characterized by constitutional symptoms and tracheobronchitis, produce yearly epidemics associated frequently with excess morbidity and mortality, and predispose the host to bacterial superinfections. Much is known about influenza viruses, but their role in respiratory infections among children in developing countries is poorly understood, and the risk factors that lead to the excess morbidity and mortality have not been identified clearly. Among the many risk factors that may be important are alterations in host immunity, malnutrition, prior or coincident infections with other microorganisms, inhaled pollutants, and lack of access to medical care. There is a great need for research that can establish more precisely the role these and other unidentified factors play in the pathogenesis of influenza infections in children in the developing world. 37 references.

  2. Postoperative infection of an abdominal mesh due to methicillin resistant Staphylococcus aureus - a case report.

    PubMed

    Ashok, R; Anuradha, K; Babu, S S; Bheerappa, N; Sastry, R A; Lakshmi, V

    2004-01-01

    Methicillin resistant Stephylococcus aureus (MRSA) infection has now become a major problem in hospitals. We present a case of postoperative infection MRSA where the primary source of the infection was found to be an abdominal mesh that was used to reinforce the abdominal wall. After one year of surgery, the patient developed wound dehiscence and discharge. MRSA was isolated from the wound, mesh, external nares, throat and axilla. Initially she was started on clindamycin and discharged from the hospital. After 5 months, patient came back to the hospital with infection at the same site. The patient was then treated with vancomycin and MRSA clearance. She responded to the treatment with complete healing of the wound and clearance of MRSA.

  3. Severe mortality in mesocosm-reared sharpsnout sea bream Diplodus puntazzo larvae due to epitheliocystis infection.

    PubMed

    Katharios, Pantelis; Papadaki, Maria; Papandroulakis, Nikos; Divanach, Pascal

    2008-10-16

    This paper describes severe mortalities recorded in sharpsnout sea bream Diplodus puntazzo larvae reared in mesocosms. The mortalities were attributed to epitheliocystis infection. The pathology associated with the disease is described using histological techniques. Microscopical examination showed a massive infection of the skin, fins, and oral cavity, with impaired feeding, respiration, and osmoregulation being the most likely cause of death. This is the first report of epitheliocystis disease in sharpsnout sea bream and in fish at such an early developmental stage. PMID:19062753

  4. Increasing burden of urinary tract infections due to intrinsic colistin-resistant bacteria in hospitals in Marseille, France.

    PubMed

    Abat, Cédric; Desboves, Guillaume; Olaitan, Abiola Olumuyiwa; Chaudet, Hervé; Roattino, Nicole; Fournier, Pierre-Edouard; Colson, Philippe; Raoult, Didier; Rolain, Jean-Marc

    2015-02-01

    The emergence of multidrug-resistant (MDR) Gram-negative bacteria has become a major public health problem, eliciting renewed interest in colistin, an old antibiotic that is now routinely used to treat MDR bacterial infections. Here we investigated whether colistin use has affected the prevalence of infections due to intrinsic colistin-resistant bacteria (CRB) in university hospitals in Marseille (France) over a 5-year period. All data from patients infected by intrinsic CRB were compiled from January 2009 to December 2013. Escherichia coli infections were used for comparison. Colistin consumption data were also collected from pharmacy records from 2008 to 2013. A total of 4847 intrinsic CRB infections, including 3150 Proteus spp., 847 Morganella spp., 704 Serratia spp. and 146 Providencia spp., were collected between 2009 and 2013. During this period, the annual incidence rate of hospital-acquired CRB infections increased from 220 per 1000 patients to 230 per 1000 patients and that of community-acquired CRB infections increased from 100 per 1000 patients to 140 per 1000 patients. In parallel, colistin consumption increased 2.2-fold from 2008 to 2013, mainly because of an increase in the use of colistin aerosol forms (from 50 unitary doses to 2926 unitary doses; P<10(-5)) that was significantly correlated with an increase in the number of patients positive for CRB admitted to ICUs and units of long-term care between 2009 and 2013 (r=0.91; P=0.03). The global rise in infections due to intrinsic CRB is worrying and surveillance is warranted to better characterise this intriguing epidemiological change. PMID:25497970

  5. Increasing burden of urinary tract infections due to intrinsic colistin-resistant bacteria in hospitals in Marseille, France.

    PubMed

    Abat, Cédric; Desboves, Guillaume; Olaitan, Abiola Olumuyiwa; Chaudet, Hervé; Roattino, Nicole; Fournier, Pierre-Edouard; Colson, Philippe; Raoult, Didier; Rolain, Jean-Marc

    2015-02-01

    The emergence of multidrug-resistant (MDR) Gram-negative bacteria has become a major public health problem, eliciting renewed interest in colistin, an old antibiotic that is now routinely used to treat MDR bacterial infections. Here we investigated whether colistin use has affected the prevalence of infections due to intrinsic colistin-resistant bacteria (CRB) in university hospitals in Marseille (France) over a 5-year period. All data from patients infected by intrinsic CRB were compiled from January 2009 to December 2013. Escherichia coli infections were used for comparison. Colistin consumption data were also collected from pharmacy records from 2008 to 2013. A total of 4847 intrinsic CRB infections, including 3150 Proteus spp., 847 Morganella spp., 704 Serratia spp. and 146 Providencia spp., were collected between 2009 and 2013. During this period, the annual incidence rate of hospital-acquired CRB infections increased from 220 per 1000 patients to 230 per 1000 patients and that of community-acquired CRB infections increased from 100 per 1000 patients to 140 per 1000 patients. In parallel, colistin consumption increased 2.2-fold from 2008 to 2013, mainly because of an increase in the use of colistin aerosol forms (from 50 unitary doses to 2926 unitary doses; P<10(-5)) that was significantly correlated with an increase in the number of patients positive for CRB admitted to ICUs and units of long-term care between 2009 and 2013 (r=0.91; P=0.03). The global rise in infections due to intrinsic CRB is worrying and surveillance is warranted to better characterise this intriguing epidemiological change.

  6. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids.

  7. First Case of Human Infection Due to Pseudomonas fulva, an Environmental Bacterium Isolated from Cerebrospinal Fluid ▿

    PubMed Central

    Almuzara, Marisa N.; Vazquez, Miryam; Tanaka, Naoto; Turco, Marisa; Ramirez, Maria S.; Lopez, Eduardo L.; Pasteran, Fernando; Rapoport, Melina; Procopio, Adriana; Vay, Carlos A.

    2010-01-01

    We report the first case of human infection due to Pseudomonas fulva. P. fulva caused acute meningitis following the placement of a drainage system in a 2-year-old female. Additionally, the isolate displayed a VIM-2 carbapenemase in a class 1 integron context. PMID:20032258

  8. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child

    PubMed Central

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  9. Nephrotic Syndrome without Hematuria due to Infection-Related Glomerulonephritis Mimicking Minimal-Change Disease in a Child.

    PubMed

    Iwafuchi, Yoichi; Morioka, Tetsuo; Morita, Takashi; Watanabe, Kanako; Oyama, Yuko; Narita, Ichiei

    2016-01-01

    Nephrotic syndrome without hematuria due to infection-related glomerulonephritis is uncommon. The present report describes a case of nephrotic syndrome due to infection-related glomerulonephritis without hematuria and hypertension in an older child. A 14-year-old boy was referred to our hospital because of a 5-day history of fever, nausea, weight gain and recent leg edema without hypertension. Laboratory data showed nephrotic-range proteinuria, hypoalbuminemia, mild hypocomplementemia and acute renal injury without hematuria. Although, due to the clinical presentation, minimal-change nephrotic syndrome was mostly suspected, a renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental mesangiolytic changes. Fine granular IgG and C3 deposits were noted by an immunofluorescent study; many relatively small electron-dense deposits were observed electron-microscopically. These findings led to the diagnosis of nephrotic syndrome due to infection-related endocapillary proliferative glomerulonephritis, although the causative organism of his nephritis was not detected. He recovered with rest and dietary cure. When we examine an acute nephrotic child, infection-related glomerulonephritis should be considered as the differential diagnosis to avoid unnecessary use of corticosteroids. PMID:26889476

  10. CT-Guided Percutaneous Drainage of Infected Collections Due to Gastric Leak After Sleeve Gastrectomy for Morbid Obesity: Initial Experience

    SciTech Connect

    Kelogrigoris, M. Sotiropoulou, E.; Stathopoulos, K.; Georgiadou, V.; Philippousis, P.; Thanos, L.

    2011-06-15

    This study was designed to evaluate the efficacy and safety of computed tomography (CT)-guided drainage in treating infected collections due to gastric leak after laparoscopic sleeve gastrectomy for morbid obesity. From January 2007 to June 2009, 21 patients (9 men and 12 women; mean age, 39.2 (range, 26-52) years) with infected collections due to gastric leak after laparoscopic sleeve gastrectomy for morbid obesity underwent image-guided percutaneous drainage. All procedures were performed using CT guidance and 8- to 12-Fr pigtail drainage catheters. Immediate technical success was achieved in all 21 infected collections. In 18 of 21 collections, we obtained progressive shrinkage of the collection with consequent clinical success (success rate 86%). In three cases, the abdominal fluid collection was not resolved, and the patients were reoperated. Among the 18 patients who avoided surgery, 2 needed replacement of the catheter due to obstruction. No major complications occurred during the procedure. The results of our study support that CT-guided percutaneous drainage is an effective and safe method to treat infected abdominal fluid collections due to gastric leak in patients who had previously underwent laparoscopic sleeve gastrectomy for morbid obesity. It may be considered both as a preparatory step for surgery and a valuable alternative to open surgery. Failure of the procedure does not, however, preclude a subsequent surgical operation.

  11. Requirement of the Pseudomonas aeruginosa CbrA Sensor Kinase for Full Virulence in a Murine Acute Lung Infection Model

    PubMed Central

    Yeung, Amy T. Y.; Janot, Laure; Pena, Olga M.; Neidig, Anke; Kukavica-Ibrulj, Irena; Hilchie, Ashley; Levesque, Roger C.; Overhage, Joerg

    2014-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the cbrA mutant was less virulent since substantially larger numbers of cbrA mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the cbrA mutant grew and persisted as well as the wild type, indicating that the decrease of in vivo virulence of the cbrA mutant did not result from growth deficiencies on particular carbon substrates observed in vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the cbrA mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes in vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of Dictyostelium discoideum amoebae to kill the cbrA mutant than to kill the wild type. Transcriptional analysis of the cbrA mutant during D. discoideum infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of P. aeruginosa against oxidative stress, and the regulation of certain virulence factors. PMID:24379284

  12. Requirement of the Pseudomonas aeruginosa CbrA sensor kinase for full virulence in a murine acute lung infection model.

    PubMed

    Yeung, Amy T Y; Janot, Laure; Pena, Olga M; Neidig, Anke; Kukavica-Ibrulj, Irena; Hilchie, Ashley; Levesque, Roger C; Overhage, Joerg; Hancock, Robert E W

    2014-03-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the cbrA mutant was less virulent since substantially larger numbers of cbrA mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the cbrA mutant grew and persisted as well as the wild type, indicating that the decrease of in vivo virulence of the cbrA mutant did not result from growth deficiencies on particular carbon substrates observed in vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the cbrA mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes in vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of Dictyostelium discoideum amoebae to kill the cbrA mutant than to kill the wild type. Transcriptional analysis of the cbrA mutant during D. discoideum infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of P. aeruginosa against oxidative stress, and the regulation of certain virulence factors.

  13. 10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation.

    PubMed

    Peghin, Maddalena; Monforte, Victor; Martin-Gomez, Maria-Teresa; Ruiz-Camps, Isabel; Berastegui, Cristina; Saez, Berta; Riera, Jordi; Ussetti, Piedad; Solé, Juan; Gavaldá, Joan; Roman, Antonio

    2016-01-01

    The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n-LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003-2013) undergoing n-LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow-up 2.56 years; IQR 1.01-4.65). Fifty-three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person-time incidence rates of Aspergillus spp. colonization and infection decreased (2003-2008, 0.19; 2009-2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003-2008, 38.1% vs 2009-2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28-41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long-term administration of prophylaxis with n-LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection.

  14. Hantavirus disease in Germany due to infection with Dobrava-Belgrade virus genotype Kurkino.

    PubMed

    Hofmann, J; Meier, M; Enders, M; Führer, A; Ettinger, J; Klempa, B; Schmidt, S; Ulrich, R G; Kruger, D H

    2014-10-01

    Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes.

  15. Listeria ivanovii Infection in Mice: Restricted to the Liver and Lung with Limited Replication in the Spleen

    PubMed Central

    Zhou, Mengying; Jiang, Mingjuan; Ren, Chenyan; Liu, Sijing; Pu, Qikang; Goldfine, Howard; Shen, Hao; Wang, Chuan

    2016-01-01

    Listeria monocytogenes (LM) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. L. ivanovii (LI) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over LM because it is not a human pathogen, but can infect other animal species. Recent studies show that recombinant LI expressing Mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the potential of LI as a live vaccine vector. However, a key barrier in the development of LI into a live vaccine vector is that its pathogenic and immunogenic characteristics have yet to be fully understood. Therefore, in this research, C57BL/6J mice were inoculated with LM or LI intravenously or intranasally, and bacterial loads, histopathologic changes, and cytokine production were determined at indicated days post inoculation. Results showed that after intravenous infection with LM or LI, bacteria were found proliferating in the liver, spleen, and lung. However, LI could only reach a heavy burden in the liver and its ability to multiply and to resist host immunity seemed limited in the spleen and lung. After intranasal inoculation with LI, bacteria were mainly localized in the lung and failed to infect liver or spleen, while LM could. In organs with heavy LI burden, lesions were isolated, localized and densely packed, compared to lesions caused by LM, which were invasive. In the liver of intravenously inoculated mice and lung of intranasally inoculate mice, LI was able to elicit comparable cytokine production with LM and cause less severe histopathologic damages, and thus could be considered as a vector for treating or preventing hepatic or pulmonary diseases. PMID:27375558

  16. Chronic lung infection by Pseudomonas aeruginosa biofilm is cured by L-Methionine in combination with antibiotic therapy

    PubMed Central

    Gnanadhas, Divya Prakash; Elango, Monalisha; Datey, Akshay; Chakravortty, Dipshikha

    2015-01-01

    Bacterial biofilms are associated with 80–90% of infections. Within the biofilm, bacteria are refractile to antibiotics, requiring concentrations >1,000 times the minimum inhibitory concentration. Proteins, carbohydrates and DNA are the major components of biofilm matrix. Pseudomonas aeruginosa (PA) biofilms, which are majorly associated with chronic lung infection, contain extracellular DNA (eDNA) as a major component. Herein, we report for the first time that L-Methionine (L-Met) at 0.5 μM inhibits Pseudomonas aeruginosa (PA) biofilm formation and disassembles established PA biofilm by inducing DNase expression. Four DNase genes (sbcB, endA, eddB and recJ) were highly up-regulated upon L-Met treatment along with increased DNase activity in the culture supernatant. Since eDNA plays a major role in establishing and maintaining the PA biofilm, DNase activity is effective in disrupting the biofilm. Upon treatment with L-Met, the otherwise recalcitrant PA biofilm now shows susceptibility to ciprofloxacin. This was reflected in vivo, in the murine chronic PA lung infection model. Mice treated with L-Met responded better to antibiotic treatment, leading to enhanced survival as compared to mice treated with ciprofloxacin alone. These results clearly demonstrate that L-Met can be used along with antibiotic as an effective therapeutic against chronic PA biofilm infection. PMID:26521707

  17. [Advances in the research of an animal model of wound due to Mycobacterium tuberculosis infection].

    PubMed

    Chen, Ling; Jia, Chiyu

    2015-12-01

    Tuberculosis ranks as the second deadly infectious disease worldwide. The incidence of tuberculosis is high in China. Refractory wound caused by Mycobacterium tuberculosis infection ranks high in misdiagnosis, and it is accompanied by a protracted course, and its pathogenic mechanism is still not so clear. In order to study its pathogenic mechanism, it is necessary to reproduce an appropriate animal model. Up to now the study of the refractory wound caused by Mycobacterium tuberculosis infection is just beginning, and there is still no unimpeachable model for study. This review describes two models which may reproduce a wound similar to the wound caused by Mycobacterium tuberculosis infection, so that they could be used to study the pathogenesis and characteristics of a tuberculosis wound in an animal.

  18. Clinical Management of an Increasing Threat: Outpatient Urinary Tract Infections Due to Multidrug-Resistant Uropathogens.

    PubMed

    Walker, Emily; Lyman, Alessandra; Gupta, Kalpana; Mahoney, Monica V; Snyder, Graham M; Hirsch, Elizabeth B

    2016-10-01

    Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrug-resistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs.

  19. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia.

    PubMed

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  20. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia

    PubMed Central

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  1. Antibiotic Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae: Systematic Evaluation of the Available Evidence

    PubMed Central

    Lourida, Panagiota; Poulikakos, Panagiotis; Rafailidis, Petros I.; Tansarli, Giannoula S.

    2014-01-01

    We sought to evaluate the effectiveness of the antibiotic treatment administered for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed and Scopus databases were systematically searched. Articles reporting the clinical outcomes of patients infected with carbapenemase-producing Enterobacteriaceae according to the antibiotic treatment administered were eligible. Twenty nonrandomized studies comprising 692 patients who received definitive treatment were included. Almost all studies reported on Klebsiella spp. In 8 studies, the majority of infections were bacteremia, while pneumonia and urinary tract infections were the most common infections in 12 studies. In 10 studies, the majority of patients were critically ill. There are methodological issues, including clinical heterogeneity, that preclude the synthesis of the available evidence using statistical analyses, including meta-analysis. From the descriptive point of view, among patients who received combination treatment, mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the monotherapy-treated patients, mortality was up to 57% for colistin and up to 80% for tigecycline. Certain regimens were administered to a small number of patients in certain studies. Three studies reporting on 194 critically ill patients with bacteremia showed individually significantly lower mortality in the combination arm than in the monotherapy arm. In the other studies, no significant difference in mortality was recorded between the compared groups. Combination antibiotic treatment may be considered the optimal option for severely ill patients with severe infections. However, well-designed randomized studies of specific patient populations are needed to further clarify this issue. PMID:24080646

  2. Cell phenotypic change due to Cryptosporidium parvum infection in immunocompetent mice.

    PubMed

    Codices, Vera; Martins, Catarina; Novo, Carlos; Pinho, Mário; de Sousa, Bruno; Lopes, Angela; Borrego, Miguel; Matos, Olga

    2013-03-01

    Cryptosporidium parvum is an intracellular parasite causing enteritis which can become life-threatening in immunocompromised host. Immunoregulatory T cells play a central role in the regulatory network of the host. Here, we proposed to characterize the populations of immune cells during infection and reinfection with C. parvum. Four-week-old BALB/C mice were inoculated with oocysts of C. parvum at days 0 and 22. Fecal and blood samples, spleens, and small intestines were collected for analysis. Peripheral blood and spleen cell populations were characterized by flow cytometry. After infection (days 0 to 21), mice presented higher values of neutrophils, eosinophils, NK cells and CD4(+)CD25(high) T cells in peripheral blood. After reinfection, this upward trend continued in the following days for all four populations in infected mice. At day 35, infected mice presented similar values to the control group, except for CD4(+)CD25(high) T cells, which remained higher in infected mice. A possible correlation between alterations in blood and spleen cell populations was also studied, but no consistent association could be established. Small intestine sections were screened for intracellular stages of the parasite but no evidence of pathology was observed. Here, we report information which may be important for the understanding of the specific cell-mediated response in immunocompetent mice to C. parvum infection. Although some questions remain unanswered and complementary studies are needed, our results are expected to contribute to a better understanding of innate and Treg cells role in the clearance process of this parasite.

  3. Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

    PubMed

    Costabile, G; d'Angelo, I; d'Emmanuele di Villa Bianca, R; Mitidieri, E; Pompili, B; Del Porto, P; Leoni, L; Visca, P; Miro, A; Quaglia, F; Imperi, F; Sorrentino, R; Ungaro, F

    2016-09-28

    Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3

  4. Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

    PubMed

    Costabile, G; d'Angelo, I; d'Emmanuele di Villa Bianca, R; Mitidieri, E; Pompili, B; Del Porto, P; Leoni, L; Visca, P; Miro, A; Quaglia, F; Imperi, F; Sorrentino, R; Ungaro, F

    2016-09-28

    Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3

  5. Bone and Joint Infections due to Haemophilus parainfluenzae: Case Report and Review of the Literature.

    PubMed

    O'Neil, Conar R; Wilson, Evan; Missaghi, Bayan

    2016-01-01

    Haemophilus parainfluenzae is a normal inhabitant of the human respiratory tract. However it is an increasingly recognized pathogen in invasive infections, particularly in the immunocompromised host and where there is disruption of the normal skin or mucosal barriers. We present a case of a 56-year-old female with a history of asplenia who developed H. parainfluenzae septic arthritis of the hip following an intra-articular steroid injection. We also summarize previously reported cases of bone and joint infections caused by H. parainfluenzae. PMID:27516778

  6. Bone and Joint Infections due to Haemophilus parainfluenzae: Case Report and Review of the Literature

    PubMed Central

    Wilson, Evan; Missaghi, Bayan

    2016-01-01

    Haemophilus parainfluenzae is a normal inhabitant of the human respiratory tract. However it is an increasingly recognized pathogen in invasive infections, particularly in the immunocompromised host and where there is disruption of the normal skin or mucosal barriers. We present a case of a 56-year-old female with a history of asplenia who developed H. parainfluenzae septic arthritis of the hip following an intra-articular steroid injection. We also summarize previously reported cases of bone and joint infections caused by H. parainfluenzae. PMID:27516778

  7. An assessment of ecological and case-control methods for estimating lung cancer risk due to indoor radon

    SciTech Connect

    Stidley, C.A.; Samet, J.M.

    1992-12-31

    Studies of underground miners indicate that indoor radon is an important cause of lung cancer. This finding has raised concern that exposure to radon also causes lung cancer in the general population. Epidemiological studies, including both case-control and ecological approaches, have directly addressed the risks of indoor residential radon; many more case-control studies are in progress. Ecological studies that associate lung-cancer rates with typical indoor radon levels in various geographic areas have not consistently shown positive associations. The results of purportedly negative ecological studies have been used as a basis for questioning the hazards of indoor radon exposure. Because of potentially serious methodologic flaws for testing hypotheses, we examined the ecological method as a tool for assessing lung-cancer risk from indoor radon exposure. We developed a simulation approach that utilizes the Environmental Protection Agency (EPA) radon survey data to assign exposures to individuals within counties. Using the computer-generated data, we compared risk estimates obtained by ecological regression methods with those obtained from other regression methods and with the {open_quotes}true{close_quotes} risks used to generate the data. For many of these simulations, the ecological models, while fitting the summary data well, gave risk estimates that differed considerably from the true risks. For some models, the risk estimates were negatively correlated with exposure, although the assumed relationship was positive. Attempts to improve the ecological models by adding smoking variables, including interaction terms, did not always improve the estimates of risk, which are easily affected by model misspecification. Because exposure situations used in the simulations are realistic, our results show that ecological methods may not accurately estimate the lung-cancer risk associated with indoor radon exposure.

  8. Characteristics of prosthetic joint infections due to Enterococcus sp. and predictors of failure: a multi-national study.

    PubMed

    Tornero, E; Senneville, E; Euba, G; Petersdorf, S; Rodriguez-Pardo, D; Lakatos, B; Ferrari, M C; Pilares, M; Bahamonde, A; Trebse, R; Benito, N; Sorli, L; del Toro, M D; Baraiaetxaburu, J M; Ramos, A; Riera, M; Jover-Sáenz, A; Palomino, J; Ariza, J; Soriano, A

    2014-11-01

    The objective of this study was to review the characteristics and outcome of prosthetic joint infections (PJI) due to Enterococcus sp. collected in 18 hospitals from six European countries. Patients with a PJI due to Enterococcus sp. diagnosed between January 1999 and July 2012 were retrospectively reviewed. Relevant information about demographics, comorbidity, clinical characteristics, microbiological data, surgical treatment and outcome was registered. Univariable and multivariable analyses were performed. A total of 203 patients met the inclusion criteria. The mean (SD) was 70.4 (13.6) years. In 59 patients the infection was diagnosed within the first 30 days (29.1%) from arthroplasty, in 44 (21.7%) between 31 and 90 days, in 54 (26.6%) between 91 days and 2 years and in 43 (21%) after 2 years. Enterococcus faecalis was isolated in 176 cases (89%). In 107 (54%) patients the infection was polymicrobial. Any comorbidity (OR 2.53, 95% CI 1.18-5.40, p 0.01), and fever (OR 2.65, 95% CI 1.23-5.69, p 0.01) were independently associated with failure. The only factor associated with remission was infections diagnosed later than 2 years (OR 0.25, 95% CI 0.09-0.71, p 0.009). In conclusion, prosthetic joint infections due to Enterococcus sp. were diagnosed within the first 2 years from arthroplasty in >70% of the patients, almost 50% had at least one comorbidity and infections were frequently polymicrobial (54%). The global failure rate was 44% and patients with comorbidities, fever, and diagnosed within the first 2 years from arthroplasty had a poor prognosis.

  9. Beyond Susceptible and Resistant, Part III: Treatment of Infections due to Gram-Negative Organisms Producing Carbapenemases

    PubMed Central

    Narayanan, Navaneeth; Johnson, Linda

    2016-01-01

    Carbapenemases are enzymes that are capable of inactivating all or almost all beta-lactam antimicrobial agents. These enzymes are frequently coexpressed with other resistance mechanisms to non–beta-lactams, leading to extremely drug-resistant pathogens. Once a curiosity, these enzymes have spread into organisms that are among the most common causes of infection, such as Klebsiella pneumoniae and Escherichia coli. Identification of these organisms has proved challenging for clinical microbiology laboratories, leading to revisions in susceptibility standards for carbapenems. Although currently a rare cause of infection in children, these carbapenem-resistant Enterobacteriaceae (CRE) are becoming endemic in a variety of healthcare settings. Management of infections due to CRE is complicated by a lack of effective treatment options and clinical data on their effectiveness. Treatment of CRE infections in children is particularly challenging because therapeutic options for CRE lack adequate data on dosing and safety in children. Use of unconventional combination treatment regimens, including agents to which the organism is resistant in vitro, may provide some benefit in the treatment of severe CRE infection. Fortunately, several agents with the potential for treatment of CRE infections have been recently approved or are in late clinical development, although few data will be available in the short term to inform use in children. PMID:27199618

  10. Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection

    PubMed Central

    Moltedo, Bruno; Li, Wenjing; Yount, Jacob S.; Moran, Thomas M.

    2011-01-01

    Migratory lung dendritic cells (DCs) transport viral antigen from the lungs to the draining mediastinal lymph nodes (MLNs) during influenza virus infection to initiate the adaptive immune response. Two major migratory DC subsets, CD103+ DCs and CD11bhigh DCs participate in this function and it is not clear if these antigen presenting cell (APC) populations become directly infected and if so whether their activity is influenced by the infection. In these experiments we show that both subpopulations can become infected and migrate to the draining MLN but a difference in their response to type I interferon (I-IFN) signaling dictates the capacity of the virus to replicate. CD103+ DCs allow the virus to replicate to significantly higher levels than do the CD11bhigh DCs, and they release infectious virus in the MLNs and when cultured ex-vivo. Virus replication in CD11bhigh DCs is inhibited by I-IFNs, since ablation of the I-IFN receptor (IFNAR) signaling permits virus to replicate vigorously and productively in this subset. Interestingly, CD103+ DCs are less sensitive to I-IFNs upregulating interferon-induced genes to a lesser extent than CD11bhigh DCs. The attenuated IFNAR signaling by CD103+ DCs correlates with their described superior antigen presentation capacity for naïve CD8+ T cells when compared to CD11bhigh DCs. Indeed ablation of IFNAR signaling equalizes the competency of the antigen presenting function for the two subpopulations. Thus, antigen presentation by lung DCs is proportional to virus replication and this is tightly constrained by I-IFN. The “interferon-resistant” CD103+ DCs may have evolved to ensure the presentation of viral antigens to T cells in I-IFN rich environments. Conversely, this trait may be exploitable by viral pathogens as a mechanism for systemic dissemination. PMID:22072965

  11. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection.

    PubMed

    Kerr, Sheena C; Fischer, Gregory J; Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M; Choera, Tsokyi; Lim, Fang Yun; Wimmerova, Michaela; Carrington, Stephen D; Yuan, Shaopeng; Lowell, Clifford A; Oscarson, Stefan; Keller, Nancy P; Fahy, John V

    2016-04-01

    The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia. PMID:27058347

  12. Cigarette Smoke-Induced Lung Disease Predisposes to More Severe Infection with Nontypeable Haemophilus influenzae: Protective Effects of Andrographolide.

    PubMed

    Tan, W S Daniel; Peh, Hong Yong; Liao, Wupeng; Pang, Chu Hui; Chan, Tze Khee; Lau, Suk Hiang; Chow, Vincent T; Wong, W S Fred

    2016-05-27

    Cigarette smoke (CS) is associated with many maladies, one of which is chronic obstructive pulmonary disease (COPD). As the disease progresses, patients are more prone to develop COPD exacerbation episodes by bacterial infection, particularly to nontypeable Haemophilus influenza (NTHi) infection. The present study aimed to develop a CS-exposed mouse model that increases inflammation induced by NTHi challenge and investigate the protective effects of andrographolide, a bioactive molecule with anti-inflammatory and antioxidant properties isolated from the plant Andrographis paniculata. Female BALB/c mice exposed to 2 weeks of CS followed by a single intratracheal instillation of NTHi developed increased macrophage and neutrophil pulmonary infiltration, augmented cytokine levels, and heightened oxidative damage. Andrographolide effectively reduced lung cellular infiltrates and decreased lung levels of TNF-α, IL-1β, CXCL1/KC, 8-OHdG, matrix metalloproteinase-8 (MMP-8), and MMP-9. The protective actions of andrographolide on CS-predisposed NTHi inflammation might be attributable to increased nuclear factor erythroid-2-related factor 2 (Nrf2) activation and decreased Kelch-like ECH-associated protein 1 (Keap1) repressor function, resulting in enhanced gene expression of antioxidant enzymes including heme oxygenase-1 (HO-1), glutathione reductase (GR), glutathione peroxidase-2 (GPx-2), glutamate-cysteine ligase modifier (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1). Taken together, these findings strongly support a therapeutic potential for andrographolide in preventing lung inflammation caused by NTHi in cigarette smokers.

  13. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection

    PubMed Central

    Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M.; Choera, Tsokyi; Yun Lim, Fang; Wimmerova, Michaela; Carrington, Stephen D.; Yuan, Shaopeng; Lowell, Clifford A.; Oscarson, Stefan; Keller, Nancy P.; Fahy, John V.

    2016-01-01

    The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia. PMID:27058347

  14. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection.

    PubMed

    Kerr, Sheena C; Fischer, Gregory J; Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M; Choera, Tsokyi; Lim, Fang Yun; Wimmerova, Michaela; Carrington, Stephen D; Yuan, Shaopeng; Lowell, Clifford A; Oscarson, Stefan; Keller, Nancy P; Fahy, John V

    2016-04-01

    The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia.

  15. Scalp Abscess Due to Streptomyces cacaoi subsp. cacaoi, First Report in a Human Infection

    PubMed Central

    Pellegrini, Gerald J.; Graziano, James C.; Ragunathan, Latha; Bhat, Malini A.; Hemashettar, Basavaraj M.

    2012-01-01

    Streptomyces cacaoi subsp. cacaoi, a Gram-positive, branching filamentous bacteria, was isolated from a scalp infection in a patient from Pondicherry, India. Phenotypic tests identified the isolate as a Streptomyces species, but 16S rRNA sequence analysis provided the species identification required for tracking of this emerging pathogen. PMID:22278841

  16. Immunization is ineffective at preventing infection and mortality due to the amphibian chytrid fungus Batrachochytrium dendrobatidis.

    PubMed

    Stice, Mary J; Briggs, Cheryl J

    2010-01-01

    The fungal pathogen Batrachochytrium dendrobatidis (Bd), the causative agent of chytridiomycosis, has been implicated in amphibian declines worldwide. It has been hypothesized that low inherent immunogenicity in Bd may be related to the high rates of morbidity and mortality that are associated with Bd-infected anuran populations. To test this idea, juvenile Rana muscosa (mountain yellow-legged frogs) were immunized with adjuvants in combination with a formalin-killed Bd culture to determine if it is possible to stimulate a protective immune response when challenged with a live inoculum of B. dendrobatidis. Three groups of juvenile R. muscosa (6 mo postmetamorphosis) were immunized with saline, Freunds Complete (FCA) and Incomplete Adjuvant (FIA), or the adjuvants in combination with a formalin-killed culture of B. dendrobatidis. The effects of immunization were modeled using survival analysis and a proportional hazards model. No significant differences were found between the groups in overall mortality, time to infection, infection prevalence, or intensity. While this study suggests that immunizing anurans against chytridiomycosis will not alter rates of infection or mortality among individuals, it does raise several questions regarding the attenuation and efficacy of anuran adaptive immune responses and whether they may be protective against this disease. PMID:20090019

  17. Postneurosurgical Central Nervous System Infection Due to Enterococcus faecalis Successfully Treated With Intraventricular Vancomycin

    PubMed Central

    Patel, Trisha; Lewis, Mark E.; Niesley, Michelle L.; Chowdhury, Mashiul

    2016-01-01

    Abstract Infections from Enterococcus faecalis and Enterococcus faecium are uncommon in the post-neurosurgical intervention setting., [1, 2, 3, 4] Intraventricular antibiotics are recommended when standard intravenous therapy fails. [5] Here we present a case of post-neurosurgical ventriculitis, meningitis, and cerebritis in an oncology patient caused by refractory Enterococcus faecalis successfully treated with intraventricular vancomycin. PMID:27226704

  18. Improved resistance to Eimeria acervulina infection in chickens due to dietary supplementation with garlic metabolites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of a compound including secondary metabolites of garlic, propyl thiosulfinate (PTS) and propyl thiosulfinatate oxide (PTSO), on in vitro and in vivo parameters of chicken gut immunity during experimental Eimeria acervulina infection were evaluated. In in vitro assays, the compound of P...

  19. Immunization is ineffective at preventing infection and mortality due to the amphibian chytrid fungus Batrachochytrium dendrobatidis.

    PubMed

    Stice, Mary J; Briggs, Cheryl J

    2010-01-01

    The fungal pathogen Batrachochytrium dendrobatidis (Bd), the causative agent of chytridiomycosis, has been implicated in amphibian declines worldwide. It has been hypothesized that low inherent immunogenicity in Bd may be related to the high rates of morbidity and mortality that are associated with Bd-infected anuran populations. To test this idea, juvenile Rana muscosa (mountain yellow-legged frogs) were immunized with adjuvants in combination with a formalin-killed Bd culture to determine if it is possible to stimulate a protective immune response when challenged with a live inoculum of B. dendrobatidis. Three groups of juvenile R. muscosa (6 mo postmetamorphosis) were immunized with saline, Freunds Complete (FCA) and Incomplete Adjuvant (FIA), or the adjuvants in combination with a formalin-killed culture of B. dendrobatidis. The effects of immunization were modeled using survival analysis and a proportional hazards model. No significant differences were found between the groups in overall mortality, time to infection, infection prevalence, or intensity. While this study suggests that immunizing anurans against chytridiomycosis will not alter rates of infection or mortality among individuals, it does raise several questions regarding the attenuation and efficacy of anuran adaptive immune responses and whether they may be protective against this disease.

  20. Cirrhosis due to chronic hepatitis E infection in a child post-bone marrow transplant.

    PubMed

    Halac, Ugur; Béland, Kathie; Lapierre, Pascal; Patey, Natacha; Ward, Pierre; Brassard, Julie; Houde, Alain; Alvarez, Fernando

    2012-05-01

    Chronic hepatitis E virus (HEV) infection occurs in immunosuppressed adults. We detected HEV ribonucleic acid in serum of an adolescent patient who had undergone bone marrow transplantation and subsequently presented with persistently increased aminotransferases and histologic chronic hepatitis, and eventually developed cirrhosis. Phylogenetic analysis revealed these HEV strains were similar to swine genotype 3a, suggesting a possible zoonosis. PMID:22341950

  1. Stenotrophomonas maltophilia Virulence and Specific Variations in Trace Elements during Acute Lung Infection: Implications in Cystic Fibrosis

    PubMed Central

    Crocetta, Valentina; Consalvo, Ada; Zappacosta, Roberta; Di Ilio, Carmine; Di Bonaventura, Giovanni

    2014-01-01

    Metal ions are necessary for the proper functioning of the immune system, and, therefore, they might have a significant influence on the interaction between bacteria and host. Ionic dyshomeostasis has been recently observed also in cystic fibrosis (CF) patients, whose respiratory tract is frequently colonized by Stenotrophomonas maltophilia. For the first time, here we used an inductively mass spectrometry method to perform a spatial and temporal analysis of the pattern of changes in a broad range of major trace elements in response to pulmonary infection by S. maltophilia. To this, DBA/2 mouse lungs were comparatively infected by a CF strain and by an environmental one. Our results showed that pulmonary ionomic profile was significantly affected during infection. Infected mice showed increased lung levels of Mg, P, S, K, Zn, Se, and Rb. To the contrary, Mn, Fe, Co, and Cu levels resulted significantly decreased. Changes of element concentrations were correlated with pulmonary bacterial load and markers of inflammation, and occurred mostly on day 3 post-exposure, when severity of infection culminated. Interestingly, CF strain – significantly more virulent than the environmental one in our murine model - provoked a more significant impact in perturbing pulmonary metal homeostasis. Particularly, exposure to CF strain exclusively increased P and K levels, while decreased Fe and Mn ones. Overall, our data clearly indicate that S. maltophilia modulates pulmonary metal balance in a concerted and virulence-dependent manner highlighting the potential role of the element dyshomeostasis during the progression of S. maltophilia infection, probably exacerbating the harmful effects of the loss of CF transmembrane conductance regulator function. Further investigations are required to understand the biological significance of these alterations and to confirm they are specifically caused by S. maltophilia. PMID:24586389

  2. Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103+ Lung Dendritic Cells during Pulmonary Tuberculosis

    PubMed Central

    Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

    2013-01-01

    Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103+ dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40+ cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype. PMID:23861965

  3. Host factors and genetic susceptibility to infections due to intracellular bacteria and fastidious organisms.

    PubMed

    Asner, S A; Morré, S A; Bochud, P-Y; Greub, G

    2014-12-01

    While genetic polymorphisms play a paramount role in tuberculosis (TB), less is known about their contribution to the severity of diseases caused by other intracellular bacteria and fastidious microorganisms. We searched electronic databases for observational studies reporting on host factors and genetic predisposition to infections caused by intracellular fastidious bacteria published up to 30 May 2014. The contribution of genetic polymorphisms was documented for TB. This includes genetic defects in the mononuclear phagocyte/T helper cell type 1 (Th1) pathway contributing to disseminated TB disease in children and genome-wide linkage analysis (GWAS) in reactivated pulmonary TB in adults. Similarly, experimental studies supported the role of host genetic factors in the clinical presentation of illnesses resulting from other fastidious intracellular bacteria. These include IL-6 -174G/C or low mannose-binding (MBL) polymorphisms, which are incriminated in chronic pulmonary conditions triggered by C. pneumoniae, type 2-like cytokine secretion polymorphisms, which are correlated with various clinical patterns of M. pneumoniae infections, and genetic variation in the NOD2 gene, which is an indicator of tubal pathology resulting from Chamydia trachomatis infections. Monocyte/macrophage migration and T lymphocyte recruitment defects are corroborated to ineffective granuloma formation observed among patients with chronic Q fever. Similar genetic polymorphisms have also been suggested for infections caused by T. whipplei although not confirmed yet. In conclusion, this review supports the paramount role of genetic factors in clinical presentations and severity of infections caused by intracellular fastidious bacteria. Genetic predisposition should be further explored through such as exome sequencing.

  4. Polyradiculopathy and Gastroparesis due to Cytomegalovirus Infection in AIDS: A Case Report and Review of Literature

    PubMed Central

    Thongpooswan, Supat; Chyn, Eric; Alfishawy, Mostafa; Restrepo, Erfidia; Berman, Charles; Ahmed, Kawser; Muralidharan, Sethu

    2015-01-01

    Patient: Female, 46 Final Diagnosis: CMV gastroparesis and radiculopathy Symptoms: Nausea • paraplegia • urinary retention • vomiting Medication: — Clinical Procedure: Lumbar puncture Specialty: Infectious Diseases Objective: Unusual clinical course Background: Cytomegalovirus (CMV) infection has been well described as an opportunistic infection of patients with human immunodeficiency virus (HIV). To the best of our knowledge, this is the first case report of a patient with AIDS and lumbosacral polyradiculopathy, associated with gastroparesis resulting from CMV infection. Case Report: A 46-year-old Hispanic woman with a history of HIV for 10 years was admitted to our hospital for nausea, vomiting, urinary retention, and generalized weakness. Bilateral lower extremity examination revealed flaccid paraplegia, decreased sensations from the groin downwards, bilateral lower extremity areflexia, and absent plantar reflexes, with enlarged urinary bladder. CMV was detected in CSF by PCR, and cervical and lumbar magnetic resonance imaging (MRI) revealed intense nodular leptomeningeal enhancement from the lower thoracic cord and extending along the conus medullaris/filum terminalis and nerve roots. Gastric emptying scintigraphy revealed severe delayed gastric emptying time. Ganciclovir was initiated and her neurological symptoms and gastrological symptoms gradually improved. Over 8 weeks, nausea and vomiting resolved and the patient was able to walk before being discharged from the hospital. Conclusions: Polyradiculopathy and gastroparesis can result from CMV infection in AIDS patients. Whether the mechanism is secondary to viral infection or immune systems remains unclear. It is important for physicians to be aware of this uncommon presentation in the antiretroviral therapy (ART) era. CMV treatment should be initiated immediately once diagnosis is confirmed. PMID:26552851

  5. Infections due to beta-lactamase-producing Neisseria gonorrhoeae at the University Hospital Medical Center, Kuala Lumpur, Malaysia.

    PubMed

    Ismail, R

    1987-01-01

    The incidence of infections due to beta-lactamase-producing Neisseria gonorrhoeae is increasing in many parts of the world. An epidemiologic survey of infections caused by beta-lactamase-producing strains of N. gonorrhoeae at the University Hospital, Kuala Lumpur, from February 1977 to December 1985 (106 months) showed that the incidence rose from 4.8% (two cases) in 1977 to 49.4% (39 cases) by the end of 1985. The highest incidence of gonococcal infections was found to be in the group aged 20-39 years; the male-to-female ratio was 1.55:1. The mean inhibitory concentrations of benzylpenicillin were 0.12 microgram/ml for non-beta-lactamase-producing strains and 16 micrograms/ml for isolates of N. gonorrhoeae that produce beta-lactamase.

  6. False-positive Chlamydiazyme results during urine sediment analysis due to bacterial urinary tract infections.

    PubMed Central

    Demaio, J; Boyd, R S; Rensi, R; Clark, A

    1991-01-01

    Our study examined whether urinary tract infections (UTIs) would cause false-positive results when urine sediment was tested with the Chlamydiazyme (CZ) system. Thirty-six infected urine samples and fifteen controls were studied. All controls were negative. Forty-seven percent of Escherichia coli UTIs (n = 30) and 100% of Klebsiella pneumoniae UTIs (n = 4) were positive on CZ testing of urine sediment. Nine E. coli UTIs positive by CZ were negative by direct fluorescent-antibody staining. When suspensions of the pure cultures were analyzed, 47% of E. coli and 100% of K. pneumoniae samples were CZ positive. False-positive results were not related to organism biotype or urine characteristics, including pH, specific gravity, and leukocyte count. We conclude that the presence of a UTI and also bacterial contamination must be ruled out prior to urine sediment testing. PMID:1885739

  7. Outbreaks of gastroenteritis due to infections with Norovirus in Switzerland, 2001-2003.

    PubMed Central

    Fretz, R.; Svoboda, P.; Lüthi, T. M.; Tanner, M.; Baumgartner, A.

    2005-01-01

    Viral infections, especially those with noroviruses are the most common cause of acute gastroenteritis in Europe. To obtain information about the epidemic situation of noroviruses in Switzerland, an initial study was launched in the German-speaking part of the country to systematically compile Norovirus outbreak information between 2001 and 2003. In total, 73 outbreaks were registered. Most affected were closed settings, e.g. nursing homes (34%) and hospitals (25%). Transmission pathways were identified in 74% of Norovirus outbreaks. In 81% of these cases person-to-person transmission was the primary route of infection and on seven occasions (13%), a foodborne transmission was the possible cause. Furthermore, Norovirus outbreak characteristics of epidemiological importance are highlighted with a discussion of four selected events. PMID:15962549

  8. Repeat corneal graft failure due to graft-to-host herpetic infection

    PubMed Central

    2013-01-01

    Background Herein, we present the case of a young female patient with keratoconus, who was subjected twice to repeat keratoplasty, and each time, she experienced a corneal graft failure. Findings Under the suspicion of herpetic eye disease, we administered topical and systemic anti-herpetic treatment after the second repeat keratoplasty. The postoperative course was uneventful, and the corneal graft is clear, until recently. Immunohistochemistry and DNA-polymerase chain reaction were negative for herpes simplex virus-1 (HSV-1) in the host cornea, but they detected HSV-1 in both transplanted corneal grafts, thereby supporting our clinical hypothesis that graft-to-host HSV-1 infection elicited this chain reaction of complications in our patient. Conclusion This clinical report illustrates in a unique way the dramatic impact an unsuspected herpetic infection in the corneal graft in cases of keratoplasty may have and underscores the necessity of suspecting and adequately treating these distinct cases. PMID:23514192

  9. Particle Deposition in Human Lungs due to Varying Cross-Sectional Ellipticity of Left and Right Main Bronchi

    NASA Astrophysics Data System (ADS)

    Roth, Steven; Oakes, Jessica; Shadden, Shawn

    2015-11-01

    Particle deposition in the human lungs can occur with every breathe. Airbourne particles can range from toxic constituents (e.g. tobacco smoke and air pollution) to aerosolized particles designed for drug treatment (e.g. insulin to treat diabetes). The effect of various realistic airway geometries on complex flow structures, and thus particle deposition sites, has yet to be extensively investigated using computational fluid dynamics (CFD). In this work, we created an image-based geometric airway model of the human lung and performed CFD simulations by employing multi-domain methods. Following the flow simulations, Lagrangian particle tracking was used to study the effect of cross-sectional shape on deposition sites in the conducting airways. From a single human lung model, the cross-sectional ellipticity (the ratio of major and minor diameters) of the left and right main bronchi was varied systematically from 2:1 to 1:1. The influence of the airway ellipticity on the surrounding flow field and particle deposition was determined.

  10. Posttraumatic Skin and Soft-Tissue Infection due to Pseudomonas fulva

    PubMed Central

    Jiménez, Gemma; Rodríguez-Granger, Javier; Sampedro, Antonio

    2016-01-01

    We report a case of posttraumatic skin and soft-tissue infection in a patient with a left thigh wound after a traffic accident. Pseudomonas fulva was isolated from a wound aspirate and was identified to the species level by Maldi-tof. The patient responded to drainage, debridement of wound, and two weeks of intravenous antibiotic therapy. Follow-up after 3 weeks was satisfactory with healthy cover of the injured area. PMID:27752373

  11. Immune reconstitution syndrome in a human immunodeficiency virus infected child due to giardiasis leading to shock.

    PubMed

    Nandy, Sneha; Shah, Ira

    2015-01-01

    Human immunodeficiency virus (HIV)-associated immune reconstitution inflammatory syndrome has been reported in association with tuberculosis, herpes zoster (shingles), Cryptococcus neoformans, Kaposi's sarcoma, Pneumocystis pneumonia, hepatitis B virus, hepatitis C virus, herpes simplex virus, Histoplasma capsulatum, human papillomavirus, and Cytomegalovirus. However, it has never been documented with giardiasis. We present a 7-year-old HIV infected girl who developed diarrhea and shock following the initiation of antiretroviral therapy, and her stool showed the presence of giardiasis. PMID:26985424

  12. First Probable Case of Subcutaneous Infection Due to Truncatella angustata: a New Fungal Pathogen of Humans?

    PubMed Central

    Żak, Iwona; Tyrak, Jerzy; Bryk, Agata

    2015-01-01

    Truncatella angustata is a coelomycetous fungus, typically associated with vascular plants as either an endophyte or a pathogen. This organism has not previously been implicated in human disease. This report describes a case of T. angustata subcutaneous infection in an immunocompetent patient. A conclusive diagnosis was achieved through partial sequencing of ribosomal DNA (rDNA) cluster. The patient was successfully treated with voriconazole followed by itraconazole. PMID:25809973

  13. Adiaspiromycosis Causing Respiratory Failure and a Review of Human Infections Due to Emmonsia and Chrysosporium spp.

    PubMed Central

    Sutton, Deanna A.; Graybill, John R.

    2012-01-01

    We report a case of a 27-year-old male who presented with respiratory distress that required mechanical ventilation. Transbronchial biopsy revealed adiaspores of the fungus Emmonsia crescens within granulomata, a condition known as adiaspiromycosis. The patient received amphotericin products and corticosteroids, followed by itraconazole, and made a full recovery. Emmonsia crescens is a saprobe with a wide distribution that is primarily a rodent pathogen. The clinical characteristics of the 20 cases of human pulmonary adiaspiromycosis reported since the last comprehensive case review in 1993 are described here, as well as other infections recently reported for the genus Emmonsia. Pulmonary adiaspiromycosis has been reported primarily in persons without underlying host factors and has a mild to severe course. It remains uncertain if the optimal management of severe pulmonary adiaspiromycosis is supportive or if should consist of antifungal treatment, corticosteroids, or a combination of the latter two. The classification of fungi currently in the genus Emmonsia has undergone considerable revision since their original description, including being grouped with the genus Chrysosporium at one time. Molecular genetics has clearly differentiated the genus Emmonsia from the Chrysosporium species. Nevertheless, there has been a persistent confusion in the literature regarding the clinical presentation of infection with fungi of these two genera; to clarify this matter, the reported cases of invasive Chrysosporium infections were reviewed. Invasive Chrysosporium infections typically occur in impaired hosts and can have a fatal course. Based on limited in vitro susceptibility data for Chrysosporium zonatum, amphotericin B is the most active drug, itraconazole susceptibility is strain-dependent, and fluconazole and 5-fluorocytosine are not active. PMID:22259200

  14. Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

    PubMed Central

    W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

    2013-01-01

    Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

  15. [Alice in Wonderland syndrome due to Epstein-Barr virus infection].

    PubMed

    Pérez Méndez, C; Martín Mardomingo, M; Otero Martínez, B; Lagunilla Herrero, L; Fernández Zurita, C

    2001-06-01

    The Alice in Wonderland syndrome refers to distortions in body image and in the apparent sizes, shapes, and spatial relations of objects seen. The syndrome is usually associated with migraine headaches and has also been reported in several viral infections. We report a 6-year-old boy who presented to the emergency department complaining of several episodes in which the ceiling, the objects and the people around him seemed very small and far away. The child presented no alteration in the level of consciousness. The episodes provoked great fear in the child. Physical examination revealed no abnormalities except pharyngoamygdalitis. Serologic studies (IgM antibodies to viral capsid antigen) confirmed Epstein-Barr virus infection. The child's symptoms resolved spontaneously within 48 hours and he continued to be asymptomatic after a 4 -month follow-up. We consider that all children presenting a clinical picture consistent with the Alice in Wonderland syndrome should undergo serological testing for Epstein Barr virus infection. Diagnosis would enable physicians to reassure the family of the temporary and benign nature of this alarming condition. PMID:11412412

  16. [In vitro antibiotic susceptibility compliance with efficacy of chemotherapy in infections due to pathogenic Burkholderias].

    PubMed

    Iliukhin, V I; Senina, T V; Trushkina, M N; Shubnikova, E V; Antonov, Iu V; Andropova, N V

    2009-01-01

    Among the known species of Burkholderia only two are obligate pathogens, i.e., B. mallei and B. pseudomallei, causative agents of glanders and melioidosis respectively. The other species are saprophytes as natural inhabitants of water reservoirs and soil, still capable of causing opportunistic infections in humans and animals under definite conditions. All the species of Burkholderia are characterized by high resistance to antibacterials, including antibiotics. By the MICs, the most efficient chemotherapeutics against pathogenic burkholderias are tetracyclines, fluoroquinolones, penems and combined sulfanilamides. In the treatment of experimental glanders and melioidosis the set of the effective drugs had the inverse variation dependence on the infection severity and the desease process rate. Co-trimoxasole showed the best results, then followed doxicycline, ciprofioxacin and ceftazidime in the diminishing succession. The modification of the method for determination of antibiotic susceptibility with addition of native blood to the medium and the subculture under the atmosphere of 5% CO2 was shown useful in estimation of the prospects of the use of chemotherapeutics for the treatment of Burkholderia infections. PMID:20201399

  17. Necrotizing meningoencephalitis and pneumonitis in a simian immunodeficiency virus-infected rhesus macaque due to Acanthamoeba.

    PubMed

    Westmoreland, S V; Rosen, J; MacKey, J; Romsey, C; Xia, D-L; Visvesvera, G S; Mansfield, K G

    2004-07-01

    Free-living amoebae of the genus Acanthamoeba can cause a fatal disease of the brain in humans called granulomatous amoebic encephalitis. We present a case of meningoencephalitis and pneumonitis in a simian immunodeficiency virus (SIV)-infected rhesus macaque caused by Acanthamoeba sp. The animal became ill 176 days after intravenous inoculation with SIVmac251 after a short history of weight loss and a sudden onset of hind limb paresis and abnormal head movements. Histopathologic examination of hematoxylin and eosin-stained tissues revealed multifocal to coalescing necrotizing neutrophilic meningoencephalitis and pneumonitis. Immunofluorescence and polymerase chain reaction were used to identify the genus of amoeba as Acanthamoeba. Immunohistochemistry of immune cell markers was used to characterize the animal's immune response to the opportunistic amoebic infection with features of both innate and adaptive cell-mediated immunity. Although not previously reported, the potential transmission to humans, either through environmental contamination or contact with an infected animal, makes this disease a threat to laboratory animal care staff and pathologists. PMID:15232140

  18. Surgical Site Infections Due to Rapidly Growing Mycobacteria in Puducherry, India

    PubMed Central

    Ragunathan, Latha; Sakthivel, Sulochana; Sasidar, A.R.; Muralidaran; Venkatachalam, G. K.

    2015-01-01

    Background: Rapidly growing Mycobacteria are increasingly recognized, nowadays as an important pathogen that can cause wide range of clinical syndromes in humans. We herein describe unrelated cases of surgical site infection caused by Rapidly growing Mycobacteria (RGM), seen during a period of 12 months. Materials and Methods: Nineteen patients underwent operations by different surgical teams located in diverse sections of Tamil Nadu, Pondicherry, Karnataka, India. All patients presented with painful, draining subcutaneous nodules at the infection sites. Purulent material specimens were sent to the microbiology laboratory. Gram stain and Ziehl-Neelsen staining methods were used for direct examination. Culture media included blood agar, chocolate agar, MacConkey agar, Sabourauds agar and Lowenstein-Jensen medium for Mycobacteria. Isolated microorganisms were identified and further tested for antimicrobial susceptibility by standard microbiologic procedures. Results: Mycobacterium fortuitum and M.chelonae were isolated from the purulent drainage obtained from wounds by routine microbiological techniques from all the specimens. All isolates analyzed for antimicrobial susceptibility pattern were sensitive to clarithromycin, linezolid and amikacin but were variable to ciprofloxacin, rifampicin and tobramycin. Conclusion: Our case series highlights that a high level of clinical suspicion should be maintained for patients presenting with protracted soft tissue lesions with a history of trauma or surgery as these infections not only cause physical but also emotional distress that affects both the patients and the surgeon. PMID:25954616

  19. A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection.

    PubMed

    Gilchuk, Pavlo; Hill, Timothy M; Guy, Clifford; McMaster, Sean R; Boyd, Kelli L; Rabacal, Whitney A; Lu, Pengcheng; Shyr, Yu; Kohlmeier, Jacob E; Sebzda, Eric; Green, Douglas R; Joyce, Sebastian

    2016-08-16

    The nature and anatomic location of the protective memory CD8(+) T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8(+) T cells and their role in lower airway infections. Memory CD8(+) T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8(+) T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3(LO) resident memory CD8(+) T (Trm) cell population that preferentially localizes to the pulmonary interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8(+) T cells into the lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce lung interstitial Trm cells may confer better protection against respiratory pathogens. PMID:27498869

  20. A Trend for Increased Risk of Revision Surgery due to Deep Infection following Fast-Track Hip Arthroplasty.

    PubMed

    Amlie, Einar; Lerdal, Anners; Gay, Caryl L; Høvik, Øystein; Nordsletten, Lars; Dimmen, Sigbjørn

    2016-01-01

    Rates of revision surgery due to deep infection following total hip arthroplasty (THA) increased at a Norwegian hospital following implementation of fast-track procedures. The purpose of this study was to determine whether selected demographic (age and sex) and clinical (body mass index, American Society of Anesthesiologists (ASA) classification, surgery duration, length of hospital stay, cemented versus uncemented prosthesis, and fast-track procedures) factors were associated with higher risk of revision surgery due to deep infection following THA. In a prospective designed study 4,406 patients undergoing primary THA between January 2001 and January 2013 where included. Rates of infection-related revision surgery within 3 months of THA were higher among males and among patients who received fast-track THA. Adjusting for sex and age, the implemented fast-track elements were significantly associated with increased risk of revision surgery. Risk of infection-related revision surgery was unrelated to body mass index, physical status, surgery duration, length of hospital stay, and prosthesis type. Because local infiltration analgesia, drain cessation, and early mobilization were introduced in combination, it could not be determined which component or combination of components imposed the increased risk. The findings in this small sample raise concern about fast-track THA but require replication in other samples. PMID:27034841

  1. A Trend for Increased Risk of Revision Surgery due to Deep Infection following Fast-Track Hip Arthroplasty

    PubMed Central

    Amlie, Einar; Lerdal, Anners; Gay, Caryl L.; Høvik, Øystein; Nordsletten, Lars; Dimmen, Sigbjørn

    2016-01-01

    Rates of revision surgery due to deep infection following total hip arthroplasty (THA) increased at a Norwegian hospital following implementation of fast-track procedures. The purpose of this study was to determine whether selected demographic (age and sex) and clinical (body mass index, American Society of Anesthesiologists (ASA) classification, surgery duration, length of hospital stay, cemented versus uncemented prosthesis, and fast-track procedures) factors were associated with higher risk of revision surgery due to deep infection following THA. In a prospective designed study 4,406 patients undergoing primary THA between January 2001 and January 2013 where included. Rates of infection-related revision surgery within 3 months of THA were higher among males and among patients who received fast-track THA. Adjusting for sex and age, the implemented fast-track elements were significantly associated with increased risk of revision surgery. Risk of infection-related revision surgery was unrelated to body mass index, physical status, surgery duration, length of hospital stay, and prosthesis type. Because local infiltration analgesia, drain cessation, and early mobilization were introduced in combination, it could not be determined which component or combination of components imposed the increased risk. The findings in this small sample raise concern about fast-track THA but require replication in other samples. PMID:27034841

  2. Perforation of the bowel due to cytomegalovirus infection in a man with AIDS: surgery is not always necessary!

    PubMed

    Yoganathan, Katie Tharshana; Morgan, Andrew Roger; Yoganathan, Kathir G

    2016-01-01

    Cytomegalovirus (CMV) infection is the most common viral opportunistic infection in immunocompromised patients and is a rare cause of bowel perforation. It invariably requires surgical intervention and is often fatal. We report a 50-year-old Caucasian man with AIDS, presented 3 weeks after developing abdominal pain and distension. He was treated for CMV retinitis in the past. His adherence to antiretroviral therapy was poor. Examination revealed a recurrence of active CMV retinitis. His abdomen was tender and distended. The plain X-ray of the abdomen revealed a double wall sign (Rigler's sign), indicating pneumoperitoneum due to the bowel perforation. The upper endoscopy was normal. His CD4 count was 30 cells/mm(3) He was treated with cidofovir infusion. He made a full recovery, without requiring any form of surgery. However, he died of adult respiratory distress syndrome 14 months later, due to iatrogenic acute pancreatitis. PMID:27440845

  3. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice.

    PubMed

    Koo, Mi-Sun; Manca, Claudia; Yang, Guibin; O'Brien, Paul; Sung, Nackmoon; Tsenova, Liana; Subbian, Selvakumar; Fallows, Dorothy; Muller, George; Ehrt, Sabine; Kaplan, Gilla

    2011-02-25

    Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the leading infectious disease causes of morbidity and mortality worldwide. Though current antibiotic regimens can cure the disease, treatment requires at least six months of drug therapy. One reason for the long duration of therapy is that the currently available TB drugs were selected for their ability to kill replicating organisms and are less effective against subpopulations of non-replicating persistent bacilli. Evidence from in vitro models of Mtb growth and mouse infection studies suggests that host immunity may provide some of the environmental cues that drive Mtb towards non-replicating persistence. We hypothesized that selective modulation of the host immune response to modify the environmental pressure on the bacilli may result in better bacterial clearance during TB treatment. For this proof of principal study, we compared bacillary clearance from the lungs of Mtb-infected mice treated with the anti-TB drug isoniazid (INH) in the presence and absence of an immunomodulatory phosphodiesterase 4 inhibitor (PDE4i), CC-3052. The effects of CC-3052 on host global gene expression, induction of cytokines, and T cell activation in the lungs of infected mice were evaluated. We show that CC-3052 modulates the innate immune response without causing generalized immune suppression. Immune modulation combined with INH treatment improved bacillary clearance and resulted in smaller granulomas and less lung pathology, compared to treatment with INH alone. This novel strategy of combining anti-TB drugs with an immune modulating molecule, if applied appropriately to patients, may shorten the duration of TB treatment and improve clinical outcome.

  4. Successful Treatment of Bloodstream Infection Due to Metallo-β-Lactamase-Producing Stenotrophomonas maltophilia in a Renal Transplant Patient.

    PubMed

    Mojica, Maria F; Ouellette, Christopher P; Leber, Amy; Becknell, M Brian; Ardura, Monica I; Perez, Federico; Shimamura, Masako; Bonomo, Robert A; Aitken, Samuel L; Shelburne, Samuel A

    2016-09-01

    Stenotrophomonas maltophilia is an emerging multidrug-resistant (MDR) opportunistic pathogen for which new antibiotic options are urgently needed. We report our clinical experience treating a 19-year-old renal transplant recipient who developed prolonged bacteremia due to metallo-β-lactamase-producing S. maltophilia refractory to conventional treatment. The infection recurred despite a prolonged course of colistimethate sodium (colistin) but resolved with the use of a novel drug combination with clinical efficacy against the patient's S. maltophilia isolate. PMID:27551008

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

    PubMed

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

    2015-08-15

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

  6. A Case of Lung Cancer Originating from Cavitary Mycobacterium xenopi Infection.

    PubMed

    Doshi, Viral K; Kulkarni, Shreedhar R; Kham, Nang M; Kapitan, Kent S

    2015-03-01

    Coexistence of Mycobacterium xenopi with lung cancer has been reported. However, lung cancer originating within a pre-existing cavity caused by M. xenopi has not. A 55-y-old woman with a history of smoking presented with complaints of chronic dry cough, night sweats, and weight loss for several months. Computed tomography (CT) scanning revealed a 3.5-cm irregular thick-walled cavity in the right lung apex. Cultures obtained from a CT-guided biopsy grew M. xenopi. The patient received standard treatment, and her clinical symptoms improved, and the radiographic lesion stabilized. However, 2 y later, a repeat chest x-ray showed the original right upper lobe cavity with an interval development of a mass adjoining the cavity. A CT-guided needle biopsy of the new mass demonstrated squamous cell carcinoma. Whenever there is a change in the radiological appearance of a cavity, a repeat biopsy should be performed to exclude lung cancer. PMID:25336532

  7. Mast cells expedite control of pulmonary murine cytomegalovirus infection by enhancing the recruitment of protective CD8 T cells to the lungs.

    PubMed

    Ebert, Stefan; Becker, Marc; Lemmermann, Niels A W; Büttner, Julia K; Michel, Anastasija; Taube, Christian; Podlech, Jürgen; Böhm, Verena; Freitag, Kirsten; Thomas, Doris; Holtappels, Rafaela; Reddehase, Matthias J; Stassen, Michael

    2014-04-01

    The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation of CMV disease in the immunocompromised host, whereas in the immunocompetent host lung-infiltrating CD8 T cells confine the infection in nodular inflammatory foci and prevent viral pathology. By using murine CMV infection as a model, we provide evidence for a critical role of mast cells (MC) in the recruitment of protective CD8 T cells to the lungs. Systemic infection triggered degranulation selectively in infected MC. The viral activation of MC was associated with a wave of CC chemokine ligand 5 (CCL5) in the serum of C57BL/6 mice that was MC-derived as verified by infection of MC-deficient Kit(W-sh/W-sh) "sash" mutants. In these mutants, CD8 T cells were recruited less efficiently to the lungs, correlating with enhanced viral replication and delayed virus clearance. A causative role for MC was verified by MC reconstitution of "sash" mice restoring both, efficient CD8 T-cell recruitment and infection control. These results reveal a novel crosstalk axis between innate and adaptive immune defense against CMV, and identify MC as a hitherto unconsidered player in the immune surveillance at a relevant site of CMV disease. PMID:24763809

  8. Fighting infections due to multidrug-resistant Gram-positive pathogens.

    PubMed

    Cornaglia, G

    2009-03-01

    Growing bacterial resistance in Gram-positive pathogens means that what were once effective and inexpensive treatments for infections caused by these bacteria are now being seriously questioned, including penicillin and macrolides for use against pneumococcal infections and-in hospitals-oxacillin for use against staphylococcal infections. As a whole, multidrug-resistant (MDR) Gram-positive pathogens are rapidly becoming an urgent and sometimes unmanageable clinical problem. Nevertheless, and despite decades of research into the effects of antibiotics, the actual risk posed to human health by antibiotic resistance has been poorly defined; the lack of reliable data concerning the outcomes resulting from antimicrobial resistance stems, in part, from problems with study designs and the methods used in resistence determination. Surprisingly little is known, too, about the actual effectiveness of the many types of intervention aimed at controlling antibiotic resistance. New antibiotics active against MDR Gram-positive pathogens have been recently introduced into clinical practice, and the antibiotic pipeline contains additional compounds at an advanced stage of development, including new glycopeptides, new anti-methicillin-resistant Staphylococcus aureus (MRSA) beta-lactams, and new diaminopyrimidines. Many novel antimicrobial agents are likely to be niche products, endowed with narrow antibacterial spectra and/or targeted at specific clinical problems. Therefore, an important educational goal will be to change the current, long-lasting attitudes of both physicians and customers towards broad-spectrum and multipurpose compounds. Scientific societies, such as the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), must play a leading role in this process.

  9. [Human infection due to Bertiella sp (cestode: Anoplocephalidae) in a man originating from Yemen in Algeria].

    PubMed

    Achir, I; Zaït, H; Hamrioui, B

    2008-04-01

    Bertiella is a frequent parasite in animals, particularly in nonhuman primates. The infestation occurs in man by accidental ingestion of the intermediate host, an acarus containing the cysticercoid larva of Bertiella studeri or Bertiella mucronata. The diagnosis is based on the morphology of the gravid proglottis and eggs with pyriform embryo which is characteristic of the Anoplocephalinae. Human infection is asymptomatic or can induce minor non specific digestive disturbances and the niclosamide is effective in one single dose. The authors report the first case of human bertiellosis in Algeria in a student originating from Yemen.

  10. [Sinonasal fungal infections are not exclusively due to mucorales and Aspergillus!].

    PubMed

    Tauziède-Espariat, Arnault; Wassef, Michel; Adle-Biassette, Homa; Alanio, Alexandre; Bretagne, Stéphane; Lanternier, Fanny; Boui, Mohammed; Bouchaud, Olivier; Vironneau, Pierre; Kania, Romain; Jouvion, Grégory; Chrétien, Fabrice; Classe, Marion

    2016-08-01

    Rhino-sinusal infections are serious diseases and possibly lethal. When they are invasive, we easily discuss apergilloses and mucormycoses. The confirmation of the diagnosis of mucormycosis need an extensive surgery for precise histopathological and mycological evaluation. The pathologist may be faced to other rare mycoses such as phaeohyphomycoses, which present different morphological features than mucormycoses and Aspergillus. Once the diagnosis is established, an appropriate antifungal treatment is quickly started. The aim of our work is to report two observations of phaeohyphomycoses, to describe their histopathological features, to discuss complementary diagnostic methods and to present the main differential diagnoses. PMID:27475007

  11. Splenic abscess due to fungal infection after kidney transplantation; a case report

    PubMed Central

    Malakoutian, Tahereh; Yarmohamadi, Maliheh; Mohammadi, Ronak; Asgari, Mojgan; Mahmoodian, Reyhaneh

    2016-01-01

    Splenic abscess is one of the rare and potentially life-threatening complications after kidney transplantation. Splenic abscess generally occurs in patients who have immunodeficiency state. It becomes more important with the increased use of immunosuppressed drugs and organ transplantation. The clinical presentation of splenic abscess is insidious, often with constitutional symptoms. Left upper quadrant tenderness is an uncommon sign. Therefore, its diagnosis is difficult and requires a high degree of clinical suspicion. We report a case under renal transplantation with recurrent fungal infection in different organs with two episodes of fungemia who died after splenectomy. PMID:27689116

  12. Splenic abscess due to fungal infection after kidney transplantation; a case report.

    PubMed

    Malakoutian, Tahereh; Yarmohamadi, Maliheh; Mohammadi, Ronak; Asgari, Mojgan; Mahmoodian, Reyhaneh

    2016-01-01

    Splenic abscess is one of the rare and potentially life-threatening complications after kidney transplantation. Splenic abscess generally occurs in patients who have immunodeficiency state. It becomes more important with the increased use of immunosuppressed drugs and organ transplantation. The clinical presentation of splenic abscess is insidious, often with constitutional symptoms. Left upper quadrant tenderness is an uncommon sign. Therefore, its diagnosis is difficult and requires a high degree of clinical suspicion. We report a case under renal transplantation with recurrent fungal infection in different organs with two episodes of fungemia who died after splenectomy. PMID:27689116

  13. Severe Acute Infection Due to Serratia marcescens Causing Respiratory Distress in An Immunocompetent Adult.

    PubMed

    Ruiz-Sada, Pablo; Escalante, Mikel; Lizarralde, Eva

    2016-01-01

    The role of Serratia marcescens changed from a harmless saprophytic microorganism to an important opportunistic human pathogen. It often causes nosocomial device-associated outbreaks and rarely serious invasive community acquired infections. We present a case of a community-acquired Serratia marcescens bacteremia leading to Respiratory Distress Syndrome in a previously healthy 51-year-old man without identifiable risk factors. Full recovery was achieved with solely medical treatment and observation in ICU during three days. To our knowledge it is an extremely uncommon presentation and just few cases have been previously reported in the literature.

  14. Environmental silica in badger lungs: a possible association with susceptibility to Mycobacterium bovis infection

    SciTech Connect

    Higgins, D.A.; Kung, I.T.; Or, R.S.

    1985-04-01

    Badger lungs contain dark granular foci (0.2 to 2.0 mm) comprising aggregates of enlarged macrophages containing birefringent crystalline particles. Particles were examined from the lungs of three badgers; many were silicates and a significant number were pure silica (SiO/sub 2/). The particles and the accompanying pathology resembled mixed dust fibrosis and silicosis in humans, diseases associated with increased susceptibility to tuberculosis.

  15. Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection.

    PubMed

    Zhou, X; Loomis-King, H; Gurczynski, S J; Wilke, C A; Konopka, K E; Ptaschinski, C; Coomes, S M; Iwakura, Y; van Dyk, L F; Lukacs, N W; Moore, B B

    2016-05-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production. Transplantation of bone marrow from Il-17a(-/-) donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more transforming growth factor beta-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest that "noninfectious" HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  16. Role of host xanthine oxidase in infection due to enteropathogenic and Shiga-toxigenic Escherichia coli.

    PubMed

    Crane, John K

    2013-01-01

    Xanthine oxidase (XO) has been recognized as an important host defense enzyme for decades. In our recent study in Infection and Immunity, we found that enteropathogenic and Shiga-toxigenic E. coli (EPEC and STEC) were far more resistant to killing by the XO pathway than laboratory E. coli strains used in the past. Although XO plus hypoxanthine substrate rarely generated enough H 2O 2 to kill EPEC and STEC, the pathogens were able to sense the H2O2 and react to it with an increase in expression of virulence factors, most notably Shiga toxin (Stx). H 2O 2 produced by XO also triggered a chloride secretory response in T84 cell monolayers studied in the Ussing chamber. Adding exogenous XO plus its substrate in vivo did not decrease the number of STEC bacteria recovered from ligated intestinal loops, but instead appeared to worsen the infection and increased the amount of Stx2 toxin produced. XO plus hypoxanthine also increases the ability of Stx2 to translocate across intestinal monolayers. With regard to EPEC and STEC, the role of XO appears more complex and subtle than what has been reported in the past, since XO also plays a role in host-pathogen signaling, in regulating virulence in pathogens, in Stx production and in toxin translocation. Uric acid produced by XO may also be in itself an immune modulator in the intestinal tract.

  17. Arsenophonus nasoniae and Rickettsiae Infection of Ixodes ricinus Due to Parasitic Wasp Ixodiphagus hookeri.

    PubMed

    Bohacsova, Monika; Mediannikov, Oleg; Kazimirova, Maria; Raoult, Didier; Sekeyova, Zuzana

    2016-01-01

    Arsenophonus nasoniae, a male-killing endosymbiont of chalcid wasps, was recently detected in several hard tick species. Following the hypothesis that its presence in ticks may not be linked to the direct occurrence of bacteria in tick's organs, we identified A. nasoniae in wasps emerging from parasitised nymphs. We confirmed that 28.1% of Ixodiphagus hookeri wasps parasitizing Ixodes ricinus ticks were infected by A. nasoniae. Moreover, in examined I. ricinus nymphs, A. nasoniae was detected only in those, which were parasitized by the wasp. However, in part of the adult wasps as well as in some ticks that contained wasp's DNA, we did not confirm A. nasoniae. We also found, that in spite of reported male-killing, some newly emerged adult wasp males were also infected by A. nasoniae. Additionally, we amplified the DNA of Rickettsia helvetica and Rickettsia monacensis (known to be Ixodes ricinus-associated bacteria) in adult parasitoid wasps. This may be related either with the digested bacterial DNA in wasp body lumen or with a role of wasps in circulation of rickettsiae among tick vectors. PMID:26901622

  18. Arsenophonus nasoniae and Rickettsiae Infection of Ixodes ricinus Due to Parasitic Wasp Ixodiphagus hookeri

    PubMed Central

    Bohacsova, Monika; Mediannikov, Oleg; Kazimirova, Maria; Raoult, Didier; Sekeyova, Zuzana

    2016-01-01

    Arsenophonus nasoniae, a male-killing endosymbiont of chalcid wasps, was recently detected in several hard tick species. Following the hypothesis that its presence in ticks may not be linked to the direct occurrence of bacteria in tick's organs, we identified A. nasoniae in wasps emerging from parasitised nymphs. We confirmed that 28.1% of Ixodiphagus hookeri wasps parasitizing Ixodes ricinus ticks were infected by A. nasoniae. Moreover, in examined I. ricinus nymphs, A. nasoniae was detected only in those, which were parasitized by the wasp. However, in part of the adult wasps as well as in some ticks that contained wasp's DNA, we did not confirm A. nasoniae. We also found, that in spite of reported male-killing, some newly emerged adult wasp males were also infected by A. nasoniae. Additionally, we amplified the DNA of Rickettsia helvetica and Rickettsia monacensis (known to be Ixodes ricinus-associated bacteria) in adult parasitoid wasps. This may be related either with the digested bacterial DNA in wasp body lumen or with a role of wasps in circulation of rickettsiae among tick vectors. PMID:26901622

  19. Experimental hepatic fibrosis due to Capillaria hepatica infection (differential features presented by rats and mice).

    PubMed

    Andrade, Stelamares Boyda de; Andrade, Zilton A

    2004-06-01

    Rats and mice are among the most susceptible hosts for the helminth Capillaria hepatica. More information on the similarities and differences between the hepatic pathology presented by these two parasite hosts are needed, since they may represent good models for the study of hepatic fibrosis. Early changes are similar for both hosts and are represented by necro-inflammatory lesions around dead parasites and their eggs and diffuse and intense reactive hepatitis. Although worms remain alive longer in mice than in rats, hepatic changes are more rapidly and deeply modulated in the former, even leading to almost complete disappearance of fibrosis. As for the rats, the modulation of the focal lesions is followed by the formation of septal fibrosis, a process where fine and long fibrous septa appear connecting portal spaces and central veins in such a way as to form a final morphologic picture of cirrhosis. Hepatic functional changes usually present good correlations with the morphologic findings at the different phases of the infection evolution. Therefore C. hepatica infection in rats and mice represent two different models of hepatic fibrosis and these differences, if properly known and understood, can be explored to answer different questions regarding several aspects of hepatic fibrosis.

  20. [Infections due to Toscana virus, West Nile virus, and other arboviruses of interest in Europe].

    PubMed

    Sánchez-Seco, Mari Paz; Navarro, José María

    2005-11-01

    Arbovirosis, viral infection transmitted by arthropods, is a widespread health problem. Recurrent outbreaks caused by some of these viruses such as dengue or West Nile strains in regions where they do not appear frequently, justify the establishment of global control measures. Tick-borne encephalitis viruses, sand fly fever viruses (Toscana, Naples and Sicily) and occasionally West Nile and Crimean-Congo fever viruses are the most frequent causes of arbovirosis in Europe, although circulation of other potentially pathogenetic viruses such as Chikungunya has also been detected. The only native arbovirosis described in Spain is infection produced by Toscana virus, which causes aseptic, usually benign meningitis. Nevertheless, some West Nile virus-associated meningo-encephalitis cases have been described in France, Portugal and countries in the Magreb region, increasing the risk of sporadic occurrence of these processes in our country. To achieve an accurate diagnosis, high clinical suspicion is required as well as highly specific laboratory techniques, mainly based on IgM detection, RT-PCR and viral culture of CSF and/or serum.

  1. Correction for ‘artificial’ electron disequilibrium due to cone-beam CT density errors: implications for on-line adaptive stereotactic body radiation therapy of lung

    NASA Astrophysics Data System (ADS)

    Disher, Brandon; Hajdok, George; Wang, An; Craig, Jeff; Gaede, Stewart; Battista, Jerry J.

    2013-06-01

    Cone-beam computed tomography (CBCT) has rapidly become a clinically useful imaging modality for image-guided radiation therapy. Unfortunately, CBCT images of the thorax are susceptible to artefacts due to scattered photons, beam hardening, lag in data acquisition, and respiratory motion during a slow scan. These limitations cause dose errors when CBCT image data are used directly in dose computations for on-line, dose adaptive radiation therapy (DART). The purpose of this work is to assess the magnitude of errors in CBCT numbers (HU), and determine the resultant effects on derived tissue density and computed dose accuracy for stereotactic body radiation therapy (SBRT) of lung cancer. Planning CT (PCT) images of three lung patients were acquired using a Philips multi-slice helical CT simulator, while CBCT images were obtained with a Varian On-Board Imaging system. To account for erroneous CBCT data, three practical correction techniques were tested: (1) conversion of CBCT numbers to electron density using phantoms, (2) replacement of individual CBCT pixel values with bulk CT numbers, averaged from PCT images for tissue regions, and (3) limited replacement of CBCT lung pixels values (LCT) likely to produce artificial lateral electron disequilibrium. For each corrected CBCT data set, lung SBRT dose distributions were computed for a 6 MV volume modulated arc therapy (VMAT) technique within the Philips Pinnacle treatment planning system. The reference prescription dose was set such that 95% of the planning target volume (PTV) received at least 54 Gy (i.e. D95). Further, we used the relative depth dose factor as an a priori index to predict the effects of incorrect low tissue density on computed lung dose in regions of severe electron disequilibrium. CT number profiles from co-registered CBCT and PCT patient lung images revealed many reduced lung pixel values in CBCT data, with some pixels corresponding to vacuum (-1000 HU). Similarly, CBCT data in a plastic lung

  2. High Mortality from Blood Stream Infection in Addis Ababa, Ethiopia, Is Due to Antimicrobial Resistance

    PubMed Central

    Seboxa, Teshale; Amogne, Wondwossen; Abebe, Workeabeba; Tsegaye, Tewodros; Azazh, Aklilu; Hailu, Workagegnehu; Fufa, Kebede; Grude, Nils; Henriksen, Thor-Henrik

    2015-01-01

    Background Managing blood stream infection in Africa is hampered by lack of bacteriological support needed for antimicrobial stewardship, and background data needed for empirical treatment. A combined pro- and retrospective approach was used to overcome thresholds in clinical research in Africa. Methods Outcome and characteristics including age, HIV infection, pancytopenia and bacteriological results were studied in 292 adult patients with two or more SIRS criteria using univariate and confirming multivariate logistic regression models. Expected randomly distributed resistance covariation was compared with observed co-resistance among gram-negative enteric bacteria in 92 paediatric blood culture isolates that had been harvested in the same hospital during the same period of time. Results Mortality was fivefold increased among patients with positive blood culture results [50.0% vs. 9.8%; OR 11.24 (4.38–25.88), p < 0.0001], and for this group of patients mortality was significantly associated with antimicrobial resistance [OR 23.28 (3.3–164.4), p = 0.002]. All 11 patients with Enterobacteriaceae resistant to 3rd. generation cephalosporins died. Eighty-nine patients had pancytopenia grade 3–4. Among patients with negative blood culture results, mortality was significantly associated with pancytopenia [OR 3.12 (1.32–7.39), p = 0.01]. HIV positivity was not associated with increased mortality. Antimicrobial resistance that concerned gram-negative enteric bacteria, regardless of species, was characterized by co-resistance between third generation cephalosporins, gentamicin, chloramphenicol, and co-trimoxazole. Conclusion Mortality was strongly associated with growth of bacteria resistant to empirical treatment, and these patients were dead or dying when bacteriological reports arrived. Because of co-resistance, alternative efficient antibiotics would not have been available in Ethiopia for 8/11 Enterobacteriaceae-infected patients with isolates resistant to third

  3. Immunolocalization of pulmonary intravascular macrophages, TLR4, TLR9 and IL-8 in normal and Pasteurella multocida-infected lungs of water buffalo (Bubalus bubalis).

    PubMed

    Sethi, R S; Brar, R S; Singh, O; Singh, B

    2011-01-01

    Water buffalo are of considerable economic significance in South East Asia, but these animals suffer from many bacterial respiratory diseases including haemorrhagic septicaemia caused by Pasteurella multocida. Bacterial respiratory diseases of animals cause lung inflammation that is characterized by the activation of Toll-like receptors (TLRs) expressed on macrophages, expression of chemokines and recruitment of neutrophils and monocytes. Pulmonary intravascular macrophages (PIMs) present in the alveolar septa play a critical role in lung inflammation, but there are no data on the immunolocalization of PIMs or the expression of TLRs and chemokines such as interleukin (IL)-8, in the lungs of water buffalo. The present study compares the occurrence of PIMs, TLR4, TLR9 and IL-8 in the lungs of normal water buffalo and those infected with P. multocida. Labelling of PIMs with the anti-human macrophage antibody (MCA874G) demonstrated an increase in this population in inflamed lungs. TLR4 and IL-8 were detected in the alveolar septa, airway epithelium and endothelium of large blood vessels of normal lungs. TLR9 expression was similar to that of TLR4, but TLR9 was not expressed by the endothelium of arteries and veins. While the expression of TLR9 and IL-8 was increased in the inflamed lungs compared with normal lungs, TLR4 labelling intensity remained unchanged or was reduced. The expression of these molecules potentially plays a role in the regulation of lung inflammation.

  4. TUBERCULOSIS AND LUNG CANCER.

    PubMed

    Tamura, Atsuhisa

    2016-01-01

    The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept

  5. Effect of Temperature on Cystic Fibrosis Lung Disease and Infections: A Replicated Cohort Study

    PubMed Central

    Collaco, Joseph M.; McGready, John; Green, Deanna M.; Naughton, Kathleen M.; Watson, Christopher P.; Shields, Timothy; Bell, Scott C.; Wainwright, Claire E.

    2011-01-01

    Background Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF). Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown. Methods Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378). Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439), the Australian CF Data Registry (ACFDR: n = 1801), and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167). Results In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001) was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001), ACFDR (1.05; p = 0.002), and ACFBAL (1.09; p = 0.003) subjects. Warmer temperatures (−0.34 points per °F; p = 0.005) and public insurance (−6.43 points; p<0.001) were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: −0.31; p<0.001; insurance: −9.11; p<0.001) and similar in the ACFDR subjects (temperature: −0.23; p = 0.057). The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function. Conclusions Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents. PMID:22125624

  6. [Cerebellar abscess due to infection with the anaerobic bacteria fusobacterium nucleatum: a case report].

    PubMed

    Shimogawa, Takafumi; Sayama, Tetsuro; Haga, Sei; Akiyama, Tomoaki; Morioka, Takato

    2015-02-01

    We report a rare case of cerebellar abscess produced by anaerobic bacteria. A 76-year-old man was admitted to our hospital with a history of fever, vomiting, and dizziness lasting 14 days. Computed tomography(CT)scan and magnetic resonance images showed the presence of a multiloculated cerebellar abscess with a right subdural abscess. The patient underwent aspiration of the abscess through a suboccipital craniotomy. Fusobacterium nucleatum, which is an anaerobic bacteria naturally present in the human oral cavity, was detected in cultures of the aspirated abscess. The patient was administered antibiotic treatment combined with hyperbaric oxygen therapy(HBO). The symptoms were briefly relieved but the cerebellar abscess recurred, which required a second aspiration. The combined treatment with antibiotics and HBO was maintained after the second operation. After 6 weeks of treatment, the cerebellar abscess was completely controlled. We conclude that antibiotic treatment combined with HBO is useful for treatment of cerebellar abscesses caused by infection with anaerobic bacteria.

  7. Pathological alterations due to motile Aeromonas infection in red swordtail fish (Xiphophorus helleri).

    PubMed

    Bunnajirakul, S; Pavasutthipaisit, S; Steinhagen, D

    2015-01-01

    A herd of red swordtail fish (Xiphophorus helleri) was reared in outdoor concrete ponds and suffered from occasional mortality. Moribund fishes showing abdominal dropsy and fin rots were sent for diagnosis. Gross necropsy findings showed enlargement of liver, spleen, and kidney in concurrence with congestion, and a severe accumulation of peritoneal fluid. Histopathological findings revealed an alteration of hepatocytes, with a severe diffuse accumulation of fat vacuoles in the cytoplasm. In the trunk kidney, severe accumulation of mononuclear cells together with cloudy swelling of the renal tubular epithelium was observed. From internal organs of the fish motile Aeromonas spp. were identified. The pathological findings might be associated with a long-term infection of affected fish fostered by common stressors such as improper feeding and poor pond environment condition (water temperature). Effective therapeutic measures comprised an advancement of keeping conditions and appropriate feeding to improve the health status in combination with the application of antibiotic substances. PMID:26527040

  8. High resolution melt analysis to track infections due to ribotype 027 Clostridium difficile.

    PubMed

    Grando, Danilla; Said, Mohamed M; Mayall, Barrie C; Gurtler, Volker

    2012-05-01

    The increased prevalence of hypervirulent ribotype 027 Clostridium difficile requires rapid identification of isolates in order to implement timely infection control strategies. High resolution melt (HRM) analysis of PCR products can identify strain variation amongst genera of bacteria. The intergenic (16S-23S rDNA) spacer region contains sequence regions conserved within genera and other sequence region variables between species within genera. We wished to investigate whether HRM analysis of PCR ribotyping products could identify ribotype 027 C. difficile. Ribotyping was performed on 93 clinical isolates and five control strains and band patterns were analysed using GelCompar II (Applied Maths, USA). Real-time PCR using ribotyping primers was performed and normalised melt curves were generated. The HRM data was then imported into ScreenClust software (QIAGEN) to generate principal component analysis graphs depicting clustered relationships of strains. Ribotyping produced clear PCR bands for 88/98 isolates tested. Dendrograms generated by GelCompar showed a diversity of ribotype patterns amongst these 88 isolates with 18 groups identified with 70% homology. One clinical isolate showed 100% homology with the control 027 strains. ScreenClust analysis of the same 88 HRM results showed clustering of isolates, with 027 strains identifiable as a unique cluster. HRM analysis correctly identified the control 027 stains and the clinical isolate shown to be 027. HRM combined with ScreenClust analysis of real-time PCR products of the 16S-23S rDNA spacer region successfully identified ribotype 027 strains. For infection control purposes this was achieved within 2-3 h of colony isolation.

  9. Salmonellosis outbreak due to chicken contact leading to a foodborne outbreak associated with infected delicatessen workers.

    PubMed

    Hedican, Erin; Miller, Ben; Ziemer, Brian; LeMaster, Pam; Jawahir, Selina; Leano, Fe; Smith, Kirk

    2010-08-01

    Salmonella is the most common bacterial cause of foodborne outbreaks in the United States. Starting in June 2007, investigation of a cluster of Salmonella Montevideo cases with indistinguishable pulsed-field gel electrophoresis (PFGE) patterns resulted in the identification of an outbreak associated with contact with chickens purchased from a single hatchery. Nine Minnesota cases from May through August 2007 were part of this outbreak. Cases with the outbreak PFGE pattern of Salmonella Montevideo continued to occur in Minnesota after August, but none of these cases reported chicken contact. The majority of these cases resided in the same town in rural Minnesota. Routine interviews revealed that all cases from these counties purchased groceries from the same local grocery store, with two specifically reporting consuming items from the grocery store delicatessen in the week before illness. As a result, an investigation into the delicatessen was initiated. Illness histories and stool samples were collected from all delicatessen employees, and food and environmental samples were collected. None of the employees reported experiencing recent gastrointestinal symptoms, but the outbreak PFGE subtype of Salmonella Montevideo was identified from stool from two food workers. Food and environmental samples collected tested negative for Salmonella. One of the positive employees reported having chickens at home, but the animals did not test positive for Salmonella. The positive food workers were excluded from work until they had two consecutive negative stool cultures for Salmonella. There was no evidence of ongoing transmission thereafter. This was an outbreak of Salmonella Montevideo infections that began as an animal-contact-associated outbreak which subsequently resulted in a foodborne outbreak associated with infected food workers. These outbreaks illustrate the complex epidemiology of salmonellosis.

  10. Soluble granzymes are released during human endotoxemia and in patients with severe infection due to gram-negative bacteria.

    PubMed

    Lauw, F N; Simpson, A J; Hack, C E; Prins, J M; Wolbink, A M; van Deventer, S J; Chaowagul, W; White, N J; van Der Poll, T

    2000-07-01

    Extracellular release of granzymes is considered to reflect the involvement of cytotoxic T lymphocytes and NK cells in various disease states. To obtain insight into granzyme release during bacterial infection, granzyme levels were measured during experimental human endotoxemia and in patients with melioidosis, a severe infection due to gram-negative bacteria. Plasma concentrations of granzyme A (GrA) and GrB increased transiently after endotoxin administration, peaking after 2-6 h. In patients with bacteremic melioidosis, GrA and GrB levels were elevated on admission and remained high during the 72-h study period. In whole blood stimulated with heat-killed Burkholderia pseudomallei, neutralization of tumor necrosis factor, interleukin-12, or interleukin-18 inhibited granzyme secretion, which was independent of interferon-gamma. Stimulation with endotoxin and other gram-negative and gram-positive bacteria also strongly induced the secretion of granzymes, suggesting that granzyme release is a general immune response during bacterial infection. The interaction between the cytokine network and granzymes may play an important immunoregulatory role during bacterial infections.

  11. Molecular Pathogenesis, Epidemiology, and Clinical Manifestations of Respiratory Infections Due to Bordetella pertussis and Other Bordetella Subspecies

    PubMed Central

    Mattoo, Seema; Cherry, James D.

    2005-01-01

    Bordetella respiratory infections are common in people (B. pertussis) and in animals (B. bronchiseptica). During the last two decades, much has been learned about the virulence determinants, pathogenesis, and immunity of Bordetella. Clinically, the full spectrum of disease due to B. pertussis infection is now understood, and infections in adolescents and adults are recognized as the reservoir for cyclic outbreaks of disease. DTaP vaccines, which are less reactogenic than DTP vaccines, are now in general use in many developed countries, and it is expected that the expansion of their use to adolescents and adults will have a significant impact on reducing pertussis and perhaps decrease the circulation of B. pertussis. Future studies should seek to determine the cause of the unique cough which is associated with Bordetella respiratory infections. It is also hoped that data gathered from molecular Bordetella research will lead to a new generation of DTaP vaccines which provide greater efficacy than is provided by today's vaccines. PMID:15831828

  12. Gross margin losses due to Salmonella Dublin infection in Danish dairy cattle herds estimated by simulation modelling.

    PubMed

    Nielsen, T D; Kudahl, A B; Østergaard, S; Nielsen, L R

    2013-08-01

    assumptions about milk yield losses for cows in the resistant or carrier stages had the greatest influence on the estimated GM losses. This was more influential in the poorer management scenarios due to increased number of infected cows. The results can be used to inform dairy farmers of the benefits of preventing introduction and controlling spread of S. Dublin. Furthermore, they can be used in cost-benefit analyses of control actions for S. Dublin both at herd and sector level.

  13. Modulation of flavonoid biosynthetic pathway genes and anthocyanins due to virus infection in grapevine (Vitis vinifera L.) leaves

    PubMed Central

    2010-01-01

    Background Symptoms of grapevine leafroll disease (GLRD) in red-fruited wine grape (Vitis vinifera L.) cultivars consist of green veins and red and reddish-purple discoloration of inter-veinal areas of leaves. The reddish-purple color of symptomatic leaves may be due to the accumulation of anthocyanins and could reflect an up-regulation of genes involved in their biosynthesis. Results We examined six putative constitutively expressed genes, Ubiquitin, Actin, GAPDH, EF1-a, SAND and NAD5, for their potential as references for normalization of gene expression in reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Using the geNorm program, a combination of two genes (Actin and NAD5) was identified as the stable set of reference genes for normalization of gene expression data obtained from grapevine leaves. By using gene-specific RT-qPCR in combination with a reliable normalization factor, we compared relative expression of the flavonoid biosynthetic pathway genes between leaves infected with Grapevine leafroll-associated virus 3 (GLRaV-3) and exhibiting GLRD symptoms and virus-free green leaves obtained from a red-fruited wine grape cultivar (cv. Merlot). The expression levels of these different genes ranged from two- to fifty-fold increase in virus-infected leaves. Among them, CHS3, F3'5'H, F3H1, LDOX, LAR1 and MybA1 showed greater than 10-fold increase suggesting that they were expressed at significantly higher levels in virus-infected symptomatic leaves. HPLC profiling of anthocyanins extracted from leaves indicated the presence of cyanidin-3-glucoside and malvidin-3-glucoside only in virus-infected symptomatic leaves. The results also showed 24% higher levels of flavonols in virus-infected symptomatic leaves than in virus-free green leaves, with quercetin followed by myricetin being the predominant compounds. Proanthocyanidins, estimated as total tannins by protein precipitation method, were 36% higher in virus-infected symptomatic

  14. A rare case of multilocus brain abscess due to Entamoeba histolytica infection in a child.

    PubMed

    Tamer, Gülden S; Öncel, Selim; Gökbulut, Sevil; Arisoy, Emin S

    2015-03-01

    Brain abscess due to Entamoeba histolytica (E. histolytica) may pose a diagnostic problem or a therapeutic challenge, as evidenced by the paucity of papers reporting complete recovery after treatment. An 11-year-old girl presented with progressive drowsiness, diminished movements of the left upper limb, and swallowing problems. Cranial MRI showed multiple, contrast-dense masses with fluid content. She was started on meropenem. Surgical drainage was performed. No bacterial or fungal growth was observed in drainage samples. Entamoeba histolytica trophozoites were detected in the tissue sample. Intravenous metronidazole was started and continued for 6 weeks, at the end of which abscesses were found and to have shrunk considerably. Intravenous therapy was switched to oral metronidazole, which was continued for 2 weeks. She regained all her preexisting abilities. Multiple brain abscesses due to E. histolytica is a very rare occurrence, and histopathologic evaluation is important in diagnosis. PMID:25737180

  15. Tilmicosin does not inhibit interleukin-8 gene expression in the bovine lung experimentally infected with Mannheimia (Pasteurella) haemolytica.

    PubMed

    Goubau, S; Morck, D W; Buret, A

    2000-10-01

    The expression of the interleukin-8 (IL-8) gene was examined by in situ hybridization in lung tissues from calves experimentally infected with Mannheimia (Pasteurella) haemolytica and treated with tilmicosin. Interleukin-8 mRNA expression was detected in alveolar areas, particularly along interlobular septa, in the lumen, and in the epithelial cells of some bronchioles. In lesional lung tissues from animals that had received tilmicosin, we found large areas with limited inflammation. There was no staining for IL-8 mRNA in these areas. In contrast, in strongly inflamed areas, the same patterns and intensities of staining for IL-8 mRNA were detected in tilmicosin- and sham-treated animals. We conclude that tilmicosin does not affect the expression of IL-8 mRNA in tissue showing microscopic signs of inflammation. Together with previous reports, this supports the view that the pro-apoptotic properties of tilmicosin on neutrophils do not compromise the host defense mechanisms required to control the infection.

  16. Liver function test results and outcomes in children with acute liver failure due to dengue infection.

    PubMed

    Chongsrisawat, Voranush; Hutagalung, Yanee; Poovorawan, Yong

    2009-01-01

    This retrospective study compared the liver function test results and outcomes between children with acute liver failure (ALF) due to dengue hemorrhagic fever (DHF) and due to other causes. We retrospectively reviewed patients less than 15 years old with a diagnosis of ALF admitted to 13 participating centers from different parts of Thailand for the years 2000 and 2001, and those admitted to King Chulalongkorn Memorial Hospital for the year 1997 to 2004. The diagnosis of ALF was based on prothrombin time (PT) prolongation to greater than 2 times the normal control value and the presence of encephalopathy without pre-existing liver disease. The patients were divided into 2 groups: group I (n=16) had DHF with ALF and group II (n=37) had ALF due to other causes. DHF patients had AST levels significantly higher than ALT levels. The mortality rate in group I (50%) was lower than in group II (72.9%), although the difference was not statistically significant. The non-DHF patients who died had a significantly longer duration of jaundice before the onset of encephalopathy and a significantly higher PT ratio compared to survivors. There were no significant differences in the duration of jaundice before the onset of encephalopathy and liver function between dengue patients who died and those who survived.

  17. Flagellin induces myeloid-derived suppressor cells: implications for Pseudomonas aeruginosa infection in cystic fibrosis lung disease.

    PubMed

    Rieber, Nikolaus; Brand, Alina; Hector, Andreas; Graepler-Mainka, Ute; Ost, Michael; Schäfer, Iris; Wecker, Irene; Neri, Davide; Wirth, Andreas; Mays, Lauren; Zundel, Sabine; Fuchs, Jörg; Handgretinger, Rupert; Stern, Martin; Hogardt, Michael; Döring, Gerd; Riethmüller, Joachim; Kormann, Michael; Hartl, Dominik

    2013-02-01

    Pseudomonas aeruginosa persists in patients with cystic fibrosis (CF) and drives CF lung disease progression. P. aeruginosa potently activates the innate immune system, mainly mediated through pathogen-associated molecular patterns, such as flagellin. However, the host is unable to eradicate this flagellated bacterium efficiently. The underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells generated in cancer and proinflammatory microenvironments and are capable of suppressing T cell responses. We hypothesized that P. aeruginosa induces MDSCs to escape T cell immunity. In this article, we demonstrate that granulocytic MDSCs accumulate in CF patients chronically infected with P. aeruginosa and correlate with CF lung disease activity. Flagellated P. aeruginosa culture supernatants induced the generation of MDSCs, an effect that was 1) dose-dependently mimicked by purified flagellin protein, 2) significantly reduced using flagellin-deficient P. aeruginosa bacteria, and 3) corresponded to TLR5 expression on MDSCs in vitro and in vivo. Both purified flagellin and flagellated P. aeruginosa induced an MDSC phenotype distinct from that of the previously described MDSC-inducing cytokine GM-CSF, characterized by an upregulation of the chemokine receptor CXCR4 on the surface of MDSCs. Functionally, P. aeruginosa-infected CF patient ex vivo-isolated as well as flagellin or P. aeruginosa in vitro-generated MDSCs efficiently suppressed polyclonal T cell proliferation in a dose-dependent manner and modulated Th17 responses. These studies demonstrate that flagellin induces the generation of MDSCs and suggest that P. aeruginosa uses this mechanism to undermine T cell-mediated host defense in CF and other P. aeruginosa-associated chronic lung diseases. PMID:23277486

  18. Toward Repositioning Niclosamide for Antivirulence Therapy of Pseudomonas aeruginosa Lung Infections: Development of Inhalable Formulations through Nanosuspension Technology.

    PubMed

    Costabile, Gabriella; d'Angelo, Ivana; Rampioni, Giordano; Bondì, Roslen; Pompili, Barbara; Ascenzioni, Fiorentina; Mitidieri, Emma; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Miro, Agnese; Quaglia, Fabiana; Imperi, Francesco; Leoni, Livia; Ungaro, Francesca

    2015-08-01

    Inhaled antivirulence drugs are currently considered a promising therapeutic option to treat Pseudomonas aeruginosa lung infections in cystic fibrosis (CF). We have recently shown that the anthelmintic drug niclosamide (NCL) has strong quorum sensing (QS) inhibiting activity against P. aeruginosa and could be repurposed as an antivirulence drug. In this work, we developed dry powders containing NCL nanoparticles that can be reconstituted in saline solution to produce inhalable nanosuspensions. NCL nanoparticles were produced by high-pressure homogenization (HPH) using polysorbate 20 or polysorbate 80 as stabilizers. After 20 cycles of HPH, all formulations showed similar properties in the form of needle-shape nanocrystals with a hydrodynamic diameter of approximately 450 nm and a zeta potential of -20 mV. Nanosuspensions stabilized with polysorbate 80 at 10% w/w to NCL (T80_10) showed an optimal solubility profile in simulated interstitial lung fluid. T80_10 was successfully dried into mannitol-based dry powder by spray drying. Dry powder (T80_10 DP) was reconstituted in saline solution and showed optimal in vitro aerosol performance. Both T80_10 and T80_10 DP were able to inhibit P. aeruginosa QS at NCL concentrations of 2.5-10 μM. NCL, and these formulations did not significantly affect the viability of CF bronchial epithelial cells in vitro at microbiologically active concentrations (i.e., ≤10 μM). In vivo acute toxicity studies in rats confirmed no observable toxicity of the NCL T80_10 DP formulation upon intratracheal administration at a concentration 100-fold higher than the anti-QS activity concentration. These preliminary results suggest that NCL repurposed in the form of inhalable nanosuspensions has great potential for the local treatment of P. aeruginosa lung infections as in the case of CF patients.

  19. Undue delay in the diagnosis of lung cancer due to the clinician's preoccupation with pre-existing tuberculosis.

    PubMed

    Revannasiddaiah, Swaroop; Madabhavi, Irappa; Thakur, Priyanka; Seam, Rajeev Kumar

    2011-01-01

    The authors report the case of a seminomadic older patient who had already received a course of antitubercular treatment and within a few weeks of completion suffered resurgence of symptoms. His treating physician assumed it to be relapse of tuberculosis and hence re-started the patient on antitubercular treatment. Though the mass lesion on CT scan procured by the primary care physician suggested the possibility of a neoplasm, areas of necrosis within the mass led to a 'cavitary appearance', which unfortunately happens to be a feature of tuberculosis. Once the patient presented to the authors, they performed cytological investigations which established that the patient had lung cancer co-existing with tuberculosis, which indeed was the reason for his progressive symptoms in spite of antitubercular treatment. PMID:22674956

  20. Cytomegalovirus infection in patients with sepsis due to bloodstream infections: lower risk and better outcomes in new versus already hospitalised intensive care unit admissions.

    PubMed

    R, Osawa; M, Wagener; Ns, Singh

    2016-09-01

    Few studies have examined cytomegalovirus (CMV) reactivation exclusively in immunocompetent patients with sepsis due to bloodstream infections. In a cohort of CMV-seropositive critically ill otherwise non-immunosuppressed patients with sepsis due to bloodstream infection, weekly testing for CMV viraemia was performed. Outcomes were assessed at 30 days or until death/discharge from the intensive care unit (ICU). CMV viraemia developed in 20% (20/100) of the patients. Age (P=0.044) and blood transfusions (P=0.022) were significantly associated with CMV viraemia. There was no difference in the primary endpoint (mortality and/or multi-organ failure) between patients with and without CMV viraemia (P=0.49). However, CMV viraemia was associated with significantly fewer ICU-free days (P=0.023) and fewer ventilator-free days (P=0.031). Patients hospitalised in the ICU for more than 48 hours prior to the onset of bloodstream infection were more likely to develop CMV viraemia (P=0.006), have high-grade viraemia (P=0.010), and fewer ICU-free days (P=0.018) and ventilator-free days (P=0.029) than those admitted within 48 hours of bloodstream infection. Thus, CMV reactivation was associated with fewer ICU- and ventilator-free days, however overall mortality was not affected. Patients already in the ICU at the onset of sepsis had higher risk of CMV reactivation and worse outcomes than new ICU-bound patients suggesting that a targeted approach for interventions for CMV could conceivably be directed towards those with a more protracted course of illness. PMID:27608339

  1. Villosiclava virens infects specifically rice and barley stamen filaments due to the unique host cell walls.

    PubMed

    Yong, Ming-Li; Fan, Lin-Lin; Li, Dan-Yang; Liu, Yi-Jia; Cheng, Fang-Min; Xu, Ying; Wang, Zheng-Yi; Hu, Dong-Wei

    2016-09-01

    Rice false smut, caused by the fungal pathogen Villosiclava virens, is one of the most important rice diseases in the world. Previous studies reported that the pathogen has less number of cell wall-degraded genes and attacks dominantly rice stamen filaments and extends intercellularly. To reveal why the fungus infects plant stamen filaments, inoculation test on barley was carried out with the similar protocol to rice. The experimental results showed that the fungus could penetrate quickly into barley stamen filaments and extends both intracellularly and intercellularly, usually resulting in severe damage of the stamen filament tissues. It also attacked young barley lodicules and grew intercellularly by chance. The light microscopic observations found that the epidermal and cortex cells in barley stamen filaments arranged loosely with very thick cell walls and large cell gaps. Cellulose microfibrils in barley stamen filament cell walls arranged very sparsely so that the cell walls looked like transparent. The cell walls were very soft and flexible, and often folded. However, V. virens extended dominantly in the noncellulose regions and seemed never to degrade microfibrils in barley and rice cell walls. This suggested that the unique structures of rice and barley stamen filaments should be fit for their function of elongation in anthesis, and also endow with the susceptibility to the fungus, V. virens. PMID:27357263

  2. Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity.

    PubMed

    Maramattom, Boby Varkey; Philips, Geetha; Sudheesh, Nittur; Arunkumar, Govindakarnavar

    2014-01-01

    Three cases of acute flaccid paralysis (AFP) with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis). Cerebrospinal fluid (CSF) polymerase chain reaction was positive for West Nile virus (WNV) in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat.

  3. Acute flaccid paralysis due to West nile virus infection in adults: A paradigm shift entity

    PubMed Central

    Maramattom, Boby Varkey; Philips, Geetha; Sudheesh, Nittur; Arunkumar, Govindakarnavar

    2014-01-01

    Three cases of acute flaccid paralysis (AFP) with preceding fever are described. One patient had a quadriparesis with a florid meningoencephalitic picture and the other two had asymmetric flaccid paralysis with fasciculations at the onset of illness. Magnetic resonance imaging in two cases showed prominent hyperintensitities in the spinal cord and brainstem with prominent involvement of the grey horn (polio-myelitis). Cerebrospinal fluid (CSF) polymerase chain reaction was positive for West Nile virus (WNV) in the index patient. All three cases had a positive WNV immunoglobulin M antibody in serum/CSF and significantly high titer of WNV neutralizing antibody in serum, clearly distinguishing the infection from other Flaviviridae such as Japanese encephalitis. WNV has been recognized in India for many decades; however, AFP has not been adequately described. WNV is a flavivirus that is spread by Culex mosquitoes while they take blood meals from humans and lineage 1 is capable of causing a devastating neuro-invasive disease with fatal consequences or severe morbidity. We describe the first three laboratory confirmed cases of WNV induced AFP from Kerala and briefly enumerate the salient features of this emerging threat. PMID:24753667

  4. Preliminary trials with praziquantel in human infections due to Schistosoma mansoni

    PubMed Central

    Katz, N.; Rocha, R.S.; Chaves, A.

    1979-01-01

    As part of a programme of multicentre trials of the tolerance and therapeutic effect of praziquantel, clinical trials were carried out in Brazil in patients with active Schistosoma mansoni infections, each of whom had a minimum geometric mean egg output of 100 eggs per gram of faeces calculated from multiple pretreatment stool examinations. The first stage was a double-blind assessment of tolerance and efficacy of oral doses of 1 × 20, 2 × 20, or 3 × 20 mg of praziquantel per kg of body weight. Subsequently, single-blind trials explored the effects of 3 × 20 mg/kg at 4-hourly intervals, and a single dose of 50 mg/kg. Side effects increased in frequency as dosage increased. Nausea, epigastric pain, headache, dizziness, and drowsiness were all noted but their severity was mild or moderate and they disappeared in 48 hours. In general, monitoring laboratory tests showed little change. Following a stringent parasitological follow-up, 96% of 28 patients followed at 1 year after treatment with either 3 × 20 mg/kg or 1 × 50 mg/kg were cured. Praziquantel seems to be a very promising drug against S. mansoni and further clinical trials should be strongly encouraged. PMID:396054

  5. Villosiclava virens infects specifically rice and barley stamen filaments due to the unique host cell walls.

    PubMed

    Yong, Ming-Li; Fan, Lin-Lin; Li, Dan-Yang; Liu, Yi-Jia; Cheng, Fang-Min; Xu, Ying; Wang, Zheng-Yi; Hu, Dong-Wei

    2016-09-01

    Rice false smut, caused by the fungal pathogen Villosiclava virens, is one of the most important rice diseases in the world. Previous studies reported that the pathogen has less number of cell wall-degraded genes and attacks dominantly rice stamen filaments and extends intercellularly. To reveal why the fungus infects plant stamen filaments, inoculation test on barley was carried out with the similar protocol to rice. The experimental results showed that the fungus could penetrate quickly into barley stamen filaments and extends both intracellularly and intercellularly, usually resulting in severe damage of the stamen filament tissues. It also attacked young barley lodicules and grew intercellularly by chance. The light microscopic observations found that the epidermal and cortex cells in barley stamen filaments arranged loosely with very thick cell walls and large cell gaps. Cellulose microfibrils in barley stamen filament cell walls arranged very sparsely so that the cell walls looked like transparent. The cell walls were very soft and flexible, and often folded. However, V. virens extended dominantly in the noncellulose regions and seemed never to degrade microfibrils in barley and rice cell walls. This suggested that the unique structures of rice and barley stamen filaments should be fit for their function of elongation in anthesis, and also endow with the susceptibility to the fungus, V. virens.

  6. Repeated lung lavage with extracorporeal membrane oxygenation treating severe acute respiratory distress syndrome due to nasogastric tube malposition for enternal nutrition: a case report.

    PubMed

    Kao, Xiaoming; Yu, Wenkui; Zhu, Weiming; Li, Ning; Li, Jieshou

    2012-01-01

    Enternal nutritional support, a frequently applied technique for providing nutrition and energy, played a pivotal role in the treatment of high risk patients. However, severe complications induced by malposition of nasogastric tube caused great danger and even death to the patients. In this case report, we present a patient with severe acute respiratory distress syndrome (ARDS) induced by bronchopleural fistula (BPF) due to malposition of nasogastric tube. Repeated lung lavage combined with extracorporeal membrane oxygenation (ECMO) was performed after transferring to the ICU of our hospital. Finally, the patient recovered and discharged 7 days after admission.

  7. Bacterial and Clinical Characteristics of Health Care- and Community-Acquired Bloodstream Infections Due to Pseudomonas aeruginosa

    PubMed Central

    Hattemer, Angela; Hauser, Alan; Diaz, Maureen; Scheetz, Marc; Shah, Nirav; Allen, Jonathan P.; Porhomayon, Jahan

    2013-01-01

    Health care-associated infections, including Pseudomonas aeruginosa bloodstream infection, have been linked to delays in appropriate antibiotic therapy and an increased mortality rate. The objective of this study was to evaluate intrinsic virulence, bacterial resistance, and clinical outcomes of health care-associated bloodstream infections (HCABSIs) in comparison with those of community-acquired bloodstream infections (CABSIs) caused by P. aeruginosa. We conducted a retrospective multicenter study of consecutive P. aeruginosa bacteremia patients at two university-affiliated hospitals. Demographic, clinical, and treatment data were collected. Microbiologic analyses included in vitro susceptibility profiles and type III secretory (TTS) phenotypes. Sixty CABSI and 90 HCABSI episodes were analyzed. Patients with HCABSIs had more organ dysfunction at the time of bacteremia (P = 0.05) and were more likely to have been exposed to antimicrobial therapy (P < 0.001) than those with CABSIs. Ninety-two percent of the carbapenem-resistant P. aeruginosa infections were characterized as HCABSIs. The 30-day mortality rate for CABSIs was 26% versus 36% for HCABSIs (P = 0.38). The sequential organ failure assessment score at the time of bacteremia (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.3) and the TTS phenotype (HR 2.1; 95% CI, 1.1 to 3.9) were found to be independent predictors of the 30-day mortality rate. No mortality rate difference was observed between CABSIs and HCABSIs caused by P. aeruginosa. Severity of illness and expression of TTS proteins were the strongest predictors of the 30-day mortality rate due to P. aeruginosa bacteremia. Future P. aeruginosa bacteremia trials designed to neutralize TTS proteins are warranted. PMID:23733476

  8. Continuous Regional Arterial Infusion Therapy for Acute Necrotizing Pancreatitis Due to Mycoplasma pneumoniae Infection in a Child

    SciTech Connect

    Nakagawa, Motoo Ogino, Hiroyuki; Shimohira, Masashi; Hara, Masaki; Shibamoto, Yuta

    2009-05-15

    A case of acute necrotizing pancreatitis due to Mycoplasma pneumoniae infection was treated in an 8-year-old girl. She experienced acute pancreatitis during treatment for M. pneumoniae. Contrast-enhanced computed tomographic scan revealed necrotizing pancreatitis. The computed tomographic severity index was 8 points (grade E). A protease inhibitor, ulinastatin, was provided via intravenous infusion but was ineffective. Continuous regional arterial infusion therapy was provided with gabexate mesilate (FOY-007, a protease inhibitor) and meropenem trihydrate, and the pancreatitis improved. This case suggests that infusion therapy is safe and useful in treating necrotizing pancreatitis in children.

  9. Enteric Infection and Subsequent Septicemia due to Attaching and Effacing Escherichia coli in a Chinchilla

    PubMed Central

    Diaz, Leslie L; Lepherd, Michelle; Scott, Joseph

    2013-01-01

    An adult male chinchilla (Chinchilla lanigera) presented with severe lethargy and tachypnea; the physical examination was otherwise unremarkable. Due to the animal's clinical condition, it was submitted for necropsy but died immediately prior to euthanasia. Clinicopathologic findings included leukocytosis with a left-shift neutrophilia and lymphopenia, azotemia, hyperphosphatemia, hyperglycemia, hyperlipemia, electrolyte imbalance, cholestasis, and hepatocellular damage. Neutrophilic enteritis with gram-negative bacterial colonization, hepatic lipidosis, interstitial pneumonia, suppurative tubulonephritis, erosive gastritis, cerebral edema, and lymphoid depletion were present microscopically. Attaching and effacing, eae-positive, Escherichia coli characterized by the presence of the intimin virulence factor was isolated from both the kidney and spleen. The cause of death was attributed to acute E. coli septicemia and subsequent disseminated intravascular coagulation. PMID:24326226

  10. [Infective endocarditis due to Bartonella henselae following a rupture of a cerebral aneurysm].

    PubMed

    de La Blanchardière, A; Fournier, P-E; Haustraete, E; du Cheyron, D; Lepage, O; Verdon, R

    2009-06-01

    We report a case of severe aortic bicuspid valve endocarditis, revealed by global cardiac failure without fever, in a 38-year-old man who had developed cerebral mycotic aneurysms nine months earlier. PCR analysis of the excised aortic valve and serological tests (even 9 months earlier) were positive for Bartonella henselae. A combination of intravenous then oral doxycyclin at 200mg/day and intravenous gentamycin at 90mg/day was given for 6 and 2 weeks respectively. The evolution was favorable on follow-up, 12 months after completion of the therapy. Only 49 cases of B. henselae endocarditis have been reported to date, none with associated mycotic aneurysm but most often located on the bicuspid aortic valve, and usually with severe valvular damage due to late diagnosis. PMID:19097835

  11. Clinical manifestations of Eosinophilic meningitis due to infection with Angiostrongylus cantonensis in children.

    PubMed

    Sawanyawisuth, Kittisak; Chindaprasirt, Jarin; Senthong, Vichai; Limpawattana, Panita; Auvichayapat, Narong; Tassniyom, Sompon; Chotmongkol, Verajit; Maleewong, Wanchai; Intapan, Pewpan M

    2013-12-01

    Eosinophilic meningitis, caused by the nematode Angiostrongylus cantonensis, is prevalent in northeastern Thailand, most commonly in adults. Data regarding clinical manifestations of this condition in children is limited and may be different those in adults. A chart review was done on 19 eosinophilic meningitis patients aged less than 15 years in Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. Clinical manifestations and outcomes were reported using descriptive statistics. All patients had presented with severe headache. Most patients were males, had fever, nausea or vomiting, stiffness of the neck, and a history of snail ingestion. Six patients had papilledema or cranial nerve palsies. It was shown that the clinical manifestations of eosinophilic meningitis due to A. cantonensis in children are different from those in adult patients. Fever, nausea, vomiting, hepatomegaly, neck stiffness, and cranial nerve palsies were all more common in children than in adults.

  12. [Brain Abscess due to Infection with Dematiaceous Fungi Cladophialophora bantiana Associated with Hypogammaglobulinemia Following Gastrectomy: A Case Report].

    PubMed

    Shimogawa, Takafumi; Sayama, Tetsuro; Haga, Sei; Akiyama, Tomoaki; Makihara, Kosuke; Morioka, Takato

    2016-01-01

    Dematiaceous fungi have melanin-like pigment in the cell wall and usually cause a variety of dermal infections in humans. Infections of the central nervous system(cerebral phaeohyphomycosis)are rare but serious, since they commonly occur in immunocompromized patients. A 76-year-old man was admitted with mild motor aphasia and underwent total excision of a mass in the left frontal lobe. With the postoperative diagnosis of brain abscess due to infection with dematiaceous fungi (C. bantiana) associated with hypogammaglobulinemia following gastrectomy, intravenous antifungal drugs including amphotericin B and fluconazole were administered. Regrowth of the abscess with intraventricular rupture was noted at about the 88th day after the initial surgery, and the patient underwent neuroendoscopic aspiration of the pus and placement of a ventricular drain. Following intraventricular administration of miconazole through ventricular drainage or an Ommaya reservoir, neuroradiological findings improved, but general and neurological conditions worsened. Further treatment was discontinued and the patient died 9 months after onset. The poor outcome in this patient is attributed to 1)intractability of dematiaceous fungi, 2)development of ventriculitis and the need for intraventricular administration of antifungal drugs, and 3)untreatable hypogammaglobulinemia following gastrectomy. PMID:26771098

  13. Pneumonia and Pleural Empyema due to a Mixed Lactobacillus spp. Infection as a Possible Early Esophageal Carcinoma Signature

    PubMed Central

    Chaini, Eleftheria; Chainis, Nikolaos D.; Ioannidis, Anastasios; Magana, Maria; Nikolaou, Chryssoula; Papaparaskevas, Joseph; Liakata, Melina-Vassiliki; Katopodis, Panagiotis; Papastavrou, Leonidas; Tegos, George P.; Chatzipanagiotou, Stylianos

    2016-01-01

    Lactobacilli are human commensals found in the gastrointestinal and genitourinary tract. Although generally conceived as non-pathogenic microorganisms, the existence of several reports implicating them in certain severe pathological entities renders this species as opportunistic pathogens. The case of a 58-year-old woman with mixed Lactobacillus infection is described. The patient was admitted in an outpatient clinic with community acquired pneumonia, and on the third day of hospitalization she presented rapid pneumonia deterioration. Subsequent imaging techniques revealed increased pleural empyema in alignment with the general deterioration of her clinical condition. Pleural fluid culture revealed the presence of Lactobacillus delbrueckii and Lactobacillus gasseri and the infection was successfully treated with clindamycin. Five months after hospital discharge and an overall good condition, the patient developed signs of dysphagia and upon re-admission an inoperable esophageal carcinoma was diagnosed. The patient succumbed to the cancer 11 months later. Herein, we report for the first time a mixed respiratory infection due to lactobacilli, possibly associated with a formerly unveiled esophageal malignancy. PMID:27734016

  14. Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014.

    PubMed

    Esposito, Susanna; Zampiero, Alberto; Bianchini, Sonia; Mori, Alessandro; Scala, Alessia; Tagliabue, Claudia; Sciarrabba, Calogero Sathya; Fossali, Emilio; Piralla, Antonio; Principi, Nicola

    2016-01-01

    To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain reaction; their nucleotides were sequenced, and they were tested for positive selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV. HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in association with one other virus in 25 (41.0%) cases and with two or more viruses in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial virus were the most common co-infecting viral agents and were found in 12 (19.7%) and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed were highly conserved. In comparison to HAdV-negative children, those infected with HAdV had a reduced frequency of lower respiratory tract involvement (36.1% vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 ± 7,737 vs 9,565 ± 3,211 cells/μL; p = 0.04), respectively, in children infected by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%) but difference did not reach statistical significant (p = 0.21). Children with high viral load were absent from child care attendance for a longer period of time (14.5 ± 7.5 vs 5.5 ± 3.2 days; p = 0.002) and had higher C reactive protein levels (41.3 ± 78.5 vs 5.4 ± 9.6 μg/dL; p = 0.03). This study has shown that

  15. Epidemiology and Clinical Characteristics of Respiratory Infections Due to Adenovirus in Children Living in Milan, Italy, during 2013 and 2014

    PubMed Central

    Esposito, Susanna; Zampiero, Alberto; Bianchini, Sonia; Mori, Alessandro; Scala, Alessia; Tagliabue, Claudia; Sciarrabba, Calogero Sathya; Fossali, Emilio; Piralla, Antonio; Principi, Nicola

    2016-01-01

    To evaluate the predominant human adenovirus (HAdV) species and types associated with pediatric respiratory infections, nasopharyngeal swabs were collected from otherwise healthy children attending an emergency room in Milan, Italy, due to a respiratory tract infection from January 1 to February 28 of two subsequent years, 2013 and 2014. The HAdVs were detected using a respiratory virus panel fast assay (xTAG RVP FAST v2) and with a HAdV-specific real-time polymerase chain reaction; their nucleotides were sequenced, and they were tested for positive selection. Among 307 nasopharyngeal samples, 61 (19.9%) tested positive for HAdV. HAdV was the only virus detected in 31/61 (50.8%) cases, whereas it was found in association with one other virus in 25 (41.0%) cases and with two or more viruses in 5 (8.2%) cases. Human Enterovirus/human rhinovirus and respiratory syncytial virus were the most common co-infecting viral agents and were found in 12 (19.7%) and 7 (11.5%) samples, respectively. Overall, the HAdV strain sequences analyzed were highly conserved. In comparison to HAdV-negative children, those infected with HAdV had a reduced frequency of lower respiratory tract involvement (36.1% vs 55.2%; p = 0.007), wheezing (0.0% vs 12.5%; p = 0.004), and hospitalization (27.9% vs 56.1%; p<0.001). Antibiotic therapy and white blood cell counts were more frequently prescribed (91.9% vs 57.1%; p = 0.04) and higher (17,244 ± 7,737 vs 9,565 ± 3,211 cells/μL; p = 0.04), respectively, in children infected by HAdV-C than among those infected by HAdV-B. On the contrary, those infected by HAdV-B had more frequently lower respiratory tract involvement (57.1% vs 29.7%) but difference did not reach statistical significant (p = 0.21). Children with high viral load were absent from child care attendance for a longer period of time (14.5 ± 7.5 vs 5.5 ± 3.2 days; p = 0.002) and had higher C reactive protein levels (41.3 ± 78.5 vs 5.4 ± 9.6 μg/dL; p = 0.03). This study has shown that

  16. Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infected mice.

    PubMed

    Berkhout, Johanna; Melchers, Maria J; van Mil, Anita C; Seyedmousavi, Seyedmojtaba; Lagarde, Claudia M; Nichols, Wright W; Mouton, Johan W

    2015-04-01

    Ceftazidime and the β-lactamase inhibitor avibactam constitute a new, potentially highly active combination in the battle against extended-spectrum-β-lactamase (ESBL)-producing bacteria. To determine possible clinical use, it is important to know the pharmacokinetic profiles of the compounds related to each other in plasma and the different compartments of infection in experimentally infected animals and in humans. We used a neutropenic murine thigh infection model and lung infection model to study pharmacokinetics in plasma and epithelial lining fluid (ELF). Mice were infected with ca. 10(6) CFU of Pseudomonas aeruginosa intramuscularly into the thigh or intranasally to cause pneumonia and were given 8 different (single) subcutaneous doses of ceftazidime and avibactam in various combined concentrations, ranging from 1 to 128 mg/kg of body weight in 2-fold increases. Concomitant samples of serum and bronchoalveolar lavage fluid were taken at up to 12 time points until 6 h after administration. Pharmacokinetics of both compounds were linear and dose proportional in plasma and ELF and were independent of the infection type, with estimated half-lives (standard deviations [SD]) in plasma of ceftazidime of 0.28 (0.02) h and of avibactam of 0.24 (0.04) h and volumes of distribution of 0.80 (0.14) and 1.18 (0.34) liters/kg. The ELF-plasma (area under the concentration-time curve [AUC]) ratios (standard errors [SE]) were 0.24 (0.03) for total ceftazidime and 0.27 (0.03) for unbound ceftazidime; for avibactam, the ratios were 0.20 (0.02) and 0.22 (0.02), respectively. No pharmacokinetic interaction between ceftazidime and avibactam was observed. Ceftazidime and avibactam showed linear plasma pharmacokinetics that were independent of the dose combinations used or the infection site in mice. Assuming pharmacokinetic similarity in humans, this indicates that similar dose ratios of ceftazidime and avibactam could be used for different types and sites of infection. PMID

  17. Genotypic and phenotypic variation in Pseudomonas aeruginosa reveals signatures of secondary infection and mutator activity in certain cystic fibrosis patients with chronic lung infections.

    PubMed

    Warren, Ashley E; Boulianne-Larsen, Carla M; Chandler, Christine B; Chiotti, Kami; Kroll, Evgueny; Miller, Scott R; Taddei, Francois; Sermet-Gaudelus, Isabelle; Ferroni, Agnes; McInnerney, Kathleen; Franklin, Michael J; Rosenzweig, Frank

    2011-12-01

    Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung is limited by genetic variation, which depends on rates of horizontal gene transfer and mutation supply. Because each may increase following secondary infection or mutator emergence, we sought to ascertain the incidence of secondary infection and genetic variability in populations containing or lacking mutators. Forty-nine strains collected over 3 years from 16 patients were phenotyped for antibiotic resistance and mutator status and were genotyped by repetitive-sequence PCR (rep-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Though phenotypic and genetic polymorphisms were widespread and clustered more strongly within than between longitudinal series, their distribution revealed instances of secondary infection. Sequence data, however, indicated that interlineage recombination predated initial strain isolation. Mutator series were more likely to be multiply antibiotic resistant, but not necessarily more variable in their nucleotide sequences, than nonmutators. One mutator and one nonmutator series were sequenced at mismatch repair loci and analyzed for gene content using DNA microarrays. Both were wild type with respect to mutL, but mutators carried an 8-bp mutS deletion causing a frameshift mutation. Both series lacked 126 genes encoding pilins, siderophores, and virulence factors whose inactivation has been linked to adaptation during chronic infection. Mutators exhibited loss of severalfold more genes having functions related to mobile elements, motility, and attachment. A 105-kb, 86-gene deletion was observed in one nonmutator that resulted in loss of virulence factors related to pyoverdine synthesis and elements of the multidrug efflux regulon. Diminished DNA repair activity may facilitate but not be absolutely required for rapid evolutionary change.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  20. Influenza A Virus Dysregulates Host Histone Deacetylase 1 That Inhibits Viral Infection in Lung Epithelial Cells

    PubMed Central

    Nagesh, Prashanth Thevkar

    2016-01-01

    ABSTRACT Viruses dysregulate the host factors that inhibit virus infection. Here, we demonstrate that human enzyme, histone deacetylase 1 (HDAC1) is a new class of host factor that inhibits influenza A virus (IAV) infection, and IAV dysregulates HDAC1 to efficiently replicate in epithelial cells. A time-dependent decrease in HDAC1 polypeptide level was observed in IAV-infected cells, reducing to <50% by 24 h of infection. A further depletion (97%) of HDAC1 expression by RNA interference increased the IAV growth kinetics, increasing it by >3-fold by 24 h and by >6-fold by 48 h of infection. Conversely, overexpression of HDAC1 decreased the IAV infection by >2-fold. Likewise, a time-dependent decrease in HDAC1 activity, albeit with slightly different kinetics to HDAC1 polypeptide reduction, was observed in infected cells. Nevertheless, a further inhibition of deacetylase activity increased IAV infection in a dose-dependent manner. HDAC1 is an important host deacetylase and, in addition to its role as a transcription repressor, HDAC1 has been lately described as a coactivator of type I interferon response. Consistent with this property, we found that inhibition of deacetylase activity either decreased or abolished the phosphorylation of signal transducer and activator of transcription I (STAT1) and expression of interferon-stimulated genes, IFITM3, ISG15, and viperin in IAV-infected cells. Furthermore, the knockdown of HDAC1 expression in infected cells decreased viperin expression by 58% and, conversely, the overexpression of HDAC1 increased it by 55%, indicating that HDAC1 is a component of IAV-induced host type I interferon antiviral response. IMPORTANCE Influenza A virus (IAV) continues to significantly impact global public health by causing regular seasonal epidemics, occasional pandemics, and zoonotic outbreaks. IAV is among the successful human viral pathogens that has evolved various strategies to evade host defenses, prevent the development of a universal

  1. Influenceable and Avoidable Risk Factors for Systemic Air Embolism due to Percutaneous CT-Guided Lung Biopsy: Patient Positioning and Coaxial Biopsy Technique—Case Report, Systematic Literature Review, and a Technical Note

    PubMed Central

    2014-01-01

    Following the first case of a systemic air embolism due to percutaneous CT-guided lung biopsy in our clinic we analysed the literature regarding this matter in view of influenceable or avoidable risk factors. A systematic review of literature reporting cases of systemic air embolism due to CT-guided lung biopsy was performed to find out whether prone positioning might be a risk factor regarding this issue. In addition, a technical note concerning coaxial biopsy practice is presented. Prone position seems to have relevance for the development and/or clinical manifestation of air embolism due to CT-guided lung biopsy and should be considered a risk factor, at least as far as lesions in the lower parts of the lung are concerned. Biopsies of small or cavitary lesions in coaxial technique should be performed using a hemostatic valve. PMID:25431666

  2. Influenceable and Avoidable Risk Factors for Systemic Air Embolism due to Percutaneous CT-Guided Lung Biopsy: Patient Positioning and Coaxial Biopsy Technique-Case Report, Systematic Literature Review, and a Technical Note.

    PubMed

    Rott, Gernot; Boecker, Frieder

    2014-01-01

    Following the first case of a systemic air embolism due to percutaneous CT-guided lung biopsy in our clinic we analysed the literature regarding this matter in view of influenceable or avoidable risk factors. A systematic review of literature reporting cases of systemic air embolism due to CT-guided lung biopsy was performed to find out whether prone positioning might be a risk factor regarding this issue. In addition, a technical note concerning coaxial biopsy practice is presented. Prone position seems to have relevance for the development and/or clinical manifestation of air embolism due to CT-guided lung biopsy and should be considered a risk factor, at least as far as lesions in the lower parts of the lung are concerned. Biopsies of small or cavitary lesions in coaxial technique should be performed using a hemostatic valve. PMID:25431666

  3. Rat strain differences in levels and effects of chronic inflammation due to intratracheal instillation of quartz on lung tumorigenesis induced by DHPN.

    PubMed

    Nakano, Yuko; Yokohira, Masanao; Hashimoto, Nozomi; Yamakawa, Keiko; Kishi, Sosuke; Ninomiya, Fumiko; Kanie, Shohei; Saoo, Kousuke; Imaida, Katsumi

    2014-10-01

    Chronic inflammatory effects of single intratracheal instillation (i.t.) of quartz on rat lung tumorigenesis were examined using 4 different animal models. At first, in order to determine an appropriate dose of quartz i.t. to promote lung tumorigenesis, F344 male rats were administrated single 0, 0.5, 1, 2 or 4 mg quartz/rat after initiation by N-bis(2-hydroxypropyl) nitrosamine (DHPN). Further studies were performed to examine strain differences of the effects of chronic inflammation caused by quartz i.t. in 3 strains of rat, i.e. F344, Wistar-Hannover and SD. Each was instilled with 2mg quartz/rat after DHPN administration and sacrificed in week 24. In addition, strain differences in generation of inflammation were determined at days 1 and 28. Finally, for determination of long-term effects period, F344 and Wistar-Hannover rats were similarly treated, but the experiment was terminated at week 52. In F344 rats, the tumor areas in DHPN treated groups showed a tendency to increase along with the dose of quartz. F344 rats demonstrated the highest and Wistar-Hannover rats the lowest sensitivity to quartz in acute and chronic phases in the 3 strains. In 52 week, in F344 rats, the multiplicity of tumors and the serum concentration of IL-6 in the group treated with DHPN and quartz were significantly increased. The present experiments indicated that chronic inflammation due to quartz instillation exerted promoting effects on lung carcinogenesis in F344, SD and Wistar-Hannover rats. The strain differences in tumor promotion appeared to correlate with inflammatory reactions to quartz and increase of IL-6.

  4. Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation.

    PubMed

    Jackson-Jones, Lucy H; Duncan, Sheelagh M; Magalhaes, Marlène S; Campbell, Sharon M; Maizels, Rick M; McSorley, Henry J; Allen, Judith E; Bénézech, Cécile

    2016-01-01

    Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production. PMID:27582256

  5. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  6. Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation

    PubMed Central

    Jackson-Jones, Lucy H.; Duncan, Sheelagh M.; Magalhaes, Marlène S.; Campbell, Sharon M.; Maizels, Rick M.; McSorley, Henry J.; Allen, Judith E.; Bénézech, Cécile

    2016-01-01

    Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production. PMID:27582256

  7. Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function

    PubMed Central

    Kim, Dong Young; Oh, Sam S.; Torgerson, Dara R.; Pino-Yanes, Maria; Hu, Donglei; Sen, Saunak; Huntsman, Scott; Eng, Celeste; Farber, Harold J.; Rodriguez-Cintron, William; Rodriguez-Santana, Jose R.; Serebrisky, Denise; Thyne, Shannon M.; Borrell, Luisa N.; Williams, L. Keoki; DuPont, William; Seibold, Max A.; Burchard, Esteban G.; Avila, Pedro C.; Kumar, Rajesh

    2016-01-01

    Background Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. Methods We included Latino children, adolescents, and young adults aged 8–21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function. Results RSV infection (OR 9.9, 95%CI 4.9–20.2) and other LRI (OR 9.1, 95%CI 7.2–11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3–50.2) and genotype-LRI (OR 11.7, 95% CI 8.8–16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted. Conclusions A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population. PMID:27556405

  8. Lung Diseases and Conditions

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Lung Diseases and Conditions Breathing is a complex process. ... your bronchial tubes ( bronchitis ) or deep in your lungs ( pneumonia ). These infections cause a buildup of mucus ...

  9. Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein.

    PubMed

    Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro; Ogihara, Takuo

    2016-08-01

    P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment.

  10. Monte Carlo estimation of radiation dose in organs of female and male adult phantoms due to FDG-F18 absorbed in the lungs

    NASA Astrophysics Data System (ADS)

    Belinato, Walmir; Santos, William S.; Silva, Rogério M. V.; Souza, Divanizia N.

    2014-03-01

    The determination of dose conversion factors (S values) for the radionuclide fluorodeoxyglucose (18F-FDG) absorbed in the lungs during a positron emission tomography (PET) procedure was calculated using the Monte Carlo method (MCNPX version 2.7.0). For the obtained dose conversion factors of interest, it was considered a uniform absorption of radiopharmaceutical by the lung of a healthy adult human. The spectrum of fluorine was introduced in the input data file for the simulation. The simulation took place in two adult phantoms of both sexes, based on polygon mesh surfaces called FASH and MASH with anatomy and posture according to ICRP 89. The S values for the 22 internal organs/tissues, chosen from ICRP No. 110, for the FASH and MASH phantoms were compared with the results obtained from a MIRD V phantoms called ADAM and EVA used by the Committee on Medical Internal Radiation Dose (MIRD). We observed variation of more than 100% in S values due to structural anatomical differences in the internal organs of the MASH and FASH phantoms compared to the mathematical phantom.

  11. Differential effect of plasma and red blood cell transfusion on acute lung injury and infection risk following liver transplantation

    PubMed Central

    Benson, Alexander B.; Burton, James R.; Austin, Gregory L.; Biggins, Scott W.; Zimmerman, Michael A.; Kam, Igal; Mandell, Susan; Silliman, Christopher C.; Rosen, Hugo; Moss, Marc

    2010-01-01

    Rationale Patients with chronic liver disease are at an increased risk of developing transfusion-associated acute lung injury (TRALI) from plasma containing blood products. Similarly, red blood cell transfusions have been associated with post-operative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive a large amount of cellular and plasma containing blood products, but it is presently unclear which blood components are associated with these post-operative complications. Results A retrospective cohort study of 525 consecutive liver transplant patients revealed a peri-operative TRALI incidence of 1.3% (7/525), 95%CI [0.6%–2.7%], associated with an increased hospital mortality (28.6% (2/7) vs. 2.9% (15/518), p=0.02) and intensive care unit (ICU) length of stay (2 days, [1–11] vs. 0 days [0–2], 0.03). Only high plasma containing blood products (plasma and platelets) were associated with the development of TRALI. A total of 14.3% (74/525) of patients developed a post-operative infection which was also associated with an increased in-hospital mortality (10.8% (8/74) vs. 2.0% (9/451), p < 0.01) and prolonged length of stay. Multivariate logistic regression identified the number of red blood cell units transfused (adj OR 1.08 95%CI [1.02–1.14], p<0.01), the presence of peri-operative renal dysfunction and re-operation to be significantly associated with post-operative infection. Conclusions Patients undergoing liver transplantation are at high risk of developing post-operative complications from blood transfusion. Plasma containing blood products were associated with the development of TRALI while red blood cells were associated with the development of post-operative infection in a dose dependent manner. PMID:21280188

  12. Depletion of M. tuberculosis GlmU from Infected Murine Lungs Effects the Clearance of the Pathogen

    PubMed Central

    Soni, Vijay; Upadhayay, Sandeep; Suryadevara, Priyanka; Samla, Ganesh; Singh, Archana; Yogeeswari, Perumal; Sriram, Dharmarajan; Nandicoori, Vinay Kumar

    2015-01-01

    M. tuberculosis N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmUMtb) is a bi-functional enzyme engaged in the synthesis of two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc, catalyzed by the C- and N-terminal domains respectively. UDP-GlcNAc is a key metabolite essential for the synthesis of peptidoglycan, disaccharide linker, arabinogalactan and mycothiols. While glmUMtb was predicted to be an essential gene, till date the role of GlmUMtb in modulating the in vitro growth of Mtb or its role in survival of pathogen ex vivo / in vivo have not been deciphered. Here we present the results of a comprehensive study dissecting the role of GlmUMtb in arbitrating the survival of the pathogen both in vitro and in vivo. We find that absence of GlmUMtb leads to extensive perturbation of bacterial morphology and substantial reduction in cell wall thickness under normoxic as well as hypoxic conditions. Complementation studies show that the acetyl- and uridyl- transferase activities of GlmUMtb are independently essential for bacterial survival in vitro, and GlmUMtb is also found to be essential for mycobacterial survival in THP-1 cells as well as in guinea pigs. Depletion of GlmUMtb from infected murine lungs, four weeks post infection, led to significant reduction in the bacillary load. The administration of Oxa33, a novel oxazolidine derivative that specifically inhibits GlmUMtb, to infected mice resulted in significant decrease in the bacillary load. Thus our study establishes GlmUMtb as a strong candidate for intervention measures against established tuberculosis infections. PMID:26489015

  13. Deficiency of autophagy protein Map1-LC3b mediates IL-17-dependent lung pathology during respiratory viral infection via ER stress associated IL-1

    PubMed Central

    Reed, Michelle; Morris, Susan H.; Owczarczyk, Anna B.; Lukacs, Nicholas W.

    2015-01-01

    While recent studies suggest that IL-1β production is modulated by macroautophagy or sensors of ER stress upon pro-inflammatory insult, autophagy and IL-1β production during viral infection has not been fully investigated. This was addressed using respiratory syncytial virus (RSV), which is associated with lung immunopathology, IL-1, and IL-17a secretion in severely infected patients. Mice deficient in the autophagy-associated protein Map1-LC3b (LC3b−/−) developed increased IL-17a-dependent lung pathology upon infection. RSV-infected LC3b−/− DCs fail to upregulate autophagosome formation, secrete IL-1β and IL-6, and elicit IL-17a production from CD4+ T cells. Bone marrow chimeras revealed both structural and hematopoietic LC3b deficiency contribute to the development of IL-17a-dependent lung pathology in vivo. Further investigation revealed airway epithelium as the primary source of IL-1β during infection, while inhibition of the ER-stress sensor IRE-1 in primary airway epithelial cells reduced IL-1β production identifying a primary ER stress pathway. Finally, blockade of IL-1 receptor signaling in RSV-infected LC3b−/− mice abolished IL-17a-dependent lung pathology. These findings provide novel mechanistic insight into the contribution of autophagy- and ER stress-dependent cytokine production that initiate and maintain aberrant Th17 responses, while identifying IL-1 as a potential therapeutic target in the treatment of severe respiratory viral infections. PMID:25669150

  14. Deficiency of autophagy protein Map1-LC3b mediates IL-17-dependent lung pathology during respiratory viral infection via ER stress-associated IL-1.

    PubMed

    Reed, M; Morris, S H; Owczarczyk, A B; Lukacs, N W

    2015-09-01

    While recent studies suggest that interleukin (IL)-1β production is modulated by macroautophagy or sensors of endoplasmic reticulum (ER) stress upon pro-inflammatory insult, autophagy and IL-1β production during viral infection has not been fully investigated. This was addressed using respiratory syncytial virus (RSV), which is associated with lung immunopathology, IL-1, and IL-17a secretion in severely infected patients. Mice deficient in the autophagy-associated protein Map1-LC3b (LC3b(-/-)) developed increased IL-17a-dependent lung pathology upon infection. RSV-infected LC3b(-/-) dendritic cells (DCs) fail to upregulate autophagosome formation, secrete IL-1β and IL-6, and elicit IL-17a production from CD4+ T cells. Bone marrow chimeras revealed that both structural and hematopoietic LC3b deficiency contribute to the development of IL-17a-dependent lung pathology in vivo. Further investigation revealed airway epithelium as the primary source of IL-1β during infection, whereas inhibition of the ER-stress sensor inositol-requiring protein-1 in primary airway epithelial cells reduced IL-1β production identifying a primary ER stress pathway. Finally, blockade of IL-1 receptor signaling in RSV-infected LC3b(-/-) mice abolished IL-17a-dependent lung pathology. These findings provide novel mechanistic insight into the contribution of autophagy- and ER stress-dependent cytokine production that initiate and maintain aberrant Th17 responses, while identifying IL-1 as a potential therapeutic target in the treatment of severe respiratory viral infections. PMID:25669150

  15. Renal trematode infection due to Paratanaisia bragai in zoo housed Columbiformes and a red bird-of-paradise (Paradisaea rubra).

    PubMed

    Unwin, Steve; Chantrey, Julian; Chatterton, James; Aldhoun, Jitka A; Littlewood, D Timothy J

    2013-12-01

    Trematode infections affect a diverse range of avian species and the organs that are parasitised are also very varied. The family Eucotylidae contains seven genera of renal flukes that parasitise various birds. In birds, mild to severe lesions have been reported for species of the genus Paratanaisia, which was originally described from columbiform and galliform specimens collected in South America and has been identified in a number of wild avian species. This paper investigates eight cases of renal trematode infection at Chester Zoo in the UK due to Paratanaisia bragai in five previously unreported species: red bird-of-paradise, Socorro dove, Mindanao bleeding heart dove, laughing dove and emerald dove. Pathological changes, which varied between species, are discussed. A known intermediate snail host Allopeas clavulinum was present in the enclosures but there was no direct evidence of trematode infection. The size of the snails, possible low prevalence and the difficulty of visualising sporocysts contributed to this. Thus the development and application of further molecular diagnostic markers that can be applied to snail tissues is warranted. Parasite identification was confirmed utilizing DNA amplification from formalin-fixed paraffin-embedded tissues using PCR and trematode specific primers. Sequencing full ssrDNA and D1-D3 lsrDNA confirmed the identity in all cases as P. bragai. However, the short 310 bp fragment used provides insufficient variation or sequence length for wider application. The epidemiology, pathology and consequences for the management of these endangered species are discussed. Preliminary work on developing an effective ante mortem diagnostic PCR test kit is also highlighted. PMID:24533313

  16. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  17. Diarrhea burden due to natural infection with enterotoxigenic Escherichia coli in a birth cohort in a rural Egyptian community.

    PubMed

    Mansour, A; Shaheen, H I; Amine, M; Hassan, K; Sanders, J W; Riddle, M S; Armstrong, A W; Svennerholm, A M; Sebeny, P J; Klena, J D; Young, S Y N; Frenck, R W

    2014-07-01

    Enterotoxigenic Escherichia coli (ETEC) is commonly associated with diarrhea in Egyptian children. Children less than 3 years old in Abu Homos, Egypt, had approximately five diarrheal episodes per child every year, and at least one of these episodes was due to ETEC. The epidemiology of ETEC diarrhea among children living in a rural Egyptian community was further evaluated in this study. Between January 2004 and April 2007, 348 neonates were enrolled and followed for 2 years. Children were visited twice weekly, and a stool sample was obtained every 2 weeks regardless of symptomatology. A stool sample was obtained whenever a child had diarrhea. From the routine stool culture, five E. coli-like colonies were selected and screened for heat-labile and heat-stable toxins by GM1 enzyme-linked immunosorbent assay (ELISA) and further typed for colonization factor antigens by dot blot assay. Incidence of ETEC infection was estimated among children with diarrhea (symptomatic) and without diarrhea (asymptomatic). Incidence of diarrhea and ETEC-associated diarrhea was 7.8 and 1.48 per child-year, respectively. High risk of repeated ETEC diarrhea was associated with being over 6 months of age, warm season, male gender, and crowded sleeping conditions. Exclusive breast-feeding was protective for repeated ETEC infection. ETEC-associated diarrhea remains common among children living in the Nile Delta. The protective role of breast-feeding demonstrates the importance of promoting exclusive breast-feeding during, at least, the first 6 months of life.

  18. Diarrhea burden due to natural infection with enterotoxigenic Escherichia coli in a birth cohort in a rural Egyptian community.

    PubMed

    Mansour, A; Shaheen, H I; Amine, M; Hassan, K; Sanders, J W; Riddle, M S; Armstrong, A W; Svennerholm, A M; Sebeny, P J; Klena, J D; Young, S Y N; Frenck, R W

    2014-07-01

    Enterotoxigenic Escherichia coli (ETEC) is commonly associated with diarrhea in Egyptian children. Children less than 3 years old in Abu Homos, Egypt, had approximately five diarrheal episodes per child every year, and at least one of these episodes was due to ETEC. The epidemiology of ETEC diarrhea among children living in a rural Egyptian community was further evaluated in this study. Between January 2004 and April 2007, 348 neonates were enrolled and followed for 2 years. Children were visited twice weekly, and a stool sample was obtained every 2 weeks regardless of symptomatology. A stool sample was obtained whenever a child had diarrhea. From the routine stool culture, five E. coli-like colonies were selected and screened for heat-labile and heat-stable toxins by GM1 enzyme-linked immunosorbent assay (ELISA) and further typed for colonization factor antigens by dot blot assay. Incidence of ETEC infection was estimated among children with diarrhea (symptomatic) and without diarrhea (asymptomatic). Incidence of diarrhea and ETEC-associated diarrhea was 7.8 and 1.48 per child-year, respectively. High risk of repeated ETEC diarrhea was associated with being over 6 months of age, warm season, male gender, and crowded sleeping conditions. Exclusive breast-feeding was protective for repeated ETEC infection. ETEC-associated diarrhea remains common among children living in the Nile Delta. The protective role of breast-feeding demonstrates the importance of promoting exclusive breast-feeding during, at least, the first 6 months of life. PMID:24829232

  19. Rituximab as Successful Adjunct Treatment in a Patient With Disseminated Nontuberculous Mycobacterial Infection Due to Acquired Anti–Interferon-γ Autoantibody

    PubMed Central

    Czaja, Christopher A.; Merkel, Patricia A.; Chan, Edward D.; Lenz, Laurel L.; Wolf, Molly L.; Alam, Rafeul; Frankel, Stephen K.; Fischer, Aryeh; Gogate, Shaila; Perez-Velez, Carlos M.; Knight, Vijaya

    2014-01-01

    An acquired immune deficiency due to interferon gamma (IFN-γ) autoantibodies was diagnosed in a 78-year-old Japanese man with treatment-refractory disseminated nontuberculous mycobacterial infection. In addition to standard antimycobacterial therapy, he was successfully treated with rituximab to eliminate B cells and thereby the autoantibody. Subsequently, he obtained a sustained remission from infection. PMID:24336756

  20. Implantation of mitral, aortic, and tricuspid bioprostheses due to infective endocarditis with necessary reimplantation of the bioprosthetic aortic valve

    PubMed Central

    Bugajski, Paweł; Olszewski, Roman; Greberski, Krzysztof; Kalawski, Ryszard

    2016-01-01

    The patient was admitted to the Department of Cardiac Surgery of the J. Struś City Hospital in Poznan due to infective endocarditis involving the aortic, mitral, and tricuspid valves. Implantation of three biological valve prostheses proceeded without complications. Starting on day 23, the patient's general condition deteriorated, with high fever. Despite postoperative antibiotic therapy, transesophageal echocardiography revealed the presence of vegetation on the bioprosthetic aortic valve. On the 46th day after the initial surgery, the patient required replacement of the aortic bioprosthesis, which exhibited the presence of numerous vegetations. The bioprosthetic mitral and tricuspid valves were not affected by the degenerative process. On the 12th day after the reimplantation of the bioprosthetic aortic valve, the patient was discharged from the hospital in good general condition. PMID:27785140

  1. Three Phases of CD8 T Cell Response in the Lung Following H1N1 Influenza Infection and Sphingosine 1 Phosphate Agonist Therapy

    PubMed Central

    Matheu, Melanie P.; Teijaro, John R.; Walsh, Kevin B.; Greenberg, Milton L.; Marsolais, David; Parker, Ian; Rosen, Hugh; Oldstone, Michael B A.; Cahalan, Michael D.

    2013-01-01

    Influenza-induced lung edema and inflammation are exacerbated by a positive feedback loop of cytokine and chemokine production termed a ‘cytokine storm’, a hallmark of increased influenza-related morbidity and mortality. Upon infection, an immune response is rapidly initiated in the lungs and draining lymph node, leading to expansion of virus-specific effector cells. Using two-photon microscopy, we imaged the dynamics of dendritic cells (DC) and virus-specific eGFP+CD8+ T cells in the lungs and draining mediastinal lymph nodes during the first two weeks following influenza infection. Three distinct phases of T cell and CD11c+ DC behavior were revealed: 1) Priming, facilitated by the arrival of lung DCs in the lymph node and characterized by antigen recognition and expansion of antigen-specific CD8+ T cells; asymmetric T cell division in contact with DCs was frequently observed. 2) Clearance, during which DCs re-populate the lung and T cells leave the draining lymph node and re-enter the lung tissue where enlarged, motile T cells come into contact with DCs and form long-lived interactions. 3) Maintenance, characterized by T-cell scanning of the lung tissue and dissociation from local antigen presenting cells; the T cells spend less time in association with DCs and migrate rapidly on collagen. A single dose of a sphingosine-1-phosphate receptor agonist, AAL-R, sufficient to suppress influenza-induced cytokine-storm, altered T cell and DC behavior during influenza clearance, delaying T cell division, cellular infiltration in the lung, and suppressing T-DC interactions in the lung. Our results provide a detailed description of T cell and DC choreography and dynamics in the lymph node and the lung during influenza infection. In addition, we suggest that phase lags in T cell and DC dynamics induced by targeting S1P receptors in vivo may attenuate the intensity of the immune response and can be manipulated for therapeutic benefit. PMID:23533579

  2. Lung CD8+ T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8+ T Cells

    PubMed Central

    Wen, Sherry C.; Schuster, Jennifer E.; Gilchuk, Pavlo; Boyd, Kelli L.; Joyce, Sebastian

    2015-01-01

    ABSTRACT Human metapneumovirus (HMPV) is a major cause of respiratory disease in infants, the elderly, and immunocompromised individuals worldwide. There is currently no licensed HMPV vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate because they are noninfectious and elicit a neutralizing antibody response. However, studies show that serum neutralizing antibodies are insufficient for complete protection against reinfection and that adaptive T cell immunity is important for viral clearance. HMPV and other respiratory viruses induce lung CD8+ T cell (TCD8) impairment, mediated by programmed death 1 (PD-1). In this study, we generated HMPV VLPs by expressing the fusion and matrix proteins in mammalian cells and tested whether VLP immunization induces functional HMPV-specific TCD8 responses in mice. C57BL/6 mice vaccinated twice with VLPs and subsequently challenged with HMPV were protected from lung viral replication for at least 20 weeks postimmunization. A single VLP dose elicited F- and M-specific lung TCD8s with higher function and lower expression of PD-1 and other inhibitory receptors than TCD8s from HMPV-infected mice. However, after HMPV challenge, lung TCD8s from VLP-vaccinated mice exhibited inhibitory receptor expression and functional impairment similar to those of mice experiencing secondary infection. HMPV challenge of VLP-immunized μMT mice also elicited a large percentage of impaired lung TCD8s, similar to mice experiencing secondary infection. Together, these results indicate that VLPs are a promising vaccine candidate but do not prevent lung TCD8 impairment upon HMPV challenge. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of acute respiratory disease for which there is no licensed vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate and induce antibodies, but T cell responses are less defined. Moreover, HMPV and other respiratory viruses induce lung CD8+ T cell (TCD8) impairment mediated by

  3. Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity.

    PubMed Central

    Lu, H.; Yang, X.; Takeda, K.; Zhang, D.; Fan, Y.; Luo, M.; Shen, C.; Wang, S.; Akira, S.; Brunham, R. C.

    2000-01-01

    BACKGROUND: Interferon (IFN)-gamma is a key to protective immunity against a variety of intracellular bacterial infections, including Chlamydia trachomatis. Interleukin (IL)-18, a recently identified Th1 cytokine, together with IL-12 is a strong stimulator for IFN-gamma production. We investigated the relative roles of IL-18 and IL- 12 in protective immunity to C. trachomatis mouse pneumonitis (MoPn) infection using gene knockout (KO) and wild-type (WT) mice. MATERIALS AND METHODS: Mice were intranasally infected with C. trachomatis MoPn and protective immunity was assessed among groups of mice by daily body weight changes, lung growth of MoPn, and histopathological appearances at day 10 postinfection. The corresponding immune responses for each group of mice at the same postinfection time point were evaluated by measuring antigen-specific antibody isotype responses and cytokine profiles. RESULTS: Our results showed that IL-18 deficiency had little or no influence on clearance of MoPn from the lung, although KO mice exhibited slightly more severe inflammatory reactions in lung tissues, as well as reduced systemic and local IFN-gamma production, compared with WT mice. Results with IL-18 KO mice were in sharp contrast to those observed with IL-12 KO mice that showed substantially reduced clearance of MoPn from the lungs, substantial reductions of antigen-specific systemic and lung IFN-gamma production, decreased ratio of MoPn-specific immunoglobulin G (IgG)2a/IgG1, and severe pathological changes in the lung with extensive polymorphonuclear, instead of mononuclear, cell infiltration. Exogenous IL-12 or IL-18 was able to increase IFN-gamma production in IL-18 KO mice; whereas, only exogenous IL-12, but not IL-18, enhanced IFN-gamma production in IL-12 KO mice. Caspase-1 is the key protease for activation of IL-18 precursor into the bioactive form, and caspase-1 KO mice also displayed similar bacterial clearance and body weight loss to that in WT mice at early stages

  4. Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus.

    PubMed

    Zhou, Yu-Feng; Shi, Wei; Yu, Yang; Tao, Meng-Ting; Xiong, Yan Q; Sun, Jian; Liu, Ya-Hong

    2015-01-01

    Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid E max model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 μg/mL, respectively. The BBCs (32-64 μg/mL) and MBECs (64-256 μg/mL) of these study strains were much higher than their corresponding BPC values (1-2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R (2) = 96.2%) and the MBIC (fT > MBIC, R (2) = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R (2) = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for

  5. Pharmacokinetic/Pharmacodynamic Correlation of Cefquinome Against Experimental Catheter-Associated Biofilm Infection Due to Staphylococcus aureus

    PubMed Central

    Zhou, Yu-Feng; Shi, Wei; Yu, Yang; Tao, Meng-Ting; Xiong, Yan Q.; Sun, Jian; Liu, Ya-Hong

    2016-01-01

    Biofilm formations play an important role in Staphylococcus aureus pathogenesis and contribute to antibiotic treatment failures in biofilm-associated infections. The aim of this study was to evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of cefquinome against an experimental catheter-related biofilm model due to S. aureus, including three clinical isolates and one non-clinical isolate. The minimal inhibitory concentration (MIC), minimal biofilm inhibitory concentration (MBIC), biofilm bactericidal concentration (BBC), minimal biofilm eradication concentration (MBEC) and biofilm prevention concentration (BPC) and in vitro time-kill curves of cefquinome were studied in both planktonic and biofilm cells of study S. aureus strains. The in vivo post-antibiotic effects (PAEs), PK profiles and efficacy of cefquinome were performed in the catheter-related biofilm infection model in murine. A sigmoid Emax model was utilized to determine the PK/PD index that best described the dose-response profiles in the model. The MICs and MBICs of cefquinome for the four S. aureus strains were 0.5 and 16 μg/mL, respectively. The BBCs (32–64 μg/mL) and MBECs (64–256 μg/mL) of these study strains were much higher than their corresponding BPC values (1–2 μg/mL). Cefquinome showed time-dependent killing both on planktonic and biofilm cells, but produced much shorter PAEs in biofilm infections. The best-correlated PK/PD parameters of cefquinome for planktonic and biofilm cells were the duration of time that the free drug level exceeded the MIC (fT > MIC, R2 = 96.2%) and the MBIC (fT > MBIC, R2 = 94.7%), respectively. In addition, the AUC24h/MBIC of cefquinome also significantly correlated with the anti-biofilm outcome in this model (R2 = 93.1%). The values of AUC24h/MBIC for biofilm-static and 1-log10-unit biofilm-cidal activity were 22.8 and 35.6 h; respectively. These results indicate that the PK/PD profiles of cefquinome could be used as valuable guidance for

  6. Exercise effects on IFN-beta expression and viral replication in lung macrophages after HSV-1 infection.

    PubMed

    Kohut, M L; Davis, J M; Jackson, D A; Jani, P; Ghaffar, A; Mayer, E P; Essig, D A

    1998-12-01

    Mice exercised to fatigue and exposed to herpes simplex virus type 1 (HSV-1) exhibit greater mortality than control mice. In this study, we examined lung macrophage resistance to HSV-1 after exercise in terms of both viral replication and interferon (IFN)-beta production. We utilized the reverse transcriptase-rapid polymerase chain reaction to measure the IFN-beta mRNA content in alveolar macrophages. IFN release was measured with a bioassay, and viral replication within the macrophage was assessed by plaque titration. Exercised (Ex) mice ran on a treadmill until fatigue while control (Con) mice remained in lanes above the treadmill. After exercise, alveolar macrophages were removed and incubated with HSV-1. Alveolar macrophage IFN-beta mRNA was greater in Ex than in Con mice. Culture supernatant from infected macrophages showed a higher degree of IFN release and a higher number of infectious viral particles in Ex vs. Con mice. It is likely that the increase in IFN-beta mRNA occurs in response to a higher degree of viral replication. These results suggest that macrophages from Ex mice are less resistant to infection with HSV-1.

  7. Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection

    SciTech Connect

    Van Loveren, H.; Rombout, P.J.; Wagenaar, S.S.; Walvoort, H.C.; Vos, J.G.

    1988-07-01

    We have investigated the effect of exposure to ozone on defense mechanisms to a respiratory infection with Listeria monocytogenes in the rat. For this purpose rats were continuously exposed to O/sub 3/ concentrations ranging from 0.25 to 2.0 mg/m3 for a period of 1 week. In this model defense to a respiratory infection with Listeria depends on acquired specific cellular immune responses, as well as on natural nonspecific defense mechanisms. The results confirm earlier findings that show that ozone exposure can suppress the capacity of macrophages to ingest and kill Listeria. Moreover, the results show that ozone can also have a suppressive effect on the development of cellular immune responses to a respiratory Listeria infection, i.e., on T/B ratios in lung draining lymph nodes, delayed-type hypersensitivity responses to Listeria antigen, and lymphoproliferative responses in spleen and lung draining lymph nodes to Listeria antigen. The effects on the specific immune responses are especially overt if exposure to the oxidant gas occurs during an ongoing primary infection. The pathological lesions induced by a pulmonary Listeria monocytogenes infection were characterized by multifocal infiltrates of histiocytic and lymphoid cells. The foci sometimes had a granulomatous appearance. Moreover, the cellularity of the interstitial tissues was increased. In the lung many diffuse alveolar macrophages could be seen in the alveoli. Ozone exposure greatly increased the severity of the lung lesions and also of liver lesions resulting from the pulmonary infection. A prominent finding was the formation of granulomas in ozone-exposed and Listeria-infected rats.

  8. NLRC4 inflammasome-mediated production of IL-1β modulates mucosal immunity in the lung against gram-negative bacterial infection.

    PubMed

    Cai, Shanshan; Batra, Sanjay; Wakamatsu, Nobuko; Pacher, Pal; Jeyaseelan, Samithamby

    2012-06-01

    Bacterial flagellin is critical to mediate NLRC4 inflammasome-dependent caspase-1 activation. However, Shigella flexneri, a nonflagellated bacterium, and a flagellin (fliC) knockout strain of Pseudomonas aeruginosa are known to activate NLRC4 in bone marrow-derived macrophages. Furthermore, the flagellin-deficient fliC strain of P. aeruginosa was used in a mouse model of peritonitis to show the requirement of NLRC4. In a model of pulmonary P. aeruginosa infection, flagellin was shown to be essential for the induction of NLRC4-dependent caspase-1 activation. Moreover, in all P. aeruginosa studies, IL-1β production was attenuated in NLRC4(-/-) mice; however, the role of IL-1β in NLRC4-mediated innate immunity in the lungs against a nonflagellated bacterium was not explored. In this article, we report that NLRC4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection. NLRC4 is essential for K. pneumoniae-induced production of IL-1β, IL-17A, and neutrophil chemoattractants (keratinocyte cell-derived chemokines, MIP-2, and LPS-induced CXC chemokines) in the lungs. NLRC4 signaling in hematopoietic cells contributes to K. pneumoniae-induced lung inflammation. Furthermore, exogenous IL-1β, but not IL-18 or IL-17A, partially rescued survival, neutrophil accumulation, and cytokine/chemokine expression in the lungs of NLRC4(-/-) mice following infectious challenge. Furthermore, IL-1R1(-/-) mice displayed a decrease in neutrophilic inflammation in the lungs postinfection. Taken together, these findings provide novel insights into the role of NLRC4 in host defense against K. pneumoniae infection.

  9. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections.

    PubMed

    Han, SeungHye; Mallampalli, Rama K

    2015-05-01

    Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.

  10. Burkholderia pyrrocinia in cystic fibrosis lung transplantation: a case report.

    PubMed

    Savi, D; De Biase, R Valerio; Amaddeo, A; Anile, M; Venuta, F; Ruberto, F; Simmonds, N; Cimino, G; Quattrucci, S

    2014-01-01

    Infection with Burkholderia species is typically considered a contraindication leading to transplantation in cystic fibrosis (CF). However, the risks posed by different Burkholderia species on transplantation outcomes are poorly defined. We present the case of a patient with CF who underwent lung transplantation due to a severe respiratory failure from chronic airways infection with Burkholderia pyrrocinia (B. cepacia genomovar IX) and pan-resistant Pseudomonas aeruginosa. The postoperative course was complicated by recurrent B. pyrrocinia infections, ultimately lea ding to uncontrollable sepsis and death. This is the first case report in CF of Burkholderia pyrrocinia infection and lung transplantation, providing further evidence of the high risk nature of the Burkholderia species.

  11. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    PubMed Central

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.

    2016-01-01

    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  12. MicroRNA expression profiles and networks in mouse lung infected with H1N1 influenza virus.

    PubMed

    Bao, Yanyan; Gao, Yingjie; Jin, Yahong; Cong, Weihong; Pan, Xin; Cui, Xiaolan

    2015-10-01

    Influenza A viruses can cause localized outbreaks and worldwide pandemics, owing to their high transmissibility and wide host range. As such, they are among the major diseases that cause human death. However, the molecular changes induced by influenza A virus infection in lung tissue are not entirely clear. Changes in microRNA (miRNA) expression occur in many pathological and physiological processes, and influenza A virus infection has been shown to alter miRNA expression in cultured cells and animal models. In this study, we mined key miRNAs closely related to influenza A virus infection and explored cellular regulatory mechanisms against influenza A virus infection, by building networks among miRNAs and genes, gene ontologies (GOs), and pathways. In this study, miRNAs and mRNAs induced by H1N1 influenza virus infection were measured by gene chips, and we found that 82 miRNAs and 3371 mRNAs were differentially expressed. The 82 miRNAs were further analyzed with the series test of cluster (STC) analysis. Three of the 16 cluster profiles identified by STC, which include 46 miRNAs in the three profiles, changed significantly. Using potential target genes of the 46 miRNAs, we looked for intersections of these genes with 3371 differentially expressed mRNAs; 719 intersection genes were identified. Based on the GO or KEGG databases, we attained GOs or pathways for all of the above intersection genes. Fisher's and χ (2) test were used to calculate p value and false discovery rate (FDR), and according to the standard of p < 0.001, 241 GOs and 76 pathways were filtered. Based on these data, miRNA-gene, miRNA-GO, and miRNA-pathway networks were built. We then extracted three classes of GOs (related to inflammatory and immune response, cell cycle, proliferation and apoptosis, and signal transduction) to build three subgraphs, and pathways strictly related with H1N1 influenza virus infection were filtered to extract a subgraph of the miRNA-pathway network. Last, according

  13. Control of influenza infection is impaired by diminished interferon-γ secretion by CD4 T cells in the lungs of toddler mice.

    PubMed

    Verhoeven, David; Perry, Sheldon; Pryharski, Karin

    2016-07-01

    Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8-10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus,